Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks' gestation: a systematic review and metaanalysis
2009; Elsevier BV; Volume: 200; Issue: 6 Linguagem: Inglês
10.1016/j.ajog.2009.04.005
ISSN1097-6868
AutoresAgustín Conde‐Agudelo, Roberto Romero,
Tópico(s)Infant Development and Preterm Care
ResumoWe conducted a systematic review and metaanalysis of randomized controlled trials to determine whether magnesium sulfate administered to women at risk of preterm delivery before 34 weeks of gestation may reduce the risk of cerebral palsy in their children. Six trials involving 4796 women and 5357 infants were included. Antenatal magnesium sulfate was associated with a significant reduction in the risk of cerebral palsy (relative risk [RR], 0.69; 95% confidence interval [CI], 0.55-0.88), moderate or severe cerebral palsy (RR, 0.64; 95% CI, 0.44-0.92), and substantial gross motor dysfunction (RR, 0.60; 95% CI, 0.43-0.83). There was no overall difference in the risk of total pediatric mortality (RR, 1.01; 95% CI, 0.89-1.14). Minor side effects were more frequent among women receiving magnesium sulfate. In conclusion, magnesium sulfate administered to women at risk of delivery before 34 weeks of gestation reduces the risk of cerebral palsy. We conducted a systematic review and metaanalysis of randomized controlled trials to determine whether magnesium sulfate administered to women at risk of preterm delivery before 34 weeks of gestation may reduce the risk of cerebral palsy in their children. Six trials involving 4796 women and 5357 infants were included. Antenatal magnesium sulfate was associated with a significant reduction in the risk of cerebral palsy (relative risk [RR], 0.69; 95% confidence interval [CI], 0.55-0.88), moderate or severe cerebral palsy (RR, 0.64; 95% CI, 0.44-0.92), and substantial gross motor dysfunction (RR, 0.60; 95% CI, 0.43-0.83). There was no overall difference in the risk of total pediatric mortality (RR, 1.01; 95% CI, 0.89-1.14). Minor side effects were more frequent among women receiving magnesium sulfate. In conclusion, magnesium sulfate administered to women at risk of delivery before 34 weeks of gestation reduces the risk of cerebral palsy. Cerebral palsy describes a group of disorders affecting the development of movement and posture, causing activity limitation, and which are attributed to nonprogressive disturbances. Insults responsible for cerebral palsy are believed to have occurred during fetal development or infancy.1Rosenbaum P. Paneth N. Leviton A. et al.A report: the definition and classification of cerebral palsy April 2006.Dev Med Child Neurol. 2007; 109: 8-14Google Scholar Cerebral palsy is the most prevalent chronic childhood motor disability with an estimated lifetime cost in 2003 of nearly $1 million per person.2Honeycutt A. Dunlap L. Chen H. al Homsi G. Grosse S. Schendel D. Economic costs associated with mental retardation, cerebral palsy, hearing loss, and vision impairment: United States, 2003.MMWR. 2004; 53: 57-59PubMed Google Scholar The prevalence of cerebral palsy reported in recent population-based studies ranges between 1.5 and 3.6 cases per 1000 live births.3Paneth N. Hong T. Korzeniewski S. The descriptive epidemiology of cerebral palsy.Clin Perinatol. 2006; 33: 251-267Abstract Full Text Full Text PDF PubMed Scopus (272) Google Scholar, 4Yeargin-Allsopp M. Van Naarden Braun K. Doernberg N.S. Benedict R.E. Kirby R.S. Durkin M.S. Prevalence of cerebral palsy in 8-year-old children in three areas of the United States in 2002: a multisite collaboration.Pediatrics. 2008; 121: 547-554Crossref PubMed Scopus (307) Google Scholar, 5Moster D. Lie R.T. Markestad T. Long-term medical and social consequences of preterm birth.N Engl J Med. 2008; 359: 262-273Crossref PubMed Scopus (958) Google Scholar The United Cerebral Palsy Foundation estimates that nearly 800,000 children and adults of all ages in the United States have cerebral palsy.6United Cerebral Palsy. Press roomVocabulary tips Cerebral Palsy - Facts & Figures.http://www.ucp.org/ucp_generaldoc.cfm/1/9/37/37-37/447Google Scholar Secular trends in the overall prevalence of cerebral palsy over the last 40 years shows a modest increase in the frequency that has been attributed to a substantial increase in cerebral palsy in very low-birthweight infants, which, in turn, is attributable to their increased survival resulting from improvements in neonatal intensive care.3Paneth N. Hong T. Korzeniewski S. The descriptive epidemiology of cerebral palsy.Clin Perinatol. 