Antibiotics for neonates born through meconium‐stained amniotic fluid

Lauren E Kelly; Sandesh Shivananda; Prashanth Murthy; Ravisha Srinivasjois; Prakeshkumar S Shah

doi:10.1002/14651858.CD006183.pub2

Antibióticos para recién nacidos con líquido amniótico teñido de meconio

Contraer todo Desplegar todo

Referencias

Referencias de los estudios incluidos en esta revisión

Ir a:

estudios excluidos
otras referencias

Basu S, Kumar A, Bhatia BD. Role of antibiotics in meconium aspiration syndrome. Annals of Tropical Pediatrics 2007;27:107‐13.

Goel A, Nangia S, Saili A, Garg A, Sharma S, Randhawa VS. Role of prophylactic antibiotics in neonates born through meconium‐stained amniotic fluid (MSAF) ‐ a randomized controlled trial. European Journal of Pediatrics 2015;174:237‐43.

Lin HC, Su BH, Tsai CH, Lin TW, Yeh TF. Role of antibiotics in management of non‐ventilated cases of meconium aspiration syndrome without risk factors for infection. Biology of the Neonate 2005;87:51‐5.

Shankar V, Paul VK, Deorari AK, Singh M. Do neonates with meconium aspiration syndrome require antibiotics?. Indian Journal of Pediatrics 1995;62:327‐31.

Referencias de los estudios excluidos de esta revisión

Ir a:

estudios incluidos
otras referencias

Adair CD, Ernest JM, Sanchez‐Ramos L, Burrus DR, Boles ML, Veille JC. Meconium‐stained amniotic fluid‐associated infectious morbidity: a randomized, double‐blind trial of ampicillin‐sulbactam prophylaxis. Obstetrics and Gynecology 1996;88:216‐20.

de Graaf MY, Verhagen E, Brand PL. Meconium‐containing amniotic fluid and what actions to take in newborn infants. Nederlands Tijdschrift voor Geneeskunde 1994;138(20):993‐5.

Edwards RK, Duff P. Prophylactic cefazolin in amnioinfusions administered for meconium‐stained amniotic fluid. Infectious Diseases in Obstetrics and Gynecology 1999;7:153‐7.

Krishnan L, Nasruddin, Prabhakar P, Bhaskaranand N. Routine antibiotic cover for newborns intubated for aspirating meconium: is it necessary?. Indian Pediatrics 1995;32:529‐31.

Pongmee P, Nagar G, Campbell S, Kumar M. Antibiotic administration for prevention or treatment of meconium aspiration syndrome in neonates: a systematic review. Jounral of Clinical Neonatology 2015;4:221‐6.

Google Scholar

Siriwachirachai T, Sangkomkamhang US, Lumbiganon P, Laopaiboon M. Antibiotics for meconium‐stained amniotic fluid in labour for preventing maternal and neonatal infections. The Cochrane Database of Systematic Reviews 2014;11:CD007772. [DOI: 10.1002/14651858.CD007772.pub3]

Vidyasagar D. The management of a neonate born with meconium stained amniotic fluid. Conference: 11th World Congress of Perinatal Medicine; Journal of Perinatal Medicine. 2013.

Google Scholar

Referencias adicionales

Ir a:

estudios incluidos
estudios excluidos

Ahanya SN, Lakshmanan J, Morgan BL, Ross MG. Meconium passage in utero: mechanisms, consequences, and management. Obstetrics and Gynecology Survey 2005;60:45‐56.

Blot P, Milliez J, Breart G, Vige P, Nessmann C, Onufryk JP, et al. Fetal tachycardia and meconium staining: a sign of fetal infection. International Journal of Gynaecology and Obstetrics 1983;21:189‐94.

Bortolucci R, Seeliger HPR. Listeriosis. In: Remington JS, Klie JO editor(s). Infectious Diseases of the Fetus and Newborn Infant. 3rd Edition. Philadelphia: WB Saunders, 1990:812‐33.

Google Scholar

Burgess AM, Hutchins GM. Inflammation of the lungs, umbilical cord and placenta associated with meconium passage in utero. Review of 123 autopsied cases. Pathology, Research and Practice 1996;192:1121‐8.

CDC guidelines. Campaign to prevent antimicrobial resistance in health care settings. 12 steps to prevent antimicrobial resistance among long term care residents. http://www.cdc.gov/drugresistance/healthcare/ltc/12steps_ltc.htm (accessed 5 June 2006).. Atlanta: Centers for Disease Control and Prevention, Atlanta: Centers for Disease Control and Prevention, 2004.

