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Pruebas de orina para el cribado del síndrome de Down

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Referencias

References to studies included in this review

Ir a:

Bahado‐Singh 1998 {published data only}

Bahado‐Singh RO, Oz UA, Deren O, Acuna E, Cermik D, Mahoney MJ, et al. A new screening protocol combining urine beta‐core fragment and ultrasonography for Down syndrome detection. American Journal of Obstetrics and Gynecology 1998;178(4):779‐82.

Bahado‐Singh 1998b {published data only}

Bahado‐Singh RO, Oz U, Kovanci E, Cermik D, Flores D, Copel J, et al. New triple screen test for Down syndrome: combined urine analytes and serum AFP. Journal of Maternal‐Fetal Medicine 1998;7(3):111‐4.

Bahado‐Singh 1999 {published data only}

Bahado‐Singh R, Oz U, Kovanci E, Cermik D, Copel J, Mahoney MJ, et al. A high‐sensitivity alternative to "routine" genetic amniocentesis: multiple urinary analytes, nuchal thickness, and age. American Journal of Obstetrics and Gynecology 1999;180(1 pt 1):169‐73.

Bahado‐Singh 1999a {published data only}

Bahado Singh, Oz U, Rinne K, Hunter D, Cole L, Mahoney MJ, et al. Elevated maternal urine level of beta‐core fragment of human chorionic gonadotropin versus serum triple test in the second‐trimester detection of Down syndrome. American Journal of Obstetrics and Gynecology 1999;181(4):929‐33.

Bahado‐Singh 2000 {published data only}

Bahado‐Singh R, Oz U, Shahabi S, Omrani A, Mahoney M, Cole L. Urine hyperglycosylated hCG plus ultrasound biometry for detection of down syndrome in the second trimester in a high‐risk population. Obstetrics & Gynecology 2000;95(6 pt 1):889‐94.
Cole LA, Omrani A, Cermik D, Singh RO, Mahoney MJ. Hyperglycosylated hCG, a potential alternative to hCG in Down syndrome screening. Prenatal Diagnosis 1998;18(9):926‐33.
Cole LA, Shahabi S, Oz UA, Bahado‐Singh RO, Mahoney MJ. Hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen) immunoassay: a new basis for gestational Down syndrome screening. Clinical Chemistry 1999;45(12):2109‐19.
Cole LA, Shahabi S, Oz UA, Rinne KM, Omrani A, Bahado‐Singh RO, et al. Urinary screening tests for fetal Down syndrome: II. Hyperglycosylated hCG. Prenatal Diagnosis 1999;19(4):351‐9.

Bahado‐Singh 2000a {published data only}

Bahado‐Singh, Oz U, Shahabi S, Mahoney MJ, Baumgarten A, Cole L. Comparison of urinary hyperglycosylated human chorionic gonadotropin concentration with the serum triple screen for Down syndrome detection in high‐risk pregnancies. American Journal of Obstetrics and Gynecology 2000;183(5):1114‐8.

Canick 1995 {published data only}

Canick JA, Kellner LH, Saller DN, Palomaki GE, Walker RP, Osathanondh R. Second‐trimester levels of maternal urinary gonadotropin peptide in down syndrome pregnancy. Prenatal Diagnosis 1995;15(8):739‐44.

Cole 1997a {published data only}

Cole LA, Jacobs M, Isozaki T, Palomaki GE, Bahado‐Singh RO, Mahoney MJ. Screening for Down syndrome using urine hCG free beta‐subunit in the second trimester of pregnancy. Prenatal Diagnosis 1997;17(12):1107‐11.

Cole 1997b {published data only}

Cole LA, Acuna E, Isozaki T, Palomaki GE, Bahado‐Singh RO, Mahoney MO. Combining beta‐core fragment and total oestriol measurements to test for Down syndrome pregnancies. Prenatal Diagnosis 1997;17(12):1125‐33.

Cole 1999b {published data only}

Cole LA, Rinne KM, Mahajan SM, Oz UA, Shahabi S, Mahoney MJ, et al. Urinary screening tests for fetal Down syndrome: I. Fresh beta‐core fragment.[see comment]. Prenatal Diagnosis 1999;19(4):340‐50.

Cuckle 1995b {published data only}

Cuckle HS, Iles RK, Chard T. Urinary beta‐core human chorionic gonadotrophin: a new approach to Down's syndrome screening. Prenatal Diagnosis 1994;14(10):953‐8.
Cuckle HS, Iles RK, Sehmi IK, Chard T, Oakey RE, Davies S, et al. Urinary multiple marker screening for Down's syndrome.[see comment]. Prenatal Diagnosis 1995;15(8):745‐51.

Cuckle 1999 {published data only}

Cuckle HS, Shahabi S, Sehmi IK, Jones R, Cole LA. Maternal urine hyperglycosylated hCG in pregnancies with Down syndrome. Prenatal Diagnosis. 1999;19(10):918‐20.

Cuckle 1999a {published data only}

Cuckle HS, Canick JA, Kellner LH. Collaborative study of maternal urine beta ‐core human chorionic gonadotrophin screening for Down syndrome. Prenatal Diagnosis 1999;19(10):911‐7.

Hsu 1999 {published data only}

Hsu JJ, Hsu TY, Hsieh TT, Soong YK, Hsieh FJ, Spencer K. Urine free beta‐hCG and total estriol for Down syndrome screening during the second trimester in an Asian population. Obstetrics & Gynecology 1999;94(1):107‐11.
Hsu JJ, Hung TH, Liou JD, Hsieh TT, Soong YK. Elevated second‐trimester maternal urine free beta‐human chorionic gonadotropin levels in Asian pregnancies with fetal chromosomal abnormalities. Fetal Diagnosis and Therapy 1998;13(6):352‐6.
Hsu JJ, Spencer K, Aitken DA, Crossley J, Choi T, Ozaki M, et al. Urinary free beta hCG, beta core fragment and total oestriol as markers of Down syndrome in the second trimester of pregnancy. Prenatal Diagnosis 1999;19:146‐58.
Hsu JJ, Spencer K, Hung TH, Hsieh TT, Soong YK. Second‐trimester maternal urine human chorionic gonadotrophin beta‐core fragment concentrations in Asian pregnancies with fetal chromosomal abnormalities. Human Reproduction 1999;14(9):2381‐5.

Isozaki 1997 {published data only}

Isozaki T, Palomaki GE, Bahado‐Singh RO, Cole LA. Screening for Down syndrome pregnancy using beta‐core fragment: prospective study. Prenatal Diagnosis 1997;17(5):407‐13.

Palomaki 2004a {published data only}

Palomaki GE, Knight GJ, Roberson MM, Cunningham GC, Lee JE, Strom CM, et al. Invasive trophoblast antigen (hyperglycosylated human chorionic gonadotropin) in second‐trimester maternal urine as a marker for down syndrome: preliminary results of an observational study on fresh samples. Clinical Chemistry 2004;50(1):182‐9.

Spencer 1996 {published data only}

Spencer K, Aitken DA, Macri JN, Buchanan PD. Urine free beta hCG and beta core in pregnancies affected by Down's syndrome. Prenatal Diagnosis 1996;16(7):605‐13.

Wald 2003 {published data only}

Wald NJ, Rodeck C, Hackshaw AK, Rudnicka A. SURUSS in perspective. Seminars in Perinatology 2005;29(4):225‐35.
Wald NJ, Rodeck C, Hackshaw AK, Rudnicka A. SURUSS in perspective.[see comment]. BJOG: an international journal of obstetrics and gynaecology 2004;111(6):521‐31.
Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM. First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). Journal of Medical Screening 2003;10(2):56‐104.
Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM, SURUSS Research Group. First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). Health Technology Assessment (Winchester, England) 2003;7(11):1‐77.

Weinans 2000 {published data only}

Weinans MJ, Butler SA, Mantingh A, Cole LA. Urinary hyperglycosylated hCG in first trimester screening for chromosomal abnormalities. Prenatal Diagnosis 2000;20(12):976‐8.

References to studies excluded from this review

Ir a:

Abbas 1995 {published data only}

Abbas A, Chard T, Nicolaides K. Fetal and maternal hCG concentration in aneuploid pregnancies. British Journal of Obstetrics and Gynaecology 1995;102(7):561‐3.

Abdul‐Hamid 2004 {published data only}

Abdul‐Hamid S, Fox R, Martin I. Maternal serum screening for trisomy 21 in women with a false positive result in last pregnancy. Journal of Obstetrics & Gynaecology 2004;24(4):374‐6.

Abraha 1999 {published data only}

Abraha HD, Noble PL, Nicolaides KH, Sherwood RA. Maternal serum S100 protein in normal and Down syndrome pregnancies. Prenatal Diagnosis 1999;19(4):334‐6.

Adekunle 1999 {published data only}

Adekunle O, Gopee A, el‐Sayed M, Thilaganathan B. Increased first trimester nuchal translucency: pregnancy and infant outcomes after routine screening for Down's syndrome in an unselected antenatal population. British Journal of Radiology 1999;72(857):457‐60.

Aitken 1993 {published data only}

Aitken DA, McCaw G, Crossley JA, Berry E, Connor JM, Spencer K, et al. First‐trimester biochemical screening for fetal chromosome abnormalities and neural tube defects. Prenatal Diagnosis 1993;13(8):681‐9.

Aitken 1996a {published data only}

Aitken DA, Syvertsen BS, Crossley JA, Berry E, Connor JM. Heat‐stable and immunoreactive placental alkaline phosphatase in maternal serum from Down's syndrome and trisomy 18 pregnancies.[see comment]. Prenatal Diagnosis 1996;16(11):1051‐4.

Aitken 1996b {published data only}

Aitken DA, Wallace EM, Crossley JA, Swanston IA, Van Pareren Y, Van Maarle M, et al. Dimeric Inhibin A as a marker for Down's syndrome in early pregnancy. New England Journal of Medicine 1996;334(19):1231‐6.

Akbas 2001 {published data only}

Akbas SH, Ozben T, Alper O, Ugur A, Yucel G, Luleci G. Maternal serum screening for Down's syndrome, open neural tube defects and trisomy 18. Clinical Chemistry & Laboratory Medicine 2001;39(6):487‐90.

Antona 1998 {published data only}

Antona D, Wallace EM, Shearing C, Ashby JP, Groome NP. Inhibin A and pro‐alphaC Inhibin A in Down syndrome and normal pregnancies. Prenatal Diagnosis 1998;18(11):1122‐6.

Antsaklis 1999 {published data only}

Antsaklis A, Papantoniou N, Mesogitis S, Michalas S, Aravantinos D. Pregnant women of 35 years of age or more: maternal serum markers or amniocentesis?. Journal of Obstetrics and Gynaecology 1999;19(3):253‐6.

Ashwood 1987 {published data only}

Ashwood ER, Cheng E, Luthy DA. Maternal serum alpha‐fetoprotein and fetal trisomy‐21 in women 35 years and older: implications for alpha‐fetoprotein screening programs. American Journal of Medical Genetics 1987;26(3):531‐9.

Asrani 2005 {published data only}

Asrani CH. Triple marker. National Journal of Homoeopathy 2005;7(3):174.

Audibert 2001b {published data only}

Audibert F, Dommergues M, Benattar C, Taieb J, Thalabard JC, Frydman R. Screening for Down syndrome using first‐trimester ultrasound and second‐trimester maternal serum markers in a low‐risk population: a prospective longitudinal study. Ultrasound in Obstetrics & Gynecology 2001;18(1):26‐31.

Axt‐Fleidner 2006 {published data only}

Axt‐Fliedner R, Schwarze A, Kreiselmaier P, Krapp M, Smrcek J, Diedrich K. Umbilical cord diameter at 11‐14 weeks of gestation: relationship to nuchal translucency, ductus venous blood flow and chromosomal defects. Fetal Diagnosis and Therapy 2006;21(4):390‐5.

Azuma 2002 {published data only}

Azuma M, Yamamoto R, Wakui Y, Minobe S, Satomura S, Fujimoto S. A novel method for the detection of Down syndrome with the use of four serum markers. American Journal of Obstetrics and Gynecology 2002;187(1):197‐201.

Baghagho 2004 {published data only}

Baghagho EE, Kharboush IF, El‐Kaffash DM, KarKour TA, Ismail SR, Mortada MM. Maternal serum alpha fetoprotein among pregnant females in Alexandria. Journal of the Egyptian Public Health Association 2004;79(1‐2):59‐81.

Bahado‐Singh 1995 {published data only}

Bahado Singh, Goldstein I, Uerpairojkit B, Copel JA, Mahoney MJ, Baumgarten A. Normal nuchal thickness in the midtrimester indicates reduced risk of Down syndrome in pregnancies with abnormal triple‐screen results. American Journal of Obstetrics and Gynecology 1995;173(4):1106‐0.

Bahado‐Singh 1996 {published data only}

Bahado‐Singh RO, Tan A, Deren O, Hunter D, Copel J, Mahoney MJ. Risk of Down syndrome and any clinically significant chromosome defect in pregnancies with abnormal triple‐screen and normal targeted ultrasonography results. American Journal of Obstetrics and Gynecology 1996;175(4 Pt 1):824‐9.

Bahado‐Singh 1999b {published data only}

Bahado‐Singh RO, Oz AU, Flores D, Cermik D, Acuna E, Mahoney MJ, et al. Nuchal thickness, urine ß‐core fragment level, and maternal age for down syndrome screening. American Journal of Obstetrics and Gynecology 1999;180(2 Pt 1):491‐5.

Bahado‐Singh 2002 {published data only}

Bahado‐Singh RO, Shahabi S, Karaca M, Mahoney MJ, Cole L, Oz UA. The comprehensive midtrimester test: high‐sensitivity Down syndrome test. American Journal of Obstetrics and Gynecology 2002;186(4):803‐8.

Bahado‐Singh 2003 {published data only}

Bahado‐Singh RO, Cheng CC, Matta P, Small M, Mahoney MJ. Combined serum and ultrasound screening for detection of fetal aneuploidy. Seminars in Perinatology 2003;27(2):145‐51.

Bar‐Hava 2001 {published data only}

Bar‐Hava I, Yitzhak M, Krissi H, Shohat M, Shalev J, Czitron B, et al. Triple‐test screening in in vitro fertilization pregnancies. Journal of Assisted Reproduction and Genetics 2001;18(4):226‐9.

Barkai 1996 {published data only}

Barkai G, Goldman B, Ries L, Chaki R, Dor J, Cuckle H. Down's syndrome screening marker levels following assisted reproduction. Prenatal Diagnosis 1996;16(12):1111‐4.

Barnabei 1995 {published data only}

Barnabei VM, Krantz DA, Macri JN, Larsen JW. Enhanced twin pregnancy detection within an open neural tube defect and Down syndrome screening protocol using free‐ß hCG and AFP. Prenatal Diagnosis 1995;15(12):1131‐4.

Bartels 1988 {published data only}

Bartels I, Lindemann A. Maternal levels of pregnancy‐specific ß 1‐glycoprotein (SP‐1) are elevated in pregnancies affected by Down's syndrome. Human Genetics 1988;80(1):46‐8.

Bartels 1993 {published data only}

Bartels I, Hoppe‐Sievert B, Bockel B, Herold S, Caesar J. Adjustment formulae for maternal serum alpha‐fetoprotein, human chorionic gonadotropin, and unconjugated oestriol to maternal weight and smoking. Prenatal Diagnosis 1993;13(2):123‐30.

Barth 1991 {published data only}

Barth WH, Frigoletto FD, Krauss CM, MacMillin MD, Stryker JM, Benacerraf BR. Ultrasound detection of fetal aneuploidy in women with elevated maternal serum alpha‐fetoprotein. Obstetrics & Gynecology 1991;77(6):897‐900.

Baviera 2004 {published data only}

Baviera G, Carbone C, Corrado F, Mastrantonio P. Placental growth hormone in Down's syndrome screening. Journal of Maternal‐Fetal & Neonatal Medicine 2004;16(4):241‐3.

Bazzett 1998 {published data only}

Bazzett LB, Yaron Y, O'Brien JE, Critchfield G, Kramer RL, Ayoub M, et al. Fetal gender impact on multiple‐marker screening results. American Journal of Medical Genetics 1998;76(5):369‐71.

Bellver 2005 {published data only}

Bellver J, Lara C, Soares SR, Ramirez A, Pellicer A, Remohi J, et al. First trimester biochemical screening for Down's syndrome in singleton pregnancies conceived by assisted reproduction. Human Reproduction 2005;20(9):2623‐7.

Benn 1995 {published data only}

Benn PA, Horne D, Briganti S, Greenstein RM. Prenatal diagnosis of diverse chromosome abnormalities in a population of women identified by triple‐marker testing as screen positive for Down syndrome. American Journal of Obstetrics and Gynecology 1995;173(2):496‐501.

Benn 1996 {published data only}

Benn PA, Horne D, Craffey A, Collins R, Ramsdell L, Greenstein R. Maternal serum screening for birth defects: results of a Connecticut regional program. Connecticut Medicine 1996;60(6):323‐7.

Benn 1997 {published data only}

Benn PA, Clive JM, Collins R. Medians for second‐trimester maternal serum alpha‐fetoprotein, human chorionic gonadotropin, and unconjugated estriol; differences between races or ethnic groups. Clinical Chemistry 1997;43(2):333‐7.

Benn 1998 {published data only}

Benn PA. Preliminary evidence for associations between second‐trimester human chorionic gonadotropin and unconjugated oestriol levels with pregnancy outcome in Down syndrome pregnancies. Prenatal Diagnosis 1998;18(4):319‐24.

Benn 2001 {published data only}

Benn PA, Ying J, Beazoglou T, Egan JF. Estimates for the sensitivity and false‐positive rates for second trimester serum screening for Down syndrome and trisomy 18 with adjustment for cross‐identification and double‐positive results. Prenatal Diagnosis 2001;21(1):46‐51.

Benn 2002 {published data only}

Benn PA, Kaminsky LM, Ying J, Borgida AF, Egan JF. Combined second‐trimester biochemical and ultrasound screening for Down syndrome. Obstetrics & Gynecology 2002;100(6):1168‐76.

Benn 2003a {published data only}

Benn PA, Fang M, Egan JFX, Horne D, Collins R. Incorporation of inhibin‐A in second‐trimester screening for Down syndrome. Obstetrics and Gynecology 2003;101(3):451‐4.

Benn 2003b {published data only}

Benn P. Improved antenatal screening for Down's syndrome. Lancet 2003;361(9360):794‐5.

Benn 2005a {published data only}

Benn P, Wright D, Cuckle H. Practical strategies in contingent sequential screening for Down syndrome. Prenatal Diagnosis 2005;25(8):645‐52.

Benn 2005b {published data only}

Benn P, Donnenfeld AE. Sequential Down syndrome screening: the importance of first and second trimester test correlations when calculating risk. Journal of Genetic Counseling 2005;14(6):409‐13.

Berry 1995 {published data only}

Berry E, Aitken DA, Crossley JA, Macri JN, Connor JM. Analysis of maternal serum alpha‐fetoprotein and free ß human chorionic gonadotrophin in the first trimester: implications for Down's syndrome screening. Prenatal Diagnosis 1995;15(6):555‐65.

Berry 1997 {published data only}

Berry E, Aitken DA, Crossley JA, Macri JN, Connor JM. Screening for Down's syndrome: changes in marker levels and detection rates between first and second trimesters. British Journal of Obstetrics and Gynaecology 1997;104(7):811‐7.

Bersinger 1994 {published data only}

Bersinger NA, Brizot ML, Johnson A, Snijders RJ, Abbott J, Schneider H, et al. First trimester maternal serum pregnancy‐associated plasma protein A and pregnancy‐specific ß 1‐glycoprotein in fetal trisomies. British Journal of Obstetrics and Gynaecology 1994;101(11):970‐4.

Bersinger 2000 {published data only}

Bersinger NA, Xin WZ. Glycosylation of pregnancy‐associated plasma protein a (PAPP‐A) and pregnancy‐specific (ß)(1)‐glycoprotein (SP1): relevance for fetal down syndrome screening and for placental function studies. Immuno‐Analyse et Biologie Specialisee 2000;15(6):402‐8.

Bersinger 2001 {published data only}

Bersinger NA, Chanson A, Crazzolara S, Hänggi W, Pescia G, Scheier M, et al. Serum levels of placenta protein markers: the relevance of differences between spontaneous and after in vitro fertilization pregnancies for fetal trisomy screening. Journal fur Fertilitat und Reproduktion 2001;11(3):7‐13.

Bersinger 2003 {published data only}

Bersinger NA, Noble P, Nicolaides KH. First‐trimester maternal serum PAPP‐A, SP1 and M‐CSF levels in normal and trisomic twin pregnancies. Prenatal Diagnosis 2003;23(2):157‐62.

Bersinger 2004 {published data only}

Bersinger NA, Wunder D, Vanderlick F, Chanson A, Pescia G, Janecek P, et al. Maternal serum levels of placental proteins after in vitro fertilisation and their implications for prenatal screening. Prenatal Diagnosis 2004;24(6):471‐7.

Bersinger 2005 {published data only}

Bersinger NA, Vanderlick F, Birkhäuser MH, Janecek P, Wunder D. First trimester serum concentrations of placental proteins in singleton and multiple IVF pregnancies: implications for Down syndrome screening. Immuno‐Analyse et Biologie Specialisee 2005;20(1):21‐7.

Biggio 2004 {published data only}

Biggio JR, Morris TC, Owen J, Stringer JSA. An outcomes analysis of five prenatal screening strategies for trisomy 21 in women younger than 35 years. American Journal of Obstetrics and Gynecology 2004;190(3):721‐9.

Bindra 2002 {published data only}

Bindra R, Heath V, Nicolaides KH. Screening for chromosomal defects by fetal nuchal translucency at 11 to 14 weeks. Clinical Obstetrics and Gynecology 2002;45(3):661‐70.

Blundell 1999 {published data only}

Blundell G, Ashby JP, Martin C, Shearing CH, Langdale‐Brown B, Keeling J, et al. Clinical follow‐up of high mid‐trimester maternal serum intact human chorionic gonadotrophin concentrations in singleton pregnancies. Prenatal Diagnosis 1999;19(3):219‐23.

Boots 1989 {published data only}

Boots LR, Davis RO, Foster JM, Goldenberg RL. Maternal serum alpha‐fetoprotein prenatal screening for Down syndrome. Alabama Medicine 1989;59(1):25‐7.

Borruto 2002 {published data only}

Borruto F, Comparetto C, Acanfora L, Bertini G, Rubaltelli FF. Role of ultrasound evaluation of nuchal translucency in prenatal diagnosis. Clinical & Experimental Obstetrics & Gynecology 2002;29(4):235‐41.

Boue 1990 {published data only}

Boue A, Muller F. Screening for Down's syndrome with maternal serum human chorionic gonadotropin at midtrimester. Current Opinion in Pediatrics 1990;2(6):1157‐60.

Bradley 1994 {published data only}

Bradley LA, Horwitz JA, Dowman AC, Ponting NR, Peterson LM. Triple marker screening for fetal Down syndrome. International Pediatrics 1994;9(3):168‐74.

Braithwaite 1996 {published data only}

Braithwaite JM, Economides DL. Nuchal translucency and screening for Down's syndrome. Contemporary Reviews in Obstetrics and Gynaecology 1996;8(2):75‐81.

Brambati 1995 {published data only}

Brambati B, Cislaghi C, Tului L, Alberti E, Amidani M, Colombo U, et al. First‐trimester Down's syndrome screening using nuchal translucency: a prospective study in women undergoing chorionic villus sampling. Ultrasound in Obstetrics & Gynecology 1995;5(1):9‐14.

Brambati 1996 {published data only}

Brambati B, Tului L, Alberti E. Sonography in the first trimester screening of trisomy 21 and other fetal aneuploidies. Early Pregnancy 1996;2(3):155‐67.

Brizot 1995a {published data only}

Brizot ML, Bersinger NA, Xydias G, Snijders RJ, Nicolaides KH. Maternal serum Schwangerschafts protein‐1 (SP1) and fetal chromosomal abnormalities at 10‐13 weeks' gestation. Early Human Development. 1995;43(1):31‐6.

Brizot 1995b {published data only}

Brizot ML, Kuhn P, Bersinger NA, Snijders RJ, Nicolaides KH. First trimester maternal serum alpha‐fetoprotein in fetal trisomies. British Journal of Obstetrics and Gynaecology 1995;102(1):31‐4.

Brizzi 1989b {published data only}

Brizzi L, Cariati E, Periti E, Nannini R, Torricelli F, Cappelli G, et al. Evaluation of maternal serum alpha‐fetoprotein and ultrasound examination to screen fetal chromosomal abnormalities. Journal of Nuclear Medicine & Allied Sciences 1989;33(3 Suppl):85‐8.

Brock 1990 {published data only}

Brock DJ, Barron L, Holloway S, Liston WA, Hillier SG, Seppala M. First‐trimester maternal serum biochemical indicators in Down syndrome. Prenatal Diagnosis 1990;10(4):245‐51.

Campogrande 2001 {published data only}

Campogrande M, Viora E, Errante G, Bastonero S, Sciarrone A, Grassi Pirrone P, et al. Correlations between first and second trimester markers for Down's syndrome screening. Journal of Medical Screening 2001;8(3):163‐4.

Canick 1988 {published data only}

Canick JA, Knight GJ, Palomaki GE, Haddow JE, Cuckle HS, Wald NJ. Low second trimester maternal serum unconjugated oestriol in pregnancies with Down's syndrome. British Journal of Obstetrics and Gynaecology 1988;95(4):330‐3.

Canick 1995b {published data only}

Canick JA, Kellner LH, Saller DN, Palomaki GE, Walker RP, Osathanondh R. Second‐trimester levels of maternal urinary gonadotropin peptide in down syndrome pregnancy. Prenatal Diagnosis 1995;15(8):739‐44.

Canini 2002 {published data only}

Canini S, Prefumo F, Famularo L, Venturini PL, Palazzese V, De Biasio P. Comparison of first trimester, second trimester and integrated Down's syndrome screening results in unaffected pregnancies. Clinical Chemistry & Laboratory Medicine 2002;40(6):600‐3.

Cans 1998 {published data only}

Cans C, Amblard F, Devillard F, Pison H, Jalbert P, Jouk PS. Population screening for aneuploidy using maternal age and ultrasound. Prenatal Diagnosis 1998;18(7):683‐92.

Carreras 1991 {published data only}

Carreras de Paz JJ, Silva Mendoza JM, Violante Diaz M, Cerrillo Hinojosa M, Ahued Ahued JR. [Proposed normal values for alpha fetoprotein in maternal serum for the detection of neural tube closure defects and Down syndrome. Preliminary study]. [Spanish]. Ginecologia y Obstetricia de Mexico 1991;59:261‐4.

Chen 1999 {published data only}

Chen FM. Integrated screening for Down's syndrome. Journal of Family Practice 1999;48(11):846‐7.

Chen 2002 {published data only}

Chen M, Lam YH, Tang MH, Lee CP, Sin SY, Tang R, et al. The effect of ethnic origin on nuchal translucency at 10‐14 weeks of gestation. Prenatal Diagnosis 2002;22(7):576‐8.

Chen 2004 {published data only}

Chen M, Lam YH, Lee CP, Tang MHY. Ultrasound screening of fetal structural abnormalities at 12 to 14 weeks in Hong Kong. Prenatal Diagnosis 2004;24(2):92‐7.

Chen 2005 {published data only}

Chen CP, Lin CJ, Wang W. Impact of second‐trimester maternal serum screening on prenatal diagnosis of Down syndrome and the use of amniocentesis in the Taiwanese population. Taiwanese Journal of Obstetrics and Gynecology 2005;44(1):31‐5.

Cheng 1993 {published data only}

Cheng EY, Luthy DA, Zebelman AM, Williams MA, Lieppman RE, Hickok DE. A prospective evaluation of a second‐trimester screening test for fetal Down syndrome using maternal serum alpha‐fetoprotein, hCG, and unconjugated estriol. Obstetrics & Gynecology 1993;81(1):72‐7.

