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Diferentes regímenes terapéuticos de sulfato de magnesio para la tocólisis en pacientes en trabajo de parto prematuro

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References

References to studies included in this review

Behrad 2003 {published data only}

Behrad V, Moossavifar N, Mojtahedzadeh M, Esmalli H, Moghtadeli P. A prospective, randomized, controlled trial of high and low doses of magnesium sulfate for acute tocolysis. Acta Medica Iranica 2003;41(2):126‐31.

Soguk 2004 {published data only}

Soguk C, Tapisiz OL, Mungan T. Low dose treatment protocol in magnesium sulfate tocolysis. International Journal of Gynecology & Obstetrics 2004;86:37‐8.

Terrone 2000 {published data only}

Terrone DA, Rinehart BK, Kimmel ES, May WL, Larmon JE, Morrison JC. A prospective, randomized, controlled trial of high and low maintenance doses of magnesium sulfate for acute tocolysis. American Journal of Obstetrics and Gynecology 2000;182(6):1477‐82.

References to studies excluded from this review

Martin 1990 {published data only}

Martin RW, Perry KG, Martin JN, Hess LW, Morrison JC. Oral magnesium for tocolysis: a comparison of magnesium gluconate and enteric‐coated magnesium chloride. Proceedings of 37th Annual Meeting of the Society for Gynecologic Investigation; 1990 March 21‐24; St Louis, USA. 1990:167.

Martin 1998 {published data only}

Martin RW, Perry KGJ, Martin JN, Seago DP, Roberts WE, Morrison JC. Oral magnesium for tocolysis: a comparison of magnesium gluconate and enteric‐coated magnesium chloride. Journal of the Mississippi State Medical Association 1998;39(5):180‐2.

Zygmunt 2003 {published data only}

Zygmunt M, Heilmann L, Berg C, Wallwiener D, Grischke E, Munstedt K, et al. Local and systemic tolerability of magnesium sulphate for tocolysis. European Journal of Obstetrics & Gynecology and Reproductive Biology 2003;107(2):168‐75.

References to ongoing studies

Namazi 2013 {published data only}

Namazi SS. Comparison of maintenance therapy and continuous intravenous therapy with magnesium sulfate in preterm labor pain management at 24‐36 weeks gestation: a randomized controlled trial. IRCT Iranian Registry of Clinical Trials (www.irct.ir) [accessed 10 January 2015].

Additional references

Abarbanel 1945

Abarbanel, AR. The spasmolysant action of magnesium ions on the tetanically contracting human gravid uterus. American Journal of Obstetrics and Gynecology 1945;49(4):473‐83.

ACOG 2012

ACOG. ACOG Practice Bulletin. Clinical management guidelines for obstetrician‐gynecologists. Number 127, June 2012. Management of preterm labor. Obstetrics & Gynecology2012; Vol. 119:1308‐17.

Bain 2012

Bain E, Middleton P, Crowther CA. Different magnesium sulphate regimens for neuroprotection of the fetus for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2012, Issue 2. [DOI: 10.1002/14651858.CD009302.pub2]

Bain 2013

Bain ES, Middleton PF, Crowther CA. Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review. BMC Pregnancy and Childbirth 2013;13(1):195.

Beck 2010

Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, et al. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bulletin of the World Health Organization 2010;88(1):31‐8.

Borna 2007

Borna S, Saeidi FM. Celecoxib versus magnesium sulfate to arrest preterm labor: randomized trial. Journal of Obstetrics and Gynaecology Research 2007;33(5):631‐4.

Borna 2008

Borna S, Sahabi N. Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial. Australian and New Zealand Journal of Obstetrics and Gynaecology 2008;48(1):58‐63.

Crowther 2014

Crowther CA, Brown J, McKinlay CJD, Middleton P. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database of Systematic Reviews 2014, Issue 8. [DOI: 10.1002/14651858.CD001060.pub2]

Dowling 2012

Dowling O, Chatterjee PK, Gupta M, Tam Tam HB, Xue X, Lewis D, et al. Magnesium sulfate reduces bacterial LPS‐induced inflammation at the maternal‐fetal interface. Placenta 2012;33(5):392‐8.