Google Scholar

Cleary GM, Wiswell TE. Meconium‐stained amniotic fluid and the meconium aspiration syndrome: an update. Pediatric Clinics of North America 1998;45:511‐29.

Craig S, Lopez A, Hoskin D, Markham F. Meconium inhibits phagocytosis and stimulates respiratory burst in alveolar macrophages. Pediatric Research 2005;57:813‐8.

Fanos V, Citaldi L. Antibacterial‐induced nephrotoxicity in the newborn. Drug Safety 1999;20:245‐67.

Florman AL, Teubner D. Enhancement of bacterial growth in amniotic fluid by meconium. Journal of Pediatrics 1969;74:111‐4.

Gelfand SL, Fanaroff JM, Walsh MC. Controversies in the treatment of meconium aspiration syndrome. Clinics in Perinatology 2004;31:445‐52.

Jiménez E, Marín ML, Martín R, Odriozola JM, Olivares M, Xaus J, et al. Is meconium from healthy newborns actually sterile?. Research in Microbiology 2008;159:187–93.

Lee JS, Stark AR. Meconium aspiration. In: Cloherty JP, Eichenwald EC, Stark AR editor(s). Manual of Neonatal Care. 5th Edition. Philadelphia: Lippincott Williams and Wilkins, 2004:402‐6.

Google Scholar

Lembet A, Gaddipati S, Holzman IR, Berkowitz RL, Bottone EJ. Meconium enhances the growth of perinatal bacterial pathogens. Mount Sinai Journal of Medicine 2003;70:126‐9.

Madan JC, Salari RC, Saxena D, Davidson L, O'Toole GA, Moore JH, et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Archives of Disease in Childhood. Fetal & Neonatal Edition 2012;97:F456–62.

Mazor M, Furman B, Wiznitzer A, Shoham‐Vardi I, Cohen J, Ghezzi F. Maternal and perinatal outcome of patients with preterm labor and meconium‐stained amniotic fluid. Obstetrics and Gynecology 1995;86:830‐3.

McCracken GH. Aminoglycoside toxicity in infants and children. The American Journal of Medicine 1986;80:172‐8.

Mshvildadze M, Neu J, Schuster J, Theriaque D, Li N. Intestinal microbial ecology in premature infants assessed with non‐culture‐based techniques. Journal of Pediatrics 2010;156:20‐5.

Natarajan CK, Sankar MJ, Jain K, Agarwal R, Paul VK. Surfactat therapy and antibiotics in neonates with meconium aspiration syndrome: a systematic review and meta‐analysis. Journal of Perinatology 2016;36:548‐53.

Rao S, Pavlova Z, Incerpi MH, Ramanathan R. Meconium‐stained amniotic fluid and neonatal morbidity in near‐term and term deliveries with acute histologic chorioamnionitis and/or funisitis. Journal of Perinatology 2001;21:537‐40.

Romero R, Hanaoka S, Mazor M, Athanassiadis AP, Callahan R, Hsu YC, et al. Meconium‐stained amniotic fluid: a risk factor for microbial invasion of the amniotic cavity. American Journal of Obstetrics and Gynecology 1991;164:859‐62.

Speer CP, Groneck P. Oxygen radicals, cytokines, adhesion molecules and lung injury in neonates. Seminars in Neonatology 1998;3:219‐28.

Tom‐Revzon C. Strategic use of antibiotics in the neonatal intensive care unit. The Journal of Perinatal and Neonatal Nursing 2004;18:241‐58.

Usta IM, Mercer BM, Sibai BM. Risk factors for meconium aspiration syndrome. Obstetrics and Gynecology 1995;86:230‐4.

Wan X, Wang W, Lui J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Medical Research Methodology 2014;14:135.

Warrier I, Du W, Nataranjan G, Salari V, Aranda J. Patterns of drug utilization in a neonatal intensive care unit. The Journal of Clinical Pharmacology 2006;46(4):449‐55.

Wiswell TE, Tuggle JM, Turner BS. Meconium aspiration syndrome: have we made a difference?. Pediatrics 1990;85:715‐21.

Wiswell TE, Henley MA. Intratracheal suctioning, systemic infection, and the meconium aspiration syndrome. Pediatrics 1992;89:203‐6.