Cheng 1999 {published data only}

Cheng PJ, Liu CM, Chang SD, Lin YT, Soong YK. Elevated second‐trimester maternal serum hCG in women undergoing haemodialysis. Prenatal Diagnosis 1999;19(10):955‐8.

Cheng 2004a {published data only}

Cheng CC, Bahado‐Singh RO, Chen SC, Tsai MS. Pregnancy outcomes with increased nuchal translucency after routine Down syndrome screening. International Journal of Gynaecology & Obstetrics 2004;84(1):5‐9.

Cheng 2004b {published data only}

Cheng PJ, Chu DC, Chueh HY, See LC, Chang HC, Weng DR. Elevated maternal midtrimester serum free ß‐human chorionic gonadotropin levels in vegetarian pregnancies that cause increased false‐positive Down syndrome screening results. American Journal of Obstetrics and Gynecology 2004;190(2):442‐7.

Chitayat 2002 {published data only}

Chitayat D, Farrell SA, Huang T, Meier C, Wyatt PR, Summers AM. Double‐positive maternal serum screening results for down syndrome and open neural tube defects: an indicator for fetal structural or chromosomal abnormalities and adverse obstetric outcomes. American Journal of Obstetrics and Gynecology 2002;187(3):758‐63.

Christiansen 2002 {published data only}

Christiansen M, Hogdall EV, Larsen SO, Hogdall C. The variation of risk estimates through pregnancy in second trimester maternal serum screening for Down syndrome. Prenatal Diagnosis 2002;22(5):385‐7.

Christiansen 2007 {published data only}

Christiansen M, Sorensen TL, Norgaard‐Pedersen B. Human placental lactogen is a first‐trimester maternal serum marker of Down syndrome. Prenatal Diagnosis 2007;27(1):1‐5.

Chung 2000 {published data only}

Chung BL, Kim YP, Nam MH. The application of three‐dimensional ultrasound to nuchal translucency thickness measurement at 10‐14 weeks of gestation. Prenatal and Neonatal Medicine 2000;5(1):17‐21.

CNGOF 1996 {published data only}

Anon. Blood screening of Down's syndrome (Trisomy 21) and reimbursement of karyotype for women under 38. Revue Francaise de Gynecologie et d'Obstetrique 1996;91(11):575‐7.

Cole 1996 {published data only}

Cole L, Isozaki T, Palomaki G, Canick J, Iles R, Kellner L, et al. Detection of ß‐core fragment in second trimester Down's syndrome pregnancies. [Review]. Early Human Development 1996;47 Suppl:S47‐S8.

Comas 2001 {published data only}

Comas C, Antolín E, Torrents M, Muñoz A, Figueras F, Echevarría M, et al. Early screening for chromosomal abnormalities: new strategies combining biochemical, sonographic and doppler parameters. Prenatal and Neonatal Medicine 2001;6(2):95‐102.

Comas 2002a {published data only}

Comas C, Torrents M, Munoz A, Antolin E, Figueras F, Echevarria M. Measurement of nuchal translucency as a single strategy in trisomy 21 screening: should we use any other marker?. Obstetrics & Gynecology 2002;100(4):648‐54.

Comas 2002b {published data only}

Comas C, Carrera JM. Early sonographic screening for chromosomal abnormalities. Ultrasound Review of Obstetrics and Gynecology 2002;2(2):88‐91.

Comstock 2006 {published data only}

Comstock CH, Malone FD, Ball RH, Nyberg DA, Saade GR, Berkowitz RL, et al. FASTER Research Consortium. Is there a nuchal translucency millimeter measurement above which there is no added benefit from first trimester serum screening?. American Journal of Obstetrics and Gynecology. 2006;195(3):843‐7.

Conde‐Agudelo 1998 {published data only}

Conde‐Agudelo A, Kafury‐Goeta AC. Triple‐marker test as screening for down syndrome: a meta‐analysis. Obstetrical and Gynecological Survey 1998;53(6):369‐76.

Crossley 1991 {published data only}

Crossley JA, Aitken DA, Connor JM. Prenatal screening for chromosome abnormalities using maternal serum chorionic gonadotrophin, alpha‐fetoprotein, and age. Prenatal Diagnosis 1991;11(2):83‐101.

Crossley 1993 {published data only}

Crossley JA, Aitken DA, Connor JM. Second‐trimester unconjugated oestriol levels in maternal serum from chromosomally abnormal pregnancies using an optimized assay.[see comment]. Prenatal Diagnosis 1993;13(4):271‐80.

Crossley 1996 {published data only}

Crossley JA, Berry E, Aitken DA, Connor JM. Insulin‐dependent diabetes mellitus and prenatal screening results: current experience from a regional screening programme. Prenatal Diagnosis 1996;16(11):1039‐42.

Crossley 2002a {published data only}

Crossley JA, Aitken DA, Waugh SM, Kelly T, Connor JM. Maternal smoking: age distribution, levels of alpha‐fetoprotein and human chorionic gonadotrophin, and effect on detection of Down syndrome pregnancies in second‐trimester screening. Prenatal Diagnosis 2002;22(3):247‐55.

Cuckle 1984 {published data only}

Cuckle HS, Wald NJ, Lindenbaum RH. Maternal serum alpha‐fetoprotein measurement: a screening test for Down syndrome. Lancet 1984;i(8383):926‐9.

Cuckle 1987a {published data only}

Cuckle HS, Wald NJ, Thompson SG. Estimating a woman's risk of having a pregnancy associated with Down's syndrome using her age and serum alpha‐fetoprotein level. British Journal of Obstetrics and Gynaecology 1987;94(5):387‐402.

Cuckle 1987b {published data only}

Cuckle HS, Nanchahal K, Wald NJ. Maternal serum alpha‐fetoprotein and ethnic origin. British Journal of Obstetrics and Gynaecology 1987;94(11):1111‐2.

Cuckle 1990 {published data only}

Cuckle HS, Wald NJ, Densem JW, Royston P, Knight GJ, Haddow JE, et al. The effect of smoking in pregnancy on maternal serum alpha‐fetoprotein, unconjugated oestriol, human chorionic gonadotrophin, progesterone and dehydroepiandrosterone sulphate levels. British Journal of Obstetrics and Gynaecology 1990;97(3):272‐4.

Cuckle 1996 {published data only}

Cuckle HS, Holding S, Jones R, Groome NP, Wallace EM. Combining Inhibin A with existing second‐trimester markers in maternal serum screening for Down's syndrome. Prenatal Diagnosis 1996;16(12):1095‐100.

Cuckle 1999b {published data only}

Cuckle HS, Sehmi I, Jones R, Evans LW. Maternal serum activin A and follistatin levels in pregnancies with Down syndrome. Prenatal Diagnosis. 1999;19(6):513‐6.

Cuckle 1999c {published data only}

Cuckle HS, Van Lith JM. Appropriate biochemical parameters in first‐trimester screening for Down syndrome.[see comment]. Prenatal Diagnosis 1999;19(6):505‐12.

Cullen 1990 {published data only}

Cullen MT, Gabrielli S, Green JJ, Rizzo N, Mahoney MJ, Salafia C, et al. Diagnosis and significance of cystic hygroma in the first trimester. Prenatal Diagnosis 1990;10(10):643‐51.

Cusick 2004 {published data only}

Cusick W, Provenzano J, Sullivan CA, Gallousis FM, Rodis JF. Fetal nasal bone length in euploid and aneuploid fetuses between 11 and 20 weeks' gestation: a prospective study. Journal of Ultrasound in Medicine 2004;23(10):1327‐33.

D'Ottavio 1997 {published data only}

D'Ottavio G, Meir YJ, Rustico MA, Pecile V, Fischer‐Tamaro L, Conoscenti G, et al. Screening for fetal anomalies by ultrasound at 14 and 21 weeks. Ultrasound in Obstetrics & Gynecology 1997;10(6):375‐80.

Dancoine 2001 {published data only}

Dancoine F, Couplet G, Mainardi A, Sukno F, Jaumain P, Nowak E, et al. Antenatal screening for Dawn's syndrome with serum markers: influence of maternal weight, smoking habits and diabetes. Immuno‐Analyse et Biologie Specialisee 2001;16(6):381‐9.

De Biasio, 1999 {published data only}

De Biasio, Siccardi M, Volpe G, Famularo L, Santi F, Canini S. First‐trimester screening for down syndrome using nuchal translucency measurement with free ß‐hCG and PAPP‐A between 10 and 13 weeks of pregnancy ‐ the combined test. Prenatal Diagnosis 1999;19(4):360‐3.

De Biasio, 2001 {published data only}

De Biasio, Ferrero S, Prefumo F, Canini S, Marchini P, Bruzzone I, et al. Down's syndrome: first trimester approach. Italian Journal of Gynaecology and Obstetrics 2001;13(1):22‐6.

De Biasio 2000 {published data only}

De Biasio P, Canini S, Prefumo F, Famularo L, Venturini PL. Extent of correlation between first and second trimester markers for Down's syndrome screening. Journal of Medical Screening 2000;7(3):163.

De Graaf 1991 {published data only}

De Graaf I, Cuckle HS, Pajkrt E, Leschot NJ, Bleker OP, Van Lith JM. Co‐variables in first trimester maternal serum screening. Prenatal Diagnosis 1991;20(3):186‐9.

De Graaf 1999 {published data only}

De Graaf I, Pajkrt E, Bilardo CM, Leschot NJ, Cuckle HS, Van Lith JM. Early pregnancy screening for fetal aneuploidy with serum markers and nuchal translucency. Prenatal Diagnosis 1999;19(5):458‐62.

DeVore 2001 {published data only}

DeVore GR, Romero R. Combined use of genetic sonography and maternal serum triple‐marker screening: an effective method for increasing the detection of trisomy 21 in women younger than 35 years.[see comment]. Journal of Ultrasound in Medicine. 2001;20(6):645‐54.

Dickerson 1994 {published data only}

Dickerson VM. Multiple marker screening. Western Journal of Medicine 1994;161(2):161.

Dimaio 1987 {published data only}

Dimaio MS, Baumgarten A, Greenstein RM, Saal HM, Mahoney MJ. Screening for fetal Down's syndrome in pregnancy by measuring maternal serum alpha‐fetoprotein levels. New England Journal of Medicine 1987;317(6):342‐6.

Doran 1986 {published data only}

Doran TA, Cadesky K, Wong PY, Mastrogiacomo C, Capello T. Maternal serum alpha‐fetoprotein and fetal autosomal trisomies. American Journal of Obstetrics and Gynecology 1986;154(2):277‐81.

Drugan 1996a {published data only}

Drugan A, Reichler A, Bronstein M, Johnson MP, Sokol RJ, Evans MI. Abnormal biochemical serum screening versus 2nd‐trimester ultrasound‐detected minor anomalies as predictors of aneuploidy in low‐risk women. Fetal Diagnosis and Therapy 1996;11(5):301‐5.

Drugan 1996b {published data only}

Drugan A, O'Brien JE, Dvorin E, Krivchenia EL, Johnson MP, Sokol RJ, et al. Multiple marker screening in multifetal gestations: failure to predict adverse pregnancy outcomes. Fetal Diagnosis and Therapy 1996;11(1):16‐9.

Drysdale 2002 {published data only}

Drysdale K, Ridley D, Walker K, Higgins B, Dean T. First‐trimester pregnancy scanning as a screening tool for high‐risk and abnormal pregnancies in a district general hospital setting. Journal of Obstetrics & Gynaecology 2002;22(2):159‐65.

Ebell 1999 {published data only}

Ebell M. Is the integrated test better for screening for Down's syndrome than the traditional triple test?. Evidence‐Based Practice 1999;2(11):4‐5.

Economides 1998 {published data only}

Economides DL, Whitlow BJ, Kadir R, Lazanakis M, Verdin SM. First trimester sonographic detection of chromosomal abnormalities in an unselected population. British Journal of Obstetrics and Gynaecology 1998;105(1):58‐62.

Erickson 2004 {published data only}

Erickson JA, Ashwood ER, Gin CA. Evaluation of a dimeric inhibin‐A assay for assessing fetal Down syndrome: establishment, comparison, and monitoring of median concentrations for normal pregnancies. Archives of Pathology & Laboratory Medicine 2004;128(4):415‐20.

Evans 1996 {published data only}

Evans MI, O'Brien JE, Dvorin E, Krivchenia EL, Drugan A, Hume RF, et al. Similarity of insulin‐dependent diabetics' and non‐insulin‐dependent diabetics' levels of ß‐hCG and unconjugated estriol with controls: no need to adjust as with alpha‐fetoprotein. Journal of the Society for Gynecologic Investigation 1996;3(1):20‐2.

Falcon 2005 {published data only}

Falcon O, Cavoretto P, Peralta CF, Csapo B, Nicolaides KH. Fetal head‐to‐trunk volume ratio in chromosomally abnormal fetuses at 11 + 0 to 13 + 6 weeks of gestation. Ultrasound in Obstetrics & Gynecology 2005;26(7):755‐60.

Falcon 2006 {published data only}

Falcon O, Faiola S, Huggon I, Allan L, Nicolaides KH. Fetal tricuspid regurgitation at the 11 + 0 to 13 + 6‐week scan: association with chromosomal defects and reproducibility of the method. Ultrasound in Obstetrics & Gynecology 2006;27(6):609‐12.

Ford 1998 {published data only}

Ford C, Moore AJ, Jordan PA, Bartlett WA, Wyldes MP, Jones AF, et al. The value of screening for Down's syndrome in a socioeconomically deprived area with a high ethnic population.[see comment]. British Journal of Obstetrics and Gynaecology 1998;105(8):855‐9.

Frishman 1997 {published data only}

Frishman GN, Canick JA, Hogan JW, Hackett RJ, Kellner LH, Saller DN. Serum triple‐marker screening in in vitro fertilization and naturally conceived pregnancies. Obstetrics & Gynecology 1997;90(1):98‐101.

Fukada 2000 {published data only}

Fukada Y, Takizawa M, Amemiya A, Yoda H, Kohno K, Hoshi K. Detection of aneuploidy with fetal nuchal translucency and maternal serum markers in Japanese women. Acta Obstetricia et Gynecologica Scandinavica 2000;79(12):1124‐5.

Ghidini 1998 {published data only}

Ghidini A, Spong CY, Grier RE, Walker CN, Pezzullo JC. Is maternal serum triple screening a better predictor of Down syndrome in female than in male fetuses?. Prenatal Diagnosis 1998;18(2):123‐6.

Goldie 1995 {published data only}

Goldie DJ, Astley JP, Beaman JM, Bickley DA, Gunneberg A, Jones SR. Screening for Down's syndrome: the first two years experience in Bristol. Journal of Medical Screening 1995;2(4):207‐10.

Gonçalves 2004 {published data only}

Gonçalves LF, Espinoza J, Lee W, Schoen ML, Devers P, Mazor M, et al. Phenotypic characteristics of absent and hypoplastic nasal bones in fetuses with down syndrome: description by 3‐dimensional ultrasonography and clinical significance. Journal of Ultrasound in Medicine 2004;23(12):1619‐27.

Goodburn 1994 {published data only}

Goodburn SF, Yates JR, Raggatt PR, Carr C, Ferguson‐Smith ME, Kershaw AJ, et al. Second‐trimester maternal serum screening using alpha‐fetoprotein, human chorionic gonadotrophin, and unconjugated oestriol: experience of a regional programme. Prenatal Diagnosis 1994;14(5):391‐402.

Grozdea 2002 {published data only}

Grozdea J, De La Farge F, Bourrouillou G, Calot M, Cambus JP, Valdiguie P. Maternal serum urea resistant alkaline phosphatase in Down syndrome pregnancy. Early Human Development 2002;67(1‐2):55‐9.

Gyselaers 2004a {published data only}

Gyselaers WJ, Vereecken AJ, Van Herck EJ, Straetmans DP, Martens GE, De Jonge ET, et al. Screening for trisomy 21 in Flanders: a 10 years review of 40.490 pregnancies screened by maternal serum. European Journal of Obstetrics, Gynecology, & Reproductive Biology 2004;115(2):185‐9.

Gyselaers 2004b {published data only}

Gyselaers WJA, Vereecken AJ, Van Herck, Straetmans DPL, De Jonge, Ombelet WUA, et al. Single‐step maternal serum screening for trisomy 21 in the era of combined or integrated screening. Gynecologic and Obstetric Investigation 2004;58(4):221‐4.

Gyselaers 2006a {published data only}

Gyselaers WJ, Vereecken AJ, Van Herck EJ, Straetmans DP, Ombelet WU, Nijhuis JG. Nuchal translucency thickness measurements for fetal aneuploidy screening: Log NT‐MoM or Delta‐NT, performer‐specific medians and ultrasound training. Journal of Medical Screening 2006;13(1):4‐7.

Gyselaers 2006b {published data only}

Gyselaers WJ, Roets ER, Van Holsbeke CD, Vereecken AJ, Van Herck EJ, Straetmans DP, et al. Sequential triage in the first trimester may enhance advanced ultrasound scanning in population screening for trisomy 21. Ultrasound in Obstetrics & Gynecology 2006;27(6):622‐7.

Hackshaw 1995 {published data only}

Hackshaw AK, Densem J, Wald NJ. Repeat maternal serum testing for Down's syndrome screening using multiple markers with special reference to free alpha and free ß‐hCG. Prenatal Diagnosis 1995;15(12):1125‐30.

Hackshaw 2001 {published data only}

Hackshaw AK, Wald NJ. Repeat testing in antenatal screening for Down syndrome using dimeric inhibin‐A in combination with other maternal serum markers. Prenatal Diagnosis 2001;21(1):58‐61.

Haddow 1992 {published data only}

Haddow JE, Palomaki GE, Knight GJ, Williams J, Pulkkinen A, Canick J, et al. Prenatal screening for Down's syndrome with use of maternal serum markers. New England Journal of Medicine 1992;327(9):588‐93.

Hafner 1995 {published data only}

Hafner E, Schuchter K, Philipp K. Screening for chromosomal abnormalities in an unselected population by fetal nuchal translucency. Ultrasound in Obstetrics & Gynecology 1995;6(5):330‐3.

Hallahan 1998 {published data only}

Hallahan TW, Krantz DA, Tului L, Alberti E, Buchanan PD, Orlandi F, et al. Comparison of urinary free ß (hCG) and ß‐core (hCG) in prenatal screening for chromosomal abnormalities. Prenatal Diagnosis 1998;18(9):893‐900.

Harrison 2006 {published data only}

Harrison G, Goldie D. Second‐trimester Down's syndrome serum screening: double, triple or quadruple marker testing?. Annals of Clinical Biochemistry 2006;43(1):67‐72.

Harry 2006 {published data only}

Harry WG, Reed KL. Nuchal translucency and first‐trimester screening. Journal of the Society for Gynecologic Investigation 2006;13(3):153‐4.

Hayashi 1995 {published data only}

Hayashi M, Kozu H. Maternal urinary ß‐core fragment of hCG/creatinine ratios and fetal chromosomal abnormalities in the second trimester of pregnancy. Prenatal Diagnosis 1995;15(1):11‐6.

Hayashi 1996 {published data only}

Hayashi M, Kozu H, Takei H. Maternal urinary free ß‐subunit of human chorionic gonadotrophin: creatinine ratios and fetal chromosomal abnormalities in the second trimester of pregnancy. British Journal of Obstetrics and Gynaecology 1996;103(6):577‐80.

Heikkila 1997 {published data only}

Heikkila A, Ryynanen M, Kirkinen P, Saarikoski S. Results and views of women in population‐wide pregnancy screening for trisomy 21 in east Finland. Fetal Diagnosis and Therapy 1997;12(2):93‐6.

Heinonen 1996 {published data only}

Heinonen S, Ryynanen M, Kirkinen P, Hippelainen M, Saarikoski S. Effect of in vitro fertilization on human chorionic gonadotropin serum concentrations and Down's syndrome screening. Fertility and Sterility 1996;66(3):398‐403.

Herman 2000 {published data only}

Herman A, Weinraub Z, Dreazen E, Arieli S, Rozansky S, Bukovsky I, et al. Combined first trimester nuchal translucency and second trimester biochemical screening tests among normal pregnancies. Prenatal Diagnosis 2000;20(10):781‐4.

Herman 2003 {published data only}

Herman A, Dreazen E, Tovbin Y, Reish O, Bukovsky I, Maymon R. Correlation and overlapping between nuchal translucency and triple test among Down syndrome‐affected pregnancies. Fetal Diagnosis and Therapy 2003;18(3):196‐200.

Herrou 1992 {published data only}

Herrou M, Leporrier N, Leymarie P. Screening for fetal Down syndrome with maternal serum hCG and oestriol: a prospective study. Prenatal Diagnosis 1992;12(11):887‐92.

Hershey 1985 {published data only}

Hershey DW, Crandall BF, Schroth PS. Maternal serum alpha‐fetoprotein screening of fetal trisomies. American Journal of Obstetrics and Gynecology 1985;153(2):224‐5.

Hershey 1986 {published data only}

Hershey DW, Crandall BF, Perdue S. Combining maternal age and serum alpha‐fetoprotein to predict the risk of Down syndrome. Obstetrics & Gynecology 1986;68(2):177‐80.

Hewitt 1993 {published data only}

Hewitt B. Nuchal translucency in the first trimester. Australian & New Zealand Journal of Obstetrics & Gynaecology 1993;33(4):389‐91.

Hogdall 1992 {published data only}

Hogdall CK, Hogdall EV, Arends J, Norgaard‐Pedersen B, Smidt‐Jensen S, Larsen SO. CA‐125 as a maternal serum marker for Down's syndrome in the first and second trimesters. Prenatal Diagnosis 1992;12(3):223‐7.

Hong Kong Practitioner 2001 {published data only}

Anon. Screening tests in pregnancy. Hong Kong Practitioner 2001;23(10):461‐5.

Howe 2000 {published data only}

Howe DT, Gornall R, Wellesley D, Boyle T, Barber J. Six year survey of screening for Down's syndrome by maternal age and mid‐trimester ultrasound scans. BMJ 2000;320(7235):606‐10.

Hsiao 1991 {published data only}

Hsiao KJ, Lee SY, Chuang HC. [Antenatal screening of maternal alpha‐fetoprotein with dried‐blood spot samples on filter paper]. [Chinese]. Journal of the Formosan Medical Association 1991;90(6):598‐604.

Hsieh 1999 {published data only}

Hsieh TT, Hsu JJ, Lo LM, Liou JD, Soong YK. Maternal urine alpha‐fetoprotein concentrations between 14 and 21 weeks of gestation. Changgeng Yi Xue Za Zhi 1999;22(2):234‐9.

Hsu 1997b {published data only}

Hsu JJ, Hsieh TT, Soong YK. Influence of maternal age and weight on second‐trimester serum alpha‐fetoprotein, total and free ß human chorionic gonadotropin levels. Changgeng Yi Xue Za Zhi. 1997;20(3):181‐6.

Hsu 1998a {published data only}

Hsu JJ, Hsieh TT, Hung TH, Chiang CH. Midtrimester maternal serum free ß‐human chorionic gonadotropin levels: normal reference values for Taiwanese women. Changgeng Yi Xue Za Zhi 1998;21(3):277‐82.

Hsu 1999b {published data only}

Hsu JJ, Hsieh TT, Hung TH, Chen KC, Soong YK. Urine free ß‐human chorionic gonadotropin levels between 14 and 21 weeks of gestation in Taiwanese pregnancies. Changgeng Yi Xue Za Zhi 1999;22(1):11‐6.

Huang 2003 {published data only}

Huang T, Summers AM, Wyatt PR, Meier C, Cote GB. Maternal serum marker medians in Aboriginal Canadian women. Prenatal Diagnosis 2003;23(2):98‐100.

Huggon 2004 {published data only}

Huggon IC, Turan O, Allan LD. Doppler assessment of cardiac function at 11‐14 weeks' gestation in fetuses with normal and increased nuchal translucency. Ultrasound in Obstetrics & Gynecology 2004;24(4):390‐8.

Hui 2003 {published data only}

Hui PW, Tang MH, Lam YH, Ng EH, Yeung WS, Ho PC. Maternal serum hCG and alpha‐fetoprotein levels in pregnancies conceived after IVF or ICSI with fresh and frozen‐thawed embryos. Human Reproduction 2003;18(3):572‐5.

Hui 2005 {published data only}

Hui PW, Tang MH, Lam YH, Yeung WS, Ng EH, Ho PC. Nuchal translucency in pregnancies conceived after assisted reproduction technology. Ultrasound in Obstetrics & Gynecology 2005;25(3):234‐8.

Hultén 2004 {published data only}

Hultén M. Combined serum and nuchal translucency screening in the first trimester achieves 85% to 90% detection rate for Down and Edward syndromes. Evidence‐Based Healthcare 2004;8(2):82‐4.

Hung 2003 {published data only}

Hung JH, Fu CY, Yuan CC, Chen CL, Yang ML, Shu LP, et al. Nuchal translucence incorporated into a one‐stage multifactorial screening model for Down syndrome prediction at second‐trimester pregnancy. Ultrasound in Medicine & Biology 2003;29(12):1667‐74.

Hurley 1993 {published data only}

Hurley PA, Ward RH, Teisner B, Iles RK, Lucas M, Grudzinskas JG. Serum PAPP‐A measurements in first‐trimester screening for Down syndrome. Prenatal Diagnosis 1993;13(10):903‐8.

Huttly 2004 {published data only}

Huttly W, Rudnicka A, Wald NJ. Second‐trimester prenatal screening markers for Down syndrome in women with insulin‐dependent diabetes mellitus. Prenatal Diagnosis 2004;24(10):804‐7.

Hwa 2004 {published data only}

Hwa HL, Yen MF, Hsieh FJ, Ko TM, Chen TH. Evaluation of second trimester maternal serum screening for Down's Syndrome using the Spiegelhalter‐Knill‐Jones (S‐KJ) approach. Journal of Perinatal Medicine 2004;32(5):407‐12.

Iles 1996 {published data only}

Iles RK. Urinary analysis for Down's syndrome: Is the measurement of urinary ß‐core the future of biochemical screening for Down's syndrome. Early Human Development 1996;47(Suppl.):S41‐S45.

Ind 1994 {published data only}

Ind TEJ, Iles RK, Cuckle HS, Chard T. Second trimester maternal serum placental alkaline phosphatase concentrations in Down's syndrome. Journal of Obstetrics and Gynaecology 1994;14(5):305‐8.

Jean‐Pierre 2005 {published data only}

Jean‐Pierre C. Fetal nasal bone: review of first trimester findings. Ultrasound Review of Obstetrics and Gynecology 2005;5(2):102‐4.

Johnson 1991 {published data only}

Johnson A, Cowchock FS, Darby M, Wapner R, Jackson LG. First‐trimester maternal serum alpha‐fetoprotein and chorionic gonadotropin in aneuploid pregnancies. Prenatal Diagnosis 1991;11(7):443‐50.

Johnson 1993 {published data only}

Johnson MP, Johnson A, Holzgreve W, Isada NB, Wapner RJ, Treadwell MC, et al. First‐trimester simple hygroma: cause and outcome. American Journal of Obstetrics and Gynecology 1993;168(1):156‐61.

Jorgensen 1999 {published data only}

Jorgensen FS, Valentin L, Salvesen KA, Jorgensen C, Jensen FR, Bang J, et al. MULTISCAN‐‐a Scandinavian multicenter second trimester obstetric ultrasound and serum screening study. Acta Obstetricia et Gynecologica Scandinavica 1999;78(6):501‐10.

Josefsson 1998 {published data only}

Josefsson A, Molander E, Selbing A. Nuchal translucency as a screening test for chromosomal abnormalities in a routine first trimester ultrasound examination. Acta Obstetricia et Gynecologica Scandinavica 1998;77(5):497‐9.

