Providing magnesium sulfate to pregnant patients before delivery in the periviable period of 22-24 weeks’ gestation was not linked to better neurodevelopmental outcomes in the newborn after accounting for receipt of prenatal corticosteroids, according to research presented at the Society for Maternal-Fetal Medicine (SMFM) 2026 Annual Pregnancy Meeting.

“The lack of association was consistent across all gestational weeks,” Margaret Page, MD, a maternal-fetal medicine fellow at The University of Alabama at Birmingham, reported. “Management of pregnant patients at risk of periviable delivery should prioritize antenatal corticosteroid administration.”

Babies born in the periviable period, between 20 weeks and 24 weeks 6 days , have a high risk for death or severe neurodevelopmental impairment. Research has shown that, for women at high risk for preterm birth who are expected to give birth within 24 hours, prenatal administration of magnesium sulfate reduces the risk for cerebral palsy in the newborn.

Caroline Pessel, MD, a maternal-fetal medicine physician and associate professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, was not involved in the study but noted the complexity of managing periviable pregnancies.

“While antenatal magnesium sulfate reduces cerebral palsy and severe motor deficits in preterm neonates less than 32 weeks, data for extremely preterm infants is scarce, and magnesium carries maternal risks,” said Pessel, who is also program director of North Shore Hospital and Long Island Jewish Medical Center’s Maternal Fetal Medicine Fellowship in New York City.

“The authors’ recommendation to prioritize antenatal corticosteroids, given their established benefit and favorable risk-benefit profile in extremely preterm gestations, is reasonable,” she said. “However, these findings may not sufficiently alter current guidelines regarding antenatal magnesium for neuroprotection.”

Page and her colleagues conducted a secondary analysis of data from the National Institute of Child Health and Human Development Neonatal Research Network Generic Database and Follow-up Study to see if an association existed between the prenatal magnesium sulfate exposure in the periviable period and the risk for severe neurodevelopmental impairment or death.

The original prospective observational study tracked newborns from 2012 to 2022 from 15 centers, including comprehensive neurodevelopmental follow-up through 2025. The follow-up involved a basic neurologic exam and a Bayley III exam when the children were 22-26 months old.

Page and her colleagues included in their analysis all 4179 singletons or twins born between 22 weeks and 24 weeks 6 days gestation, excluding those who died within 12 hours after birth without delivery room resuscitation and those lost to follow-up.

They compared outcomes of death and severe neurodevelopmental impairment  between the 3242 of infants (78%) exposed in utero to magnesium sulfate to the 937 unexposed infants (22%). Severe neurodevelopmental impairment was defined as a gross motor function classification system level of 4 or 5, a motor or cognitive composite score below 70 on the Bayley exam, blindness in both eyes, or severe hearing impairment in both ears.

Secondary outcomes included less severe neurodevelopmental impairment, cerebral palsy at varying levels of severity, grade 3 or 4 intracranial hemorrhage, and seizures at discharge or follow-up.

The mothers were a median of 28 years old; 46.7% were Black, 46.7% were White. About half the women had a high school education or less, and nearly all received prenatal care. Just over half the mothers (55%) had ruptured membranes.

Mothers who received magnesium sulfate, compared to those who did not receive it, were more likely to have hypertension (23% vs 14%) and a cesarean delivery (55% vs 46%). Nearly all mothers who received magnesium sulfate also received corticosteroids (98%) and most received antibiotics (86%). Among those who didn’t receive magnesium sulfate, 56% received corticosteroids, and 53% received antibiotics before delivery.

More infants exposed to magnesium sulfate were born at later gestational ages than unexposed infants: 21% of unexposed infants and 9% of exposed infants were born at 22 weeks, whereas 54% of exposed infants and 41% of unexposed infants were born at 24 weeks. Those exposed to magnesium sulfate also had a higher average birth weight (610 grams) than unexposed infants (590 grams). Rates of small-for-gestational age were 9% for exposed infants and 4% for unexposed infants.

At 2 years old, 63% of infants exposed to magnesium sulfate had died or had severe neurodevelopmental impairment compared to 70% of unexposed infants. After adjustment for covariates, including gestational age at birth and exposure to corticosteroids, however, there was no significant difference in primary outcomes between exposed and unexposed infants (adjusted odds ratio [aOR], 1.00; 95% CI, 0.65-1.25). There was also no significant difference between those exposed vs unexposed to magnesium sulfate when stratified by gestational age at delivery.

When the researchers calculated the difference between the groups with adjustment for all covariates except corticosteroids, the risk for death and severe neurodevelopmental impairment was lower for those exposed to magnesium sulfate than unexposed (aOR, 0.78), which suggests the effect may be largely due to administration of prenatal steroids.

Some of the secondary outcomes were more frequent among unexposed infants than exposed infants, but none remained significantly different after adjustment for confounders.

“Despite its prospective nature and large cohort, the nonrandomized study design presents significant limitations,” Pessel said. “Confounding factors, such as indications for preterm birth, infection, concurrent interventions, and timing of magnesium, hinder isolating magnesium’s independent effect and comparing exposed vs unexposed groups.”

No external funding was noted for the study. Page and Pessel reported having no disclosures.

Tara Haelle is a science/health journalist based in Dallas.