Wiswell TE, Bent RC. Meconium staining and the meconium aspiration syndrome. Unresolved issues. Pediatric Clinics of North America 1993;40:955‐81.

Wiswell TE, Gannon CM, Jacob J, Goldsmith L, Szlyd E, Weiss K, et al. Delivery room management of the apparently vigorous meconium‐stained neonate: results of the multicenter, international collaborative trial. Pediatrics 2000;105:1‐7.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

estudios excluidos

Basu 2007

Methods	Randomised controlled trial 1. Masking of randomisation: yes 2. Masking of intervention: yes 3. Completeness of follow‐up: yes 4. Masking of outcome assessment: partial
Participants	Location: India Inclusion criteria: diagnosis of MAS, must meet all 5 criteria: (1) delivery through MSAF; (2) retrieval of meconium from below the larynx on endotracheal tube suction; (3) development of respiratory distress within 4 hours of birth and persisting beyond 24 hours; (4) chest radiograph showing features of infiltration with or without hyperinflation and/or atelectasis; and (5) absence of any other explanation for respiratory distress Antibiotics group (N = 72) Male = 39/72 Median (IQR) BW (grams) = 2450 (2190‐2900) Median (IQR) GA (weeks) = 39.0 (37.0‐42.0) Control group (N = 74) Male = 39/74 Median (IQR) BW (grams) = 2450 (2170‐2700) Median (IQR) GA (weeks) = 39.0 (37.0‐41.52) Exclusion criteria: (1) sepsis; any maternal or fetal risk factor for sepsis (e.g. intrapartum fever > 37.5°C, chorioamnionitis and prolonged rupture of membrane, < 35 weeks' gestation, low birth weight ‐ < 2000 g); development of clinical signs of sepsis after birth (e.g. poor feeding, lethargy, temperature instability, sclerema, delayed capillary filling time (> 3 seconds) with a positive blood culture and/or any 2 laboratory criteria suggestive of sepsis (i.e. total leucocyte count < 5000/109 cells/L or > 30,000/109 cells/L; band/segmented neutrophils ratio above 0.2; raised micro‐ESR > 5 mm in 1st hour on 1st day of life or > 15 mm at any time; and raised C‐reactive protein (> 1000 pg/L)); (2) settling of respiratory distress within 24 hours of birth; and (3) presence of any congenital malformation
Interventions	Antibiotics: 100 mg/kg/d ampicillin divided into 2 doses and 15 mg/kg/d amikacin divided into 2 doses for 7 days Control: No antibiotics
Outcomes	Primary outcome: Sepsis; clinical signs suggestive of sepsis along with a positive blood culture or any 2 laboratory criteria suggestive of sepsis Secondary outcomes: Duration of respiratory distress Duration of oxygen requirement Duration of hospital stay Requirement of IV fluids Commencement and achievement of full feeds Clearing of chest radiograph
Notes	No clinical trials registration number or funding source reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation sequence
Allocation concealment (selection bias)	Low risk	Allocation concealed
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Parents/attendants, radiologists, and statisticians were blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Radiologists were blinded. Clinicians could not be blinded, as 1 group received no treatment
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants accounted for and the number of participants lost to follow‐up was similar in both groups (N = 4 in the antibiotics group; N = 5 in the control group). Two participants died ‐ 1 in each group ‐ and were removed from analysis following randomisation
Selective reporting (reporting bias)	Unclear risk	No access to protocol
Other bias	Low risk

Goel 2015

Methods	Open‐label randomised controlled trial 1. Masking of randomisation: yes 2. Masking of intervention: yes 3. Completeness of follow‐up: yes 4. Masking of outcome assessment: yes
Participants	Location: India Inclusion criteria: all full‐term infants born as singleton cephalic presentation through MSAF Antibiotics group (N = 121) Male = 81/121 Mean (SD) BW (grams) = 2784.35 (447.19) Median (IQR) GA (weeks) = 39 (38‐40) Control group (N = 129) Male = 74/129 Mean (SD) BW = 2640.90 (427.5) Median (IQR) GA = 39 (38‐40) Exclusion criteria: major congenital malformation or refusal of consent by parents
Interventions	Antibiotics: Prophylactic IV antibiotics, piperacillin‐tazobactam 100 mg/kd/d, and amikacin 15 mg/kg/d for 3 days Control: No antibiotics
Outcomes	Primary outcome: Incidence of sepsis Secondary outcomes: Incidence of MAS Severity of MAS MAS complications HIE Duration of stay in hospital Mortality
Notes	Registered with clinical trial registry (NCT01290003). This research received no specific grant from any funding agency in public, commercial, or not‐for‐profit sectors
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Block‐randomised, computer‐generated
Allocation concealment (selection bias)	Low risk	Allocation concealed
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Treating clinician and nursery personnel were described as blinded; on‐duty physician completed randomisation assignment
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Treating clinician and nursery personnel were described as blinded. Unclear how treating clinician could be blinded, as control group received no intervention
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants accounted for in analysis
Selective reporting (reporting bias)	Low risk	Reported outcomes match those prospectively registered with clinicaltrials.gov
Other bias	Low risk