2006; 33: 251-267Abstract Full Text Full Text PDF PubMed Scopus (272) Google Scholar, 5Moster D. Lie R.T. Markestad T. Long-term medical and social consequences of preterm birth.N Engl J Med. 2008; 359: 262-273Crossref PubMed Scopus (958) Google ScholarSee related editorial, page 589Preterm birth is a major risk factor for cerebral palsy, and the risk increases markedly with decreasing gestational age.7Himpens E. Van den Broeck C. Oostra A. Calders P. Vanhaesebrouck P. Prevalence, type, distribution, and severity of cerebral palsy in relation to gestational age: a meta-analytic review.Dev Med Child Neurol. 2008; 50: 334-340Crossref PubMed Scopus (195) Google Scholar Currently, infants born at less than 34 weeks of gestation constitute about 25% of all new cases of cerebral palsy.5Moster D. Lie R.T. Markestad T. Long-term medical and social consequences of preterm birth.N Engl J Med. 2008; 359: 262-273Crossref PubMed Scopus (958) Google Scholar, 8Himmelmann K. Hagberg G. Beckung E. Hagberg B. Uvebrant P. The changing panorama of cerebral palsy in Sweden: IX, prevalence and origin in the birth-year period 1995-1998.Acta Paediatr. 2005; 94: 287-294Crossref PubMed Google Scholar Multiple pregnancy is associated with an increased risk of cerebral palsy. This has been attributed, at least in part, to preterm birth. However, fetal or neonatal death of a member of a multiple gestation, twin-to-twin transfusion syndrome, or intrapartum problems also contribute.9Petterson B. Blair E. Watson L. Stanley F. Adverse outcome after multiple pregnancy.Baillieres Clin Obstet Gynaecol. 1998; 12: 1-17Abstract Full Text PDF PubMed Scopus (30) Google Scholar, 10Scher A.I. Petterson B. Blair E. et al.The risk of mortality or cerebral palsy in twins: a collaborative population-based study.Pediatr Res. 2002; 52: 671-681Crossref PubMed Scopus (186) Google ScholarSeveral observational studies have reported an association of antenatal treatment with magnesium sulfate for preterm labor or preeclampsia with a decreased risk of cerebral palsy in low-birthweight or preterm infants. In 1995, Nelson and Grether11Nelson K.B. Grether J.K. Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants?.Pediatrics. 1995; 95: 263-269PubMed Google Scholar reported a case-control study investigating whether in utero exposure to magnesium sulfate was used to prevent convulsions in preeclampsia or whether a tocolytic agent was associated with a lower prevalence of cerebral palsy in infants born weighing less than 1500 g. Children with cerebral palsy were less likely to have been exposed to magnesium sulfate than were control subjects (odds ratio [OR], 0.14; 95% confidence interval [CI], 0.05-0.51) suggesting a protective effect of magnesium sulfate against cerebral palsy in these very low-birthweight infants. Although some observational studies have reported similar findings,12Hauth J.C. Goldenberg R.L. Nelson K.G. DuBard M.B. Peralta M.A. Gaudier F.L. Reduction of cerebral palsy with maternal MgSO4 treatment in newborns weighing 500-1000 g [abstract].Am J Obstet Gynecol. 1995; 172: 419Google Scholar, 13Schendel D.E. Berg C.J. Yeargin-Allsopp M. Boyle C.A. Decoufle P. Prenatal magnesium sulfate exposure and the risk for cerebral palsy or mental retardation among very low-birth-weight children aged 3 to 5 years.JAMA. 1996; 276: 1805-1810Crossref PubMed Google Scholar, 14Wiswell T.E. Graziani L.J. Caddell J.L. Vecchione N. Stanley C. Spitzer A.R. Maternally administered megnesium sulphate protects against early brain injury and long-term adverse neurodevelopmental outcomes in preterm infants: a prospective study [abstract].Pediatr Res. 1996; 39: 253PubMed Google Scholar, 15Matsuda Y. Kouno S. Hiroyama Y. et al.Intrauterine infection, magnesium sulfate exposure and cerebral palsy in infants born between 26 and 30 weeks of gestation.Eur J Obstet Gynecol Reprod Biol. 2000; 91: 159-164Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar others have reported no association between the administration of magnesium sulfate and the subsequent risk of cerebral palsy.16Paneth N. Jetton J. Pinto-Martin J. Susser M. Magnesium sulfate in labor and risk of neonatal brain lesions and cerebral palsy in low birth weight infants The Neonatal Brain Hemorrhage Study Analysis Group.Pediatrics. 