Doyle 2009

Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD004661.pub3]

Duley 2010a

Duley L, Gülmezoglu AM, Henderson‐Smart DJ, Chou D. Magnesium sulphate and other anticonvulsants for women with pre‐eclampsia. Cochrane Database of Systematic Reviews 2010, Issue 11. [DOI: 10.1002/14651858.CD000025.pub2]

Duley 2010b

Duley LJ, Henderson‐Smart D, Chou D. Magnesium sulphate versus phenytoin for eclampsia. Cochrane Database of Systematic Reviews 2010, Issue 10. [DOI: 10.1002/14651858.CD000128.pub2]

Duley 2010c

Duley L, Henderson‐Smart DJ, Walker GJA, Chou D. Magnesium sulphate versus diazepam for eclampsia. Cochrane Database of Systematic Reviews 2010, Issue 12. [DOI: 10.1002/14651858.CD000127.pub2]

Duley 2010d

Duley L, Matar HE, Almerie MQ, Hall DR. Alternative magnesium sulphate regimens for women with pre‐eclampsia and eclampsia. Cochrane Database of Systematic Reviews 2010, Issue 8. [DOI: 10.1002/14651858.CD007388.pub2]

FDA 2013

FDA, U.S. Food, Drug Administration. FDA Recommends against prolonged use of magnesium sulfate to stop pre‐term labour due to bone changes in exposed babies. Drug Safety Communications, U.S. Food and Drug Administration2013.

Flenady 2014a

Flenady V, Reinebrant HE, Liley HG, Tambimuttu EG, Papatsonis DNM. Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database of Systematic Reviews 2014, Issue 6. [DOI: 10.1002/14651858.CD004452.pub3]

Flenady 2014b

Flenady V, Wojcieszek AM, Papatsonis DNM, Stock OM, Murray L, Jardine LA, et al. Calcium channel blockers for inhibiting preterm labour and birth. Cochrane Database of Systematic Reviews 2014, Issue 6. [DOI: 10.1002/14651858.CD002255.pub2]

Glock 1993

Glock JL, Morales WJ. Efficacy and safety of nifedipine versus magnesium sulfate in the management of preterm labor: a randomized study. American Journal of Obstetrics and Gynecology 1993;169(4):960‐4.

Goldenberg 2008

Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008;371:75‐84.

Grimes 2006

Grimes DA, Nanda K. Magnesium sulfate tocolysis: time to quit. Obstetrics & Gynecology 2006;108(4):986‐9.

Haas 2012

Haas DM, Caldwell DM, Kirkpatrick P, McIntosh JJ, Welton NJ. Tocolytic therapy for preterm delivery: systematic review and network meta‐analysis. BMJ 2012;345(7879):e6226.

Haghighi 1999

Haghighi L. Prevention of preterm delivery: nifedipine or magnesium sulfate. International Journal of Gynaecology and Obstetrics 1999;66(3):297‐8.

Hall 1957

Hall DG. Serum magnesium in pregnancy. Obstetrics & Gynecology 1957;9(2):158‐62.

Han 2013

Han S, Crowther CA, Moore V. Magnesium maintenance therapy for preventing preterm birth after threatened preterm labour. Cochrane Database of Systematic Reviews 2013, Issue 5. [DOI: 10.1002/14651858.CD000940.pub3]

Higgins 2011

Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

How 2006

How HY, Zafaranchi L, Stella CL, Recht K, Maxwell RA, Sibai B, et al. Tocolysis in women with preterm labor between 32 0/7 and 34 6/7 weeks of gestation: a randomized controlled pilot study. American Journal of Obstetrics and Gynecology 2006;194(4):976‐81.

James 2010

James MF. Magnesium in obstetrics. Best Practice and Research Clinical Obstetrics and Gynaecology 2010;24(3):327‐37.

Klauser 2012

Klauser CK, Briery CM, Keiser SD, Martin RW, Kosek MA, Morrison JC. Effect of antenatal tocolysis on neonatal outcomes. Journal of Maternal Fetal & Neonatal Medicine 2012;25(12):2778‐81.

Larmon 1999

Larmon JE, Ross BS, May WL, Dickerson GA, Fischer RG, Morrison JC. Oral nicardipine versus intravenous magnesium sulfate for the treatment of preterm labor. American Journal of Obstetrics and Gynecology 1999;181(6):1432‐7.

Lewis 2005

Lewis DF. Magnesium sulfate: the first‐line tocolytic. Obstetrics and Gynecology Clinics of North America 2005;32(3):485‐500.