Lin 2005

Methods	Randomised controlled trial 1. Masking of randomisation: unclear 2. Masking of intervention: unclear 3. Completeness of follow‐up: no 4. Masking of outcome assessment: unclear
Participants	Location: Taiwan Inclusion criteria: MAS; diagnosed by presence of meconium below the vocal cord, accompanied by respiratory distress with tachypnoea, retraction, or cyanosis of the babies and an abnormal chest X‐ray (atelectasis, linear or patchy infiltration) Antibiotics group (N =132) Male = 72/132 Mean (SD) BW (grams) = 3280 (395) Mean (SD) GA (weeks) = 37.3 (3.9) Control group (N = 127) Male = 69/127 Mean (SD) BW (grams) = 3450 (320) Mean (SD) GA (weeks) = 38.5 (3.3) Exclusion criteria: congential malformation, obvious congential infection (signs or symptoms of TORCHS), cyanotic congenital heart disease, maternal fever, amnionitis, foetal tachycardia, prolonged rupture of membrane > 24 hours, respiratory failure requiring ventilation
Interventions	Antibiotics: 100 mg/kg/d ampicillin and 5.0 mg/kg/d gentamicin for 3 days Control: No antibiotics
Outcomes	Blood cultures for infection Mortality Tachypnoea Duration of oxygen therapy Duration of CPAP Incidence of nasal CPAP Incidence of pulmonary air leaks
Notes	No clinical trial registration number or funding source reported. Corresponding study author contacted for comment but could not be reached
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No data provided
Allocation concealment (selection bias)	Unclear risk	No data provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No data provided
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No data provided
Incomplete outcome data (attrition bias) All outcomes	High risk	N = 158 (antibiotics), N = 148 (control) recruited, but only 132/158 and 127/148 followed until 2 months of age. Significant post‐randomisation exclusions
Selective reporting (reporting bias)	Unclear risk	No data provided on which outcomes were predesignated as primary or secondary. No access to protocol

Shankar 1995

Methods	Randomised controlled trial 1. Masking of randomisation: unclear 2. Masking of intervention: unclear 3. Completeness of follow‐up: yes 4. Masking of outcome assessment: no
Participants	Location: India Inclusion criteria: MAS diagnosis if (1) born with meconium‐stained liquor, (2) born with respiratory distress lasting beyond 4 hours of age, and (3) documented presence of meconium in trachea at the time of tracheal suction or suggestive radiographic findings Antibiotics group (N = 20) Male = 12/20 Mean (SD) BW (grams) = 2650 (640) Mean (SD) GA (weeks) = 39.0 (1.95) Control group (N = 20) Male = 11/20 Mean (SD) BW (grams) = 3060 (600) Mean (SD) GA (weeks) = 38.8 (1.71) Exclusion criteria: maternal fever within 2 weeks before delivery, rupture of membranes of over 12 hours' duration, positive sepsis screen at time of enrolment
Interventions	Antibiotics: IV gentamicin 6 mg/kg/d q 8 hours for 7 days Control: No antibiotics
Outcomes	Duration of respiratory distress RDS score at 24 hours RDS score at 48 hours Incidence of mechanical ventilation Incidence of secondary infection Incidence of pulmonary air leaks Mortality
Notes	Unclear which outcome was designated as primary. No sample size calculation or trial registration number or funding support reported. Corresponding study author contacted for comment but could not be reached
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No data provided
Allocation concealment (selection bias)	Unclear risk	No data provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Nursery staff was not blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No data provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Outcome data were reported for all 42 randomised neonates
Selective reporting (reporting bias)	Unclear risk	No data provided on which outcomes were predesignated as primary or secondary
Other bias	Unclear risk	No data provided