Jou 2001 {published data only}

Jou HJ, Shih JC, Wu SC, Li TC, Tzeng CY, Hsieh FJ. First‐trimester Down's syndrome screening by fetal nuchal translucency measurement in Taiwan. Journal of the Formosan Medical Association 2001;100(4):257‐61.

Kagan 2006 {published data only}

Kagan KO, Avgidou K, Molina FS, Gajewska K, Nicolaides KH. Relation between increased fetal nuchal translucency thickness and chromosomal defects.[see comment]. Obstetrics & Gynecology 2006;107(1):6‐10.

Kautzmann 1995 {published data only}

Kautzmann M, Solis RL, Luberta A, Fernandez JL, Navarro J, Rodriguez L, et al. Study of the efficiency of screening for trisomy 21 based on maternal serum levels of AFP and hCG combined with maternal age. Journal of Clinical Ligand Assay 1995;18(3):181‐5.

Keith 1992 {published data only}

Keith D. Maternal serum screening for neural tube defects and Down syndrome. Clinical Laboratory Science 1992;5(5):274‐6.

Kelekci 2004 {published data only}

Kelekci S, Yazicioglu HF, Oguz S, Inan I, Yilmaz B, Sonmez S. Nasal bone measurement during the 1st trimester: is it useful?. Gynecologic & Obstetric Investigation 2004;58(2):91‐5.

Kellner 1995a {published data only}

Kellner LH, Weiner Z, Weiss RR, Neuer M, Martin GM, Mueenuddin M, et al. Triple marker (alpha‐fetoprotein, unconjugated estriol, human chorionic gonadotropin) versus alpha‐fetoprotein plus free‐ß subunit in second‐trimester maternal serum screening for fetal Down syndrome: a prospective comparison study.[see comment]. American Journal of Obstetrics and Gynecology 1995;173(4):1306‐9.

Kellner 1995b {published data only}

Kellner LH, Weiss RR, Weiner Z, Neuer M, Martin GM, Schulman H, et al. The advantages of using triple‐marker screening for chromosomal abnormalities. American Journal of Obstetrics and Gynecology 1995;172(3):831‐6.

Kellner 1997 {published data only}

Kellner LH, Canick JA, Palomaki GE, Neveux LM, Saller DN, Walker RP, et al. Levels of urinary ß‐core fragment, total oestriol, and the ratio of the two in second‐trimester screening for Down syndrome. Prenatal Diagnosis 1997;17(12):1135‐41.

Knight 1990 {published data only}

Knight GJ, Palomaki GE. Maternal serum alpha fetoprotein screening for fetal down syndrome. Journal of Clinical Immunoassay 1990;13(1):23‐9.

Knight 2001 {published data only}

Knight GJ, Palomaki GE, Neveux LM, Haddow JE, Lambert‐Messerlian GM. Clinical validation of a new dimeric inhibin‐A assay suitable for second trimester Down's syndrome screening. Journal of Medical Screening 2001;8(1):2‐7.

Knight 2005 {published data only}

Knight GJ, Palomaki GE, Neveux LM, Smith DE, Kloza EM, Pulkkinen A, et al. Integrated serum screening for Down syndrome in primary obstetric practice. Prenatal Diagnosis 2005;25(12):1162‐7.

Koos 2006 {published data only}

Koos BJ. First‐trimester screening: lessons from clinical trials and implementation. Current Opinion in Obstetrics and Gynecology 2006;18(2):152‐5.

Kornman 1996 {published data only}

Kornman LH, Morssink LP, Beekhuis JR, de Wolf BT, Heringa MP, Mantingh A. Nuchal translucency cannot be used as a screening test for chromosomal abnormalities in the first trimester of pregnancy in a routine ultrasound practice.[see comment]. Prenatal Diagnosis 1996;16(9):797‐805.

Kornman 1997 {published data only}

Kornman LH, Morssink LP, Wortelboer MJ, Beekhuis JR, de Wolf BT, Pratt JJ, et al. Maternal urinary ß‐core hCG in chromosomally abnormal pregnancies in the first trimester. Prenatal Diagnosis 1997;17(2):135‐9.

Kramer 1998 {published data only}

Kramer RL, Yaron Y, O'Brien JE, Critchfield G, Ayoub M, Johnson MP, et al. Effect of adjustment of maternal serum alpha‐fetoprotein levels in insulin‐dependent diabetes mellitus. American Journal of Medical Genetics 1998;75(2):176‐8.

Krantz 1996 {published data only}

Krantz DA, Larsen JW, Buchanan PD, Macri JN. First‐trimester Down syndrome screening: free ß‐human chorionic gonadotropin and pregnancy‐associated plasma protein A. American Journal of Obstetrics and Gynecology 1996;174(2):612‐6.

Krantz 2005 {published data only}

Krantz DA, Hallahan TW, Macri VJ, Macri JN. Maternal weight and ethnic adjustment within a first‐trimester Down syndrome and trisomy 18 screening program. Prenatal Diagnosis 2005;25(8):635‐40.

Kulch 1993 {published data only}

Kulch P, Keener S, Matsumoto M, Crandall BF. Racial differences in maternal serum human chorionic gonadotropin and unconjugated oestriol levels. Prenatal Diagnosis 1993;13(3):191‐5.

Lai 1998 {published data only}

Lai FM, Yeo GS. Down syndrome screening in Singapore‐‐the effectiveness of a second trimester serum screening policy modelled on 29,360 pregnancies in KK Women's and Children's Hospital. Singapore Medical Journal 1998;39(2):69‐75.

Lai 2003 {published data only}

Lai TH, Chen SC, Tsai MS, Lee FK, Wei CF. First‐trimester screening for Down syndrome in singleton pregnancies achieved by intrauterine insemination. Journal of Assisted Reproduction and Genetics 2003;20(8):327‐31.

Laigaard 2006a {published data only}

Laigaard J, Cuckle H, Wewer UM, Christiansen M. Maternal serum ADAM12 levels in Down and Edwards' syndrome pregnancies at 9‐12 weeks' gestation. Prenatal Diagnosis 2006;26(8):689‐91.

Laigaard 2006b {published data only}

Laigaard J, Spencer K, Christiansen M, Cowans NJ, Larsen SO, Pedersen BN, et al. ADAM 12 as a first‐trimester maternal serum marker in screening for Down syndrome. Prenatal Diagnosis 2006;26(10):973‐9.

Lam 1997 {published data only}

Lam YH, Tang MH, Tang LC, Lee CP, Ho PK. Second‐trimester maternal urinary gonadotrophin peptide screening for fetal Down syndrome in Asian women. Prenatal Diagnosis 1997;17(12):1101‐6.

Lam 1998 {published data only}

Lam YH, Ghosh A, Tang MH, Tang LC, Lee CP, Sin SY, et al. Second‐trimester maternal serum alpha‐fetoprotein and human chorionic gonadotrophin screening for Down's syndrome in Hong Kong. Prenatal Diagnosis 1998;18(6):585‐9.

Lam 1999a {published data only}

Lam YH, Yeung WS, Tang MH, Ng EH, So WW, Ho PC. Maternal serum alpha‐fetoprotein and human chorionic gonadotrophin in pregnancies conceived after intracytoplasmic sperm injection and conventional in‐vitro fertilization. Human Reproduction 1999;14(8):2120‐3.

Lam 1999b {published data only}

Lam YH, Tang MH. Second‐trimester maternal serum inhibin‐A screening for fetal Down syndrome in Asian women. Prenatal Diagnosis 1999;19(5):463‐7.

Lam 2000 {published data only}

Lam YH, Tang MH, Lee CP, Sin SY, Tang R, Wong HS, et al. Acceptability of serum screening as an alternative to cytogenetic diagnosis of down syndrome among women 35 years or older in Hong Kong. Prenatal Diagnosis 2000;20(6):487‐90.

Lam 2001 {published data only}

Lam YH, Tang MH. The effect of fetal gender on second‐trimester maternal serum inhibin‐A concentration. Prenatal Diagnosis 2001;21(8):662‐4.

Lambert‐Messerlian 1996 {published data only}

Lambert‐Messerlian GM, Canick JA, Palomaki GE, Schneyer AL. Second trimester levels of maternal serum inhibin A, total inhibin, alpha inhibin precursor, and activin in Down's syndrome pregnancy. Journal of Medical Screening 1996;3(2):58‐62.

Lambert‐Messerlian 1998 {published data only}

Lambert‐Messerlian, Luisi S, Florio P, Mazza V, Canick JA, Petraglia F. Second trimester levels of maternal serum total activin A and placental inhibin/activin alpha and ßA subunit messenger ribonucleic acids in Down syndrome pregnancy. European Journal of Endocrinology 1998;138(4):425‐9.

Lehavi 2005 {published data only}

Lehavi O, Aizenstein O, Evans MI, Yaron Y. 2nd‐trimester maternal serum human chorionic gonadotropin and alpha‐fetoprotein levels in male and female fetuses with Down syndrome. Fetal Diagnosis and Therapy 2005;20(3):235‐8.

Leung 2006 {published data only}

Leung TY, Spencer K, Leung TN, Fung TY, Lau TK. Higher median levels of free ß‐hCG and PAPP‐A in the first trimester of pregnancy in a Chinese ethnic group. Implication for first trimester combined screening for Down's syndrome in the Chinese population. Fetal Diagnosis and Therapy 2006;21(1):140‐3.

Leymarie 1993 {published data only}

Leymarie P, Leporrier N. Maternal serum markers and prenatal screening for Down syndrome. Archives Francaises de Pediatrie 1993;50(5):455‐7.

Li 1998 {published data only}

Li G, Huang X. [Clinical uses of maternal serum markers in the prenatal diagnosis] [Chinese]. Chung‐Hua Fu Chan Ko Tsa Chih 1998;33(4):252‐4.

Li 1999 {published data only}

Li W, Zhou Y. [Measurement of pregnancy‐associated plasma protein A in maternal peripheral blood and Down syndrome] [Chinese]. Chung‐Hua Fu Chan Ko Tsa Chih 1999;34(10):631‐3.

Liao 1997 {published data only}

Liao S, Wang Y, Ye G. [AFP, uE3, ß‐hCG levels applied for prenatal diagnosis of Down's syndrome]. [Chinese]. Chung‐Hua Fu Chan Ko Tsa Chih 1997;32(11):655‐8.

Liao 2001 {published data only}

Liao AW, Heath V, Kametas N, Spencer K, Nicolaides KH. First‐trimester screening for trisomy 21 in singleton pregnancies achieved by assisted reproduction. Human Reproduction 2001;16(7):1501‐4.

Lim 2002 {published data only}

Lim KI, Pugash D, Dansereau J, Wilson RD. Nuchal index: a gestational age independent ultrasound marker for the detection of Down syndrome. Prenatal Diagnosis 2002;22(13):1233‐7.

Lippman 1987 {published data only}

Lippman A, Evans JA. Screening for maternal serum alpha‐fetoprotein: what about the low side?. Canadian Medical Association Journal 1987;136(8):801‐4.

Liu 2003 {published data only}

Liu JT, Hao N, Sun NH, Wang FY, Xu YH, Gai MY, et al. [Screening by maternal serum markers for Down's syndrome]. [Chinese]. Chung‐Kuo i Hsueh Ko Hsueh Yuan Hsueh Pao Acta Academiae Medicinae Sinicae 2003;25(2):156‐9.

Lustig 1988 {published data only}

Lustig L, Clarke S, Cunningham G, Schonberg R, Tompkinson G. California's experience with low MS‐AFP results. American Journal of Medical Genetics 1988;31(1):211‐22.

MacDonald 1991 {published data only}

MacDonald ML, Wagner RM, Slotnick RN. Sensitivity and specificity of screening for Down syndrome with alpha‐fetoprotein, hCG, unconjugated estriol, and maternal age.[see comment]. Obstetrics & Gynecology 1991;77(1):63‐8.

Macintosh 1994 {published data only}

Macintosh MCM, Iles R, Teisner B, Sharma K, Chard T, Grudzinskas J, et al. Maternal serum human chorionic gonadotrophin and pregnancy‐associated plasma protein A, markers for fetal Down syndrome at 8‐14 weeks. Prenatal Diagnosis 1994;14(3):203‐8.

Macintosh 1997 {published data only}

Macintosh MCM, Nicolaides KH, Noble P, Chard T, Gunn L, Iles R. Urinary ß‐core hCG: screening for aneuploidies in early pregnancy (11‐14 weeks' gestation). Prenatal Diagnosis 1997;17(5):401‐5.

Macri 1994 {published data only}

Macri JN, Kasturi RV, Krantz DA, Cook EJ, Moore ND, Young JA, et al. Maternal serum Down syndrome screening: free ß‐protein is a more effective marker than human chorionic gonadotropin.[see comment]. American Journal of Obstetrics and Gynecology 1990;163(4):1248‐53.
Macri JN, Spencer K, Garver K, Buchanan PD, Say B, Carpenter NJ, et al. Maternal serum free ß hCG screening: results of studies including 480 cases of Down syndrome.[see comment]. Prenatal Diagnosis 1994;14(2):97‐103.
Spencer K, Macri JN. Early detection of Down's syndrome using free ß human choriogonadotropin. Annals of Clinical Biochemistry 1992;19(3):349‐50.

Macri 1996 {published data only}

Macri JN, Anderson RW, Krantz DA, Larsen JW, Buchanan PD. Prenatal maternal dried blood screening with alpha‐fetoprotein and free ß‐human chorionic gonadotropin for open neural tube defect and Down syndrome. American Journal of Obstetrics and Gynecology 1996;174(2):566‐72.

Malone 1998 {published data only}

Malone FD, D'Alton ME. Ultrasound clinics. Fetal nuchal fold translucency screening. Contemporary OB/GYN 1998;43(3):117‐8.

Malone 2003 {published data only}

Malone FD, D'Alton ME. First‐trimester sonographic screening for Down syndrome. Obstetrics and Gynecology 2003;102(5):1066‐79.

Mangione 2001 {published data only}

Mangione R, Guyon F, Taine L, Wen ZQ, Roux D, Vergnaud A, et al. Pregnancy outcome and prognosis in fetuses with increased first‐trimester nuchal translucency. Fetal Diagnosis and Therapy 2001;16(6):360‐3.

Maymon 2001a {published data only}

Maymon R, Shulman A. Comparison of triple serum screening and pregnancy outcome in oocyte donation versus IVF pregnancies. Human Reproduction 2001;16(4):691‐5.

Maymon 2001b {published data only}

Maymon R, Dreazen E, Buckovsky I, Weinraub Z, Herman A. Does a 'notched' nuchal translucency indicate Down syndrome fetuses or other adverse pregnancy outcome?. Prenatal Diagnosis 2001;21(5):403‐8.

Maymon 2002 {published data only}

Maymon R, Shulman A. Serial first‐ and second‐trimester Down's syndrome screening tests among IVF‐versus naturally‐conceived singletons. Human Reproduction 2002;17(4):1081‐5.

Maymon 2004 {published data only}

Maymon R, Shulman A. Integrated first‐ and second‐trimester Down syndrome screening test among unaffected IVF pregnancies. Prenatal Diagnosis 2004;24(2):125‐9.

Maymon 2005 {published data only}

Maymon R, Cuckle H, Jones R, Reish O, Sharony R, Herman A. Predicting the result of additional second‐trimester markers from a woman's first‐trimester marker profile: a new concept in Down syndrome screening. Prenatal Diagnosis 2005;25(12):1102‐6.

McDuffie 1996 {published data only}

McDuffie RS, Haverkamp AD, Stark CF, Haverkamp C, Barth CK. Prenatal screening using maternal serum alpha‐fetoprotein, human chorionic gonadotropin, and unconjugated estriol: two‐year experience in a health maintenance organization. Journal of Maternal‐Fetal Medicine 1996;5(2):70‐3.

Meier 2002 {published data only}

Meier C, Huang T, Wyatt PR, Summers AM. Accuracy of expected risk of Down syndrome using the second‐trimester triple test. Clinical Chemistry 2002;48(4):653‐5.

Merkatz 1984 {published data only}

Merkatz IR, Nitowsky HM, Macri JN, Johnson WE. An association between low maternal serum alpha‐fetoprotein and fetal chromosomal abnormalities. American Journal of Obstetrics and Gynecology 1984;148(7):886‐94.

Merz 2005 {published data only}

Merz E. The fetal nasal bone in the first trimester ‐ precise assessment using 3D sonography. Ultraschall in der Medizin 2005;26(5):365‐6.

Metzenbauer 2001 {published data only}

Metzenbauer M, Hafner E, Hoefinger D, Schuchter K, Stangl G, Ogris E, et al. Three‐dimensional ultrasound measurement of the placental volume in early pregnancy: method and correlation with biochemical placenta parameters. Placenta 2001;22(6):602‐5.

Metzenbauer 2002 {published data only}

Metzenbauer M, Hafner E, Schuchter K, Philipp K. First‐trimester placental volume as a marker for chromosomal anomalies: preliminary results from an unselected population. Ultrasound in Obstetrics & Gynecology 2002;19(3):240‐2.

Mikic 1999 {published data only}

Mikic TS, Johnson P. Second trimester maternal serum ß human chorionic gonadotrophin and pregnancy outcome. British Journal of Obstetrics and Gynaecology 1999;106(6):598‐600.

Miller 1991 {published data only}

Miller CH, O'Brien TJ, Chatelain S, Butler BB, Quirk JG. Alteration in age‐specific risks for chromosomal trisomy by maternal serum alpha‐fetoprotein and human chorionic gonadotropin screening. Prenatal Diagnosis 1991;11(3):153‐8.

Milunsky 1989 {published data only}

Milunsky A, Jick SS, Bruell CL, Maclaughlin DS, Tsung Y‐K, Jick H, et al. Predictive values relative risks and overall benefits of high and low maternal serum alpha fetoprotein screening in singleton pregnancies ‐ new epidemiological data. American Journal of Obstetrics and Gynecology 1989;161(2):291‐7.

Milunsky 1996 {published data only}

Milunsky A, Nebiolo L. Maternal serum triple analyte screening and adverse pregnancy outcome. Fetal Diagnosis and Therapy 1996;11(4):249‐53.

Minobe 2002 {published data only}

Minobe S. [A study on the screening of prenatal trisomy 21 using the fucosylated alpha‐fetoprotein ratio measured by a liquid‐phase binding assay]. [Japanese]. Hokkaido Igaku Zasshi ‐ Hokkaido Journal of Medical Science 2002;77(6):527‐32.

Miyamura 1999 {published data only}

Miyamura T, Saito N, Touno A, Nagata S, Hidaki T, Ishimaru T, et al. Multicenter study for maternal serum triple markers to establish Japanese standards: maternal serum marker study group, Japan Association of Prenatal Diagnostics. Acta Obstetrica et Gynaecologica Japonica 1999;51(11):1042‐8.

Moghadam 1998 {published data only}

Moghadam S, Engel W, Bougoussa M, Hennen G, Igout A, Sancken U. Maternal serum placental growth hormone and insulinlike growth factor binding proteins 1 and 3 in pregnancies affected by fetal aneuploidy and other abnormalities: implications for prenatal diagnosis of trisomy 21. Fetal Diagnosis and Therapy 1998;13(5):291‐7.

Monni 2000 {published data only}

Monni G, Zoppi MA, Ibba RM, Putzolu M, Floris M. Nuchal translucency in multiple pregnancies. Croatian Medical Journal 2000;41(3):266‐9.

Monni 2002 {published data only}

Monni G, Zoppi MA. New ultrasonographic markers of aneuploidies: nasal bones. Ultrasound Review of Obstetrics and Gynecology 2002;2(4):229‐34.

Mooney 1994 {published data only}

Mooney RA, Peterson J, French CA, Saller DN, Arvan DA. Effectiveness of combining maternal serum alpha‐fetoprotein and hCG in a second‐trimester screening program for Down syndrome. Obstetrics and Gynecology 1994;84(2):298‐303.

Muller 1994 {published data only}

Muller F, Bussieres L, Pelissier MC, Oury JF, Boue C, Uzan S, et al. Do racial differences exist in second‐trimester maternal hCG levels? A study of 23,369 women. Prenatal Diagnosis 1994;14(7):633‐6.

Muller 1996b {published data only}

Muller F, Dommergues M, Bussieres L, Aegerter P, Le Fiblec B, Uzan S, et al. Prenatal screening for Down syndrome: should first trimester ultrasound replace maternal serum screening?. Early Human Development 1996;47 Suppl:S37‐S39.

Muller 1999 {published data only}

Muller F, Ngo S, Rebiffe M, Oury JF, Uzan S, Satge D. Maternal serum s100b protein is ineffective for Down syndrome screening. Prenatal Diagnosis 1999;19(11):1086.

Muller 2002a {published data only}

Muller F, Dreux S, Oury JF, Luton D, Uzan S, Uzan M, et al. Down syndrome maternal serum marker screening after 18 weeks' gestation. Prenatal Diagnosis 2002;22(11):1001‐4.

Muller 2002b {published data only}

Muller F, Forestier F, Dingeon B, for the ABA Study Group. Second trimester trisomy 21 maternal serum marker screening. Results of a countrywide study of 854,902 women. Prenatal Diagnosis 2002;22(10):925‐9.

Muller 2003 {published data only}

Muller F, Dreux S, Lemeur A, Sault C, Desgres J, Bernard MA, et al. Medically assisted reproduction and second‐trimester maternal serum marker screening for Down syndrome. Prenatal Diagnosis 2003;23(13):1073‐6.

Murta 2002 {published data only}

Murta CG, Moron AF, Avila MA, Weiner CP. Application of ductus venosus Doppler velocimetry for the detection of fetal aneuploidy in the first trimester of pregnancy. Fetal Diagnosis and Therapy 2002;17(5):308‐14.

Musone 2000 {published data only}

Musone R, Bonafiglia R, Menditto A, Paccone M, Cassese E, Russo G, et al. Fetuses with cystic hygroma. A retrospective study. Panminerva Medica 2000;42(1):39‐43.

Musto 1986 {published data only}

Musto JD, Pizzolante JM, Chesarone VP, Sassi AM, Sane R. Alpha‐fetoprotein: an enhanced‐sensitivity assay for neural tube defect and Down syndrome evaluation. Clinical Chemistry 1986;32(7):1412.

Myrick 1990 {published data only}

Myrick JE, Caudill SP, Hubert IL, Robinson MK, Adams MJ, Pueschel SM. Identification of haptoglobin alpha‐2FF variants in mid‐trimester maternal serum as potential markers for Down syndrome. Applied & Theoretical Electrophoresis 1990;1(5):233‐41.

Neveux 1996a {published data only}

Neveux LM, Palomaki GE, Larrivee DA, Knight GJ, Haddow JE. Refinements in managing maternal weight adjustment for interpreting prenatal screening results. Prenatal Diagnosis 1996;16(12):1115‐9.

Neveux 1996b {published data only}

Neveux LM, Palomaki GE, Knight GJ, Haddow JE. Multiple marker screening for Down syndrome in twin pregnancies. Prenatal Diagnosis 1996;16(1):29‐34.

Ng 2004 {published data only}

Ng EK, El‐Sheikhah A, Chiu RW, Chan KC, Hogg M, Bindra R, et al. Evaluation of human chorionic gonadotropin ß‐subunit mRNA concentrations in maternal serum in aneuploid pregnancies: a feasibility study. Clinical Chemistry 2004;50(6):1055‐7.

Nicolaides 1992 {published data only}

Nicolaides KH, ZAR G, Snijders RJM, Gosden CM. Fetal nuchal oedema associated malformations and chromosomal defects. Fetal Diagnosis and Therapy 1992;7(2):123‐31.

Nicolaides 2000 {published data only}

Nicolaides KH, Cicero S, Liao AW. One‐stop clinic for assessment of risk of chromosomal defects at 12 weeks of gestation. Prenatal and Neonatal Medicine 2000;5(3):145‐54.

Nicolaides 2004 {published data only}

Nicolaides KH. Nuchal translucency and other first‐trimester sonographic markers of chromosomal abnormalities. American Journal of Obstetrics and Gynecology 2004;191(1):45‐67.

Nicolaides 2005a {published data only}

Nicolaides KH, Wegrzyn P. [First trimester diagnosis of chromosomal defects][Polish]. Ginekologia Polska 2005;76(1):1‐8.

Nicolaides 2005b {published data only}

Nicolaides KH, Wegrzyn P. [Sonographic features of chromosomal defects at 11(+0) to 13(+6) weeks of gestation] [Polish]. Ginekologia Polska 2005;76(6):423‐30.

Nicolaides 2005c {published data only}

Nicolaides KH, Wegrzyn P. [Increased nuchal translucency with normal karyotype]. [Polish]. Ginekologia Polska 2005;76(8):593‐601.

Nicolaides 2005d {published data only}

Nicolaides KH, Wegrzyn P. [Fetal nuchal translucency]. [Polish]. Ginekologia Polska 2005;76(3):179‐86.

Nicolaides 2005e {published data only}

Nicolaides KH, Wegrzyn P. [Fetal nuchal translucency thickness and risk for chromosomal defects]. [Polish]. Ginekologia Polska 2005;76(4):257‐63.

Nicolaides 2005f {published data only}

Nicolaides Kypros H. First‐trimester screening for chromosomal abnormalities. Seminars in Perinatology (Philadelphia) 2005;29(4):190‐4.

Niemimaa 2001 {published data only}

Niemimaa M, Heinonen S, Seppala M, Hippelainen M, Martikainen H, Ryynanen M. First‐trimester screening for Down's syndrome in in vitro fertilization pregnancies. Fertility & Sterility 2001;76(6):1282‐3.

Niemimaa 2002 {published data only}

Niemimaa M, Suonpaa M, Heinonen S, Seppala M, Bloigu R, Ryynanen M. Maternal serum human chorionic gonadotrophin and pregnancy‐associated plasma protein A in twin pregnancies in the first trimester. Prenatal Diagnosis 2002;22(3):183‐5.

Niemimaa 2003 {published data only}

Niemimaa M, Heinonen S, Seppala M, Ryynanen M. The influence of smoking on the pregnancy‐associated plasma protein A, free ß human chorionic gonadotrophin and nuchal translucency. BJOG: an international journal of obstetrics and gynaecology 2003;110(7):664‐7.

Noble 1997 {published data only}

Noble PL, Snijders RJ, Abraha HD, Sherwood RA, Nicolaides KH. Maternal serum free ß‐hCG at 10 to 14 weeks of gestation in trisomic twin pregnancies. British Journal of Obstetrics and Gynaecology 1997;104(6):741‐3.

Norgaard‐Pedersen 1990 {published data only}

Norgaard‐Pedersen B, Larsen SO, Arends J, Svenstrup B, Tabor A. Maternal serum markers in screening for Down syndrome. Clinical Genetics 1990;37(1):35‐43.

Norton 1992 {published data only}

Norton ME, Golbus MS. Maternal serum CA 125 for aneuploidy detection in early pregnancy. Prenatal Diagnosis 1992;12(9):779‐81.

O'Brien 1997a {published data only}

Brien JE, Dvorin E, Yaron Y, Ayoub M, Johnson MP, Hume RF, et al. Differential increases in AFP, hCG, and uE3 in twin pregnancies: Impact on attempts to quantify Down syndrome screening calculations. American Journal of Medical Genetics 1997;73(2):109‐12.

O'Brien 1997b {published data only}

Brien JE, Dvorin E, Drugan A, Johnson MP, Yaron Y, Evans MI. Race‐ethnicity‐specific variation in multiple‐marker biochemical screening: Alpha‐fetoprotein, hCG, and estriol. Obstetrics and Gynecology 1997;89(3):355‐8.

Odibo 2004 {published data only}

Odibo AO, Sehdev HM, Dunn L, McDonald R, Macones GA. The association between fetal nasal bone hypoplasia and aneuploidy. Obstetrics & Gynecology 2004;104(6):1229‐33.