1997; 99: E1Crossref PubMed Google Scholar, 17O'Shea T.M. Klinepeter K.L. Dillard R.G. Prenatal events and the risk of cerebral palsy in very low birth weight infants.Am J Epidemiol. 1998; 147: 362-369Crossref PubMed Scopus (124) Google Scholar, 18Wilson-Costello D. Borawski E. Friedman H. Redline R. Fanaroff A.A. Hack M. Perinatal correlates of cerebral palsy and other neurologic impairment among very low birth weight children.Pediatrics. 1998; 102: 315-322Crossref PubMed Scopus (135) Google Scholar, 19Boyle C.A. Yeargin-Allsopp M. Schendel D.E. Holmgreen P. Oakley G.P. Tocolytic magnesium sulfate exposure and risk of cerebral palsy among children with birth weights less than 1,750 grams.Am J Epidemiol. 2000; 152: 120-124Crossref PubMed Scopus (33) Google Scholar, 20Grether J.K. Hoogstrate J. Walsh-Greene E. Nelson K.B. Magnesium sulfate for tocolysis and risk of spastic cerebral palsy in premature children born to women without preeclampsia.Am J Obstet Gynecol. 2000; 183: 717-725Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar, 21Costantine M.M. How H.Y. Coppage K. Maxwell R.A. Sibai B.M. Does peripartum infection increase the incidence of cerebral palsy in extremely low birthweight infants?.Am J Obstet Gynecol. 2007; 196: e6-e8Abstract Full Text Full Text PDF PubMed Scopus (33) Google ScholarIn response to the conflicting evidence from observational studies, several randomized controlled trials of magnesium sulfate administered to mothers for fetal neuroprotection have been performed. A recent systematic review that assessed the effects of magnesium sulfate as a fetal neuroprotective agent when given to women considered at risk of preterm birth concluded that this therapy reduced the risk of cerebral palsy and substantial gross motor dysfunction in early childhood.22Doyle L.W. Crowther C.A. Middleton P. Marret S. Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus.Cochrane Database Syst Rev. 2009; 1 (CD004661)Google Scholar This review, however, based its main conclusions on metaanalysis that included preterm infants less than 37 weeks of gestational age and did not perform any economic evaluation for estimating the cost-effectiveness of this intervention for the prevention of cerebral palsy.We carried out a systematic review and metaanalysis of all available randomized controlled trials to determine the efficacy and safety of antenatal administration of magnesium sulfate to women at risk of preterm delivery before 34 weeks of gestational age for the prevention of cerebral palsy in their children.Materials and methodsThe systematic review was conducted after a prospectively prepared protocol and reported using the Quality of Reporting of Metaanalysis (QUOROM) guidelines for metaanalysis of randomized controlled trials.23Moher D. Cook D.J. Eastwood S. Olkin I. Rennie D. Stroup D.F. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement, Quality of Reporting of Meta-analyses.Lancet. 1999; 354: 1896-1900Abstract Full Text Full Text PDF PubMed Scopus (3917) Google ScholarSearchWe searched PubMed, Embase, Cinahl, and Lilacs (all from inception to March 31, 2009), ISI Web of Science (http://www.isiknowledge.com) (1960 to March 31, 2009), the Cochrane Central Register of Controlled Trials (http://www.mrw.interscience.wiley.com/cochrane/cochrane_clcentral_articles_fs.html) (1960 to March 31, 2009), and Research Registers of ongoing trials (www.clinicaltrials.gov, www.controlled-trials.com, www.centerwatch.com, www.actr.org.au, www.nrr.nhs.uk, and www.umin.ac.jp/ctr) using a combination of key words and text words related to magnesium, cerebral palsy, and neuroprotection. Proceedings of the Society for Maternal-Fetal Medicine and international meetings on cerebral palsy, reference lists of