BW: birth weight

CPAP: continuous positive airway pressure

ESR: erythrocyte sedimentation rate

GA: gestational age

HIE: hypoxic‐ischaemic encephalopathy

IQR: interquartile ratio

MAS: meconium aspiration syndrome

MSAF: meconium‐stained amniotic fluid

RDS: respiratory distress syndrome

SD: standard deviation

TORCHS: acronym for a group of in utero infections that may induce major foetal malformations

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos

Study	Reason for exclusion
Adair 1996	Antibiotics not administered to neonates
de Graff 1994	Article not available in English
Edwards 1999	Antibiotics not administered to neonates
Krishnan 1995	Not a randomised controlled trial
Pongmee 2015	Review; not a randomised controlled trial
Siriwachirachai 2014	Review; not a randomised controlled trial
Vidyasagar 2013	Not a randomised controlled trial

Data and analyses

Open in table viewer

Comparison 1. Antibiotics versus control (no antibiotics) in symptomatic neonates

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of confirmed sepsis in first 28 days Show forest plot	3	445	Risk Difference (M‐H, Fixed, 95% CI)	0.00 [‐0.02, 0.03]
Open in figure viewer Analysis 1.1 Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 1 Incidence of confirmed sepsis in first 28 days.
2 Mortality (before discharge) Show forest plot	3	445	Risk Difference (M‐H, Fixed, 95% CI)	0.00 [‐0.01, 0.02]
Open in figure viewer Analysis 1.2 Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 2 Mortality (before discharge).
3 Duration of oxygen therapy, days Show forest plot	2	405	Mean Difference (IV, Fixed, 95% CI)	‐0.85 [‐1.19, ‐0.52]
Open in figure viewer Analysis 1.3 Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 3 Duration of oxygen therapy, days.
4 Duration of hospital stay, days Show forest plot	1	146	Mean Difference (IV, Fixed, 95% CI)	0.16 [‐1.15, 1.47]
Open in figure viewer Analysis 1.4 Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 4 Duration of hospital stay, days.
5 Incidence of pulmonary air leak syndrome Show forest plot	3	445	Risk Ratio (M‐H, Fixed, 95% CI)	1.50 [0.62, 3.67]
Open in figure viewer Analysis 1.5 Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 5 Incidence of pulmonary air leak syndrome.
6 Incidence of mechanical ventilation Show forest plot	3	445	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [0.52, 2.67]
Open in figure viewer Analysis 1.6 Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 6 Incidence of mechanical ventilation.
7 Time to clear chest radiograph, days Show forest plot	1	146	Mean Difference (IV, Fixed, 95% CI)	‐1.31 [‐3.04, 0.42]
Open in figure viewer Analysis 1.7 Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 7 Time to clear chest radiograph, days.
8 Incidence of respiratory failure Show forest plot	2	405	Risk Difference (M‐H, Fixed, 95% CI)	0.01 [‐0.03, 0.05]
Open in figure viewer Analysis 1.8 Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 8 Incidence of respiratory failure.
9 Duration of respiratory distress, hours Show forest plot	1	40	Mean Difference (IV, Random, 95% CI)	‐1.20 [‐25.59, 23.19]
Open in figure viewer Analysis 1.9 Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 9 Duration of respiratory distress, hours.