Ognibene 1999 {published data only}

Ognibene A, Ciuti R, Tozzi P, Messeri G. Maternal serum superoxide dismutase (SOD): a possible marker for screening Down syndrome affected pregnancies.[see comment]. Prenatal Diagnosis 1999;19(11):1058‐60.

Olajide 1989 {published data only}

Olajide F, Kitau MJ, Chard T. Maternal serum AFP levels in the first trimester of pregnancy. European Journal of Obstetrics, Gynecology, & Reproductive Biology 1989;30(2):123‐8.

Onda 1996 {published data only}

Onda T, Kitagawa M, Takeda O, Sago H, Kubonoya K, Iinuma K, et al. Triple marker screening in native Japanese women. Prenatal Diagnosis 1996;16(8):713‐7.

Onda 1998 {published data only}

Onda T, Tanaka T, Takeda O, Kitagawa M, Kuwabara Y, Yamamoto H, et al. Agreement between predicted risk and prevalence of Down syndrome in second‐trimester triple‐marker screening in Japan. Prenatal Diagnosis 1998;18(9):956‐8.

Onda 2000 {published data only}

Onda T, Tanaka T, Yoshida K, Nakamura Y, Kudo R, Yamamoto H, et al. Triple marker screening for trisomy 21, trisomy 18 and open neural tube defects in singleton pregnancies of native Japanese pregnant women. Journal of Obstetrics & Gynaecology Research 2000;26(6):441‐7.

Orlandi 2002 {published data only}

Orlandi F, Rossi C, Allegra A, Krantz D, Hallahan T, Orlandi E, et al. First trimester screening with free ß‐hCG, PAPP‐A and nuchal translucency in pregnancies conceived with assisted reproduction. Prenatal Diagnosis 2002;22(8):718‐21.

Páez 2004 {published data only}

Páez L, Peña E, González F, Bello F, Bellorín J, Espinoza F, et al. Plasma protein "A" and chorionic gonadotropin at first trimester pregnancy. Informe Medico 2004;6(2):99‐109.

Palka 1998 {published data only}

Palka G, Guanciali Franchi P, Papponetti M, Marcuccitti J, Morizio E, Calabrese G, et al. Prenatal diagnosis using the triple test. Minerva Ginecologica 1998;50(10):411‐5.

Palomaki 1989 {published data only}

Palomaki GE, Williams J, Haddow JE. Combining maternal serum alpha‐fetoprotein measurements and age to screen for Down syndrome in pregnant women under age 35. American Journal of Obstetrics and Gynecology 1989;160(3):575‐81.

Palomaki 1993 {published data only}

Palomaki GE, Knight GJ, Haddow JE, Canick JA, Wald NJ, Kennard A. Cigarette smoking and levels of maternal serum alpha‐fetoprotein, unconjugated estriol, and hCG: impact on Down syndrome screening. Obstetrics and Gynecology 1993;81(5):675‐8.

Palomaki 1994 {published data only}

Palomaki GE, Knight GJ, Haddow JE. Human chorionic gonadotropin and unconjugated oestriol measurements in insulin‐dependent diabetic pregnant women being screened for fetal Down syndrome. Prenatal Diagnosis 1994;14(1):65‐8.

Palomaki 1996 {published data only}

Palomaki GE, Neveux LM, Haddow JE. Can reliable Down's syndrome detection rates be determined from prenatal screening intervention trials?. Journal of Medical Screening 1996;3(1):12‐7.

Palomaki 2005 {published data only}

Palomaki GE, Knight GJ, Neveux LM, Pandian R, Haddow JE. Maternal serum invasive trophoblast antigen and first‐trimester Down syndrome screening. Clinical Chemistry 2005;51(8):1499‐504.

Panburana 2001 {published data only}

Panburana P, Ajjimakorn S, Tungkajiwangoon P. First trimester Down Syndrome screening by nuchal translucency in a Thai population. International Journal of Gynaecology & Obstetrics 2001;75(3):311‐2.

Pandya 1994 {published data only}

Pandya PP, Brizot ML, Kuhn P, Snijders RJ, Nicolaides KH. First‐trimester fetal nuchal translucency thickness and risk for trisomies. Obstetrics & Gynecology 1994;84(3):420‐3.

Pandya 1995 {published data only}

Pandya PP, Santiago C, Snijders RJM, Nicolaides KH. First trimester fetal nuchal translucency. Current Opinion in Obstetrics and Gynecology 1995;7(2):95‐102.

Paul 2001 {published data only}

Paul C, Krampl E, Skentou C, Jurkovic D, Nicolaides KH. Measurement of fetal nuchal translucency thickness by three‐dimensional ultrasound. Ultrasound in Obstetrics & Gynecology 2001;18(5):481‐4.

Peralta 2005 {published data only}

Peralta CF, Falcon O, Wegrzyn P, Faro C, Nicolaides KH. Assessment of the gap between the fetal nasal bones at 11 to 13 + 6 weeks of gestation by three‐dimensional ultrasound. Ultrasound in Obstetrics & Gynecology 2005;25(5):464‐7.

Perenc 1998 {published data only}

Perenc M, Dudarewicz L, Kaluzewski B. Analysis of triple test results in 27 cases of twin pregnancies. Acta Geneticae Medicae et Gemellologiae 1998;47(3‐4):249‐54.

Perheentupa 2002 {published data only}

Perheentupa A, Ruokonen A, Tuomivaara L, Ryynänen M, Martikainen H. Maternal serum (ß)‐HCG and (alpha)‐fetoprotein concentrations in singleton pregnancies following assisted reproduction. Human Reproduction 2002;17(3):794‐7.

Perona 1998 {published data only}

Perona M, Mancini G, Dall'Amico D, Guaraldo V, Carbonara A. Influence of smoking habits on Down's syndrome risk evaluation at mid‐trimester through biochemical screening. International Journal of Clinical & Laboratory Research 1998;28(3):179‐82.

Petervari 2000 {published data only}

Petervari L, Varga A, Tanko A, Szabo L, Godo G. [Significance of nuchal edema in fetuses of pregnant women under 35 years of age]. [Hungarian]. Orvosi Hetilap 2000;141(8):399‐402.

Petrocik 1989 {published data only}

Petrocik E, Wassman ER, Kelly JC. Prenatal screening for Down syndrome with maternal serum human chorionic gonadotropin levels.[see comment]. American Journal of Obstetrics and Gynecology 1989;161(5):1168‐73.

Phillips 1992 {published data only}

Phillips OP, Elias S, Shulman LP, Andersen RN, Morgan CD, Simpson JL. Maternal serum screening for fetal Down syndrome in women less than 35 years of age using alpha‐fetoprotein, hCG, and unconjugated estriol: a prospective 2‐year study. Obstetrics & Gynecology 1992;80(3):353‐8.

Phillips 1993 {published data only}

Phillips OP, Shulman LP, Elias S, Simpson JL. Maternal serum screening for fetal Down syndrome using alpha‐ fetoprotein, human chorionic gonadotrophin, and unconjugated estriol in adolescents. Adolescent and Pediatric Gynecology 1993;6(2):91‐4.

Pinette 2003 {published data only}

Pinette MG, Egan JF, Wax JR, Blackstone J, Cartin A, Benn PA. Combined sonographic and biochemical markers for Down syndrome screening. Journal of Ultrasound in Medicine 2003;22(11):1185‐90.

Platt 2004 {published data only}

Platt LD, Greene N, Johnson A, Zachary J, Thom E, Krantz D, et al. Sequential pathways of testing after first‐trimester screening for trisomy 21. Obstetrics and Gynecology 2004;104(4):661‐6.

Podobnik 1995 {published data only}

Podobnik M, Singer Z, Podobnik‐Sarkanji S, Bulic M. First trimester diagnosis of cystic hygromata using transvaginal ultrasound and cytogenetic evaluation. Journal of Perinatal Medicine 1995;23(4):283‐91.

Prefumo 2002 {published data only}

Prefumo F, Thilaganathan B. Agreement between predicted risk and prevalence of Down syndrome in first trimester nuchal translucency screening. Prenatal Diagnosis 2002;22(10):917‐8.

Prefumo 2004 {published data only}

Prefumo F, Sairam S, Bhide A, Penna L, Hollis B, Thilaganathan B. Maternal ethnic origin and fetal nasal bones at 11‐14 weeks of gestation. BJOG: an international journal of obstetrics & gynaecology 2004;111(2):109‐12.

Price 1998 {published data only}

Price KM, Van Lith JM, Silman R, Mantingh A, Grudzinskas JG. First trimester maternal serum concentrations of fetal antigen 2 in normal pregnancies and those affected by trisomy 21. Human Reproduction 1998;13(6):1706‐8.

Raty 2000 {published data only}

Raty R, Virtanen A, Koskinen P, Laitinen P, Forsstrom J, Salonen R, et al. Maternal midtrimester serum AFP and free ß‐hCG levels in in vitro fertilization twin pregnancies. Prenatal Diagnosis 2000;20(3):221‐3.

Räty 2002 {published data only}

Räty R, Virtanen A, Koskinen P, Anttila L, Forsström J, Laitinen P, et al. Serum free (ß)‐HCG and alpha‐fetoprotein levels in IVF, ICSI and frozen embryo transfer pregnancies in maternal mid‐trimester serum screening for Down's syndrome. Human Reproduction 2002;17(2):481‐4.

Rembouskos 2004 {published data only}

Rembouskos G, Cicero S, Longo D, Vandecruys H, Nicolaides KH. Assessment of the fetal nasal bone at 11‐14 weeks of gestation by three‐dimensional ultrasound. Ultrasound in Obstetrics & Gynecology 2004;23(3):232‐6.

Ren 1992 {published data only}

Ren S‐G, Braunstein GD. Human chorionic gonadotropin. Seminars in Reproductive Endocrinology 1992;10(2):95‐105.

Renier 1998 {published data only}

Renier MA, Vereecken A, Van Herck E, Straetmans D, Ramaekers P, Buytaert P. Second trimester maternal dimeric inhibin‐A in the multiple‐marker screening test for Down's syndrome. Human Reproduction 1998;13(3):744‐8.

Resta 1990 {published data only}

Resta RG, Nyberg D. The role of ultrasound in screening for Down syndrome. Birth Defects: Original Article Series 1990;26(3):104.

Reynders 1997 {published data only}

Reynders CS, Pauker SP, Benacerraf BR. First trimester isolated fetal nuchal lucency: significance and outcome. Journal of Ultrasound in Medicine 1997;16(2):101‐5.

Reynolds 1989 {published data only}

Reynolds TM, Penney MD. The mathematical basis of multivariate risk screening: with special reference to screening for Down's syndrome associated pregnancy. Annals of Clinical Biochemistry 1989;27(5):452‐8.

Reynolds 1999 {published data only}

Reynolds TM, Schaeffer HJ, Schlensker S. Estimation of Down's syndrome risks in the first trimester of pregnancy: experience of testing with PAPP‐A, total hCG and free ß‐ hCG levels in maternal blood samples in a German population. Clinical Laboratory 1999;45(1‐2):49‐53.

Ribbert 1996 {published data only}

Ribbert LS, Kornman LH, de Wolf BT, Simons AH, Jansen CA, Beekhuis JR, et al. Maternal serum screening for fetal Down syndrome in IVF pregnancies. Prenatal Diagnosis 1996;16(1):35‐8.

Rice 2005 {published data only}

Rice JD, McIntosh SF, Halstead AC. Second‐trimester maternal serum screening for Down syndrome in in vitro fertilization pregnancies. Prenatal Diagnosis 2005;25(3):234‐8.

Rich 1991 {published data only}

Rich N, Boots L, Davis R, Finley S. Efficiency of maternal serum hCG AFP and free estriol in the identification of trisomy 21 and other complications of pregnancy. Journal of the Alabama Academy of Science 1991;62(2‐3):135.

Roberts 1995 {published data only}

Roberts LJ, Bewley S, Mackinson AM, Rodeck CH. First trimester fetal nuchal translucency: problems with screening the general population. 1. British Journal of Obstetrics and Gynaecology 1995;102(5):381‐5.

Robertson 1991 {published data only}

Robertson EF. Maternal serum screening for neural tube defects and Down's syndrome.[see comment]. Medical Journal of Australia 1991;155(2):67‐8.

Rode 2003 {published data only}

Rode L, Wojdemann KR, Shalmi AC, Larsen SO, Sundberg K, Norgaard‐Pedersen B, et al. Combined first‐ and second‐trimester screening for Down syndrome: an evaluation of proMBP as a marker. Prenatal Diagnosis 2003;23(7):593‐8.

Ronge 2006 {published data only}

Ronge R. Combined first trimester screening for Down's syndrome is superior to quadruple test. Geburtshilfe und Frauenheilkunde 2006;66(4):332.

Rose 1995 {published data only}

Rose NC, Mennuti MT. Multiple marker screening for women 35 and older. Contemporary OB/GYN 1995;40(9):55‐6.

Ross 1997 {published data only}

Ross HL, Elias S. Maternal serum screening for fetal genetic disorders. Obstetrics & Gynecology Clinics of North America 1997;24(1):33‐47.

Rotmensch 1996 {published data only}

Rotmensch S, Liberati M, Kardana A, Copel JA, Ben‐Rafael Z, Cole LA. Nicked free ß‐subunit of human chorionic gonadotropin: a potential new marker for Down syndrome screening. American Journal of Obstetrics and Gynecology 1996;174(2):609‐11.

Rotmensch 1999 {published data only}

Rotmensch S, Celentano C, Shalev J, Vishne TH, Lipitz S, Ben‐Rafael Z, et al. Midtrimester maternal serum screening after multifetal pregnancy reduction in pregnancies conceived by in vitro fertilization. Journal of Assisted Reproduction and Genetics 1999;16(1):8‐12.

Rozenberg 2006 {published data only}

Rozenberg P, Bussieres L, Chevret S, Bernard JP, Malagrida L, Cuckle H, et al. Screening for Down syndrome using first‐trimester combined screening followed by second‐trimester ultrasound examination in an unselected population. American Journal of Obstetrics and Gynecology 2006;195(5):1379‐87.

Rudnicka 2002 {published data only}

Rudnicka AR, Wald NJ, Huttly W, Hackshaw AK. Influence of maternal smoking on the birth prevalence of Down syndrome and on second trimester screening performance. Prenatal Diagnosis 2002;22(10):893‐7.

Ryall 1992 {published data only}

Ryall RG, Staples AJ, Robertson EF, Pollard AC. Improved performance in a prenatal screening programme for Down's syndrome incorporating serum‐free hCG subunit analyses. Prenatal Diagnosis 1992;12(4):251‐61.

Ryall 2001 {published data only}

Ryall RG, Callen D, Cocciolone R, Duvnjak A, Esca R, Frantzis N, et al. Karyotypes found in the population declared at increased risk of Down syndrome following maternal serum screening. Prenatal Diagnosis 2001;21(7):553‐7.

Sabriá 2002 {published data only}

Sabriá J, Cabrero D, Bach C. Aneuploidy screening: ultrasound versus biochemistry. Ultrasound Review of Obstetrics and Gynecology 2002;2(4):221‐8.

Sacchini 2003 {published data only}

Sacchini C, El‐Sheikhah A, Cicero S, Rembouskos G, Nicolaides KH. Ear length in trisomy 21 fetuses at 11‐14 weeks of gestation. Ultrasound in Obstetrics & Gynecology 2003;22(5):460‐3.

Saller 1997 {published data only}

Saller DN, Canick JA, Kellner LH, Rose NC, Garza J, French CA, et al. Maternal serum analyte levels in pregnancies with fetal Down syndrome resulting from translocations. American Journal of Obstetrics and Gynecology 1997;177(4):879‐81.

Salomon 2001 {published data only}

Salomon LJ, Bernard JP, Taupin P, Benard C, Ville Y. Relationship between nuchal translucency at 11‐14 weeks and nuchal fold at 20‐24 weeks of gestation. Ultrasound in Obstetrics & Gynecology 2001;18(6):636‐7.

Salonen 1997 {published data only}

Salonen R, Turpeinen U, Kurki L, Lappalainen M, Ammala P, Hiilesmaa V, et al. Maternal serum screening for Down's syndrome on population basis. Acta Obstetricia et Gynecologica Scandinavica 1997;76(9):817‐21.

Saltvedt 2005 {published data only}

Saltvedt S, Almstrom H, Kublickas M, Valentin L, Bottinga R, Bui TH, et al. Screening for Down syndrome based on maternal age or fetal nuchal translucency: a randomized controlled trial in 39,572 pregnancies. Ultrasound in Obstetrics & Gynecology 2005;25(6):537‐45.

Saridogan 1996 {published data only}

Saridogan E, Djahanbakhch O, Naftalin AA. Screening for Down's syndrome: experience in an inner city health district. British Journal of Obstetrics and Gynaecology 1996;103(12):1205‐11.

Savoldelli 1993 {published data only}

Savoldelli G, Binkert F, Achermann J, Schmid W. Ultrasound screening for chromosomal anomalies in the first trimester of pregnancy. Prenatal Diagnosis 1993;13(6):513‐8.

Schiott 2006 {published data only}

Schiott KM, Christiansen M, Petersen OB, Sorensen TL, Uldbjerg N. The "Consecutive Combined Test"‐‐using double test from week 8 + 0 and nuchal translucency scan, for first trimester screening for Down syndrome. Prenatal Diagnosis 2006;26(12):1105‐9.

Schuchter 1998 {published data only}

Schuchter K, Wald N, Hackshaw AK, Hafner E, Liebhart E. The distribution of nuchal translucency at 10‐13 weeks of pregnancy. Prenatal Diagnosis 1998;18(3):281‐6.

Scott 1995 {published data only}

Scott F, Boogert A, Smart S, Anderson J. Maternal serum screening and routine 18‐week ultrasound in the detection of all chromosomal abnormalities. Australian & New Zealand Journal of Obstetrics & Gynaecology 1995;35(2):165‐8.

Seeds 1990 {published data only}

Seeds JW, Watson WJ. Ultrasound and maternal serum alpha‐fetoprotein screening: a complementary relationship. Ultrasound Quarterly 1990;8(2):145‐66.

Seki 1995 {published data only}

Seki K, Mitsui C, Nagata I. Measurement of urinary free ß‐human chorionic gonadotropin by immunoradiometric assay. Gynecologic and Obstetric Investigation 1995;40(3):162‐7.

Shenhav 2003 {published data only}

Shenhav S, Gemer O, Sherman DJ, Peled R, Segal S. Midtrimester triple‐test levels in women with chronic hypertension and altered renal function. Prenatal Diagnosis 2003;23(2):166‐7.

Shintaku 1989 {published data only}

Shintaku Y, Takabayashi T, Sasaki H, Ozawa N, Shinkawa O, Hamazaki Y, et al. [Screening for chromosomal anomalies with maternal serum alpha‐fetoprotein]. [Japanese]. Nippon Sanka Fujinka Gakkai Zasshi ‐ Acta Obstetrica et Gynaecologica Japonica 1989;41(2):185‐90.

Shulman 2003 {published data only}

Shulman A, Maymon R. Mid‐gestation Down syndrome screening test and pregnancy outcome among unstimulated assisted‐conception pregnancies. Prenatal Diagnosis 2003;23(8):625‐8.

Simon‐Bouy 1999 {published data only}

Simon‐Bouy B. [Markers for trisomy 21][French]. Fertilite Contraception Sexualite 1999;27(9):289‐91.

Simpson 1986 {published data only}

Simpson JL, Baum LD, Marder R, Elias S, Ober C, Martin AO. Maternal serum alpha‐fetoprotein screening: low and high values for detection of genetic abnormalities. American Journal of Obstetrics and Gynecology 1986;155(3):593‐7.

Smith 1990 {published data only}

Smith C, Grube GL, Wilson S. Maternal serum alpha‐fetoprotein screening and the role of ultrasound. Journal of Diagnostic Medical Sonography 1990;6(6):312‐6.

Smith 1996 {published data only}

Smith ER, Petersen J, Okorodudu AO, Bissell MG. Does the addition of unconjugated estriol in maternal serum screening improve the detection of trisomy 21? A meta‐analysis. Clinical Laboratory Management Review 1996;10(2):176‐81.

Smith 1999 {published data only}

Smith NC, Hau C. A six year study of the antenatal detection of fetal abnormality in six Scottish health boards. British Journal of Obstetrics and Gynaecology 1999;106(3):206‐12.

Smith‐Bindman 2001 {published data only}

Smith‐Bindman R, Hosmer W, Feldstein VA, Deeks JJ, Goldberg JD. Second‐trimester ultrasound to detect fetuses with Down syndrome: a meta‐analysis.[see comment]. JAMA 2001;285(8):1044‐55.

Smith‐Bindman 2003 {published data only}

Smith‐Bindman R, Chu P, Bacchetti P, Waters JJ, Mutton D, Alberman E. Prenatal screening for Down syndrome in England and Wales and population‐based birth outcomes. American Journal of Obstetrics and Gynecology 2003;187(4):980‐5.

Snijders 1995 {published data only}

Snijders RJM, Sebire NJ, Nicolaides KH. Maternal age and gestational age‐specific risk for chromosomal defects. Fetal Diagnosis and Therapy 1995;10(6):356‐67.

Snijders 1999 {published data only}

Snijders RJM, Sundberg K, Holzgreve W, Henry G, Nicolaides KH. Maternal age‐ and gestation‐specific risk for trisomy 21. Ultrasound in Obstetrics & Gynecology 1999;13(3):167‐70.

Soergel 2006 {published data only}

Soergel P, Pruggmayer M, Schwerdtfeger R, Muhlhaus K, Scharf A. Screening for trisomy 21 with maternal age, fetal nuchal translucency and maternal serum biochemistry at 11‐14 weeks: a regional experience from Germany. Fetal Diagnosis and Therapy 2006;21(3):264‐8.

Sokol 1998 {published data only}

Sokol AI, Kramer RL, Yaron Y, O'Brien JE, Muller F, Johnson MP, et al. Age‐specific variation in aneuploidy incidence among biochemical screening programs. American Journal of Obstetrics and Gynecology 1998;179(4):971‐3.

Sonek 2003 {published data only}

Sonek JD. Nasal bone evaluation with ultrasonography: a marker for fetal aneuploidy. Ultrasound in Obstetrics & Gynecology 2003;22(1):11‐5.

Spencer 1985 {published data only}

Spencer K, Carpenter P. Screening for Down's syndrome using serum alpha fetoprotein: a retrospective study indicating caution. BMJ (Clinical Research Ed.) 1985;290(6486):1940‐3.

Spencer 1991a {published data only}

Spencer K. Evaluation of an assay of the free ß‐subunit of choriogonadotropin and its potential value in screening for Down's syndrome. Clinical Chemistry 1991;37(6):809‐14.

Spencer 1991b {published data only}

Spencer K. Maternal serum CA125 is not a second trimester marker for Down's syndrome. Annals of Clinical Biochemistry 1991;28(3):299‐300.

Spencer 1992 {published data only}

Spencer K, Coombes EJ, Mallard AS, Ward AM. Free ß human choriogonadotropin in Down's syndrome screening: a multicentre study of its role compared with other biochemical markers.[see comment]. Annals of Clinical Biochemistry 1992;29(5):506‐18.

Spencer 1993a {published data only}

Spencer K, Carpenter P. Prospective study of prenatal screening for Down's syndrome with free ß human chorionic gonadotrophin.[see comment]. BMJ 1993;307(6907):764‐9.

Spencer 1993b {published data only}

Spencer K, Macri JN, Carpenter P, Anderson R, Krantz DA. Stability of intact chorionic gonadotropin (hCG) in serum, liquid whole blood, and dried whole‐blood filter‐paper spots: impact on screening for Down syndrome by measurement of free ß‐hCG subunit. Clinical Chemistry 1993;39(6):1064‐8.

Spencer 1993c {published data only}

Spencer K, Wood PJ, Anthony FW. Elevated levels of maternal serum inhibin immunoreactivity in second trimester pregnancies affected by Down's syndrome. Annals of Clinical Biochemistry 1993;30(Pt 2):219‐20.

Spencer 1993d {published data only}

Spencer K, Macri JN, Anderson RW, Aitken DA, Berry E, Crossley JA, et al. Dual analyte immunoassay in neural tube defect and Down's syndrome screening: results of a multicentre clinical trial. Annals of Clinical Biochemistry 1993;30(4):394‐401.

Spencer 1993e {published data only}

Spencer K. Free alpha‐subunit of human chorionic gonadotropin in Down syndrome. American Journal of Obstetrics and Gynecology 1993;168(1):132‐5.

Spencer 1995 {published data only}

Spencer K. The influence of gravidity on Down's syndrome screening with free ß hCG. Prenatal Diagnosis 1995;15(1):87‐9.

Spencer 1996a {published data only}

Spencer K, Wallace EM, Ritoe S. Second‐trimester dimeric inhibin‐A in Down's syndrome screening. Prenatal Diagnosis 1996;16(12):1101‐10.

Spencer 1997 {published data only}

Spencer K, Noble P, Snijders RJ, Nicolaides KH. First‐trimester urine free ß hCG, ß core, and total oestriol in pregnancies affected by Down's syndrome: implications for first‐trimester screening with nuchal translucency and serum free ß hCG. Prenatal Diagnosis 1997;17(6):525‐38.

Spencer 1998a {published data only}

Spencer K. The influence of smoking on maternal serum AFP and free ß hCG levels and the impact on screening for Down syndrome. Prenatal Diagnosis 1998;18(3):225‐34.

Spencer 1998b {published data only}

Spencer K, Carpenter P. Is prostate‐specific antigen a marker for pregnancies affected by Down syndrome?. Clinical Chemistry 1998;44(11):2362‐5.

Spencer 1999a {published data only}

Spencer K. Second trimester prenatal screening for Down's syndrome using alpha‐fetoprotein and free ß hCG: a seven year review. British Journal of Obstetrics and Gynaecology 1999;106(12):1287‐93.

Spencer 1999b {published data only}

Spencer K. Accuracy of Down's syndrome risks produced in a prenatal screening program. Annals of Clinical Biochemistry 1999;36(1):101‐3.

Spencer 2000a {published data only}

Spencer K, Berry E, Crossley JA, Aitken DA, Nicolaides KH. Is maternal serum total hCG a marker of trisomy 21 in the first trimester of pregnancy?. Prenatal Diagnosis 2000;20(4):311‐7.

Spencer 2000b {published data only}

Spencer K. Screening for trisomy 21 in twin pregnancies in the first trimester using free ß‐hCG and PAPP‐A, combined with fetal nuchal translucency thickness. Prenatal Diagnosis 2000;20(2):91‐5.

Spencer 2000c {published data only}

Spencer K. The influence of smoking on maternal serum PAPP‐A and free ß hCG levels in the first trimester of pregnancy. Prenatal Diagnosis 1999;19(11):1065‐6.

Spencer 2000d {published data only}

Spencer K, Ong CY, Liao AW, Nicolaides KH. The influence of parity and gravidity on first trimester markers of chromosomal abnormality. Prenatal Diagnosis 2000;20(10):792‐4.

Spencer 2000e {published data only}

Spencer K. The influence of fetal sex in screening for Down syndrome in the second trimester using AFP and free ß‐hCG. Prenatal Diagnosis 2000;20(8):648‐51.

Spencer 2000f {published data only}

Spencer K, Ong CY, Liao AW, Nicolaides KH. The influence of ethnic origin on first trimester biochemical markers of chromosomal abnormalities. Prenatal Diagnosis 2000;20(6):491‐4.

Spencer 2000g {published data only}

Spencer K, Tul N, Nicolaides KH. Maternal serum free ß‐hCG and PAPP‐A in fetal sex chromosome defects in the first trimester. Prenatal Diagnosis 2000;20(5):390‐4.

Spencer 2000h {published data only}

Spencer K. Second‐trimester prenatal screening for Down syndrome and the relationship of maternal serum biochemical markers to pregnancy complications with adverse outcome. Prenatal Diagnosis 2000;20(8):652‐6.