identified studies, textbooks, previously published systematic reviews, and review articles were also searched. No language restrictions were applied. All searches were carried independently by the 2 authors and results were merged. For studies that resulted in multiple publications, the data from the publication with the largest sample size were used and supplemented if additional information appeared in the other publications.Study selectionWe included randomized controlled trials comparing magnesium sulfate with placebo or no magnesium sulfate for women at risk of preterm birth before 34 weeks of gestation, whose primary aim was to prevent cerebral palsy and other neurologic abnormalities in the unborn infant or if the primary aim was otherwise but data on cerebral palsy were reported for the infants. Quasirandomized studies were excluded. We classified trials according to aim of the treatment with magnesium sulfate into 2 groups: “neuroprotection of the fetus” and “other aims.”All published studies deemed suitable were retrieved and reviewed independently by the 2 authors to determine inclusion. Disagreements were resolved through consensus.Outcome measuresThe primary outcomes of interest were cerebral palsy and total pediatric mortality (fetal death + any mortality of live births that occurred during the 2 years of corrected age after the birth). We included total pediatric mortality because it is a competing outcome that would preclude the assessment of cerebral palsy. Prespecified secondary outcomes for the neonate and infant included mild cerebral palsy, any intraventricular hemorrhage, moderate or severe cerebral palsy, grade III or IV intraventricular hemorrhage, periventricular leukomalacia, Apgar score < 7 at 5 minutes, neonatal seizures, respiratory distress syndrome, need for supplemental oxygen at 36 weeks, bronchopulmonary dysplasia, mechanical ventilation, necrotizing enterocolitis, substantial gross motor dysfunction, major neurologic disability, any neurologic impairment, Bayley mental development index < 70 and < 85, Bayley psychomotor development index < 70 and < 85, blindness, and deafness. For the mother, secondary outcomes were death, cardiac or respiratory arrest, pulmonary edema, respiratory depression, hypotension, tachycardia, severe postpartum hemorrhage, cesarean delivery, and clinical and self-assessed maternal side effects of the infusion such as flushing, nausea or vomiting, sweating, problems at injection site, stopping of infusion because of adverse effects, and any side effect.Study quality assessmentWe assessed study methodologic quality using a modified scoring system proposed by Jadad et al,24Jadad A.R. Moore R.A. Carroll D. et al.Assessing the quality of reports of randomized clinical trials: is blinding necessary?.Control Clin Trials. 1996; 17: 1-12Abstract Full Text PDF PubMed Scopus (13357) Google Scholar which is based on 3 items: randomization, blinding, and follow-up. Points were awarded on the basis of the quality of randomization (2 points: computer-generated random numbers or similar; 1 point: not described; 0 points: quasirandomized or not randomized [we excluded such studies]); double blinding (2 points: neither the person doing the assessments nor the study participant could identify the intervention being assessed; 1 point: not described; 0 points: no blinding or inadequate method), and follow-up (2 points: number or reasons for dropouts and withdrawals described, and assessment of primary outcomes in ≥ 95% of randomized fetuses; 1 point: number or reasons for dropouts and withdrawals described but assessment of primary outcomes in < 95% of randomized fetuses; 0 points: number or reasons for dropouts and withdrawals not described). In addition, we assessed concealment of allocation as follows: 2 points: adequate method (central randomization; or drug containers or opaque, sealed envelopes that were sequentially numbered and opened sequentially only after they have been irreversibly assigned to the participant); 0 points: no concealment of allocation or inadequate method or not described. Thus, the total score ranged from 0 (lowest quality) to 8 (highest quality). The methodologic quality of included trials was assessed individually by the 2 reviewers who were not associated with any of the trials. When differences in scoring existed, a consensus was reached.Data abstractionOne reviewer (A.C.