Open in table viewer

Comparison 2. Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of confirmed sepsis in first 28 days Show forest plot	1	250	Risk Difference (M‐H, Fixed, 95% CI)	‐0.01 [‐0.07, 0.04]
Open in figure viewer Analysis 2.1 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 1 Incidence of confirmed sepsis in first 28 days.
2 Mortality (before discharge) Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.22, 5.18]
Open in figure viewer Analysis 2.2 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 2 Mortality (before discharge).
3 Duration of mechanical ventilation, days Show forest plot	1	250	Mean Difference (IV, Fixed, 95% CI)	0.26 [0.15, 0.37]
Open in figure viewer Analysis 2.3 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 3 Duration of mechanical ventilation, days.
4 Duration of oxygen therapy, days Show forest plot	1	250	Mean Difference (IV, Fixed, 95% CI)	0.43 [0.13, 0.73]
Open in figure viewer Analysis 2.4 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 4 Duration of oxygen therapy, days.
5 Incidence of suspected sepsis Show forest plot	1	250	Risk Difference (M‐H, Fixed, 95% CI)	‐0.03 [‐0.10, 0.05]
Open in figure viewer Analysis 2.5 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 5 Incidence of suspected sepsis.
6 Incidence of intracranial haemorrhage Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.01, 8.64]
Open in figure viewer Analysis 2.6 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 6 Incidence of intracranial haemorrhage.
7 Incidence of azotaemia Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	3.20 [0.13, 77.73]
Open in figure viewer Analysis 2.7 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 7 Incidence of azotaemia.
8 Incidence of oliguria Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	3.20 [0.13, 77.73]
Open in figure viewer Analysis 2.8 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 8 Incidence of oliguria.
9 Incidence of diarrhoea Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	0.12 [0.01, 2.18]
Open in figure viewer Analysis 2.9 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 9 Incidence of diarrhoea.
10 Incidence of mechanical ventilation Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	2.13 [0.55, 8.34]
Open in figure viewer Analysis 2.10 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 10 Incidence of mechanical ventilation.
11 Incidence of respiratory distress (Downe's score) Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [0.81, 1.72]
Open in figure viewer Analysis 2.11 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 11 Incidence of respiratory distress (Downe's score).
12 Duration of respiratory distress, hours Show forest plot	1	250	Mean Difference (IV, Fixed, 95% CI)	6.87 [4.22, 9.52]
Open in figure viewer Analysis 2.12 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 12 Duration of respiratory distress, hours.
13 Incidence of MAS Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.67, 2.04]
Open in figure viewer Analysis 2.13 Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 13 Incidence of MAS.

Figure 1

Figure 1. Study flow diagram.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

Figure 2. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Forest plot of comparison: Incidence of confirmed sepsis in symptomatic neonates within the first 28 days.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

Forest plot of comparison: Mortality in symptomatic neonates (before discharge).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 1 Incidence of confirmed sepsis in first 28 days.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 2 Mortality (before discharge).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 3 Duration of oxygen therapy, days.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 4 Duration of hospital stay, days.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 5 Incidence of pulmonary air leak syndrome.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 6 Incidence of mechanical ventilation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.7

Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 7 Time to clear chest radiograph, days.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.8

Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 8 Incidence of respiratory failure.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.9

Comparison 1 Antibiotics versus control (no antibiotics) in symptomatic neonates, Outcome 9 Duration of respiratory distress, hours.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 1 Incidence of confirmed sepsis in first 28 days.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.2

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 2 Mortality (before discharge).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.3

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 3 Duration of mechanical ventilation, days.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.4

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 4 Duration of oxygen therapy, days.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.5

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 5 Incidence of suspected sepsis.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.6

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 6 Incidence of intracranial haemorrhage.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.7

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 7 Incidence of azotaemia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.8

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 8 Incidence of oliguria.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.9

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 9 Incidence of diarrhoea.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.10

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 10 Incidence of mechanical ventilation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.11

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 11 Incidence of respiratory distress (Downe's score).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.12

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 12 Duration of respiratory distress, hours.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.13

Comparison 2 Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates, Outcome 13 Incidence of MAS.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings for the main comparison. Antibiotics compared with control (no antibiotics) in symptomatic neonates born through meconium‐stained amniotic fluid

