Children born before 27 weeks’ gestation had lower combined risk of death or severe neurodevelopmental impairment when exposed to antenatal corticosteroids and magnesium sulfate together, compared with exposure of either or neither therapy, according to a prospective observational study published in Obstetrics & Gynecology.
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“If there is sufficient time to administer antenatal corticosteroids, there should similarly be sufficient time to administer magnesium sulfate,” wrote Samuel J. Gentle, MD, of the University of Alabama at Birmingham, and colleagues. “Given the lower rate of severe neurodevelopmental impairment or death in children exposed to both antenatal corticosteroids and magnesium sulfate in the present study, compared with those exposed to antenatal corticosteroids alone, increasing the rates of magnesium sulfate exposure through quality improvement or other interventions may improve infant outcomes.”
Although previous randomized controlled trials had shown neurologic benefits of each therapy independently in preterm children, few data exist on extremely preterm children, the authors noted. They also pointed out differences in the findings when they analyzed neurodevelopmental outcomes and death separately.
“Whereas exposure to both therapies was associated with a lower rate of death, exposure to magnesium sulfate in addition to antenatal corticosteroids was not associated with a lower rate of severe neurodevelopmental impairment or components of severe neurodevelopmental impairment including Bayley scores, bilateral hearing impairment, and cerebral palsy,” Dr Gentle and his coauthors wrote.
The researchers used prospectively collected data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Generic Database to track 3,093 children born extremely preterm – from 22 weeks 0 days to 26 weeks 6 days – during 2011-2014.
The researchers compared outcomes of death or severe neurodevelopmental impairment when the children were 18-26 months of corrected age based on whether they had been exposed to antenatal corticosteroids alone (betamethasone or dexamethasone) or antenatal corticosteroids in addition to magnesium sulfate. Severe neurodevelopmental impairment included “severe cerebral palsy, motor or cognitive composite score less than 70 on the Bayley-III exam, bilateral blindness, or bilateral severe functional hearing impairment with or without amplification.”
The researchers also looked at severe neurodevelopmental impairment and death among children with only magnesium sulfate exposure or with no exposure to steroids or magnesium.
In the study population, 73% of infants had been exposed to both therapies, 16% had been exposed to only corticosteroids, 3% to only magnesium sulfate, and 8% to neither therapy.
“Importantly, a larger proportion of mothers unexposed to either therapy, compared with both therapies, received high school or less education or had no maternal private health insurance which may suggest health inequity as a driver for antenatal therapy exposure rates,” Dr. Gentle and associates noted.
Children whose mothers received corticosteroids and magnesium had a 27% lower risk of severe neurodevelopmental impairment or death, compared with those whose mothers only received corticosteroids (adjusted odds ratio, 0.73). Just over a third of children exposed to both interventions (36%) had severe neurodevelopmental impairment or died, compared with 44% of those exposed only to steroids.
Similarly, corticosteroids and magnesium together were associated with approximately half the risk of death or severe neurodevelopmental impairment, compared with magnesium alone (aOR, 0.49) and 34% lower risk, compared with neither therapy (aOR 0.66).
When the researchers uncoupled the outcomes, severe neurodevelopmental impairment rates were similar among all exposure groups, but rates of death were lower among those who received both therapies than among those who received just one or neither therapy.
“The therapeutic mechanism for neuroprotection in children exposed to magnesium sulfate is unclear but may result from neuronal stabilization or anti-inflammatory properties,” Dr. Gentle and colleagues said.
They also compared rates in the exposure groups of grade 3-4 intracranial hemorrhage, which has been linked to poor neurodevelopmental outcomes in extremely preterm children.
“The rate of grade 3-4 intracranial hemorrhage did not differ between children exposed to both antenatal corticosteroids and magnesium sulfate and those exposed to antenatal corticosteroids alone,” they said. “These findings further support data from randomized controlled trials showing benefit for antenatal corticosteroids but not for magnesium sulfate.”
They further noted a Cochrane Review that found significantly reduced risk of severe or any intracranial hemorrhage among children exposed to antenatal corticosteroids. No similar reduction in intracranial hemorrhage occurred in a separate Cochrane Review of antenatal magnesium sulfate trials.
The research was funded by the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Center for Advancing Translational Sciences. One author is a consultant for Mednax who has received travel funds. Another author disclosed Catholic Health Professionals of Houston paid honorarium for an ethics talk he gave.
SOURCE: Gentle SJ et al. Obstet. Gynecol. 2020. doi: 10.1097/AOG.0000000000003882.