Lurie 2004

Lurie S, Gur D, Sadan O, Glezerman M. Relationship between uterine contractions and serum magnesium levels in patients treated for threatened preterm labour with intravenous magnesium sulphate. Journal of Obstetrics and Gynaecology 2004;24(3):247‐8.

Lyell 2007

Lyell DJ, Pullen K, Campbell L, Ching S, Druzin ML, Chitkara U, et al. Magnesium sulfate compared with nifedipine for acute tocolysis of preterm labor: a randomized controlled trial. Obstetrics & Gynecology 2007;110(1):61‐7.

McWhorter 2004

McWhorter J, Carlan SJ, O'Leary TD, Richichi K, O'Brien WF. Rofecoxib versus magnesium sulfate to arrest preterm labor: a randomized trial. Obstetrics & Gynecology 2004;103(5 Pt 1):923‐30.

Mittendorf 1997

Mittendorf R, Covert R, Boman J, Khoshnood B, Lee K, Siegler M. Is tocolytic magnesium sulphate associated with increased total paediatric mortality?. Lancet 1997;350(9090):1517‐8.

Morales 1993

Morales WJ, Madhav H. Efficacy and safety of indomethacin compared with magnesium sulfate in the management of preterm labor: a randomized study. American Journal of Obstetrics and Gynecology 1993;169(1):97‐102.

Nassar 2006

Nassar AH, Sakhel K, Maarouf H, Naassan GR, Usta IM. Adverse maternal and neonatal outcome of prolonged magnesium sulfate tocolysis. Acta Obstetricia et Gynecologica Scandinavica 2006;85(9):1099‐103.

Neilson 2014

Neilson JP, West HM, Dowswell T. Betamimetics for inhibiting preterm labour. Cochrane Database of Systematic Reviews 2014, Issue 2. [DOI: 10.1002/14651858.CD004352.pub3]

Pryde 2009

Pryde PG, Mittendorf R. Contemporary usage of obstetric magnesium sulfate: indication, contraindication, and relevance of dose. Obstetrics & Gynecology 2009;114(3):669‐73.

RevMan 2014 [Computer program]

The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Schorr 1997

Schorr SJ. Ketorolac is a safe and effective drug for acute tocolysis. Acta Diabetologica Latina 1997;176:S7.

Steer 1977

Steer CM, Petrie RH. A comparison of magnesium sulfate and alcohol for the prevention of premature labor. American Journal of Obstetrics and Gynecology 1977;129(1):1‐4.

Tam Tam 2011

Tam Tam HB, Dowling O, Xue X, Lewis D, Rochelson B, Metz CN. Magnesium sulfate ameliorates maternal and fetal inflammation in a rat model of maternal infection. American Journal of Obstetrics and Gynecology 2011;204(4):364.e1‐364.e8.

Tsatsaris 2004

Tsatsaris V, Cabrol D, Carbonne B. Pharmacokinetics of tocolytic agents. Clinical Pharmacokinetics 2004;43(13):833‐44.

WHO 1992

World Health Organization. Pregnancy, childbirth and the puerperium. http://www.who.int/classifications/icd/en/ [accessed 24 May 2011]1992.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Behrad 2003

Methods

Randomised controlled trial.

Participants

Setting: Imam Reza’s Hospital, Iran.

Participants: women (n = 100; 50 in the low‐dose group, 50 in the high‐dose group) between 24‐35 weeks' gestation with spontaneous preterm labour. Singleton and twin pregnancies were included.

Definition of preterm labour: uterine contractions of more than 4 contractions per 20 minutes plus 1 of: cervical dilatation of at least 1 cm but less than 5 cm diameter, cervical effacement ≥ 80%, and/or progressive cervical dilatation and effacement.

Exclusion criteria: higher‐order multiple gestations, rupture of membranes, non‐reassuring fetal assessment (abnormalities of the fetal heart rate pattern), evidence of intrauterine infection (temperature ≥ 38°C, leucocytosis, uterine tenderness, malodorous discharge), vaginal bleeding, patients with a history of diabetes mellitus, myasthenia gravis, any other neuromuscular diseases, impaired renal function (serum creatinine > 1.2 mg/dL), hypotension (mean arterial pressure < 70 mm Hg), maternal bradycardia (heart rate < 60 beats per minute), atrioventricular block, inability or refusal to provide informed consent.

Interventions

All women

  • Bed rest in the labour unit.

  • Corticosteroids: intramuscular dexamethasone 5 mg, 4 doses given 12 hours apart.