Antibiotics compared with control (no antibiotics) in symptomatic neonates born through meconium‐stained amniotic fluid
Patient or population: symptomatic neonates born through meconium‐stained amniotic fluid Setting: neonatal intensive care unit Intervention: antibiotics Comparison: control (no antibiotics)
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with control (no antibiotics)	Risk with antibiotics
Incidence of confirmed sepsis in first 28 days	Study population		Not estimable	445 (3 RCTs)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to unclear risk of bias due to methodological limitations, including a large number of dropouts; and imprecision resulting from a small sample size
	9 per 1000	0 per 1000 (0 to 0)
Mortality (before discharge)	Study population		RR 1.69 (0.23 to 12.53)	445 (3 RCTs)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to unclear risk of bias due to methodological limitations, including a large number of dropouts; and imprecision resulting from a small sample size
	5 per 1000	8 per 1000 (1 to 57)
Duration of oxygen therapy, days	Mean duration of oxygen therapy (days) was 0	MD 0.85 days lower (1.19 lower to 0.52 lower)	‐	405 (2 RCTs)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to unclear risk of bias due to methodological limitations, including a large number of dropouts; and imprecision resulting from a small sample size
Duration of hospital stay, days	Mean duration of hospital stay (days) was 0	MD 0.16 days higher (1.15 lower to 1.47 higher)	‐	146 (1 RCT)	⊕⊕⊕⊝ MODERATE	Evidence was downgraded owing to imprecision resulting from a small sample size
Incidence of mechanical ventilation	Study population		RR 1.18 (0.52 to 2.67)	445 (3 RCTs)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to unclear risk of bias due to methodological limitations, including a large number of dropouts; and imprecision resulting from a small sample size
	45 per 1000	53 per 1000 (24 to 121)
Incidence of respiratory failure	Study population		RR 1.20 (0.51 to 2.83)	405 (2 RCTs)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to unclear risk of bias due to methodological limitations, including a large number of dropouts; and imprecision resulting from a small sample size
	41 per 1000	47 per 1000 (20 to 113)
*The risk in the intervention group (and its 95% confidence interval) is based on assumed risk in the comparison group and relative effect of the intervention (and its 95% CI) CI: confidence interval; OR: odds ratio; RR: risk ratio
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to the estimate of effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of effect but may be substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Summary of findings for the main comparison. Antibiotics compared with control (no antibiotics) in symptomatic neonates born through meconium‐stained amniotic fluid

Ir a la tabla de la revisión

Summary of findings 2. Antibiotics compared with control (no antibiotics) in asymptomatic neonates born through meconium‐stained amniotic fluid

Antibiotics compared with control (no antibiotics) in asymptomatic neonates born through meconium‐stained amniotic fluid
Patient or population: asymptomatic neonates born through meconium‐stained amniotic fluid Setting: neonatal intensive care unit Intervention: antibiotics Comparison: control (no antibiotics)
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with control (no antibiotics)	Risk with antibiotics
Incidence of confirmed sepsis in first 28 days	Study population		Not estimable	250 (1 RCT)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to very serious imprecision, as the results from this study have not been replicated
	54 per 1000	0 per 1000 (0 to 0)
Mortality (before discharge)	Study population		RR 1.07 (0.22 to 5.18)	250 (1 RCT)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to very serious imprecision, as the results from this study have not been replicated
	23 per 1000	25 per 1000 (5 to 120)
Duration of oxygen therapy, days	Mean duration of oxygen therapy (days) was 0	MD 0.43 days higher (0.13 higher to 0.73 higher)	‐	250 (1 RCT)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to very serious imprecision, as the results from this study have not been replicated
Incidence of suspected sepsis	Study population		Not estimable	250 (1 RCT)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to very serious imprecision, as the results from this study have not been replicated
	109 per 1000	0 per 1000 (0 to 0)
Incidence of mechanical ventilation	Study population		RR 2.13 (0.55 to 8.34)	250 (1 RCT)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to very serious imprecision, as the results from this study have not been replicated
	23 per 1000	50 per 1000 (13 to 194)
Duration of respiratory distress, hours	Mean duration of respiratory distress (hours) was 0	MD 6.87 higher (4.22 higher to 9.52 higher)	‐	250 (1 RCT)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to very serious imprecision, as the results from this study have not been replicated
Incidence of MAS	Study population		RR 1.17 (0.67 to 2.04)	250 (1 RCT)	⊕⊕⊝⊝ LOW	Evidence was downgraded owing to very serious imprecision, as the results from this study have not been replicated
	155 per 1000	181 per 1000 (104 to 316)
*The risk in the intervention group (and its 95% confidence interval) is based on assumed risk in the comparison group and relative effect of the intervention (and its 95% CI) CI: confidence interval; OR: odds ratio; RR: risk ratio
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to the estimate of effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of effect but may be substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Summary of findings 2. Antibiotics compared with control (no antibiotics) in asymptomatic neonates born through meconium‐stained amniotic fluid

Ir a la tabla de la revisión

Comparison 1. Antibiotics versus control (no antibiotics) in symptomatic neonates

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of confirmed sepsis in first 28 days Show forest plot	3	445	Risk Difference (M‐H, Fixed, 95% CI)	0.00 [‐0.02, 0.03]

