Antenatal magnesium for preterm delivery reduces risk of cerebral palsy among surviving very preterm infants.

Abstract

Commentary on: Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY, Mercer BM, Iams JD, Wapner RJ, Sorokin Y, Alexander JM, Harper M, Thorp JM Jr, Ramin SM, Malone FD, Carpenter M, Miodovnik M, Moawad A, O'Sullivan MJ, Peaceman AM, Hankins GD, Langer O, Caritis SN, Roberts JM. Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Networks. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008; 359(9):895–905. PMID 18753646. The current American College of Obstetricians and Gynecologists (ACOG) Committee Opinion supports the use of magnesium sulphate for foetal neuroprotection before 32 weeks of gestation 1. The clinical trial reviewed here is the largest and most recent to inform these guidelines 2. This randomised control trial (RCT), aimed to determine if the administration of magnesium sulphate to women at high risk of preterm delivery would reduce the risk of cerebral palsy (CP), found a reduction in moderate/severe CP at two years of age following antenatal magnesium sulphate exposure (RR 0.55, 95% CI 0.32–0.95) 2. These results were consistent with previous RCTs primarily evaluating the neuroprotective benefits of magnesium sulphate on the incidence of CP in preterm infants 3-5. Additionally, a Cochrane review concluded that 63 women were needed to prevent one diagnosis of CP 6. Further investigation is warranted to provide updated and unified guidelines regarding the use of magnesium sulphate for foetal neuroprotection. There was significant heterogeneity in treatment regimens between RCTs with no trial sharing the same loading dose, treatment dose, duration of dosing or retreatment regimen of magnesium sulphate 2-6. Additionally, although no serious maternal complications of antenatal magnesium exposure have been reported, there were several minor complications, including a 50% increase in maternal hypotension, leading to a 3.2-fold increase in cessation of therapy 6. Optimal treatment regimens would likely lead to a refined understanding of treatment effect size, better protocol adherence, and ultimately improved neurodevelopmental outcomes. The results of this trial should be considered in the context of advances in neonatal medicine affecting neurodevelopmental outcomes. Specifically, during the time of this study's enrolment, the American Academy of Pediatrics (AAP) recommended against routine use of postnatal corticosteroids in preterm infants because of its negative effect on neurodevelopmental outcomes 7. This recommendation significantly curtailed the use of early postnatal steroids, potentially altering neurodevelopmental outcomes if differed between treatment groups 7. Additionally, there has been increased survival of infants 22–23 weeks of gestation 8. Currently, there are no RCTs that investigate the neuroprotective benefit of magnesium sulphate in <24 weeks of gestation. It has been 20 years since recruitment started and nearly 10 years since the publication of this landmark trial has influenced the practice of obstetricians in the United States 2. In that same time, there continue to be advances in the care of extremely low birthweight infants impacting changes in survival and neurodevelopmental outcomes. Although many institutions follow ACOG recommendations of administering antenatal magnesium sulphate in preterm delivery, there are no recommendations for magnesium sulphate treatment regimens or gestational age thresholds presumably leading to a variety of clinical practices 1. Perhaps it is time to repeat this clinical trial in a new era to help elucidate both the optimal treatment regimen as well as the effect of antenatal magnesium exposure in the setting of preterm labour and delivery on neurodevelopmental outcomes. In the meantime, this trial remains consistent with available evidence supporting antenatal magnesium sulphate exposure in preterm infants to reduce CP. https://ebneo.org/2017/10/antenatal-magnesium-for-preterm-delivery-reduces-risk-of-cerebral-palsy-among-surviving-very-preterm-infants/ None. None.