Spencer 2000i {published data only}

Spencer K, Ong CY, Liao AW, Papademetriou D, Nicolaides KH. The influence of fetal sex in screening for trisomy 21 by fetal nuchal translucency, maternal serum free ß‐hCG and PAPP‐A at 10‐14 weeks of gestation. Prenatal Diagnosis 2000;20(8):673‐5.

Spencer 2001 {published data only}

Spencer K. Age related detection and false positive rates when screening for Down's syndrome in the first trimester using fetal nuchal translucency and maternal serum free ßhCG and PAPP‐A. BJOG: an international journal of obstetrics and gynaecology 2001;108(10):1043‐6.

Spencer 2001a {published data only}

Spencer K, Liao AW, Ong CY, Geerts L, Nicolaides KH. First trimester maternal serum placenta growth factor (PIGF) concentrations in pregnancies with fetal trisomy 21 or trisomy 18. Prenatal Diagnosis 2001;21(9):718‐22.

Spencer 2001b {published data only}

Spencer K, Liao AW, Ong CY, Geerts L, Nicolaides KH. Maternal serum levels of dimeric Inhibin A in pregnancies affected by trisomy 21 in the first trimester. Prenatal Diagnosis 2001;21(6):441‐4.

Spencer 2001c {published data only}

Spencer K, Liao AW, Skentou H, Ong CY, Nicolaides KH. Maternal serum levels of total activin‐A in first‐trimester trisomy 21 pregnancies. Prenatal Diagnosis 2001;21(4):270‐3.

Spencer 2001d {published data only}

Spencer K. Screening for trisomy 21 in twin pregnancies in the first trimester: does chorionicity impact on maternal serum free ß‐hCG or PAPP‐A levels?. Prenatal Diagnosis 2001;21(9):715‐7.

Spencer 2002a {published data only}

Spencer K, Nicolaides KH. A first trimester trisomy 13/trisomy 18 risk algorithm combining fetal nuchal translucency thickness, maternal serum free ß‐hCG and PAPP‐A. Prenatal Diagnosis 2002;22(10):877‐9.

Spencer 2002b {published data only}

Spencer K. Accuracy of Down syndrome risks produced in a first‐trimester screening programme incorporating fetal nuchal translucency thickness and maternal serum biochemistry. Prenatal Diagnosis 2002;22(3):244‐6.

Spencer 2002c {published data only}

Spencer K, Cuckle HS. Screening for chromosomal anomalies in the first trimester: does repeat maternal serum screening improve detection rates?. Prenatal Diagnosis 2002;22(10):903‐6.

Spencer 2002d {published data only}

Spencer K, Crossley JA, Aitken DA, Nix AB, Dunstan FD, Williams K. Temporal changes in maternal serum biochemical markers of trisomy 21 across the first and second trimester of pregnancy. Annals of Clinical Biochemistry 2002;39(6):567‐76.

Spencer 2003a {published data only}

Spencer K, Crossley JA, Aitken DA, Nix AB, Dunstan FD, Williams K. The effect of temporal variation in biochemical markers of trisomy 21 across the first and second trimesters of pregnancy on the estimation of individual patient‐specific risks and detection rates for Down's syndrome. Annals of Clinical Biochemistry 2003;40(3):219‐31.

Spencer 2003b {published data only}

Spencer K. The influence of different sample collection types on the levels of markers used for Down's syndrome screening as measured by the Kryptor Immunosassay system. Annals of Clinical Biochemistry 2003;40(2):166‐8.

Spencer 2003c {published data only}

Spencer K, Bindra R, Nicolaides KH. Maternal weight correction of maternal serum PAPP‐A and free ß‐hCG MoM when screening for trisomy 21 in the first trimester of pregnancy. Prenatal Diagnosis 2003;23(10):851‐5.

Spencer 2003d {published data only}

Spencer K, Nicolaides KH. Screening for trisomy 21 in twins using first trimester ultrasound and maternal serum biochemistry in a one‐stop clinic: a review of three years experience. BJOG: an international journal of obstetrics and gynaecology 2003;110(3):279‐80.

Spencer 2004 {published data only}

Spencer K, Bindra R, Cacho AM, Nicolaides KH. The impact of correcting for smoking status when screening for chromosomal anomalies using maternal serum biochemistry and fetal nuchal translucency thickness in the first trimester of pregnancy. Prenatal Diagnosis 2004;24(3):169‐73.

Spencer 2005a {published data only}

Spencer K, Cicero S, Atzei A, Otigbah C, Nicolaides KH. The influence of maternal insulin‐dependent diabetes on fetal nuchal translucency thickness and first‐trimester maternal serum biochemical markers of aneuploidy. Prenatal Diagnosis 2005;25(10):927‐9.

Spencer 2005b {published data only}

Spencer K, Heath V, El‐Sheikhah A, Ong CY, Nicolaides KH. Ethnicity and the need for correction of biochemical and ultrasound markers of chromosomal anomalies in the first trimester: a study of Oriental, Asian and Afro‐Caribbean populations. Prenatal Diagnosis 2005;25(5):365‐9.

Spencer 2005c {published data only}

Spencer K. First trimester maternal serum screening for Down's syndrome: an evaluation of the DPC Immulite 2000 free ß‐hCG and pregnancy‐associated plasma protein‐A assays.[see comment]. Annals of Clinical Biochemistry 2005;42(1):30‐40.

Spong 1999 {published data only}

Spong CY, Ghidini A, Stanley‐Christian H, Meck JM, Seydel FD, Pezzullo JC. Risk of abnormal triple screen for Down syndrome is significantly higher in women with female fetuses. Prenatal Diagnosis 1999;19(4):337‐9.

Stevens 1998 {published data only}

Stevens SL. The use of nuchal lucency as a screening tool in first trimester sonography. Journal of Diagnostic Medical Sonography 1998;14(6):251‐4.

Stoll 1992 {published data only}

Stoll C. A new approach of prenatal prevention of constitutional disabilities ‐ the study of markers of maternal serum. Journal de Medecine de Strasbourg 1992;23(1):25‐7.

Su 2002a {published data only}

Su YN, Hsu JJ, Lee CN, Cheng WF, Kung CC, Hsieh FJ. Raised maternal serum placenta growth factor concentration during the second trimester is associated with Down syndrome. Prenatal Diagnosis 2002;22(1):8‐12.

Suchet 1995 {published data only}

Suchet IB. Ultrasonography of the fetal neck in the first and second trimesters. Part 2. Anomalies of the posterior nuchal region. Canadian Association of Radiologists Journal 1995;46(5):344‐52.

Suchy 1990 {published data only}

Suchy SF, Yeager MT. Down syndrome screening in women under 35 with maternal serum hCG. Obstetrics & Gynecology 1990;76(1):20‐4.

Summers 2003a {published data only}

Summers AM, Farrell SA, Huang T, Meier C, Wyatt PR. Maternal serum screening in Ontario using the triple marker test. Journal of Medical Screening 2003;10(3):107‐11.

Summers 2003b {published data only}

Summers AM, Huang T, Meier C, Wyatt PR. The implications of a false positive second‐trimester serum screen for Down syndrome. Obstetrics & Gynecology 2003;101(6):1301‐6.

Suntharasaj 2005 {published data only}

Suntharasaj T, Ratanasiri T, Chanprapaph P, Kengpol C, Kor‐anantakul O, Leetanaporn R, et al. Variability of nuchal translucency measurement: a multicenter study in Thailand. Gynecologic & Obstetric Investigation 2005;60(4):201‐5.

Sutton 2004 {published data only}

Sutton JM, Cole LA. Sialic acid‐deficient invasive trophoblast antigen (sd‐ITA): a new urinary variant for gestational Down syndrome screening. Prenatal Diagnosis 2004;24(3):194‐7.

Suzuki 1998 {published data only}

Suzuki Y, Takada J, Iwaki T, Isaka K, Takayama M. Screening for trisomy 21 in the first trimester by measurement of serum PAPP‐A and free ß‐hCG. Acta Obstetrica et Gynaecologica Japonica 1998;50(1):37‐40.

Tabor 1987 {published data only}

Tabor A, Larsen SO, Nielsen J, Nielsen J, Philip J, Pilgaard B, et al. Screening for Down's syndrome using an iso‐risk curve based on maternal age and serum alpha‐fetoprotein level. British Journal of Obstetrics and Gynaecology 1987;94(7):636‐42.

Tanski 1999 {published data only}

Tanski S, Rosengren SS, Benn PA. Predictive value of the triple screening test for the phenotype of Down syndrome. American Journal of Medical Genetics 1999;85(2):123‐6.

Thilaganathan 1998 {published data only}

Thilaganathan B, Khare M, Williams B, Wathen NC. Influence of ethnic origin on nuchal translucency screening for Down's syndrome. Ultrasound in Obstetrics & Gynecology 1998;12(2):112‐4.

Thilaganathan 1999 {published data only}

Thilaganathan B. First‐trimester nuchal translucency and maternal serum biochemical screening for Down's syndrome: a happy union?. Ultrasound in Obstetrics & Gynecology 1999;13(4):229‐30.

Tislaric 2002 {published data only}

Tislaric D, Brajenovic‐Milic B, Ristic S, Latin V, Zuvic‐Butorac M, Bacic J, et al. The influence of smoking and parity on serum markers for Down's syndrome screening. Fetal Diagnosis and Therapy 2002;17(1):17‐21.

Torok 1997 {published data only}

Torok O, Veress L, Szabo M, Zsupan I, Buczko Z, Bolodar A, et al. [Biochemical and ultrasonic screening of chromosomal aneuploidies in the second trimester of pregnancy]. [Hungarian]. Orvosi Hetilap 1997;138(3):123‐7.

Tsai 2001 {published data only}

Tsai MS, Huang YY, Hwa KY, Cheng CC, Lee FK. Combined measurement of fetal nuchal translucency, maternal serum free ß‐hCG, and pregnancy‐associated plasma protein A for first‐trimester Down's syndrome screening. Journal of the Formosan Medical Association 2001;100(5):319‐25.

Valerio 1996 {published data only}

Valerio D, Aiello R, Altieri V, Fagnoni P. Maternal serum screening of fetal chromosomal abnormalities by AFP, UE3, hCG and free‐ß hCG. Prospective and retrospective results. Minerva Ginecologica 1996;48(5):169‐73.

Van Blerk 1992 {published data only}

Van Blerk M, Smitz J, De Catte L, Kumps C, Van der Elst J, Van Steirteghem AC. Second‐trimester cancer antigen 125 and Down's syndrome.[see comment]. Prenatal Diagnosis 1992;12(12):1062‐6.

Van Heesch, 2006 {published data only}

Van Heesch PN, Schielen PC, Wildhagen MF, Den Hollander K, Steegers EA, Wildschut HI. Combined first trimester screening for trisomy 21: lack of agreement between risk calculation methods. Journal of Perinatal Medicine 2006;34(2):162‐5.

Van Lith 1991 {published data only}

Van Lith JM, Mantingh A, Beekhuis JR, De Bruijn HW, Breed AS. First trimester CA 125 and Down's syndrome. British Journal of Obstetrics and Gynaecology 1991;98(5):493‐4.

Van Lith 1993 {published data only}

Van Lith JM, Mantingh A, De Bruijn HW. Maternal serum CA 125 levels in pregnancies with chromosomally‐normal and ‐abnormal fetuses. Dutch Working Party on Prenatal Diagnosis. Prenatal Diagnosis 1993;13(12):1123‐31.

Van Lith 1994 {published data only}

Van Lith JM, Mantingh A, Pratt JJ. First‐trimester maternal serum immunoreactive inhibin in chromosomally normal and abnormal pregnancies. Dutch Working Party on Prenatal Diagnosis. Obstetrics and Gynecology 1994;83(5 Pt 1):661‐4.

Veress 1986 {published data only}

Veress L, Szabo M, Horvath K, Polgar K, Papp Z. [Low maternal serum alpha‐fetoprotein concentration and Down syndrome]. [Hungarian]. Orvosi Hetilap 1986;127(20):1232‐3.

Veress 1988 {published data only}

Veress L, Szabo M, Polgar K, Takacs L, Papp Z. [Prenatal screening for Down's syndrome by measuring the AFP concentration in the maternal serum]. [Hungarian]. Orvosi Hetilap 1988;129(31):1677.

Vintzileos 2003 {published data only}

Vintzileos A, Walters C, Yeo L. Absent nasal bone in the prenatal detection of fetuses with trisomy 21 in a high‐risk population. Obstetrics & Gynecology 2003;101(5):905‐8.

Wald 1988a {published data only}

Wald NJ, Cuckle HS, Densem JW, Nanchahal K, Royston P, Chard T, et al. Maternal serum screening for Down's syndrome in early pregnancy. BMJ 1988;297(6653):883‐7.

Wald 1988b {published data only}

Wald NJ, Cuckle HS, Densem JW, Nanchahal K, Canick JA, Haddow JE, et al. Maternal serum unconjugated oestriol as an antenatal screening test for Down's syndrome. British Journal of Obstetrics and Gynaecology 1988;95(4):334‐41.

Wald 1991 {published data only}

Wald N, Cuckle H, Wu TS, George L. Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in twin pregnancies: implications for screening for Down's syndrome. British Journal of Obstetrics and Gynaecology 1991;98(9):905‐8.

Wald 1992a {published data only}

Wald NJ, Kennard A, Densem JW, Cuckle HS, Chard T, Butler L. Antenatal maternal serum screening for Down's syndrome: results of a demonstration project.[see comment]. BMJ 1992;305(6850):391‐4.

Wald 1992b {published data only}

Wald NJ, Cuckle HS, Densem JW, Stone RB. Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in pregnancies with insulin‐dependent diabetes: implications for screening for Down's syndrome. British Journal of Obstetrics and Gynaecology 1992;99(1):51‐3.

Wald 1992c {published data only}

Wald NJ, Cuckle HS, Densem JW, Kennard A, Smith D. Maternal serum screening for Down's syndrome: the effect of routine ultrasound scan determination of gestational age and adjustment for maternal weight.[see comment]. British Journal of Obstetrics and Gynaecology 1992;99(2):144‐9.

Wald 1993 {published data only}

Wald N, Densem J, Stone R, Cheng R. The use of free ß‐hCG in antenatal screening for Down's syndrome.[see comment]. British Journal of Obstetrics and Gynaecology 1993;100(6):550‐7.

Wald 1994a {published data only}

Wald NJ, Densem JW. Maternal serum free alpha‐human chorionic gonadotrophin levels in twin pregnancies: implications for screening for Down's syndrome. Prenatal Diagnosis 1994;14(8):717‐9.

Wald 1994b {published data only}

Wald NJ, Watt HC. Choice of serum markers in antenatal screening for Down's syndrome. Journal of Medical Screening 1994;1(2):117‐20.

Wald 1996a {published data only}

Wald NJ, Watt HC. Serum markers for Down's syndrome in relation to number of previous births and maternal age. Prenatal Diagnosis 1996;16(8):699‐703.

Wald 1996b {published data only}

Wald NJ, George L, Smith D, Densem JW, Petterson K. Serum screening for Down's syndrome between 8 and 14 weeks of pregnancy. International Prenatal Screening Research Group.[see comment]. British Journal of Obstetrics and Gynaecology. 1996;103(5):407‐12.

Wald 1996d {published data only}

Wald NJ, Watt HC, George L. Maternal serum inhibin‐A in pregnancies with insulin‐dependent diabetes mellitus: implications for screening for Down's syndrome. Prenatal Diagnosis 1996;16(10):923‐6.

Wald 1996e {published data only}

Wald NJ, Densem JW, George L, Muttukrishna S, Knight PG. Prenatal screening for Down's syndrome using inhibin‐A as a serum marker. Prenatal Diagnosis 1996;16(2):143‐53.

Wald 1997 {published data only}

Wald NJ, Hackshaw AK. Combining ultrasound and biochemistry in first‐trimester screening for Down's syndrome.[see comment]. Prenatal Diagnosis 1997;17(9):821‐9.

Wald 1998 {published data only}

Wald NJ, Watt HC, Haddow JE, Knight GJ. Screening for Down syndrome at 14 weeks of pregnancy. Prenatal Diagnosis 1998;18(3):291‐3.

Wald 1999a {published data only}

Wald NJ, Hackshaw AK, Diamandis EP, Melegos DN. Maternal serum prostate‐specific antigen and Down syndrome in the first and second trimesters of pregnancy. Prenatal Diagnosis 1999;19(7):674‐6.

Wald 1999b {published data only}

Wald NJ, Watt HC, Norgaard‐Pederson B, Christiansen M. SP1 in pregnancies with Down syndrome in the first trimester of pregnancy. Prenatal Diagnosis 1999;19(6):517‐20.

Wald 1999c {published data only}

Wald NJ, White N, Morris JK, Huttly WJ, Canick JA. Serum markers for Down's syndrome in women who have had in vitro fertilisation: implications for antenatal screening. British Journal of Obstetrics and Gynaecology 1999;106(12):1304‐6.

Wald 1999d {published data only}

Wald NJ, Watt HC, Hackshaw AK. Integrated screening for Down's syndrome on the basis of tests performed during the first and second trimesters.[see comment]. New England Journal of Medicine 1999;341(7):461‐7.

Wald 2003b {published data only}

Wald NJ, Rish S, Hackshaw AK. Combining nuchal translucency and serum markers in prenatal screening for Down syndrome in twin pregnancies. Prenatal Diagnosis 2003;23(7):588‐92.

Wald 2003c {published data only}

Wald NJ, Huttly WJ, Hackshaw AK. Antenatal screening for Down's syndrome with the quadruple test.[see comment]. Lancet 2003;361(9360):835‐6.

Wald 2006 {published data only}

Wald NJ, Rudnicka AR, Bestwick JP. Sequential and contingent prenatal screening for Down syndrome. Prenatal Diagnosis 2006;26(9):769‐77.

Wallace 1994 {published data only}

Wallace EM, Harkness LM, Burns S, Liston WA. Evaluation of maternal serum immunoreactive inhibin as a first trimester marker of Down's syndrome. Clinical Endocrinology 1994;41(4):483‐6.

Wallace 1997 {published data only}

Wallace EM, Crossley JA, Ritoe SC, Groome NP, Aitken DA. Maternal serum inhibin‐A in pregnancies complicated by insulin dependent diabetes mellitus. British Journal of Obstetrics and Gynaecology 1997;104(8):946‐8.

Ward 2005 {published data only}

Ward A. Nuchal translucency measurement. Synergy (http://www.highbeam.com/doc/1P3‐866108421.html) (accessed 2007)2005.

Watt 1996a {published data only}

Watt HC, Wald NJ, Smith D, Kennard A, Densem J. Effect of allowing for ethnic group in prenatal screening for Down's syndrome. Prenatal Diagnosis 1996;16(8):691‐8.

Watt 1996b {published data only}

Watt HC, Wald NJ, George L. Maternal serum inhibin‐A levels in twin pregnancies: implications for screening for Down's syndrome. Prenatal Diagnosis 1996;16(10):927‐9.

Weinans 2001 {published data only}

Weinans MJN, Pratt JJ, de Wolf HM, Mantingh A. First‐trimester maternal serum human thyroid‐stimulating hormone in chromosomally normal and Down syndrome pregnancies. Prenatal Diagnosis 2001;21(9):723‐5.

Weinans 2004 {published data only}

Weinans MJN, Kooij L, Müller MA, Bilardo KM, Van Lith JMM, Tymstra T. A comparison of the impact of screen‐positive results obtained from ultrasound and biochemical screening for Down syndrome in the first trimester: a pilot study. Prenatal Diagnosis 2004;24(5):347‐51.

Welborn 1994 {published data only}

Welborn JL, Timm NS. Trisomy 21 and cystic hygromas in early gestational age fetuses. American Journal of Perinatology 1994;11(1):19‐20.

Wenstrom 1993 {published data only}

Wenstrom KD, Williamson RA, Grant SS, Hudson JD, Getchell JP. Evaluation of multiple‐marker screening for Down syndrome in a statewide population. American Journal of Obstetrics and Gynecology 1993;169(4):793‐7.

Wenstrom 1995a {published data only}

Wenstrom KD, Owen J, Boots L, Ethier M. The influence of maternal weight on human chorionic gonadotropin in the multiple‐marker screening test for fetal Down syndrome. American Journal of Obstetrics and Gynecology 1995;173(4):1297‐300.

Wenstrom 1995b {published data only}

Wenstrom KD, Desai R, Owen J, Dubard MB, Boots L. Comparison of multiple‐marker screening with amniocentesis for the detection of fetal aneuploidy in women greater than or equal 35 years old. American Journal of Obstetrics and Gynecology 1995;173(4):1287‐92.

Whitlow 1998a {published data only}

Whitlow BJ, Lazanakis ML, Kadir RA, Chatzipapas I, Economides DL. The significance of choroid plexus cysts, echogenic heart foci and renal pyelectasis in the first trimester. Ultrasound in Obstetrics & Gynecology 1998;12(6):385‐90.

Whitlow 1998b {published data only}

Whitlow BJ, Economides DL. First trimester detection of fetal abnormalities in an unselected population. Contemporary Reviews in Obstetrics and Gynaecology 1998;10(4):245‐53.

Whitlow 1999 {published data only}

Whitlow BJ, Chatzipapas IK, Lazanakis ML, Kadir RA, Economides DL. The value of sonography in early pregnancy for the detection of fetal abnormalities in an unselected population. British Journal of Obstetrics and Gynaecology 1999;106(9):929‐36.

Williamson 1994 {published data only}

Williamson R. Expanded maternal serum alpha fetoprotein screening. Iowa Medicine 1994;84(9):397‐400.

Wilson 2000 {published data only}

Wilson K. New first‐trimester prenatal screening for down syndrome. Laboratory Medicine 2000;31(11):591.

Wojdemann 2001 {published data only}

Wojdemann KR, Larsen SO, Shalmi A, Sundberg K, Christiansen M, Tabor A. First trimester screening for Down syndrome and assisted reproduction: no basis for concern. Prenatal Diagnosis 2001;21(7):563‐5.

Wong 2003 {published data only}

Wong SF, Choi H, Ho LC. Nasal bone hypoplasia: is it a common finding amongst chromosomally normal fetuses of southern Chinese women?. Gynecologic & Obstetric Investigation 2003;56(2):99‐101.

Wright 2006 {published data only}

Wright D, Bradbury I, Cuckle H, Gardosi J, Tonks A, Standing S, et al. Three‐stage contingent screening for Down syndrome. Prenatal Diagnosis 2006;26(6):528‐34.

Yagel 1998 {published data only}

Yagel S, Anteby EY, Hochner‐Celnikier D, Ariel I, Chaap T, Ben Neriah Z. The role of midtrimester targeted fetal organ screening combined with the "triple test" and maternal age in the diagnosis of trisomy 21: a retrospective study. American Journal of Obstetrics and Gynecology 1998;178(1):40‐4.

Yamamoto 2001a {published data only}

Yamamoto R, Azuma M, Kishida T, Yamada H, Satomura S, Fujimoto S. Total alpha‐fetoprotein and Lens culinaris agglutinin‐reactive alpha‐fetoprotein in fetal chromosomal abnormalities. BJOG: an international journal of obstetrics and gynaecology 2001;108(11):1154‐8.

Yamamoto 2001b {published data only}

Yamamoto R, Azuma M, Hoshi N, Kishida T, Satomura S, Fujimoto S. Lens culinaris agglutinin‐reactive alpha‐fetoprotein, an alternative variant to alpha‐fetoprotein in prenatal screening for Down's syndrome. Human Reproduction 2001;16(11):2438‐44.

Yamamoto 2001c {published data only}

Yamamoto R, Azuma M, Wakui Y, Kishida T, Yamada H, Okuyama K, et al. Alpha‐fetoprotein microheterogeneity: a potential biochemical marker for Down's syndrome. Clinica Chimica Acta 2001;304(1‐2):137‐41.

Yaron 2001 {published data only}

Yaron Y, Wolman I, Kupferminc MJ, Ochshorn Y, Many A, Orr‐Urtreger A. Effect of fetal gender on first trimester markers and on Down syndrome screening. Prenatal Diagnosis 2001;21(12):1027‐30.

Ye 1995 {published data only}

Ye G, Liao S, Zhao X. The possibility of prenatal screening for fetal abnormalities in second‐trimester pregnancies by measuring AFP, ß‐HCG and uE‐3 levels. Xi'an Yike Daxue Xuebao 1995;16(4):408‐11.

Yoshida 2000 {published data only}

Yoshida K, Kuwabara Y, Tanaka T, Onda T, Kudo R, Yamamoto H, et al. Dimeric Inhibin A as a fourth marker for Down's syndrome maternal serum screening in native Japanese women. Journal of Obstetrics and Gynaecology Research 2000;26(3):171‐4.

Zeitune 1991 {published data only}

Zeitune M, Aitken DA, Crossley JA, Yates JR, Cooke A, Ferguson‐Smith MA. Estimating the risk of a fetal autosomal trisomy at mid‐trimester using maternal serum alpha‐fetoprotein and age: a retrospective study of 142 pregnancies. Prenatal Diagnosis 1991;11(11):847‐57.

Zelop 2005 {published data only}

Zelop CM, Milewski E, Brault K, Benn P, Borgida AF, Egan JFX. Variation of fetal nasal bone length in second‐trimester fetuses according to race and ethnicity. Journal of Ultrasound in Medicine 2005;24(11):1487‐9.

Zhao 1998 {published data only}

Zhao Xiaolan, Ye Guoling, Liu Qi. Using maternal serum PAPP‐A and other pregnancy‐associated proteins in screening for fetal abnormalities. Xi'an Yike Daxue Xuebao 1998;19(1):94‐6, 110.

Zoppi 2003 {published data only}

Zoppi MA, Ibba RM, Floris M, Manca F, Axiana C, Monni G. Changes in nuchal translucency thickness in normal and abnormal karyotype fetuses. BJOG: an international journal of obstetrics and gynaecology 2003;110(6):584‐8.

Additional references

Ir a:

Alfirevic 2003

Alfirevic Z, Sundberg K, Brigham S. Amniocentesis and chorionic villus sampling for prenatal diagnosis. Cochrane Database of Systematic Reviews 2003, Issue 3. [DOI: 10.1002/14651858.CD003252]

Alfirevic 2004

Alfirevic Z, Neilson JP. Antenatal screening for Down's syndrome. BMJ 2004;9(329(7470)):811‐2.

Alldred 2010

Alldred SK, Deeks JJ, Neilson JP, Alfirevic Z. Antenatal screening for Down's syndrome: generic protocol. Cochrane Database of Systematic Reviews 2010, Issue 4. [DOI: 10.1002/14651858.CD007384.pub2]

Alldred 2012

Alldred SK, Deeks JJ, Guo B, Neilson JP, Alfirevic Z. Second trimester serum tests for Down's Syndrome screening. Cochrane Database of Systematic Reviews 2012, Issue 6. [DOI: 10.1002/14651858.CD009925]

Bersinger 1995

Bersinger NA, Zakher A, Huber U, Pescia G, Schneider H. A sensitive enzyme immunoassay for pregnancy‐associated plasma protein A (PAPP‐A): a possible first trimester method of screening for Down syndrome and other trisomies. Archives of Gynecology and Obstetrics 1995;256(4):185‐92.

Bogart 1987

Bogart MH, Pandian MR, Jones OW. Abnormal maternal serum chorionic gonadotropin levels in pregnancies with fetal chromosome abnormalities. Prenatal Diagnosis 1987;7(9):623‐30.

Bossuyt 2003

Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. BMJ 2003;326(7379):41‐4. [PUBMED: 12511463]

Cole 1999a

Cole LA, Shahabi S, Oz UA, Bahado‐Singh RO, Mahoney MJ. Hyperglycosylated hCG (invasive trophoblast antigen) immunoassay: a new basis for gestational Down syndrome screening. Clinical Chemistry 1999;45:2109‐19.