  • Antibiotics: ampicillin 2 g every 6 hours for Group B Streptococcal prophylaxis if birth appeared imminent.

Low‐dose group

  • Loading dose: 4 g intravenous magnesium sulphate in a 20% solution over 20 minutes.

  • Maintenance dose: 2 g/h magnesium sulphate by continuous infusion.

High‐dose group

  • Loading dose: 6 g intravenous magnesium sulphate.

  • Maintenance dose: 2 g/h magnesium sulphate by continuous infusion. Increased by 1 g/h in the presence of continued contractions or cervical dilatation/effacement, hourly until successful tocolysis or failure of treatment.

Outcomes

Primary

  • Median time to successful tocolysis (minutes).

  • Serious neonatal morbidity and death.

Secondary

  • For the mother: self‐reported side effects; mode of birth.

  • For the infant: birthweight, Apgar score less than 8 at 1 minute; Apgar score less than 8 at 5 minutes; respiratory distress; hypoglycaemia; bradycardia; hypocalcaemia.

  • Health services outcomes: number of days in neonatal intensive care unit; length of stay.

  • Total amount of time in the labour and delivery unit (minutes).

Notes

Mean age of women: 23.8 ± 5.2 years in the low‐dose group; 24 ± 4.4 years in the high‐dose group.

Twin gestations: 3/50 in the low‐dose group; 1/50 in the high‐dose group.

Approval for this study was granted from the institutional review board of the University of Mashhad Medical Sciences.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomly assigned by computer‐generated number allocation.

Allocation concealment (selection bias)

Low risk

Consecutively numbered opaque envelopes.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No details were given regarding blinding.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No details were given regarding blinding.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up were reported.

Selective reporting (reporting bias)

Low risk

No obvious risk of selecting reporting.

Other bias

Low risk

No obvious risk of other bias.

Soguk 2004

Methods

Randomised controlled trial.

Participants

Setting: Sekai Tahir Burak Women Health Education and Research Hospital, Ankara, Turkey.

Participants: women (n = 100; 50 in the low‐dose group, 50 in the high‐dose group) between 28‐34 weeks' gestation with preterm labour that was unresponsive to intravenous fluid therapy and sedation.

Definition of preterm labour: not stated.

Exclusion criteria: not stated.

Interventions

Low‐dose group

  • Loading dose: nil.

  • Maintenance dose: 1 g/h magnesium sulphate infusion.

High‐dose group ('standard dose group')

  • Loading dose: 4 g intravenous magnesium sulphate given over 20 minutes.

  • Maintenance dose: 2 g/h magnesium sulphate continuous infusion.

Outcomes

Primary

  • Amount of time to achieve tocolysis ('contraction stopping time').

Secondary

  • Average duration of magnesium sulphate infusion.

  • Biophysical profile score at 1 hour after commencing infusion.

  • Biophysical profile score at 6 hours after commencing infusion.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Participants received low‐dose or standard dose therapy 'randomly'.

Allocation concealment (selection bias)

Unclear risk

No information was given on allocation concealment.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No information was given on blinding.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information was given on blinding.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Insufficient information to make the judgement.

Selective reporting (reporting bias)

High risk

No outcomes were listed a priori. It is unclear if the outcomes reported were the pre‐specified primary and secondary outcomes.

Other bias

Low risk

No obvious risk of other bias.

Terrone 2000

Methods

Randomised controlled trial.

Participants

Setting: University of Mississippi Medical Center, Mississippi, USA.

Participants: women (n = 160; 78 in the low‐dose group, 82 in the high‐dose group) between 24‐34 weeks' gestation with spontaneous preterm labour. Singleton and twin pregnancies were included.

Definition of preterm labour: advancement seen on cervical examination with uterine contractions while the patient was admitted to the triage unit OR dilatation of 2 cm and effacement of 80% with ≥ 6 uterine contractions per hour.

Exclusion criteria: higher‐order multiple gestations, rupture of membranes, non reassuring fetal assessment, evidence of intrauterine infection, treatment with any tocolytic agent before maternal transport, women who could not tolerate high doses of magnesium sulphate (for example, women with renal failure), inability or refusal to provide informed consent.

Interventions

All women

  • Corticosteroids: intramuscular betamethasone 12 mg, 2 doses given 24 hours apart.