2 Mortality (before discharge) Show forest plot	3	445	Risk Difference (M‐H, Fixed, 95% CI)	0.00 [‐0.01, 0.02]

3 Duration of oxygen therapy, days Show forest plot	2	405	Mean Difference (IV, Fixed, 95% CI)	‐0.85 [‐1.19, ‐0.52]

4 Duration of hospital stay, days Show forest plot	1	146	Mean Difference (IV, Fixed, 95% CI)	0.16 [‐1.15, 1.47]

5 Incidence of pulmonary air leak syndrome Show forest plot	3	445	Risk Ratio (M‐H, Fixed, 95% CI)	1.50 [0.62, 3.67]

6 Incidence of mechanical ventilation Show forest plot	3	445	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [0.52, 2.67]

7 Time to clear chest radiograph, days Show forest plot	1	146	Mean Difference (IV, Fixed, 95% CI)	‐1.31 [‐3.04, 0.42]

8 Incidence of respiratory failure Show forest plot	2	405	Risk Difference (M‐H, Fixed, 95% CI)	0.01 [‐0.03, 0.05]

9 Duration of respiratory distress, hours Show forest plot	1	40	Mean Difference (IV, Random, 95% CI)	‐1.20 [‐25.59, 23.19]

Comparison 1. Antibiotics versus control (no antibiotics) in symptomatic neonates

Ir a la tabla de la revisión

Comparison 2. Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of confirmed sepsis in first 28 days Show forest plot	1	250	Risk Difference (M‐H, Fixed, 95% CI)	‐0.01 [‐0.07, 0.04]

2 Mortality (before discharge) Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.22, 5.18]

3 Duration of mechanical ventilation, days Show forest plot	1	250	Mean Difference (IV, Fixed, 95% CI)	0.26 [0.15, 0.37]

4 Duration of oxygen therapy, days Show forest plot	1	250	Mean Difference (IV, Fixed, 95% CI)	0.43 [0.13, 0.73]

5 Incidence of suspected sepsis Show forest plot	1	250	Risk Difference (M‐H, Fixed, 95% CI)	‐0.03 [‐0.10, 0.05]

6 Incidence of intracranial haemorrhage Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.01, 8.64]

7 Incidence of azotaemia Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	3.20 [0.13, 77.73]

8 Incidence of oliguria Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	3.20 [0.13, 77.73]

9 Incidence of diarrhoea Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	0.12 [0.01, 2.18]

10 Incidence of mechanical ventilation Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	2.13 [0.55, 8.34]

11 Incidence of respiratory distress (Downe's score) Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [0.81, 1.72]

12 Duration of respiratory distress, hours Show forest plot	1	250	Mean Difference (IV, Fixed, 95% CI)	6.87 [4.22, 9.52]

13 Incidence of MAS Show forest plot	1	250	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.67, 2.04]

Comparison 2. Antibiotics versus control (no antibiotics) for prevention in asymptomatic neonates

Ir a la tabla de la revisión

	Idioma de la Revisión Cochrane Escoja su idioma de preferencia para las revisiones Cochrane y otros contenidos. Las secciones sin una traducción aparecerán en inglés.

	Idioma de la web Escoja su idioma de preferencia para la web de la Biblioteca Cochrane.

Idioma de la Revisión Cochrane

Idioma de la web

Referencias

Referencias de los estudios incluidos en esta revisión

Basu 2007 {published data only}

Goel 2015 {published data only}

Lin 2005 {published data only}

Shankar 1995 {published data only}

Referencias de los estudios excluidos de esta revisión

Adair 1996 {published data only}

de Graff 1994 {published data only}

Edwards 1999 {published data only}

Krishnan 1995 {published data only}

Pongmee 2015 {published data only}

Siriwachirachai 2014 {published data only}

Vidyasagar 2013 {published data only}

Referencias adicionales

Ahanya 2005

Blot 1983

Bortolucci 1990

Burgess 1996

CDC 2004

Cleary 1998

Craig 2005

Fanos 1999

Florman 1969

Gelfand 2004

Jiménez 2008

Lee 2004

Lembet 2003

Madan 2012

Mazor 1995

McCracken 1986

Mshvildadze 2010

Natarajan 2016

Rao 2001

Romero 1991

Speer 1998

Tom‐Revzon 2004

Usta 1995

Wan 2014

Warrier 2006

Wiswell 1990

Wiswell 1992

Wiswell 1993

Wiswell 2000

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

Copiar o descargar referencia

Idioma de la Revisión Cochrane

Idioma de la web

Instituciones a las que se accedió previamente

Usuarios institucionales

Instituciones a las que se accedió previamente

Otras opciones de acceso