Cuckle 1995a

Cuckle HS, Holding S, Jones R, Wallace EM, Groome NP. Maternal serum dimeric inhibin A in second‐trimester Down's syndrome pregnancies. Prenatal Diagnosis1995; Vol. 15, issue 4:385‐6.

Macri 1990

Macri JN, Kasturi RV, Krantz DA, Cook EJ, Moore ND, Young JA, et al. Maternal serum Down syndrome screening: free beta‐protein is a more effective marker than human chorionic gonadotropin. American Journal of Obstetrics and Gynecology 1990;163(4 Pt 1):1248‐53.

Macri 1993

Macri JN, Spencer K, Aitken D, Garver K, Buchanan PD, Muller F, et al. First‐trimester free beta (hCG) screening for Down syndrome. Prenatal Diagnosis 1993;13(7):557‐62.

Mol 1999

Mol BW, Lijmer JG, Van der Meulen J, Pajkrt E, Bilardo CM, Bossuyt PM. Effect of study design on the association between nuchal translucency measurement and Down syndrome. Obstetrics and Gynecology 1999;94(5 Pt 2):864‐9.

Penrose 1933

Penrose LS. The relative effects of parental and maternal age in mongolism. Journal of Genetics 1933;27:219‐24.

Steele 1966

Steele MW, Breg WR. Chromosome analysis of human amniotic‐fluid cells. Lancet 1966;i:383‐5.

Vaklenti 1968

Vaklenti C, Schutta E.J, Kehaty T. Prenatal diagnosis of Down's syndrome. Lancet 1968;ii:220.

Wald 2003a

Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM, SURUSS Research Group. First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). Health Technology Assessment (Winchester, England) 2003;7(11):1‐77.

Wallace 1995

Wallace EM, Grant VE, Swanston IA, Groome NP. Evaluation of maternal serum dimeric inhibin A as a first‐trimester marker of Down's syndrome. Prenatal Diagnosis 1995;15(4):359‐62.

Whiting 2003

Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Medical Research Methodology 2003;3:25.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

Bahado‐Singh 1998

Clinical features and settings

High‐risk referral for invasive testing.

Participants

511 participants.

USA.

August 1996 to January 1997.

Singleton pregnancies.

Pregnant women.

Mean age 37.1 years (SD 2.8 years).

15‐24 weeks' gestation.

Study design

Prospective cohort study.

Target condition and reference standard(s)

Down's syndrome: 18 cases.

Reference standard: amniocentesis.

Index and comparator tests

Mid‐trimester urine ß‐core fragment testing (monoclonal antibody B210 assay, 2‐step sandwich method, standardised for creatinine).

Follow‐up

100% karyotyping.

Aim of study

To ascertain the screening efficiency of a new mid‐trimester Down’s syndrome detection protocol that combines maternal urine testing and ultrasonographic examination.

Notes

Amniocentesis was being conducted on the basis of maternal age. Women who have amniocentesis just due to abnormal screening results were excluded from the study.

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Amniocentesis.

Partial verification avoided?
All tests

Yes

All women received a reference standard.

Differential verification avoided?
All tests

Yes

All women underwent the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

No

Reference standard interpreted with knowledge of index test results.  

Index test results blinded?
All tests

Yes

Urine testing was conducted blind from the results of amniocentesis.  

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Bahado‐Singh 1998b

Clinical features and settings

High‐risk referral for invasive testing.

Participants

356 participants: 10 cases and 346 controls.

USA.

Dates not reported.

Singleton pregnancies.

Pregnant women.

14‐24 weeks' gestation.

Study design

Case‐control study.

Target condition and reference standard(s)

Down's syndrome: 10 cases.

Reference standard: amniocentesis.

Index and comparator tests

Seond trimester urine ß‐core fragment testing (monoclonal antibody B210 assay, 2‐step sandwich method, standardised for creatinine).

Second trimester serum AFP.

Risk cut points of 1/10, 1/20, 1/30, 1/58, 1/270, 1/526.

Follow‐up

100% karyotyping.

Aim of study

To determine Down's syndrome screening efficiency of a new protocol that combines maternal serum AFP and beta core fragment/total oestriol ratio.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Amniocentesis.

Partial verification avoided?
All tests

Yes

All women underwent a reference standard.

Differential verification avoided?
All tests

Yes

All women underwent the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

No

Reference standard interpreted with knowledge of index test results.

Index test results blinded?
All tests

Yes

Index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Bahado‐Singh 1999

Clinical features and settings

High‐risk referral for invasive testing.

Participants

457 participants.

USA.

August 1996 ‐ June 1997.

Pregnant women.

Mean age 37.1 years.

Singleton pregnancies.

15‐24 weeks' gestation.

Study design

Prospective cohort study.

Target condition and reference standard(s)

Down's syndrome: 13 cases.

Reference standard: amniocentesis.

Index and comparator tests

Maternal age.

Urinary ß core fragment (monoclonal antibody B210 assay, 2‐step sandwich method, standardised for creatinine).

Urinary beta core fragment/total urinary oestriol ratio.

Follow‐up

100% karyotyping.

Aim of study

To evaluate Down's syndrome screening efficiency of a new algorithm of multiple urinary biochemical and ultrasound markers.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Amniocentesis.

Partial verification avoided?
All tests

Yes

All women received a reference standard.

Differential verification avoided?
All tests

Yes

All women received the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

No

Reference standard interpreted with knowledge of index test results. 

Index test results blinded?
All tests

Yes

Index test interpreted without knowledge of reference standard results. 

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Bahado‐Singh 1999a

Clinical features and settings

High‐risk referral for invasive testing.

Participants

926 participants.

USA.

November 1995 ‐ March 1999.

Pregnant women.

Singleton pregnancies.

15‐24 weeks' gestation.

Euploid/Down's karyotype only.

Study design

Prospective cohort study.

Target condition and reference standard(s)

Down's syndrome: 21 cases.

Reference standard: amniocentesis.

Index and comparator tests

Maternal age.

Second trimester urinary ß core fragment (Spot specimens of urine ‐ 2‐step sandwich assay B120 monoclonal antibody).

Second trimester serum AFP.

Frozen serum samples tested for second trimester uE3 and free ßhCG (details of serum testing methods not given).

Follow‐up

100% karyotyping.

Aim of study

To compare Down's syndrome screening efficiency of elevated maternal urine level of beta core fragment with that of a traditional serum triple test.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Amniocentesis.

Partial verification avoided?
All tests

Yes

All women received a reference standard.

Differential verification avoided?
All tests

Yes

All women had the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

No

Reference standard interpreted with knowledge of index test results.  

Index test results blinded?
All tests

Yes

Index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Bahado‐Singh 2000

Clinical features and settings

High‐risk referral for invasive testing.

Participants

1016 participants.

USA.

May 1995 ‐ June 1998.

Singleton pregnancies.

Pregnant women.

Mean age 37.1 years (19.3‐46 years).

14‐24 weeks' gestation.

Euploid or Down's pregnancies only.

Study design

Prospective cohort study.

Target condition and reference standard(s)

Down's syndrome: 23 cases.

Reference standard: amniocentesis.

Index and comparator tests

Second trimester urinary hyperglycosylated hCG (Specific monoclonal antibody developed. 2‐step enzyme immunometric assay standardised for creatinine levels).

Follow‐up

100% karyotyping.

Aim of study

To evaluate the measurement of levels of urine hyperglycosylated hCG in conjunction with ultrasound biometry for Down's syndrome risk prediction in an at risk group.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Amniocentesis.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

Yes

All women had the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

No

Reference standard interpreted with knowledge of index test results.

Index test results blinded?
All tests

Yes

Index test interpreted without knowledge of reference standard results.  

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Bahado‐Singh 2000a

Clinical features and settings

High‐risk referral for invasive testing.

Participants

524 participants.

USA ‐ single hospital.

August 1995 ‐ April 1999.

Singleton pregnancies.

Pregnant women.

Mean age 36.6 years (SD 5.3 years) in those with Down’s detected and 37.0 years (SD 3.4 years) in those with euploid pregnancies.

14‐22 weeks' gestation.

Study design

Prospective cohort study.

Target condition and reference standard(s)

Down's syndrome: 24 cases.

Reference standard: amniocentesis.

Index and comparator tests

Maternal age.

Second trimester serum hCG (IMX total β‐hCG kit, Abbott Laboratories), uE3 (DSL‐1400 Ultra‐sensitive unconjugated Estriol Radioimmunoassay kit) and AFP (IMX AFP kit, Abbott Laboratories).

Second trimester urinary beta core fragment (Spot specimens of urine ‐ 2‐step sandwich assay B120 monoclonal antibody).

Frozen samples tested for second trimester urinary hyperglycosylated hCG (Specific monoclonal antibody developed. 2‐step enzyme immunometric assay standardised for creatinine levels).

Follow‐up

100% karyotyping.

Aim of study

To compare the concentration of hyperglycosylated human chorionic gonadotropin with serum triple screen for second trimester Down’s syndrome detection.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Amniocentesis.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

Yes

All women had the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

Yes

Reference standard interpreted without knowledge of index test results. 

Index test results blinded?
All tests

Unclear

Unclear if index test interpreted with knowledge of reference standard results.  

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Canick 1995

Clinical features and settings

Referral for termination of pregnancy, amniocentesis or routine examination.

Participants

105 participants: 14 cases and 91 controls.

USA.

Dates not reported.

Singleton pregnancies.

Pregnant women.

15‐21 weeks' gestation.

Study design

Case‐control study.

Target condition and reference standard(s)

Down's syndrome: 14 cases.

Reference standard: karyotyping on termination of pregnancy or amniocentesis.

Index and comparator tests

Maternal age.

Frozen samples tested for:

second trimester urinary gonadotropin peptide (Triton UGP EIA assay, Alameda);

second trimester serum hCG (MAIAclone hCG assay, Serono‐Baker Diagnostics, Allentown).

Follow‐up

No details given for any follow‐up to birth. Reported that the fetal karyotype of control samples was not always known but assumed that none were aneuploid pregnancies.

Aim of study

To assess whether urinary gonadotropin peptide is better than serum hCG as a second trimester screening marker.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Routine screening and selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Karyotyping or follow‐up to birth.

Partial verification avoided?
All tests

No

Not all women received a reference standard.

Differential verification avoided?
All tests

No

Women had different reference standards.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

Yes

Reference standard interpreted without knowledge of index test results.

Index test results blinded?
All tests

Unclear

Unclear if index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements

Withdrawals explained?
All tests

No

No details of withdrawals given.
Cole 1997a

Clinical features and settings

High‐risk referral for invasive testing.

Participants

722 participants.

USA – single hospital.

August 1995 ‐ May 1996.

Pregnant women.

Singleton pregnancy.

12‐24 weeks' gestation.

Study design

Cohort study.

Target condition and reference standard(s)

Down's syndrome: 13 cases.

Reference standard: amniocentesis.

Index and comparator tests

Second trimester urinary hCG free beta subunit (Immunoenzymometric assay with autoantibody FBT11).

Follow‐up

100% karyotyping.

Aim of study

To evaluate use of second trimester urinary free beta‐subunit for Down's syndrome screening.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Amniocentesis.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

Yes

All women had the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

Yes

Reference standard interpreted without knowledge of index test results.

Index test results blinded?
All tests

Yes

Index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Cole 1997b

Clinical features and settings

High‐risk referral for invasive testing.

Participants

492 participants.

USA – single hospital.

August 1995 ‐ May 1996.

Pregnant women.

Singleton pregnancy.

12‐24 weeks' gestation.

Study design

Prospective cohort study.

Target condition and reference standard(s)

Down's syndrome: 12 cases.

Reference standard: amniocentesis.

Index and comparator tests

Second trimester urinary hCG free beta subunit (B210 2‐step sandwich assay).

Second trimester urinary total oestriol (radioimmunoassay, kit from Diagnostics Products Corporation, Los Angeles).

Follow‐up

100% karyotyping.

Aim of study

To evaluate use of urinary free beta core fragment combined with urinary total oestriol for Down's syndrome screening.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Routine screening of typical pregnant population.

Acceptable reference standard?
All tests

Yes

Amniocentesis.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

Yes

All women had the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

Yes

Reference standard interpreted without knowledge of index test results.

Index test results blinded?
All tests

Unclear

Unclear if index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Cole 1999b

Clinical features and settings

High‐risk referral for invasive testing.

Participants

1157 participants.

USA – 3 hospitals.

May 1995 ‐ March 1998.

Pregnant women.

Singleton pregnancy.

11‐22 weeks' gestation.

Study design

Prospective cohort study.

Target condition and reference standard(s)

Down's syndrome: 23 cases.

Reference standards: amniocentesis or CVS.

Index and comparator tests

Urinary hCG beta‐core subunit (B210 2‐step sandwich assay).

Urinary total oestriol (radioimmunoassay, kit by Diagnostic Products Corporation, Los Angeles).

Follow‐up

100% karyotyping.

Aim of study

To evaluate use of urinary free beta‐subunit for Down's syndrome screening.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Amniocentesis or CVS.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

No

Women had CVS or amniocentesis depending on their stage of pregnancy.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

Yes

Reference standard interpreted without knowledge of index test results.

Index test results blinded?
All tests

Yes

Index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Cuckle 1995b

Clinical features and settings

High‐risk referral for invasive testing and testing for bacterial analysis.

Participants

315 participants.

UK.

Dates not specified.

Pregnant women: 24 cases undergoing invasive testing and 294 controls undergoing testing for bacterial analysis

11‐23 weeks' gestation.

Study design

Case‐control study.

Target condition and reference standard(s)

Down's syndrome: 24 cases.

Reference standards: amniocentesis or CVS for cases and follow‐up for controls.

Index and comparator tests

Urinary beta core fragment (Modified radioimmunoassay method).

Urinary total oestrogen (continuous flow reaction based on the Kuber method).

Follow‐up

No details given of methods of follow‐up.

Aim of study

To evaluate the use of multiple urinary markers rather than serum in order to screen for Down's syndrome.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Karyotyping or follow‐up to birth.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

No

Women had different reference standards.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

Yes

Reference standard interpreted without knowledge of index test results.

Index test results blinded?
All tests

Yes

Index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements. 

Withdrawals explained?
All tests

No

No details of withdrawals given.
Cuckle 1999

Clinical features and settings

High‐risk referral for invasive testing and routine screening.

Participants

349 participants: 45 cases and 304 controls.

UK.

Dates not specified.

Pregnant women.

14‐19 weeks' gestation.

Study design

Retrospective case‐control study.

Target condition and reference standard(s)

Down's syndrome: 45 cases.

Reference standard: amniocentesis, CVS or follow‐up to birth.

Index and comparator tests

Frozen samples tested for urinary hyperglycosylated hCG (Immunoassays by 'Cole' method corrected for creatinine levels using Jaffes method).

Follow‐up

Details of follow‐up not reported.

Aim of study

To determine the distribution of hyperglycosylated hCG levels in pregnancies with Down's syndrome.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Routine screening of typical pregnant population.

Acceptable reference standard?
All tests

Yes

Amniocentesis, CVS or follow‐up.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

No

Women had different reference standards.

Incorporation avoided?
All tests

Yes

Index tests did not form part of the reference standard.

Reference standard results blinded?
All tests

Yes

Reference standard conducted before the index test.

Index test results blinded?
All tests

Unclear

Index test conducted after the reference standard and no evidence of blinding.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Cuckle 1999a

Clinical features and settings

High‐risk referral for invasive testing and routine screening.

Participants

6730 participants.

USA, UK and other European countries –multicentre study.

Dates not reported.

Pregnant women.

14‐19 weeks' gestation.

Study design

Prospective cohort study.

Target condition and reference standard(s)

Down's syndrome: 39 cases.

Reference standard: amniocentesis, CVS or postnatal examination.

Index and comparator tests

Maternal urine beta core hCG (Chiron manual assay).

Follow‐up

Methods of follow‐up not reported.

Aim of study

A prospective evaluation of urine beta core hCG for Down's syndrome.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice. 

Acceptable reference standard?
All tests

Yes

Karyotyping or follow‐up to birth.

Partial verification avoided?
All tests

Unclear

Unclear if all women received a reference standard.

Differential verification avoided?
All tests

No

Women had different reference standards.

Incorporation avoided?
All tests

Yes

Index tests did not form part of the reference standard.

Reference standard results blinded?
All tests

No

Reference standard interpreted with knowledge of index test results.

Index test results blinded?
All tests

Yes

Index test conducted without knowledge of the reference standard.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Hsu 1999

Clinical features and settings

High‐risk referral for invasive testing.

Participants

474 participants: 69 cases and 405 controls.

Taiwan and UK.

Dates not specified.

Pregnant women.

Median age cases 36.0 years (21‐44 years), controls 34.5 years (23‐43 years).

14‐26 weeks' gestation.

Study design

Retrospective case‐control study.

Target condition and reference standard(s)

Down's syndrome: 69 cases.

Reference standard: amniocentesis.

Index and comparator tests

Maternal age.

Urinary beta core fragment (UGP) (UGF‐EIA Toa kit).

Urinary free beta hCG (CIS immunoradiometric assay).

Urinary total oestriol (Orthoclinical diagnostics oestriol (total) II radioimmunoassay kit).

All adjusted for creatinine concentration.

Modelled to standardised population for England and Wales 1991‐1994. Cases from Taiwan.

Follow‐up

100% karyotyping.

Aim of study

To investigate levels of urinary beta core fragment, free beta hCG and total oestriol in a new large set of Down's syndrome pregnancies.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Amniocentesis.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

Yes

All women had the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

Yes

Reference standard interpreted without knowledge of index test results.

Index test results blinded?
All tests

Unclear

Unclear if index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice. 

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements. 

Withdrawals explained?
All tests

No

No details of withdrawals given.
Isozaki 1997

Clinical features and settings

High‐risk referral for invasive testing.

Participants

726 participants.

USA ‐ single centre.

August 1995 – May 1996.

Pregnant women.

Mean age 35.4 years (SD 4.0 years) in mothers of Down’s syndrome babies and 37 years (SD 4.3 years) in mothers of healthy babies.

Singleton pregnancies.

12‐24 weeks' gestation.

Study design

Prospective cohort study.

Target condition and reference standard(s)

Down's syndrome: 13 cases.

Reference standard: amniocentesis.

Index and comparator tests

Urinary beta core fragment (B210 monoclonal antibody, 2‐step sandwich assay).

Follow‐up

100% karyotyping.

Aim of study

To present data for prospectively collected samples of urinary beta core fragment for Down’s syndrome screening.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice. 

Acceptable reference standard?
All tests

Yes

Amniocentesis.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

Yes

All women had the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

Yes

Reference standard interpreted without knowledge of index test results.

Index test results blinded?
All tests

Yes

Index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice. 

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements. 

Withdrawals explained?
All tests

No

No details of withdrawals given.
Palomaki 2004a

Clinical features and settings

High‐risk referral for invasive testing.

Participants

2,055 participants.

USA – multicentre study.

January 2001 ‐ January 2003.

Pregnant women with mean age 38.9 years.

15‐20 weeks' gestation.

Study design

Prospective cohort study.

Target condition and reference standard(s)

Down's syndrome: 28 cases.

Reference standard: amniocentesis.

Index and comparator tests

Urinary invasive trophoblastic antigen (ITA) (B207 (detection) and B152 (capture) anti‐hCG monoclonal antibodies).

Follow‐up

100% karyotyping.

Aim of study

To evaluate ITA as a potential marker for Down's syndrome in the second trimester of pregnancy.

Notes

Clean catch of random urine provided. Sent same day at 4 degrees Celcius on an ice pack. Aliquoted into 1 mL plastic tubes. 1 urine aliquot shipped to lab for testing. Rest stored at ‐70 degrees Celcius. Most samples assayed within 24 hours of reaching lab and all within 48 hours. Anti‐ITA antibody produced. Sample corrected for creatinine levels.

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk population as done in practice.

Acceptable reference standard?
All tests

Yes

Amniocentesis.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

Yes

All women had the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

Yes

Reference standard interpreted without knowledge of index test results.

Index test results blinded?
All tests

Yes

Index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Spencer 1996

Clinical features and settings

High‐risk referral for invasive testing.

Participants

429 participants: 29 cases and 400 controls.

UK.

Date not specified.

Pregnant women.

Singleton pregnancies.

14‐24 (cases) and 9‐22 (controls) weeks' gestation.

Study design

Case‐control study.

Target condition and reference standard(s)

Down's syndrome: 29 cases.

Reference standards: amniocentesis or CVS.

Index and comparator tests

Urine free beta hCG (CIS immunoradiometric assay).

Urinary beta core fragment (Ciba Corning diagnostics UGP enzyme immunoassay).

Follow‐up

100% karyotyping.

Aim of study

To evaluate whether free beta hCG is elevated in the urine of pregnancies affected by Down's syndrome and investigate whether urine free beta hCG may be used as possible screening markers.

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

Amniocentesis or CVS.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

No

Women had different reference standards.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

Yes

Reference standard interpreted without knowledge of index test results.

Index test results blinded?
All tests

Yes

Index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice. 

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Wald 2003

Clinical features and settings

Routine screening.

Participants

606 participants: 101 cases, 505 controls matched for gestation, duration of storage and centre.

UK and Austria ‐ multicentre trial.

September 1996 ‐ April 2000.

Pregnant women.

9‐13 and 14‐20 weeks' gestation.

Study design

Case‐control study.

Target condition and reference standard(s)

Down's syndrome: 101 cases.

Reference standards: invasive testing (following second trimester screening) or follow‐up to birth.

Index and comparator tests

First trimester NT (midsagittal section, optimal magnification of thickness of translucent space between inner skin surface and fascia covering cervical spine (white black interface (outer) ‐ black white interface (inner), 41 models of ultrasound machine, 20 minutes allotted scanning time).

First and second trimester serum AFP, hCG, uE3, PAPP‐A, free beta hCG (time resolved fluoroimmunoassay, AutoDELFIA).

First and second trimester inhibin A (Sandwich enzyme‐linked immunosorbent assay, Oxford Bio‐innovation).

First and second trimester urinary beta core fragment, total hCG, ITA and free beta hCG (ITA and beta core fragment, Quest diagnostics USA).

Follow‐up

Follow‐up by: 1) Staff at local hospitals completed a study outcome form at, or just after. delivery, 2) Study records of CVS, amniocentesis or karyotype at birth linked to information from cytogenic laboratories, 3) Study records linked to records of cases of Down's syndrome from the National Down's Syndrome Cytogenetic Register, 4) Information obtained from local obstetrical outcome records, 5) Forms sent to all women with a request to return details of the outcome of their pregnancy, 6) Individual searches in respect of women whose outcomes of pregnancy had not been obtained by any of the previous methods. 4% of women in the total cohort did not have a documented outcome of pregnancy. Unclear if any of these women were included in this nested case‐control study.

Aim of study

To identify the most effective, safe and cost‐effective strategy for antenatal screening for Down's syndrome using NT, maternal serum and urine markers in the first and second trimesters of pregnancy and maternal age in various combinations.

Notes

Performance of screening assessed at 17 weeks' gestation. Study tried to be non‐interventional in the first trimester ‐ second trimester testing was aimed to be used as the basis for any referral for invasive testing.

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Routine screening of typical pregnant population.

Acceptable reference standard?
All tests

Yes

Karyotyping or follow‐up to birth.

Partial verification avoided?
All tests

Unclear

Unclear if all women received a reference standard.

Differential verification avoided?
All tests

No

Women received different reference standards.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

No

Reference standard interpreted with knowledge of index test results.

Index test results blinded?
All tests

Unclear

Serum testing conducted after reference standard and unclear if interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice. 

Uninterpretable results reported?
All tests

Yes

Rates of NT failure on average 9%. Pre‐10 weeks' gestation, > 33% failure rate, declined to 7% at 12 weeks.

Withdrawals explained?
All tests

No

No details of withdrawals given.
Weinans 2000

Clinical features and settings

High‐risk referral for invasive testing.

Participants

63 participants: 8 cases and 55 controls matched for gestational and maternal age, maternal weight, duration of storage and smoking history.

The Netherlands – single hospital.

October 1997 to May 1999.

Pregnant women.

10‐11 weeks' gestation.

Study design

Case‐control study.

Target condition and reference standard(s)

Down's syndrome: 8 cases.

Reference standard: CVS.

Index and comparator tests

Urinary hyperglycosylated hCG, (procedures previously described in Cole 1999a).

Follow‐up

100% karyotyping.

Aim of study

To investigate the value of H‐hCG measurements in very early pregnancy (prior to 12 weeks' gestation).

Notes

Table of Methodological Quality

Item

Authors' judgement

Description

Representative spectrum?
All tests

Yes

Selective testing of high‐risk women as done in practice.

Acceptable reference standard?
All tests

Yes

CVS.

Partial verification avoided?
All tests

Yes

All women had a reference standard.

Differential verification avoided?
All tests

Yes

All women had the same reference standard.

Incorporation avoided?
All tests

Yes

Reference standard was independent of the index test.

Reference standard results blinded?
All tests

Yes

Reference standard interpreted without knowledge of index test results.

Index test results blinded?
All tests

Yes

Index test interpreted without knowledge of reference standard results.

Relevant clinical information?
All tests

Yes

Information available as would be in standard clinical practice.

Uninterpretable results reported?
All tests

No

No details given for test failures/uninterpretable measurements.

Withdrawals explained?
All tests

No

No details of withdrawals given.

AFP: alpha‐fetoprotein
ßhCG: beta human chorionic gonadotrophin
CVS: chorionic villus sampling
hCG: human chorionic gonadotrophin
ITA: invasive trophoblast antigen
NT: nuchal translucency
PAPP‐A: Pregnancy‐associated plasma protein A
SD: standard deviation
uE3: unconjugated oestriol

Characteristics of excluded studies [ordered by study ID]

Ir a:

Study

Reason for exclusion

Abbas 1995

Unable to extract useful data.

Abdul‐Hamid 2004

No Down's syndrome pregnancies.

Abraha 1999

Unable to extract useful data.

Adekunle 1999

Unable to extract useful information.

Aitken 1993

Unable to extract useful data.

Aitken 1996a

Fewer than 80% of pregnancies had gestational age confirmed by USS.

Aitken 1996b

Fewer than 80% of pregnancies had gestational age confirmed by USS.

Akbas 2001

Less than 5 Down's syndrome pregnancies.

Antona 1998

Likely fewer than 80% of pregnancies dated by USS.

Antsaklis 1999

Women screened at greater than 24 weeks' gestation.

Ashwood 1987

Unable to extract useful data.

Asrani 2005

Review article.

Audibert 2001b

Data were not relevant to this review ‐ this study was not looking at urine tests for Down's syndrome screening

Axt‐Fleidner 2006

Unable to extract useful data.

Azuma 2002

Unable to extract useful data.

Baghagho 2004

Unable to obtain paper.

Bahado‐Singh 1995

USS markers greater than 14 weeks' gestation.

Bahado‐Singh 1996

USS markers greater than 14 weeks' gestation.

Bahado‐Singh 1999b

USS markers greater than 14 weeks' gestation.

Bahado‐Singh 2002

USS markers greater than 14 weeks' gestation.

Bahado‐Singh 2003

Review article.

Bar‐Hava 2001

No Down's pregnancies in study population.

Barkai 1996

No Down's pregnancies in study population.

Barnabei 1995

No Down's pregnancies in study population.

Bartels 1988

Unable to extract useful data.

Bartels 1993

No Down's pregnancies in study population.

Barth 1991

Second trimester ultrasound study.

Baviera 2004

Unclear method of confirmation of gestational age.

Bazzett 1998

Male versus female fetuses.

Bellver 2005

No Down's syndrome pregnancies in study.

Benn 1995

Less than 80% follow‐up.

Benn 1996

Less than 80% follow‐up.

Benn 1997

No Down's pregnancies in study population.

Benn 1998

Less than 80% follow‐up.