  • Antibiotics: penicillin given for Group B Streptococcal prophylaxis if birth appeared imminent.

Low‐dose group

  • Loading dose: 4 g intravenous magnesium sulphate.

  • Maintenance dose: 2 g/h intravenous magnesium sulphate by continuous infusion. Increased by 1 g/h in the presence of continued contractions or cervical dilatation/effacement, hourly until successful tocolysis or failure of treatment.

High‐dose group

  • Loading dose: 4 g intravenous magnesium sulphate

  • Maintenance dose: 5 g/h intravenous magnesium sulphate by continuous infusion. Increased by 1 g/h in the presence of continued contractions or cervical dilatation/effacement, hourly until successful tocolysis or failure of treatment.

Outcomes

Primary

  • Median time to successful tocolysis (minutes).

Secondary

  • Median time in labour and delivery unit (minutes).

  • For the mother: pulmonary oedema; mode of birth ; self‐reported adverse effects (headache, flushing, no side effects).

  • For the infant: Apgar score less than 8 at 1 minute; Apgar score less than 8 at 5 minutes.

Notes

Mean age of women: 24 ± 5.1 years in the low‐dose group; 24 ± 4.8 years in the high‐dose group.

Twin gestations: 2/70 in the low‐dose group; 3/78 in the high‐dose group.

Approval for this study was granted from the institutional review board of The University of Mississippi Medical Centre.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number allocation, assigned by selection of the next numbered envelope.

Allocation concealment (selection bias)

Low risk

Consecutively numbered opaque envelopes.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No information was given on blinding.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information was given on blinding.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

12 women excluded from analysis due to treatment failure and subsequent birth (8 in the low‐dose group and 4 in the high‐dose group).

No losses to follow‐up were reported.

Selective reporting (reporting bias)

Low risk

No obvious risk of selective reporting.

Other bias

Low risk

No obvious risk of other bias.

°C: degrees Celsius
cm: centimetre(s)
g: gram(s)
g/h: gram(s) per hour
mg: milligram(s)
mg/dL: milligrams per decilitre
mm Hg: millimetres of mercury

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Martin 1990

Randomised controlled trial.

Setting: University of Mississippi Medical Center, Mississippi, USA.

Participants: women (n = 44; 23 magnesium gluconate, 21 magnesium chloride) with preterm labour.

Definition of preterm labour: not stated.

Intervention: oral magnesium gluconate compared with oral magnesium chloride given for maintenance tocolysis after the successful arrest of labour with parenteral magnesium sulphate.

Reason for exclusion

This study did not examine different treatment regimens of parenteral magnesium sulphate as single agent tocolytic therapy for the arrest of preterm labour. Rather, it examined the use of different oral magnesium preparations for maintenance tocolysis given after the successful arrest of labour with parenteral magnesium sulphate.

Martin 1998

Randomised controlled trial.

Setting: University of Mississippi Medical Center, Mississippi, USA.

Participants: women (n = 47; 25 magnesium gluconate, 22 magnesium chloride) with preterm labour.

Definition of preterm labour: presence of regular uterine contractions with a change in cervical exam.

Intervention: oral magnesium gluconate compared with oral magnesium chloride given for maintenance tocolysis after the successful arrest of labour with parenteral magnesium sulphate.

Reason for exclusion

This study did not examine different treatment regimens of parenteral magnesium sulphate as single agent tocolytic therapy for the arrest of preterm labour. Rather, it examined the use of different oral magnesium preparations for maintenance tocolysis given after the successful arrest of labour with parenteral magnesium sulphate.

Zygmunt 2003

Open‐label, randomised, parallel‐group, actively controlled study.

Setting: three study centres in Germany (Hessian, Giessen, Heidelberg).

Participants: women (n = 46; 23 in treatment group) with preterm labour with indication for single agent tocolysis therapy with magnesium sulphate.

Definition of preterm labour: not stated.

Intervention: loading dose of 4 g magnesium sulphate administered over 30 minutes. Maintenance dose of 1‐2 g/h magnesium sulphate up to 21 days via (1) ready to use infusion solution with 24 g magnesium sulphate per 500 mL OR (2) infusion solution concentrate, diluted in carrier solution before administration 20 g/500 mL.