-A.) scanned abstracts and titles. Potentially relevant articles were acquired and data were extracted in duplicate from all reports and recorded on a piloted form independently by the 2 reviewers. There was no blinding by authorship. All outcome data were further verified with the original articles. Information was extracted on study characteristics (randomization procedure, allocation concealment, blind assessment at baseline and follow-up, follow-up period, intention-to-treat analysis, and losses to follow-up), participants (inclusion and exclusion criteria, numbers of mothers and infants in randomized groups, baseline characteristics, and country and date of recruitment), details of intervention (aim, loading dose, maintenance dose, median total dose, duration, and retreatment), and outcomes (number of outcome events including mortality and morbidity). The number of infants was used as the denominator for primary (cerebral palsy and pediatric mortality), neonatal, and infant neurodevelopmental outcomes. When maternal outcomes were presented, numerators and denominators were calculated based on the number of mothers. In an attempt to obtain additional data, we contacted 3 authors by e-mail of whom 1 responded. Disagreements in extracted data were resolved by discussion among reviewers.Statistical analysisStatistical analysis was performed according to the guidelines of the Cochrane Collaboration.25Deeks J.J. Higgins J.P.T. Altman D.G. Analysing data and undertaking meta-analyses The Cochrane Collaboration, 2008.in: Higgins J.P.T. Green S. Cochrane handbook for systematic reviews of interventions. Version 5.0.1. Wiley, Hoboen, NJ2008Google Scholar We analyzed outcomes on an intend-to-treat basis. If this was not clear from the original article, then we carried out reanalysis where possible. If data for similar outcomes from 2 or more separate studies were available, we combined the data in a metaanalysis and calculated a summary relative risk (RR) with associated 95% CI. Heterogeneity of the results among studies was tested with the quantity I2, which describes the percentage of total variation across studies that is due to heterogeneity rather than chance.26Higgins J.P. Thompson S.G. Deeks J.J. Altman D.G. Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560Crossref PubMed Scopus (38334) Google Scholar A value of 0% indicates no observed heterogeneity, whereas I2 values of 50% or more indicate a substantial level of heterogeneity.26Higgins J.P. Thompson S.G. Deeks J.J. Altman D.G. Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560Crossref PubMed Scopus (38334) Google Scholar We planned to pool data across studies using a fixed-effects model if substantial statistical heterogeneity was not present. We used random-effects models to pool data across studies if the I2 values were ≥ 50%.We conducted sensitivity analyses to explore the robustness of findings for the primary outcomes according to statistical model (fixed effects vs random effects), modified Jadad quality score (> 4 vs ≤ 4), and completeness of follow-up of randomized fetuses (≥ 95% vs < 95%). Additional subgroup analyses were planned to assess the primary outcomes by primary aim of the treatment with magnesium sulfate (neuroprotective vs other aims), median total dose of magnesium sulfate used (≤ 4 g vs > 4 g), gestational age at trial entry (< 34, < 32, and < 30 weeks), and plurality (singleton and multiple pregnancy). The metaanalysis by plurality of pregnancy, however, was not possible because there were not sufficient data available from the great majority of studies.We assessed publication and related biases visually by examining the symmetry of funnel plots and statistically by using the Egger test.27Egger M. Davey Smith G. Schneider M. Minder C. Bias in meta-analyses detected by a simple graphical test.BMJ. 1997; 315: 629-634Crossref PubMed Scopus (33149) Google Scholar The larger the deviation of the intercept of the regression line