Benn 2001

Statistical modelling (computer simulation).

Benn 2002

Modelled data.

Benn 2003a

Less than 80% of pregnancies dated by USS.

Benn 2003b

Editorial.

Benn 2005a

No Down's pregnancies included.

Benn 2005b

Mathematical model.

Berry 1995

Less than 80% of pregnancies USS dated.

Berry 1997

Less than 80% of pregnancies USS dated.

Bersinger 1994

Gestational age not USS estimated.

Bersinger 2000

Unable to extract useful data.

Bersinger 2001

No Down's syndrome pregnancies in study population.

Bersinger 2003

Unable to extract useful data.

Bersinger 2004

No Down's syndrome pregnancies in study population.

Bersinger 2005

No Down's syndrome pregnancies in study population.

Biggio 2004

Cost‐effectiveness analysis.

Bindra 2002

Review article.

Blundell 1999

Unable to extract useful data.

Boots 1989

Population risk factor calculations.

Borruto 2002

Unable to extract useful data.

Boue 1990

Review article.

Bradley 1994

Screen‐negative population gestations not confirmed by ultrasound.

Braithwaite 1996

Review article.

Brambati 1995

USS screening inclusive of women greater than 14 weeks' gestation.

Brambati 1996

Review article.

Brizot 1995a

Unable to extract useful data.

Brizot 1995b

Unable to extract useful data.

Brizzi 1989b

Second trimester ultrasound.

Brock 1990

Unable to extract useful data.

Campogrande 2001

Unable to extract useful data.

Canick 1988

Unable to extract useful data.

Canick 1995b

Unable to extract useful data.

Canini 2002

No Down's syndrome pregnancies in study population.

Cans 1998

Second trimester ultrasound.

Carreras 1991

Second trimester ultrasound.

Chen 1999

Review article.

Chen 2002

No Down's syndrome pregnancies in study population.

Chen 2004

Less than 5 Down's cases in study population.

Chen 2005

Unable to extract useful data.

Cheng 1993

Likely that fewer than 80% of gestational age confirmed by USS.

Cheng 1999

Case series. No Down's syndrome pregnancies in study population.

Cheng 2004a

No Down's syndrome pregnancies in study population.

Cheng 2004b

No Down's syndrome pregnancies in study population.

Chitayat 2002

Less than 5 Down's cases in study population.

Christiansen 2002

Unable to extract useful data.

Christiansen 2007

Unable to extract useful data.

Chung 2000

Less than 5 Down's syndrome pregnancies in study population.

CNGOF 1996

Unable to obtain translation.

Cole 1996

Review article.

Comas 2001

USS at greater than 14 weeks.

Comas 2002a

USS at greater than 14 weeks.

Comas 2002b

USS at greater than 14 weeks.

Comstock 2006

Unable to extract useful data.

Conde‐Agudelo 1998

Review article.

Crossley 1991

Less than 80% of pregnancies had gestational age confirmation by ultrasound.

Crossley 1993

Less than 80% of pregnancies had gestational age confirmation by ultrasound.

Crossley 1996

No Down's syndrome pregnancies in study population.

Crossley 2002a

Adjustment factors for smokers.

Cuckle 1984

Gestational age not confirmed by USS.

Cuckle 1987a

Gestational age not confirmed by USS.

Cuckle 1987b

No gestational age limits given.

Cuckle 1990

Paper presenting adjustment factors.

Cuckle 1996

Data modelled on 4 meta‐analysed studies.

Cuckle 1999b

Unable to extract useful data.

Cuckle 1999c

Review article.

Cullen 1990

Abnormal scans only in study population.

Cusick 2004

Less than 5 Down's syndrome pregnancies in study population.

D'Ottavio 1997

Second trimester USS.

Dancoine 2001

No Down's syndrome pregnancies in study population.

De Biasio 2000

Unable to extract useful information.

De Biasio, 1999

Unable to ascertain whether overlapping populations between several papers ‐ attempted to contact author with no response.

De Biasio, 2001

Unable to ascertain whether overlapping populations between several papers ‐ attempted to contact author with no response.

De Graaf 1991

Unable to extract useful data.

De Graaf 1999

Modelled data.

DeVore 2001

Second trimester ultrasound.

Dickerson 1994

Comment.

Dimaio 1987

Gestational age by USS only in screen‐positive population.

Doran 1986

Ultrasound confirmation of gestational age performed in screen‐positive women only.

Drugan 1996a

Second trimester ultrasound.

Drugan 1996b

Unable to extract useful data.

Drysdale 2002

Fewer than 5 Down's syndrome pregnancies in population.

Ebell 1999

Review article.

Economides 1998

Unable to extract useful data.

Erickson 2004

No Down's syndrome pregnancies in population.

Evans 1996

No Down's syndrome pregnancies in population.

Falcon 2005

Unable to extract useful data.

Falcon 2006

Unable to extract useful data.

Ford 1998

Audit.

Frishman 1997

No Down's syndrome pregnancies in population.

Fukada 2000

Unable to extract useful data.

Ghidini 1998

Comparison of male versus female fetuses.

Goldie 1995

Fewer than 80% of study population had gestational age confirmed by USS.

Gonçalves 2004

Greater than 14 weeks USS screening.

Goodburn 1994

Likely that fewer than 80% of pregnancies had gestational age estimated by USS.

Grozdea 2002

Unable to extract useful data.

Gyselaers 2004a

Less than 80% follow‐up.

Gyselaers 2004b

Less than 80% follow‐up.

Gyselaers 2006a

Unaffected pregnancies only.

Gyselaers 2006b

Unable to extract useful data.

Hackshaw 1995

No Down's syndrome pregnancies in population.

Hackshaw 2001

No Down's syndrome pregnancies in population

Haddow 1992

Less than 80% of pregnancies had gestational age confirmed by ultrasound scan.

Hafner 1995

Less than 5 Down's pregnancies in study population.

Hallahan 1998

Gestational age greater than 24 weeks.

Harrison 2006

Less than 80% of pregnancies had gestational age confirmed by USS.

Harry 2006

Editorial.

Hayashi 1995

Unable to extract useful data.

Hayashi 1996

Less than 5 Down's pregnancies in study population.

Heikkila 1997

Fewer than 80% of pregnancies had gestational age confirmed by USS.

Heinonen 1996

No Down's syndrome pregnancies in population.

Herman 2000

No Down's syndrome pregnancies in study population.

Herman 2003

Correlation between markers, not evaluation of screening tests.

Herrou 1992

Unable to extract useful data.

Hershey 1985

Gestation unclear.

Hershey 1986

Gestation based on LMP.

Hewitt 1993

Unable to extract useful data.

Hogdall 1992

Unclear method of determination of gestational age. Unable to extract useful data.

Hong Kong Practitioner 2001

CME.

Howe 2000

Second trimester USS.

Hsiao 1991

Unable to obtain translation.

Hsieh 1999

No Down's syndrome pregnancies in study population.

Hsu 1997b

Adjustment factors.

Hsu 1998a

No Down's syndrome pregnancies in study population.

Hsu 1999b

No Down's pregnancies.

Huang 2003

No Down's syndrome pregnancies in study population.

Huggon 2004

Study of cardiac function in pregnancies with normal and abnormal NT results.

Hui 2003

No Down's syndrome pregnancies in population.

Hui 2005

No Down's syndrome pregnancies in population.

Hultén 2004

Editorial/commentary.

Hung 2003

Modelling.

Hurley 1993

Unable to extract useful data.

Huttly 2004

No Down's syndrome pregnancies in population.

Hwa 2004

Less than 5 Down's pregnancies in population.

Iles 1996

Review.

Ind 1994

Unable to extract useful data.

Jean‐Pierre 2005

Review article.

Johnson 1991

Gestatiojnal age estimated by USS in fewer than 80% of cases.

Johnson 1993

Normal pregnancies only.

Jorgensen 1999

Gestation greater than 14 weeks for USS.

Josefsson 1998

No Down's syndrome pregnancies in study population.

Jou 2001

Less than 5 Down's syndrome pregnancies in study population.

Kagan 2006

Screen‐positive pregnancies only.

Kautzmann 1995

Fewer than 80% pregnancies had gestational age estimated by USS.

Keith 1992

Summary article.

Kelekci 2004

Less than 5 Down's syndrome pregnancies in population.

Kellner 1995a

Less than 5 Down's syndrome pregnancies in population.

Kellner 1995b

Less than 80% follow‐up. Unable to ascertain proportion of population with gestational age confirmed by USS.

Kellner 1997

Assumption of normal karyotype without reference standard in significant proportion of control pregnancies.

Knight 1990

Review article.

Knight 2001

Validation of a specific assay.

Knight 2005

Less than 80% of pregnancies had gestational age confirmed by USS.

Koos 2006

Review article.

Kornman 1996

Less than 5 Down's syndrome pregnancies in population.

Kornman 1997

Unable to extract useful information.

Kramer 1998

No Down's syndrome pregnancies in study population.

Krantz 1996

Modelled data.

Krantz 2005

Adjustment factor.

Kulch 1993

No Down's cases in population.

Lai 1998

Modelled population.

Lai 2003

No Down's syndrome pregnancies in study population.

Laigaard 2006a

Unable to extract useful data.

Laigaard 2006b

Simulation.

Lam 1997

Unable to extract useful data.

Lam 1998

Fewer than 80% pregnancies had gestational age estimated by USS.

Lam 1999a

No Down's syndrome pregnancies in population.

Lam 1999b

Unable to extract useful data.

Lam 2000

Study of women's decisions about screening.

Lam 2001

Male versus female fetuses.

Lambert‐Messerlian 1996

Fewer than 80% of pregnancies USS dated.

Lambert‐Messerlian 1998

Unable to extract useful data.

Lehavi 2005

Down's syndrome pregnancies only.

Leung 2006

Unable to separate twins from singletons therefore unable to extract useful data.

Leymarie 1993

Appears to be a review article (French).

Li 1998

Unable to obtain translation.

Li 1999

Unable to obtain translation.

Liao 1997

Unable to obtain translation.

Liao 2001

Unable to extract useful data.

Lim 2002

Second trimester ultrasound.

Lippman 1987

Editorial.

Liu 2003

Unable to obtain translation.

Lustig 1988

Gestational age by LMP only.

MacDonald 1991

Fewer than 80% of gestational ages estimated by USS.

Macintosh 1994

Unable to extract useful data.

Macintosh 1997

Unable to extract useful data.

Macri 1994

Likely fewer than 80% evaluated for gestational age by ultrasound examination.

Macri 1996

Likely fewer than 80% evaluated for gestational age by ultrasound examination.

Malone 1998

Review article.

Malone 2003

Review article.

Mangione 2001

Abnormal screening results only.

Maymon 2001a

No Down's syndrome pregnancies in study population.

Maymon 2001b

No normal test results included therefore unable to extract meaningful data.

Maymon 2002

No Down's syndrome pregnancies in study population.

Maymon 2004

No Down's syndrome pregnancies in study population.

Maymon 2005

Modelled data.

McDuffie 1996

USS dating on screen‐positive women only.

Meier 2002

Observed versus expected cases of Down's syndrome in a population.

Merkatz 1984

Gestational age not confirmed by USS.

Merz 2005

Editorial.

Metzenbauer 2001

Normal pregnancies only.

Metzenbauer 2002

Unable to extract useful data.

Mikic 1999

No Down's syndrome pregnancies in study population.

Miller 1991

Unable to extract useful data.

Milunsky 1989

Fewer than 80% gestational age estimated by USS.

Milunsky 1996

Fewer than 80% gestational age estimated by USS.

Minobe 2002

Gestational age greater than specified limits.

Miyamura 1999

Unable to extract useful data.

Moghadam 1998

Unable to extract useful data.

Monni 2000

Less than 5 Down's syndrome pregnancies.

Monni 2002

Review article.

Mooney 1994

Greater than 24 weeks' gestation.

Muller 1994

No Down's syndrome pregnancies in study population.

Muller 1996b

Unable to extract useful data.

Muller 1999

Unable to extract useful data.

Muller 2002a

Getstional age greater than 24 weeks.

Muller 2002b

Unable to extract meaningful data ‐ unable to separate double and triple test data.

Muller 2003

No Down's syndrome pregnancies in study population.

Murta 2002

Unable to extract useful data.

Musone 2000

Unable to extract useful data.

Musto 1986

Fewer than 80% USS dated.

Myrick 1990

Unable to extract useful data.

Neveux 1996a

No Down's syndrome pregnancies in population.

Neveux 1996b

Unable to extract useful data.

Ng 2004

Unable to extract useful data.

Nicolaides 1992

Study of outcomes of abnormal NT results.

Nicolaides 2000

Review article.

Nicolaides 2004

Review article.

Nicolaides 2005a

Unable to obtain translation ‐ appears to be a review article.

Nicolaides 2005b

Unable to obtain translation ‐ appears to be a review article.

Nicolaides 2005c

Unable to obtain translation ‐ appears to be a review article.

Nicolaides 2005d

Unable to obtain translation ‐ appears to be a review article.

Nicolaides 2005e

Unable to obtain translation ‐ appears to be a review article.

Nicolaides 2005f

Review article.

Niemimaa 2001

No Down's pregnancies in study population.

Niemimaa 2002

No Down's syndrome pregnancies in population.

Niemimaa 2003

No Down's syndrome pregnancies in population.

Noble 1997

Unable to extract useful data.

Norgaard‐Pedersen 1990

Less than 80% of gestational ages confirmed by USS.

Norton 1992

Unable to extract useful data.

O'Brien 1997a

No Down's syndrome pregnancies in population.

O'Brien 1997b

No Down's syndrome pregnancies in population.

Odibo 2004

Gestational age greater than 14 weeks in USS population.

Ognibene 1999

Unable to extract useful data.

Olajide 1989

Unable to extract useful data.

Onda 1996

Unable to extract useful data.

Onda 1998

Unable to extract useful data.

Onda 2000

Less than 80% follow‐up.

Orlandi 2002

No Down's syndrome pregnancies in study population.

Palka 1998

Twin data used in calculation of the median.

Palomaki 1989

Fewer than 80% USS dated.

Palomaki 1993

No Down's syndrome pregnancies in population.

Palomaki 1994

No Down's syndrome pregnancies in population.

Palomaki 1996

Meta‐analysis.

Palomaki 2005

Unable to extract meaningful data.

Panburana 2001

Less than 5 Down's syndrome pregnancies in population.

Pandya 1994

Study of outcomes of abnormal NT results.

Pandya 1995

Review article.

Paul 2001

Unable to extract useful data.

Peralta 2005

Unable to extract useful data.

Perenc 1998

No Down's syndrome pregnancies in study population.

Perheentupa 2002

No Down's syndrome pregnancies in population.

Perona 1998

Smokers versus non smokers.

Petervari 2000

Unable to extract useful data.

Petrocik 1989

Likely fewer than 80% USS dated.

Phillips 1992

Gestational age confirmed by USS in less than 80% of population.

Phillips 1993

Gestational age confirmed by USS in less than 80% of population.

Pinette 2003

Women screened prior to recruitment.

Platt 2004

Unable to extract useful data.

Podobnik 1995

Abnormal results only.

Prefumo 2002

Comparison of prevalence and prediction.

Prefumo 2004

Comparison of a marker in women of different ethnic origins.

Price 1998

Unable to extract useful data.

Páez 2004

Unable to obtain translation.

Raty 2000

No Down's syndrome pregnancies in population.

Rembouskos 2004

Unable to extract useful data.

Ren 1992

Review article.

Renier 1998

Method of ascertainment of gestational age unclear. Twin gestations included in general population.

Resta 1990

Second trimester USS.

Reynders 1997

Fewer than 5 Down's cases.

Reynolds 1989

Explanation of mathematical techniques.

Reynolds 1999

Unable to extract useful data.

Ribbert 1996

No Down's syndrome pregnancies in study population.

Rice 2005

Down's syndrome pregnancies excluded from study.

Rich 1991

Unable to extract useful data.

Roberts 1995

No Down's syndrome pregnancies in study population.

Robertson 1991

Editorial.

Rode 2003

No Down's pregnancies.

Ronge 2006

Editorial ‐ summary of FASTER trial results.

Rose 1995

Review article.

Ross 1997

Review article.

Rotmensch 1996

Unable to extract useful data.

Rotmensch 1999

No Down's syndrome pregnancies in study population.

Rozenberg 2006

USS greater than 14 weeks' gestation.

Rudnicka 2002

No Down's syndrome pregnancies in population.

Ryall 1992

Unable to determine method of confirmation of gestational age.

Ryall 2001

High‐risk results only included (i.e. no screen‐negative group for comparison).

Räty 2002

No Down's pregnancies in population.

Sabriá 2002

Unable to ascertain how numbers calculated and from which populations.

Sacchini 2003

Unable to extract useful data.

Saller 1997

Down's syndrome secondary to Robertsonian translocation only. No controls.

Salomon 2001

No Down's syndrome pregnancies in population.

Salonen 1997

Fewer than 80% had gestational age estimated by USS.

Saltvedt 2005

Gestation greater than 14 weeks for nuchal scanning.

Saridogan 1996

Down's syndrome and Edward's syndrome affected pregnancies only.

Savoldelli 1993

Unable to extract useful data.

Schiott 2006

Unable to extract useful data.

Schuchter 1998

No Down's pregnancies in study population.

Scott 1995

Less than 5 Down's syndrome pregnancies in study population.

Seeds 1990

Review article.

Seki 1995

No Down's syndrome pregnancies in study population.

Shenhav 2003

No Down's syndrome pregnancies.

Shintaku 1989

Unable to extract useful data.

Shulman 2003

No Down's syndrome pregnancies in population.

Simon‐Bouy 1999

Review article.

Simpson 1986

Gestational age confirmed by USS in less than 80% of population.

Smith 1990

Analysis of screen‐positive results.

Smith 1996

Review/meta‐analysis.

Smith 1999

Unable to extract useful data.

Smith‐Bindman 2001

Meta‐analysis of second trimester ultrasound markers.

Smith‐Bindman 2003

Population study, not examining DTA.

Snijders 1995

Study of prevalence, not screening.

Snijders 1999

Study of prevalence, not screening.

Soergel 2006

Less than 80% follow‐up.

Sokol 1998

Observation of Down's prevalence stratified by age.

Sonek 2003

Editorial.

Spencer 1985

Fewer than 80% USS dated.

Spencer 1991a

Likely fewer than 80% USS dated.

Spencer 1991b

Unable to extract useful data.

Spencer 1992

Unable to extract useful data.

Spencer 1993a

Fewer than 80% USS dated.

Spencer 1993b

No Down's pregnancies in study population.

Spencer 1993c

Unable to extract useful data.

Spencer 1993d

Fewer than 80% of pregnancies had gestational age confirmed by USS.

Spencer 1993e

Unable to extract useful data.

Spencer 1995

No Down's pregnancies in population.

Spencer 1996a

Fewer than 80% of pregnancies had gestational age confirmed by USS.

Spencer 1997

Statistical modelling, aneuploid pregnancies only in study population.

Spencer 1998a

No Down's pregnancies in population.

Spencer 1998b

Unable to extract useful data.

Spencer 1999a

Review.

Spencer 1999b

Statistical methods paper.

Spencer 2000a

Examination of median shifts rather than an evaluation of screening.

Spencer 2000b

No Down's syndrome pregnancies in population.

Spencer 2000c

No Down's syndrome pregnancies in population.

Spencer 2000d

No Down's cases.

Spencer 2000e

Male versus female fetuses.

Spencer 2000f

No Down's cases in population.

Spencer 2000g

No Down's pregnancies in population.

Spencer 2000h

No Down's pregnancies in population.

Spencer 2000i

Comparsison of fetal sex.

Spencer 2001

No Down's syndrome pregnancies in population.

Spencer 2001a

Unable to extract useful data.

Spencer 2001b

Unable to extract useful data.

Spencer 2001c

Unable to extract useful data.

Spencer 2001d

No Down's syndrome pregnancies in population.

Spencer 2002a

No Down's pregnancies.

Spencer 2002b

Risk validation study.

Spencer 2002c

No Down's syndrome pregnancies in population.

Spencer 2002d

Demonstration of median changes with time, rather than evaluation of screening.

Spencer 2003a

No Down's pregnancies in population.

Spencer 2003b

No Down's pregnancies in population.

Spencer 2003c

Calculation of weight correction factor.

Spencer 2003d

Fewer than 5 Down's syndrome pregnancies.

Spencer 2004

Calculation of smoking correction factor.

Spencer 2005a

No Down's pregnancies.

Spencer 2005b

No Down's pregnancies.

Spencer 2005c

Comparison of 2 different assays ‐ not actual screening evaluation.

Spong 1999

Comparison of male and female fetuses.

Stevens 1998

Literature review.

Stoll 1992

Review article.

Su 2002a

Unable to extract useful data.

Suchet 1995

Review article.

Suchy 1990

Unable to ascertain method of confirmation of gestational age.

Summers 2003a

Fewer than 80% had gestational age estimated by USS.

Summers 2003b

No Down's syndrome pregnancies in study population.

Suntharasaj 2005

Examination of inter‐observer variation in NT scanning.

Sutton 2004

Unable to extract useful data.

Suzuki 1998

Unable to extract useful data.

Tabor 1987

Geststional age not confirmed by USS.

Tanski 1999

Information on screen‐positive pregnancies only.

Thilaganathan 1998

No Down's syndrome pregnancies in study population.

Thilaganathan 1999

Editorial.

Tislaric 2002

No Down's syndrome pregnancies in population.

Torok 1997

Unable to extract useful data.

Tsai 2001

Less than 5 Down's syndrome pregnancies in study population.

Valerio 1996

Fewer than 80% pregnancies had gestational age estimated by USS.

Van Blerk 1992

Unable to extract useful data.

Van Heesch, 2006

No Down's syndrome pregnancies in study population. Software comparison study.

Van Lith 1991

Unable to extract useful data.

Van Lith 1993

Unable to extract useful data.

Van Lith 1994

Unable to extract useful data.

Veress 1986

Unable to extract useful data.

Veress 1988

Unable to extract useful data.

Vintzileos 2003

Second trimester USS.

Wald 1988a

Less than 80% had gestational age confirmed by ultrasound.

Wald 1988b

Gestational age not confirmed by USS.

Wald 1991

No Down's pregnancies in study.

Wald 1992a

Less than 80% had gestational age confirmed by ultrasound.

Wald 1992b

No Down's pregnancies in study.

Wald 1992c

No Down's pregnancies in study.

Wald 1993

Fewer than 80% had gestational age estimated by USS

Wald 1994a

No Down's syndrome pregnancies in population.

Wald 1994b

Review article.

Wald 1996a

No Down's pregnancies.

Wald 1996b

Fewer than 80% had gestational age estimated by USS

Wald 1996d

No Down's syndrome pregnancies in population.

Wald 1996e

Gestational age greater than 24 weeks.

Wald 1997

Data modelled on 3 separate populations of women.

Wald 1998

Unable to extract useful data.

Wald 1999a

Unable to extract useful data.

Wald 1999b

Gestational age not confirmed by USS.

Wald 1999c

No Down's syndrome pregnancies.

Wald 1999d

Modelled on several studies, some of which have no USS dating.

Wald 2003b

No cases.

Wald 2003c

Less than 80% had gestational age confirmed by USS.

Wald 2006

Modelled on SURRUS data.

Wallace 1994

Unable to extract useful data.

Wallace 1997

No Down's syndrome pregnancies in study population.

Ward 2005

Review article.

Watt 1996a

No Downs syndrome pregnancies in study population.

Watt 1996b

No Down's syndrome pregnancies in study population.

Weinans 2001

Unable to extract useful data.

Weinans 2004

Study of women's views on screening.

Welborn 1994

Abnormal results only (cystic hygroma).

Wenstrom 1993

Less than 80% of pregnancies had gestational age confirmed by USS.

Wenstrom 1995a

Adjustment factors.

Wenstrom 1995b

Less than 80% of pregnancies had gestational age confirmed by USS.

Whitlow 1998a

Unable to extract useful data.

Whitlow 1998b

Unable to extract useful data.

Whitlow 1999

Unable to extract useful data.

Williamson 1994

Fewer than 80% had gestational age estimated by USS.

Wilson 2000

Review.

Wojdemann 2001

No Down's syndrome pregnancies in study population.

Wong 2003

Less than 5 Down's syndrome pregnancies in population.

Wright 2006

Mathematical model.

Yagel 1998

Second trimester USS.

Yamamoto 2001a

Unable to extract useful data.

Yamamoto 2001b

Method of determination of gestational age unclear.

Yamamoto 2001c

Unable to extract useful data.

Yaron 2001

Male versus female fetuses.

Ye 1995

Unable to obtain translation.

Yoshida 2000

Fewer than 80% pregnancies had gestational age estimated by USS.

Zeitune 1991

Only aneuploid pregnancies included in study.

Zelop 2005

No Down's cases in population.

Zhao 1998

Unable to obtain translation.

Zoppi 2003

Inappropriate study design.

Data

Presented below are all the data for all of the tests entered into the review.

Open in table viewer
Tests. Data tables by test

Test

No. of studies

No. of participants

1 Betacore, 1st trimester urine test, 5% FPR Show forest plot

1

516
Test 1
Betacore, 1st trimester urine test, 5% FPR.

Betacore, 1st trimester urine test, 5% FPR.

2 Betacore, 2nd trimester urine test, 5% FPR Show forest plot

6

9613
Test 2
Betacore, 2nd trimester urine test, 5% FPR.

Betacore, 2nd trimester urine test, 5% FPR.

3 Betacore, 2nd trimester urine test, cutpoint mixed Show forest plot

7

10124
Test 3
Betacore, 2nd trimester urine test, cutpoint mixed.

Betacore, 2nd trimester urine test, cutpoint mixed.

4 Gonadotropin, 2nd trimester urine test, risk 1:100 Show forest plot

1

105
Test 4
Gonadotropin, 2nd trimester urine test, risk 1:100.

Gonadotropin, 2nd trimester urine test, risk 1:100.

5 Gonadotropin, 2nd trimester urine test, risk 1:384 Show forest plot

1

105
Test 5
Gonadotropin, 2nd trimester urine test, risk 1:384.

Gonadotropin, 2nd trimester urine test, risk 1:384.

6 Gonadotropin, 2nd trimester urine test, 95% percentile Show forest plot

1

105
Test 6
Gonadotropin, 2nd trimester urine test, 95% percentile.

Gonadotropin, 2nd trimester urine test, 95% percentile.

7 ITA, 1st trimester urine test, 5% FPR Show forest plot

2

579
Test 7
ITA, 1st trimester urine test, 5% FPR.

ITA, 1st trimester urine test, 5% FPR.

8 ITA, 2nd trimester urine test, 3.74MoM Show forest plot

1

2051
Test 8
ITA, 2nd trimester urine test, 3.74MoM.

ITA, 2nd trimester urine test, 3.74MoM.

9 ITA, 2nd trimester urine test, 5% FPR Show forest plot

3

2748
Test 9
ITA, 2nd trimester urine test, 5% FPR.

ITA, 2nd trimester urine test, 5% FPR.

10 Total hCG, 1st trimester urine test, 5% FPR Show forest plot

1

516
Test 10
Total hCG, 1st trimester urine test, 5% FPR.

Total hCG, 1st trimester urine test, 5% FPR.

11 Total hCG, 2nd trimester urine test, 5% FPR Show forest plot

1

390
Test 11
Total hCG, 2nd trimester urine test, 5% FPR.

Total hCG, 2nd trimester urine test, 5% FPR.

12 Free ßhCG, 1st trimester urine test, 5% FPR Show forest plot

1

516
Test 12
Free ßhCG, 1st trimester urine test, 5% FPR.

Free ßhCG, 1st trimester urine test, 5% FPR.

13 Free ßhCG, 2nd trimester urine test, 5% FPR Show forest plot

3

1517
Test 13
Free ßhCG, 2nd trimester urine test, 5% FPR.

Free ßhCG, 2nd trimester urine test, 5% FPR.