Reason for exclusion

This study did not examine different treatment regimens of parenteral magnesium sulphate as single agent tocolytic therapy for the arrest of preterm labour. All women were given the same treatment regimen using two different preparations of magnesium sulphate (ready to use infusion solution versus infusion solution concentrate diluted in carrier solution).

g: gram(s)
g/h: gram(s) per hour
mL: millilitre(s)

Characteristics of ongoing studies [ordered by study ID]

Namazi 2013

Trial name or title

Comparison of maintenance therapy and continuous intravenous therapy with magnesium sulphate in preterm labour pain management at 24‐36 weeks' gestation: a randomized controlled trial.

Methods

Single‐arm, single‐blinded, randomised controlled trial.

Participants

Setting: Shariati Hospital, Bandar Abbas, Hormozgan, Iran.

Participants: women (n = 70) with preterm labour pains, between 24‐36 weeks’ gestation.

Inclusion criteria: presence of ≥ 4 uterine contractions during 20 minutes, cervical dilatation less than 4 cm, effacement less than 80%.

Exclusion criteria: co‐existing medical disease (including diabetes mellitus, asthma, cardiovascular disease), pre‐eclampsia, uterine bleeding, rupture of membranes, placenta decolman, intrauterine infection, urinary tract infection, fetal anomalies, previous preterm labour pain, lack of decreasing uterine contractions during first 2 hours after administration of magnesium sulphate, patient requiring administration of magnesium sulphate after 24 hours.

Interventions

Low‐dose group (Group A)

  • Loading dose: 4 g intravenous magnesium sulphate (in 200 cc 5% dextrose in water) given over 15‐20 minutes.

  • Maintenance dose: 2 g/h magnesium sulphate infusion for 10 hours.

High‐dose group (Group B)

  • Loading dose: 4 g intravenous magnesium sulphate (in 200 cc 5% dextrose in water) given over 15‐20 minutes.

  • Maintenance dose: 2 g/h magnesium sulphate infusion for 12 hours.

Outcomes

Primary

  • Amount of time to achieve tocolysis ('stopping labour pains' and 'controlling uterine contractions').

  • Preterm birth less than 37 weeks' gestation.

Secondary

  • Length of stay in neonatal intensive care unit (days).

  • For the mother: duration of pregnancy after intervention (days).

  • For the infant: Apgar score at 5 minutes.

Starting date

2013‐03‐20.

Contact information

Seyed Shojaeddin Namazi.

Notes

Approval for this study was granted from the Student Research Committee, Hormozgan University of Medical Sciences.

cc: cubic centimetre(s)
cm: centimetre(s)
g: gram(s)
g/h: gram(s) per hour

Data and analyses

Open in table viewer
Comparison 1. Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Fetal, neonatal and infant death Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.43 [0.12, 1.56]

Analysis 1.1

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 1 Fetal, neonatal and infant death.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 1 Fetal, neonatal and infant death.

2 Fetal death Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.06, 15.55]

Analysis 1.2

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 2 Fetal death.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 2 Fetal death.

3 Neonatal death Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.07, 1.57]

Analysis 1.3

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 3 Neonatal death.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 3 Neonatal death.

4 Respiratory distress syndrome Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.31 [0.11, 0.88]

Analysis 1.4

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 4 Respiratory distress syndrome.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 4 Respiratory distress syndrome.

5 Hypocalcaemia, osteopenia or fracture Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.5

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 5 Hypocalcaemia, osteopenia or fracture.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 5 Hypocalcaemia, osteopenia or fracture.

5.1 Hypocalcaemia

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.99]

6 Mode of birth Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.6

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 6 Mode of birth.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 6 Mode of birth.

6.1 Caesarean birth

2

248

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.59, 1.37]

7 Pulmonary oedema Show forest plot

1

148

Risk Ratio (M‐H, Fixed, 95% CI)

4.49 [0.22, 92.03]

Analysis 1.7

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 7 Pulmonary oedema.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 7 Pulmonary oedema.

8 Self‐reported adverse effects Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 1.8

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 8 Self‐reported adverse effects.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 8 Self‐reported adverse effects.

8.1 Flushing

2

248

Risk Ratio (M‐H, Random, 95% CI)

1.64 [0.89, 3.03]

8.2 Headache

2

248

Risk Ratio (M‐H, Random, 95% CI)

1.78 [0.95, 3.31]

8.3 Nausea

1

100

Risk Ratio (M‐H, Random, 95% CI)

1.27 [0.73, 2.20]

9 Admission to neonatal intensive care unit Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.46 [0.19, 1.12]

Analysis 1.9

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 9 Admission to neonatal intensive care unit.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 9 Admission to neonatal intensive care unit.

