Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis

Abstract

BackgroundBabies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal magnesium sulphate, compared with no magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which magnesium sulphate treatment was received, or the dose and timing of the administration of magnesium sulphate.Methods and findingsTrials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to magnesium sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [magnesium] and [preterm or premature or neuroprotection or 'cerebral palsy']. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of magnesium sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with magnesium sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to magnesium sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, magnesium sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54...

Protection of brain development by antenatal magnesium sulphate for infants born preterm

“…They can surpass the limitations of standard meta‐analyses, because they use data that is superior both in quantity and quality, allow for greater scope in their analyses, and provide more detailed, robust results. An individual personal data meta‐analysis was undertaken by the AMICABLE group to explore the interaction between treatment and participant characteristics . In that study, the five randomized controlled trials aforementioned were included (i.e.…”

“…An individual personal data meta-analysis was undertaken by the AMICABLE group to explore the interaction between treatment and participant characteristics. 34 In that study, the five randomized controlled trials aforementioned were included (i.e. 5493 females and 6131 infants).…”

“…The overall relative risk of CP among survivors after antenatal magnesium sulphate was 0.68 (95% CI: 0.54-0.87), and the number needed to treat was 46. Magpie: Altman et al 27 Doyle et al 30 Conde-Agudelo et al 31 Costantine et al 32 Zeng et al 33 Crowther et al 34 Paediatric mortality a Interestingly, analysis of the four trials with fetal neuroprotective intent revealed that magnesium sulphate also reduced the combined risk of fetal/infant death and CP (relative risk 0.86, 95% CI: 0.75-0.99). In agreement with the results of the randomized controlled trials and metaanalyses, magnesium sulphate treatment had no effect on neonatal and paediatric mortality, or neonatal morbidity (respiratory distress syndrome, chronic lung disease, intraventricular haemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, or retinopathy of preterm birth).…”

The Research Cycle: Improving Care and Outcomes for Newborn Infants

“…The randomised controlled trial (RCT) is the optimal design for determining efficacy and effectiveness, provided it is large enough to detect important effect sizes [14]. For example, prompted by the observed association of antenatal magnesium sulfate with a lower risk of cerebral palsy, clinical investigators, internationally, undertook RCTs to provide causal evidence of the neuro-protective effects of magnesium in very-low-birth-weight infants [15]. …”

Magnesium supplementation during pregnancy

“…Сульфат магния, широко применяемый в акушерстве с целью профилакти-ки неврологических осложнений у плода при преждевре-менных родах, снижает активность матриксных металло-протеиназ-9 и, таким образом, оказывает нейропротек-тивный эффект [12]. Значительное количество исследова-ний доказывает снижение риска и предотвращение раз-вития детского церебрального паралича на фоне терапии сульфатом магния при преждевременных родах с целью нейропротекции [13]. Также доказано, что назначение сульфата магния при преждевременных родах значитель-но снижает риск развития кровоизлияния в мозг у недо-ношенного новорожденного [14].…”