14 Oestriol, 2nd trimester urine test, 5% FPR Show forest plot

2

1472
Test 14
Oestriol, 2nd trimester urine test, 5% FPR.

Oestriol, 2nd trimester urine test, 5% FPR.

15 Betacore to oestriol ratio, 2nd trimester urine test, 5% FPR Show forest plot

2

1649
Test 15
Betacore to oestriol ratio, 2nd trimester urine test, 5% FPR.

Betacore to oestriol ratio, 2nd trimester urine test, 5% FPR.

16 Betacore and oestriol, 2nd trimester 5% FPR Show forest plot

1

315
Test 16
Betacore and oestriol, 2nd trimester 5% FPR.

Betacore and oestriol, 2nd trimester 5% FPR.

17 AFP and ITA, 2nd trimester urine test, 3% FPR Show forest plot

1

524
Test 17
AFP and ITA, 2nd trimester urine test, 3% FPR.

AFP and ITA, 2nd trimester urine test, 3% FPR.

18 AFP and ITA, 2nd trimester urine test, 5% FPR Show forest plot

1

524
Test 18
AFP and ITA, 2nd trimester urine test, 5% FPR.

AFP and ITA, 2nd trimester urine test, 5% FPR.

19 AFP and ITA, 2nd trimester urine test,10% FPR Show forest plot

1

524
Test 19
AFP and ITA, 2nd trimester urine test,10% FPR.

AFP and ITA, 2nd trimester urine test,10% FPR.

20 AFP and ITA, 2nd trimester urine test, 15% FPR Show forest plot

1

524
Test 20
AFP and ITA, 2nd trimester urine test, 15% FPR.

AFP and ITA, 2nd trimester urine test, 15% FPR.

21 AFP, uE3 and ITA, 2nd trimester urine test, 3% FPR Show forest plot

1

524
Test 21
AFP, uE3 and ITA, 2nd trimester urine test, 3% FPR.

AFP, uE3 and ITA, 2nd trimester urine test, 3% FPR.

22 AFP, uE3 and ITA, 2nd trimester urine test, 5% FPR Show forest plot

1

524
Test 22
AFP, uE3 and ITA, 2nd trimester urine test, 5% FPR.

AFP, uE3 and ITA, 2nd trimester urine test, 5% FPR.

23 AFP, uE3 and ITA, 2nd trimester urine test, 10% FPR Show forest plot

1

524
Test 23
AFP, uE3 and ITA, 2nd trimester urine test, 10% FPR.

AFP, uE3 and ITA, 2nd trimester urine test, 10% FPR.

24 AFP, uE3 and ITA, 2nd trimester urine test, 15% FPR Show forest plot

1

524
Test 24
AFP, uE3 and ITA, 2nd trimester urine test, 15% FPR.

AFP, uE3 and ITA, 2nd trimester urine test, 15% FPR.

25 Age, betacore, 2nd trimester urine test, 1% FPR Show forest plot

2

2083
Test 25
Age, betacore, 2nd trimester urine test, 1% FPR.

Age, betacore, 2nd trimester urine test, 1% FPR.

26 Age, betacore, 2nd trimester urine test, 3% FPR Show forest plot

2

2083
Test 26
Age, betacore, 2nd trimester urine test, 3% FPR.

Age, betacore, 2nd trimester urine test, 3% FPR.

27 Age, betacore, 2nd trimester urine test, 5% FPR Show forest plot

5

3419
Test 27
Age, betacore, 2nd trimester urine test, 5% FPR.

Age, betacore, 2nd trimester urine test, 5% FPR.

28 Age, betacore, 2nd trimester urine test, 10% FPR Show forest plot

1

926
Test 28
Age, betacore, 2nd trimester urine test, 10% FPR.

Age, betacore, 2nd trimester urine test, 10% FPR.

29 Age, betacore, 2nd trimester urine test, 15% FPR Show forest plot

1

953
Test 29
Age, betacore, 2nd trimester urine test, 15% FPR.

Age, betacore, 2nd trimester urine test, 15% FPR.

30 Age, betacore, 2nd trimester urine test, 20% FPR Show forest plot

1

926
Test 30
Age, betacore, 2nd trimester urine test, 20% FPR.

Age, betacore, 2nd trimester urine test, 20% FPR.

31 Age, ITA, 2nd trimester urine test, 5% FPR Show forest plot

1

1016
Test 31
Age, ITA, 2nd trimester urine test, 5% FPR.

Age, ITA, 2nd trimester urine test, 5% FPR.

32 Age, oestriol, 2nd trimester urine test, 5% FPR Show forest plot

1

474
Test 32
Age, oestriol, 2nd trimester urine test, 5% FPR.

Age, oestriol, 2nd trimester urine test, 5% FPR.

33 Age, free ßhCG, 2nd trimester urine test, 5% FPR Show forest plot

2

879
Test 33
Age, free ßhCG, 2nd trimester urine test, 5% FPR.

Age, free ßhCG, 2nd trimester urine test, 5% FPR.

34 Age, betacore to oestriol ratio, 2nd trimester urine test, 1% FPR Show forest plot

1

1157
Test 34
Age, betacore to oestriol ratio, 2nd trimester urine test, 1% FPR.

Age, betacore to oestriol ratio, 2nd trimester urine test, 1% FPR.

35 Age, betacore to oestriol ratio, 2nd trimester urine test, 3% FPR Show forest plot

1

1157
Test 35
Age, betacore to oestriol ratio, 2nd trimester urine test, 3% FPR.

Age, betacore to oestriol ratio, 2nd trimester urine test, 3% FPR.

36 Age, betacore to oestriol ratio, 2nd trimester urine test, 5% FPR Show forest plot

3

2088
Test 36
Age, betacore to oestriol ratio, 2nd trimester urine test, 5% FPR.

Age, betacore to oestriol ratio, 2nd trimester urine test, 5% FPR.

37 Age, free ßhCG to oestriol ratio, 2nd trimester urine test, 5% FPR Show forest plot

1

474
Test 37
Age, free ßhCG to oestriol ratio, 2nd trimester urine test, 5% FPR.

Age, free ßhCG to oestriol ratio, 2nd trimester urine test, 5% FPR.

38 Age, oestriol and free ßhCG, 2nd trimester, 5% FPR Show forest plot

1

474
Test 38
Age, oestriol and free ßhCG, 2nd trimester, 5% FPR.

Age, oestriol and free ßhCG, 2nd trimester, 5% FPR.

39 Age, betacore to free ßhCG ratio, 2nd trimester, 5% FPR Show forest plot

1

474
Test 39
Age, betacore to free ßhCG ratio, 2nd trimester, 5% FPR.

Age, betacore to free ßhCG ratio, 2nd trimester, 5% FPR.

40 Age, betacore and oestriol, 2nd trimester 1% FPR Show forest plot

1

1157
Test 40
Age, betacore and oestriol, 2nd trimester 1% FPR.

Age, betacore and oestriol, 2nd trimester 1% FPR.

41 Age, betacore and oestriol, 2nd trimester, 3% FPR Show forest plot

1

1157
Test 41
Age, betacore and oestriol, 2nd trimester, 3% FPR.

Age, betacore and oestriol, 2nd trimester, 3% FPR.

42 Age, betacore and oestriol, 2nd trimester, 5% FPR Show forest plot

2

1631
Test 42
Age, betacore and oestriol, 2nd trimester, 5% FPR.

Age, betacore and oestriol, 2nd trimester, 5% FPR.

43 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:10 Show forest plot

1

356
Test 43
Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:10.

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:10.

44 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:20 Show forest plot

1

356
Test 44
Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:20.

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:20.

45 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:30 Show forest plot

1

356
Test 45
Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:30.

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:30.

46 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:58 Show forest plot

1

356
Test 46
Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:58.

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:58.

47 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:270 Show forest plot

1

356
Test 47
Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:270.

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:270.

48 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:526 Show forest plot

1

356
Test 48
Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:526.

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:526.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Figuras y tablas -
Figure 1

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Detection rates (% sensitivity) at a 5% false positive rate for the five most evaluated or best performing test strategies. The estimates are shown with 95% confidence intervals. The test strategies are ordered on the plot according to decreasing detection rate. The number of studies, cases and women included for each test strategy are shown on the horizontal axis.
Figuras y tablas -
Figure 2

Detection rates (% sensitivity) at a 5% false positive rate for the five most evaluated or best performing test strategies. The estimates are shown with 95% confidence intervals. The test strategies are ordered on the plot according to decreasing detection rate. The number of studies, cases and women included for each test strategy are shown on the horizontal axis.

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Betacore, 1st trimester urine test, 5% FPR.
Figuras y tablas -
Test 1

Betacore, 1st trimester urine test, 5% FPR.

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Betacore, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 2

Betacore, 2nd trimester urine test, 5% FPR.

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Betacore, 2nd trimester urine test, cutpoint mixed.
Figuras y tablas -
Test 3

Betacore, 2nd trimester urine test, cutpoint mixed.

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Gonadotropin, 2nd trimester urine test, risk 1:100.
Figuras y tablas -
Test 4

Gonadotropin, 2nd trimester urine test, risk 1:100.

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Gonadotropin, 2nd trimester urine test, risk 1:384.
Figuras y tablas -
Test 5

Gonadotropin, 2nd trimester urine test, risk 1:384.

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Gonadotropin, 2nd trimester urine test, 95% percentile.
Figuras y tablas -
Test 6

Gonadotropin, 2nd trimester urine test, 95% percentile.

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ITA, 1st trimester urine test, 5% FPR.
Figuras y tablas -
Test 7

ITA, 1st trimester urine test, 5% FPR.

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ITA, 2nd trimester urine test, 3.74MoM.
Figuras y tablas -
Test 8

ITA, 2nd trimester urine test, 3.74MoM.

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ITA, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 9

ITA, 2nd trimester urine test, 5% FPR.

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Total hCG, 1st trimester urine test, 5% FPR.
Figuras y tablas -
Test 10

Total hCG, 1st trimester urine test, 5% FPR.

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Total hCG, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 11

Total hCG, 2nd trimester urine test, 5% FPR.

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Free ßhCG, 1st trimester urine test, 5% FPR.
Figuras y tablas -
Test 12

Free ßhCG, 1st trimester urine test, 5% FPR.

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Free ßhCG, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 13

Free ßhCG, 2nd trimester urine test, 5% FPR.

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Oestriol, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 14

Oestriol, 2nd trimester urine test, 5% FPR.

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Betacore to oestriol ratio, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 15

Betacore to oestriol ratio, 2nd trimester urine test, 5% FPR.

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Betacore and oestriol, 2nd trimester 5% FPR.
Figuras y tablas -
Test 16

Betacore and oestriol, 2nd trimester 5% FPR.

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AFP and ITA, 2nd trimester urine test, 3% FPR.
Figuras y tablas -
Test 17

AFP and ITA, 2nd trimester urine test, 3% FPR.

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AFP and ITA, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 18

AFP and ITA, 2nd trimester urine test, 5% FPR.

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AFP and ITA, 2nd trimester urine test,10% FPR.
Figuras y tablas -
Test 19

AFP and ITA, 2nd trimester urine test,10% FPR.

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AFP and ITA, 2nd trimester urine test, 15% FPR.
Figuras y tablas -
Test 20

AFP and ITA, 2nd trimester urine test, 15% FPR.

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AFP, uE3 and ITA, 2nd trimester urine test, 3% FPR.
Figuras y tablas -
Test 21

AFP, uE3 and ITA, 2nd trimester urine test, 3% FPR.

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AFP, uE3 and ITA, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 22

AFP, uE3 and ITA, 2nd trimester urine test, 5% FPR.

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AFP, uE3 and ITA, 2nd trimester urine test, 10% FPR.
Figuras y tablas -
Test 23

AFP, uE3 and ITA, 2nd trimester urine test, 10% FPR.

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AFP, uE3 and ITA, 2nd trimester urine test, 15% FPR.
Figuras y tablas -
Test 24

AFP, uE3 and ITA, 2nd trimester urine test, 15% FPR.

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Age, betacore, 2nd trimester urine test, 1% FPR.
Figuras y tablas -
Test 25

Age, betacore, 2nd trimester urine test, 1% FPR.

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Age, betacore, 2nd trimester urine test, 3% FPR.
Figuras y tablas -
Test 26

Age, betacore, 2nd trimester urine test, 3% FPR.

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Age, betacore, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 27

Age, betacore, 2nd trimester urine test, 5% FPR.

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Age, betacore, 2nd trimester urine test, 10% FPR.
Figuras y tablas -
Test 28

Age, betacore, 2nd trimester urine test, 10% FPR.

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Age, betacore, 2nd trimester urine test, 15% FPR.
Figuras y tablas -
Test 29

Age, betacore, 2nd trimester urine test, 15% FPR.

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Age, betacore, 2nd trimester urine test, 20% FPR.
Figuras y tablas -
Test 30

Age, betacore, 2nd trimester urine test, 20% FPR.

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Age, ITA, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 31

Age, ITA, 2nd trimester urine test, 5% FPR.

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Age, oestriol, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 32

Age, oestriol, 2nd trimester urine test, 5% FPR.

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Age, free ßhCG, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 33

Age, free ßhCG, 2nd trimester urine test, 5% FPR.

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Age, betacore to oestriol ratio, 2nd trimester urine test, 1% FPR.
Figuras y tablas -
Test 34

Age, betacore to oestriol ratio, 2nd trimester urine test, 1% FPR.

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Age, betacore to oestriol ratio, 2nd trimester urine test, 3% FPR.
Figuras y tablas -
Test 35

Age, betacore to oestriol ratio, 2nd trimester urine test, 3% FPR.

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Age, betacore to oestriol ratio, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 36

Age, betacore to oestriol ratio, 2nd trimester urine test, 5% FPR.

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Age, free ßhCG to oestriol ratio, 2nd trimester urine test, 5% FPR.
Figuras y tablas -
Test 37

Age, free ßhCG to oestriol ratio, 2nd trimester urine test, 5% FPR.

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Age, oestriol and free ßhCG, 2nd trimester, 5% FPR.
Figuras y tablas -
Test 38

Age, oestriol and free ßhCG, 2nd trimester, 5% FPR.

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Age, betacore to free ßhCG ratio, 2nd trimester, 5% FPR.
Figuras y tablas -
Test 39

Age, betacore to free ßhCG ratio, 2nd trimester, 5% FPR.

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Age, betacore and oestriol, 2nd trimester 1% FPR.
Figuras y tablas -
Test 40

Age, betacore and oestriol, 2nd trimester 1% FPR.

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Age, betacore and oestriol, 2nd trimester, 3% FPR.
Figuras y tablas -
Test 41

Age, betacore and oestriol, 2nd trimester, 3% FPR.

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Age, betacore and oestriol, 2nd trimester, 5% FPR.
Figuras y tablas -
Test 42

Age, betacore and oestriol, 2nd trimester, 5% FPR.

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Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:10.
Figuras y tablas -
Test 43

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:10.

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Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:20.
Figuras y tablas -
Test 44

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:20.

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Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:30.
Figuras y tablas -
Test 45

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:30.

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Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:58.
Figuras y tablas -
Test 46

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:58.

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Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:270.
Figuras y tablas -
Test 47

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:270.

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Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:526.
Figuras y tablas -
Test 48

Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:526.

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Summary of findings Performance of urine tests with or without maternal age

Review Question

What is the accuracy of urine based markers for screening for Down's syndrome?

Population

Pregnant women at less than 24 weeks' gestation confirmed by ultrasound, who had not undergone previous testing for Down’s syndrome. Most studies were undertaken in women identified to be high risk based on maternal age

Settings

All settings

Numbers of studies, pregnancies and Down's syndrome cases

19 studies (reported in 29 publications) involving 18,013 pregnancies of which 527 were Down's syndrome pregnancies.

Index tests

Risk scores computed using maternal age and first and second trimester urine markers for AFP; ITA; ß‐core fragment; free ßhCG; total hCG; oestriol (also termed as uE3); gonadotropin peptide.

Reference standards

Chromosomal verification (amniocentesis and CVS undertaken during pregnancy, and postnatal karyotyping) and postnatal macroscopic inspection.

Study limitations

Seven studies only used selective chromosomal verification during pregnancy, and were at risk of under‐ascertainment of Down's syndrome cases due loss of the pregnancy to miscarriage between the serum test and the reference standard.

Test

Studies

Women (Cases)

Sensitivity* (95% CI)

Specificity* (95% CI)

Threshold

Test without maternal age

Single tests

First trimester free ßhCG

1

516 (86)

5 (1 to 11)

95 (92 to 97)

5% FPR

First trimester ß‐core fragment

1

516 (86)

10 (5 to 19)

95 (92 to 97)

5% FPR

First trimester ITA

2

579 (94)

15 (2 to 62)

95

5% FPR

First trimester total hCG

1

516 (86)

17 (10 to 27)

95 (92 to 97)

5% FPR

Second trimester oestriol

2

1472 (47)

23 (8 to 49)

95

5% FPR

Second trimester total hCG

1

390 (65)

31 (20 to 43)

95 (92 to 97)

5% FPR

Second trimester free ßhCG

3

1517 (107)

32 (12 to 63)

95

5% FPR

Second trimester ß‐core fragment

6

9613 (193)

41 (20 to 66)

95

5% FPR

Second trimester ITA

3

2748 (131)

43 (35 to 51)

95

5% FPR

Second trimester ß‐core fragment to oestriol ratio

2

1649 (35)

74 (58 to 86)

95

5% FPR

Second trimester gonadotropin test

1

105 (14)

93 (66 to 100)

95 (88 to 98)

1:384 risk

Double tests

Second trimester AFP and ITA

1

524 (24)

79 (58 to 93)

95 (93 to 97)

5% FPR

Second trimester ß‐core fragment and oestriol

1

315 (24)

83 (63 to 95)

95 (92 to 97)

5% FPR

Triple tests

Second trimester AFP, uE3 and ITA

1

524 (24)

79 (58 to 93)

95 (93 to 97)

5% FPR

Test with maternal age

Single tests

Second trimester oestriol

1

474 (69)

49 (37 to 62)

95 (92 to 97)

5% FPR

Second trimester ß‐core fragment

5

3419 (155)

56 (45 to 66)

95

5% FPR

Second trimester free ßhCG

2

879 (98)

57 (47 to 67)

95

5% FPR

Second trimester free ßhCG to oestriol ratio

1

474 (69)

64 (51 to 75)

95 (92 to 97)

5% FPR

Second trimester ß‐core fragment to free ßhCG

1

474 (69)

67 (54 to 78)

95 (92 to 97)

5% FPR

Second trimester ITA

1

1016 (23)

70 (47 to 87)

95 (93 to 96)

5% FPR

Second trimester ß‐core fragment to oestriol ratio

3

2088 (105)

71 (51 to 86)

95

5% FPR

Double tests

Second trimester oestriol and free ßhCG

1

474 (69)

68 (56 to 79)

95 (92 to 97)

5% FPR

Second trimester ß‐core fragment and oestriol

2

1631 (92)

73 (57 to 85)

95

5% FPR

Second trimester AFP and ß‐core fragment to oestriol ratio

1

356 (10)

90 (55 to 100)

95 (93 to 97)

1:58 risk

*Tests evaluated by at least one study are presented in the table. Where two studies reported the same threshold, estimates of summary sensitivity and summary specificity were obtained by using univariate fixed effects logistic regression models to pool sensitivities and specificities separately. if the threshold used was a 5% FPR, then only the sensitivities were pooled.

AFP: alpha‐fetoprotein; ßhCG: beta human chorionic gonadotrophin;CI: confidence interval; CVS: chorionic villus sampling; FPR: false positive rate; hCG: beta human chorionic gonadotrophin;ITA: invasive trophoblast antigen; uE3: unconjugated oestriol

Figuras y tablas -
Summary of findings Performance of urine tests with or without maternal age
Ir a la tabla de la revisión
Table 1. Direct comparisons of the diagnostic accuracy of five urine tests in combination with maternal age

Ratio of DORs (95% CI); P values (studies)

Second trimester AFP and ß‐core fragment to oestriol ratio, risk 1:58

Second trimester ß‐core fragment and oestriol, 5% FPR

Second trimester ITA, 5% FPR

Second trimester ß‐core fragment to oestriol ratio, 5% FPR

Second trimester ß‐core fragment and oestriol, 5% FPR

–

Second trimester ITA, 5% FPR

–

–

Second trimester ß‐core fragment to oestriol ratio, 5% FPR

–

1.5 (0.7 to 3.0); P = 0.27 (K = 2)

Second trimester ß‐core fragment, 5% FPR

–

2.2 (1.1 to 4.5); P = 0.02 (K = 2)

–

1.5 (0.8 to 2.8); P = 0.21 (K = 3)

Direct comparisons were made using only data from studies that compared each pair of tests in the same population. Ratio of diagnostic odds ratios (DOR)s were computed by division of the DOR for the test in the column by the DOR for the test in the row. If the ratio of DORs is greater than one, then the diagnostic accuracy of the test in the column is higher than that of the test in the row; if the ratio is less than one, the diagnostic accuracy of the test in the row is higher than that of the test in the column.

AFP: alpha‐fetoprotein; CI: confidence interval; DORs: diagnostic odds ratio; FPR: false positive rate; ITA: invasive trophoblast antigen

Figuras y tablas -
Table 1. Direct comparisons of the diagnostic accuracy of five urine tests in combination with maternal age
Ir a la tabla de la revisión
Table 2. Indirect comparisons of the diagnostic accuracy of five urine tests in combination with maternal age

Ratio of DOR (95% CI); P value

Second trimester AFP and ß‐core fragment to oestriol ratio, risk 1:58

Second trimester ß‐core fragment and oestriol, 5% FPR

Second trimester ITA, 5% FPR

Second trimester ß‐core fragment to oestriol ratio, 5% FPR

Studies

1

2

1

3

Studies

DOR (95% CI)

186 (22, 1560)

50 (30 to 84)

43 (17 to 110)

38 (24 to 59)

Second trimester ß‐core fragment and oestriol, 5% FPR

2

50 (30 to 84)

3.7 (0.4 to 33.0); P = 0.24

Second trimester ITA, 5% FPR

1

43 (17 to 110)

4.3 (0.4 to 44.0); P = 0.22

1.2 (0.4 to 3.4); P = 0.78

Second trimester ß‐core fragment to oestriol ratio, 5% FPR

3

38 (24 to 59)

4.9 (0.6 to 43.4); P = 0.15

1.3 (0.7 to 2.6); P = 0.41

1.1 (0.4 to 3.2); P = 0.80

Second trimester ß‐core fragment, 5% FPR

5

25 (18 to 36)

7.3 (0.8 to 63.1); P = 0.07

2.0 (1.1 to 3.7); P = 0.03

1.7 (0.6 to 4.6); P = 0.30

1.5 (0.8 to 2.6); P = 0.18

Indirect comparisons were made using all available data. Ratio of diagnostic odds ratios (DOR)s were computed by division of the DOR for the test in the column by the DOR for the test in the row. If the ratio of DORs is greater than one, then the diagnostic accuracy of the test in the column is higher than that of the test in the row; if the ratio is less than one, the diagnostic accuracy of the test in the row is higher than that of the test in the column.

AFP: alpha‐fetoprotein; CI: confidence interval; DORs: diagnostic odds ratio; FPR: false positive rate; ITA: invasive trophoblast antigen

Figuras y tablas -
Table 2. Indirect comparisons of the diagnostic accuracy of five urine tests in combination with maternal age
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Table Tests. Data tables by test

Test

No. of studies

No. of participants

1 Betacore, 1st trimester urine test, 5% FPR Show forest plot

1

516

2 Betacore, 2nd trimester urine test, 5% FPR Show forest plot

6

9613

3 Betacore, 2nd trimester urine test, cutpoint mixed Show forest plot

7

10124

4 Gonadotropin, 2nd trimester urine test, risk 1:100 Show forest plot

1

105

5 Gonadotropin, 2nd trimester urine test, risk 1:384 Show forest plot

1

105

6 Gonadotropin, 2nd trimester urine test, 95% percentile Show forest plot

1

105

7 ITA, 1st trimester urine test, 5% FPR Show forest plot

2

579

8 ITA, 2nd trimester urine test, 3.74MoM Show forest plot

1

2051

9 ITA, 2nd trimester urine test, 5% FPR Show forest plot

3

2748

10 Total hCG, 1st trimester urine test, 5% FPR Show forest plot

1

516

11 Total hCG, 2nd trimester urine test, 5% FPR Show forest plot

1

390

12 Free ßhCG, 1st trimester urine test, 5% FPR Show forest plot

1

516

13 Free ßhCG, 2nd trimester urine test, 5% FPR Show forest plot

3

1517

14 Oestriol, 2nd trimester urine test, 5% FPR Show forest plot

2

1472

15 Betacore to oestriol ratio, 2nd trimester urine test, 5% FPR Show forest plot

2

1649

16 Betacore and oestriol, 2nd trimester 5% FPR Show forest plot

1

315

17 AFP and ITA, 2nd trimester urine test, 3% FPR Show forest plot

1

524

18 AFP and ITA, 2nd trimester urine test, 5% FPR Show forest plot

1

524

19 AFP and ITA, 2nd trimester urine test,10% FPR Show forest plot

1

524

20 AFP and ITA, 2nd trimester urine test, 15% FPR Show forest plot

1

524

21 AFP, uE3 and ITA, 2nd trimester urine test, 3% FPR Show forest plot

1

524

22 AFP, uE3 and ITA, 2nd trimester urine test, 5% FPR Show forest plot

1

524

23 AFP, uE3 and ITA, 2nd trimester urine test, 10% FPR Show forest plot

1

524

24 AFP, uE3 and ITA, 2nd trimester urine test, 15% FPR Show forest plot

1

524

25 Age, betacore, 2nd trimester urine test, 1% FPR Show forest plot

2

2083

26 Age, betacore, 2nd trimester urine test, 3% FPR Show forest plot

2

2083

27 Age, betacore, 2nd trimester urine test, 5% FPR Show forest plot

5

3419

28 Age, betacore, 2nd trimester urine test, 10% FPR Show forest plot

1

926

29 Age, betacore, 2nd trimester urine test, 15% FPR Show forest plot

1

953

30 Age, betacore, 2nd trimester urine test, 20% FPR Show forest plot

1

926

31 Age, ITA, 2nd trimester urine test, 5% FPR Show forest plot

1

1016

32 Age, oestriol, 2nd trimester urine test, 5% FPR Show forest plot

1

474

33 Age, free ßhCG, 2nd trimester urine test, 5% FPR Show forest plot

2

879

34 Age, betacore to oestriol ratio, 2nd trimester urine test, 1% FPR Show forest plot

1

1157

35 Age, betacore to oestriol ratio, 2nd trimester urine test, 3% FPR Show forest plot

1

1157

36 Age, betacore to oestriol ratio, 2nd trimester urine test, 5% FPR Show forest plot

3

2088

37 Age, free ßhCG to oestriol ratio, 2nd trimester urine test, 5% FPR Show forest plot

1

474

38 Age, oestriol and free ßhCG, 2nd trimester, 5% FPR Show forest plot

1

474

39 Age, betacore to free ßhCG ratio, 2nd trimester, 5% FPR Show forest plot

1

474

40 Age, betacore and oestriol, 2nd trimester 1% FPR Show forest plot

1

1157

41 Age, betacore and oestriol, 2nd trimester, 3% FPR Show forest plot

1

1157

42 Age, betacore and oestriol, 2nd trimester, 5% FPR Show forest plot

2

1631

43 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:10 Show forest plot

1

356

44 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:20 Show forest plot

1

356

45 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:30 Show forest plot

1

356

46 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:58 Show forest plot

1

356

47 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:270 Show forest plot

1

356

48 Age, AFP and betacore to oestriol ratio, 2nd trimester, risk 1:526 Show forest plot

1

356
Figuras y tablas -
Table Tests. Data tables by test
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