from zero, the greater was the asymmetry and the more likely it was that the metaanalysis would yield biased estimates of effect. As suggested by Egger, we considered P < .1 to indicate significant asymmetry.We also calculated the number needed to treat (NNT) for an additional beneficial outcome and the NNT for an additional harmful outcome with their 95% CIs for outcomes in which the treatment effect was significant at the 5% level (the 95% CI for the absolute risk difference did not include zero).28Altman D.G. Confidence intervals for the number needed to treat.BMJ. 1998; 317: 1309-1312Crossref PubMed Scopus (705) Google Scholar NNT was computed from the results of metaanalysis of RRs as follows:NNT=∣1/Controlgroupeventrate×(1−relativerisk)∣ In this review, NNT for an additional beneficial outcome is the number of women at risk of preterm delivery before 34 weeks of gestation who need to be treated with magnesium sulfate rather than with placebo to prevent 1 case of cerebral palsy. The NNT for an additional harmful outcome is the number of women at risk of preterm delivery before 34 weeks of gestation who need to be treated with magnesium sulfate rather than with placebo for 1 additional woman to be harmed by an adverse event.We estimated the hypothetical impact of universal use of magnesium sulfate in American women at high risk of preterm delivery before 34 weeks of gestational age to prevent cerebral palsy in their children. Initially, we calculated the total number of new cases of cerebral palsy diagnosed each year in the United States among infants born before 34 weeks of gestational age using published data on the total number of new cases of cerebral palsy recognized each year in the United States and the percentage of infants with cerebral palsy born before 34 weeks of gestational age. Then, the total number of new cases of cerebral palsy among infants born before 34 weeks of gestational age was multiplied by the summary RR and the upper and lower bounds of its 95% CI obtained in our metaanalysis to estimate the hypothetical number of new cases of cerebral palsy with corresponding 95% CI that could be prevented annually using this intervention.Finally, we performed an economic evaluation to calculate the incremental cost of preventing 1 case of cerebral palsy in the United States through use of antenatal magnesium sulfate in women at risk of preterm delivery before 34 weeks of gestational age. First, we searched data published recently on the total cost per patient of administrating magnesium sulfate as a tocolytic agent in the United States. Then, the incremental cost of preventing 1 case of cerebral palsy (with corresponding 95% CI) by using antenatal magnesium sulfate was estimated by multiplying the total cost per patient of administering magnesium sulfate by the NNT for benefit and the upper and lower bounds of its 95% CI obtained in our analysis. All statistical analyses were performed with the StatsDirect version 2.7.2 (StatsDirect Ltd, Cheshire, United Kingdom).ResultsThe flow of the search is shown in Figure 1. Of the 331 potentially relevant citations identified, 5 studies (6 trials) published in 7 articles fulfilled the inclusion criteria after a detailed review of 92 studies.29Mittendorf R. Covert R. Boman J. Khoshnood B. Lee K.S. Siegler M. Is tocolytic magnesium sulphate associated with increased total paediatric mortality?.Lancet. 1997; 350: 1517-1518Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar, 30Mittendorf R. Dambrosia J. Pryde P.G. et al.Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants.Am J Obstet Gynecol. 2002; 186: 1111-1118Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar, 31Crowther C.A. Hiller J.E. Doyle L.W. et al.Australasian Collaborative Trial of Magnesium Sulphate (ACTOMg SO4) Collaborative GroupEffect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial.JAMA. 2003; 290: 2669-2676Crossref PubMed Scopus (415) Google Scholar, 32Magpie Trial Follow-Up Study Collaborative GroupThe Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia: outcome for children at 18 months.BJOG. 2007; 114: 289-299Crossref PubMed Scopus (133) Google Scholar, 33Marret S. Marpeau L. Zupan-Simunek V. et al.PREMAG trial groupMagnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial*.BJOG. 2007; 114: 310-318Crossref PubMed Scopus (188) Google Scholar, 34Marret S. Marpeau L. Bénichou J. Benefit of magnesium sulfate given before very preterm birth to protect infant brain.Pediatrics. 