10 Length of stay neonatal intensive care unit (days) Show forest plot

1

100

Mean Difference (IV, Fixed, 95% CI)

‐3.10 [‐5.48, ‐0.72]

Analysis 1.10

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 10 Length of stay neonatal intensive care unit (days).

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 10 Length of stay neonatal intensive care unit (days).

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 2

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 3

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

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 1 Fetal, neonatal and infant death.
Figures and Tables -
Analysis 1.1

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 1 Fetal, neonatal and infant death.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 2 Fetal death.
Figures and Tables -
Analysis 1.2

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 2 Fetal death.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 3 Neonatal death.
Figures and Tables -
Analysis 1.3

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 3 Neonatal death.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 4 Respiratory distress syndrome.
Figures and Tables -
Analysis 1.4

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 4 Respiratory distress syndrome.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 5 Hypocalcaemia, osteopenia or fracture.
Figures and Tables -
Analysis 1.5

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 5 Hypocalcaemia, osteopenia or fracture.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 6 Mode of birth.
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Analysis 1.6

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 6 Mode of birth.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 7 Pulmonary oedema.
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Analysis 1.7

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 7 Pulmonary oedema.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 8 Self‐reported adverse effects.
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Analysis 1.8

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 8 Self‐reported adverse effects.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 9 Admission to neonatal intensive care unit.
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Analysis 1.9

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 9 Admission to neonatal intensive care unit.

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 10 Length of stay neonatal intensive care unit (days).
Figures and Tables -
Analysis 1.10

Comparison 1 Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials, Outcome 10 Length of stay neonatal intensive care unit (days).

Summary of findings for the main comparison. Different treatment regimens of magnesium sulphate for tocolysis in women in preterm labour

Different treatment regimens of magnesium sulphate for tocolysis in women in preterm labour

Patient or population: Women in preterm labour
Intervention: High‐dose magnesium sulphate
Comparison: Low‐dose magnesium sulphate

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with low‐dose (as defined by the trialist) magnesium sulphate

Risk with high‐dose (as defined by the trialist) magnesium sulphate

Fetal, neonatal and infant death

Study population

RR 0.43
(0.12 to 1.56)

100
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

140 per 1000

60 per 1000
(17 to 218)

Respiratory distress syndrome

Study population

RR 0.31
(0.11 to 0.88)

100
(1 RCT)

⊕⊕⊝⊝
LOW 1 3

260 per 1000

81 per 1000
(29 to 229)

*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; RCT: Randomised controlled trial.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the 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.

1 Evidence is based on a single trial

2 Evidence of wide confidence intervals crossing the line of no effect

3 No evidence of blinding of participants, personnel or outcome assessors

Figures and Tables -
Summary of findings for the main comparison. Different treatment regimens of magnesium sulphate for tocolysis in women in preterm labour
Comparison 1. Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Fetal, neonatal and infant death Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.43 [0.12, 1.56]

2 Fetal death Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.06, 15.55]

3 Neonatal death Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.07, 1.57]

4 Respiratory distress syndrome Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.31 [0.11, 0.88]

5 Hypocalcaemia, osteopenia or fracture Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Hypocalcaemia

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.99]

6 Mode of birth Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 Caesarean birth

2

248

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.59, 1.37]

7 Pulmonary oedema Show forest plot

1

148

Risk Ratio (M‐H, Fixed, 95% CI)

4.49 [0.22, 92.03]

8 Self‐reported adverse effects Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

8.1 Flushing

2

248

Risk Ratio (M‐H, Random, 95% CI)

1.64 [0.89, 3.03]

8.2 Headache

2

248

Risk Ratio (M‐H, Random, 95% CI)

1.78 [0.95, 3.31]

8.3 Nausea

1

100

Risk Ratio (M‐H, Random, 95% CI)

1.27 [0.73, 2.20]

9 Admission to neonatal intensive care unit Show forest plot

1

100

Risk Ratio (M‐H, Fixed, 95% CI)

0.46 [0.19, 1.12]

10 Length of stay neonatal intensive care unit (days) Show forest plot

1

100

Mean Difference (IV, Fixed, 95% CI)

‐3.10 [‐5.48, ‐0.72]

Figures and Tables -
Comparison 1. Magnesium sulphate high‐dose versus low‐dose regimen ‐ all included trials