2008; 121: 225-226Crossref PubMed Scopus (44) Google Scholar, 35Rouse D.J. Hirtz D.G. Thom E. et al.A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy.N Engl J Med. 2008; 359: 895-905Crossref PubMed Scopus (481) Google Scholar Because the study by Mittendorf et al29Mittendorf R. Covert R. Boman J. Khoshnood B. Lee K.S. Siegler M. Is tocolytic magnesium sulphate associated with increased total paediatric mortality?.Lancet. 1997; 350: 1517-1518Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar, 30Mittendorf R. Dambrosia J. Pryde P.G. et al.Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants.Am J Obstet Gynecol. 2002; 186: 1111-1118Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar had 2 arms (tocolytic and neuroprotective), it was considered as 2 separate trials in this review. Of the other 4 studies included, 3 studies31Crowther C.A. Hiller J.E. Doyle L.W. et al.Australasian Collaborative Trial of Magnesium Sulphate (ACTOMg SO4) Collaborative GroupEffect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial.JAMA. 2003; 290: 2669-2676Crossref PubMed Scopus (415) Google Scholar, 33Marret S. Marpeau L. Zupan-Simunek V. et al.PREMAG trial groupMagnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial*.BJOG. 2007; 114: 310-318Crossref PubMed Scopus (188) Google Scholar, 35Rouse D.J. Hirtz D.G. Thom E. et al.A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy.N Engl J Med. 2008; 359: 895-905Crossref PubMed Scopus (481) Google Scholar evaluated magnesium sulfate as an infant neuroprotective agent, and 1 study32Magpie Trial Follow-Up Study Collaborative GroupThe Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia: outcome for children at 18 months.BJOG. 2007; 114: 289-299Crossref PubMed Scopus (133) Google Scholar assessed the efficacy of magnesium sulfate for preventing eclampsia. Eighty-seven studies were excluded, the main reason being the lack of data on cerebral palsy and/or pediatric mortality in randomized controlled trials on magnesium sulfate for preventing preterm birth or eclampsia. Overall agreement on the inclusion of studies was 100% (κ = 1.00). The 6 trials included a total of 4796 women and 5357 infants.The characteristics of included studies are presented in Table 1. Two studies were performed in the United States,29Mittendorf R. Covert R. Boman J. Khoshnood B. Lee K.S. Siegler M. Is tocolytic magnesium sulphate associated with increased total paediatric mortality?.Lancet. 1997; 350: 1517-1518Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar, 35Rouse D.J. Hirtz D.G. Thom E. et al.A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy.N Engl J Med. 2008; 359: 895-905Crossref PubMed Scopus (481) Google Scholar 1 each in France,33Marret S. Marpeau L. Zupan-Simunek V. et al.PREMAG trial groupMagnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial*.BJOG. 2007; 114: 310-318Crossref PubMed Scopus (188) Google Scholar Australia, and New Zealand,31Crowther C.A. Hiller J.E. Doyle L.W. et al.Australasian Collaborative Trial of Magnesium Sulphate (ACTOMg SO4) Collaborative GroupEffect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial.JAMA. 2003; 290: 2669-2676Crossref PubMed Scopus (415) Google Scholar and the remaining study was conducted in 19 countries across 5 continents.32Magpie Trial Follow-Up Study Collaborative GroupThe Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia: outcome for children at 18 months.BJOG. 2007; 114: 289-299Crossref PubMed Scopus (133) Google Scholar Trials included women with gestational ages < 34 weeks29Mittendorf R. Covert R. Boman J. Khoshnood B. Lee K.S. Siegler M. Is tocolytic magnesium sulphate associated with increased total paediatric mortality?.Lancet. 1997; 350: 1517-1518Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar (165 infants), < 33 weeks33Marret S. Marpeau L. Zupan-Simunek V. et al.PREMAG trial groupMagnesium sulphate g
Referência(s)