Antenatal corticosteroids reduce neonatal mortality in preterm births

Antenatal corticosteroids reduce neonatal mortality in preterm births | Image Credit: © ondrooo – © ondrooo – stock.adobe.com.

Neonatal mortality is reduced by administration of antenatal corticosteroids (ACS), among infants born preterm according to a recent study published in JAMA Network Open.¹

Data has indicated reduced neonatal morbidity and mortality among infants following an ACS course, which has been identified as the most effective intervention among pregnant patients at an increased risk of preterm birth.² The timing of administration has been linked to the intervention’s effects, but there is little data about how quickly they take effect and how long benefits persist.¹

“These questions… are of major importance as they may determine whether ACS should be administered in cases in which preterm birth is imminent, determine the optimal timing of ACS administration, and guide the timing of a repeat (rescue) course of ACS,” wrote investigators.

The national retrospective cohort study was conducted to determine the link between the timing of ACS administration and neonatal morbidity and mortality among preterm infants. Singleton and twin live neonates born from 23- to 31-weeks’ gestation and admitted to level 3 neonatal intensive care units (NICU) were included in the analysis.

Exclusion criteria included triplets and higher-order gestations, major congenital anomalies, unknown timing of ACS administration, over 1 course of ACS, chronic steroid treatment, and an interval between treatment and birth of at least 8 weeks. Outcome, risk factor, and practice data was obtained from the Canadian Preterm Birth Network and Canadian Neonatal Network.

Thirty-one NICUs provided data for the analysis. The ACS administration to birth interval was defined as the exposure, measured as the time from the first ACS dose administration to birth. Neonates without ACS exposure were included as controls. Categories of exposure included no ACS, under 24 hours, 24 hours to 7 days, 8 to 14 days, and over 14 days before birth.

Neonatal mortality before hospital discharge was reported as the primary outcome. The secondary outcome of mortality or severe neurologic injury was defined by grade 3 or 4 intraventricular hemorrhage based on the criteria of Papile et al. Covariates included plurality, maternal age, birth weight below the tenth percentile, and hypertensive disorders of pregnancy.

There were 7950 neonates included in the final analysis, 15% with no ACS exposure, 29% exposure under 24 hours before birth, 32% 24 hours to 7 days, 11% 8 to 14 days, and 14% over 14 days.

Mothers without ACS administration had a slightly reduced mean age and lower rates of nulliparity, twin pregnancy, gestational diabetes, hypertensive complications, magnesium sulfate prophylaxis, and cesarean delivery vs those using ACS. Overall neonatal mortality and composite outcome of neonatal mortality or severe neurologic injury rates were 8% and 14%, respectively.

Links were found between ACS administration and reductions in the risks of study outcomes. Administration between 24 hours and 7 days or between 8 and 14 days before birth led to the most significant reduction, with adjusted risk ratios (ARRs) of 0.50 and 0.51, respectively.

The smallest reduction with an ARR of 0.75 was reported for administration under 24 hours before birth. However, reduced odds of neonatal mortality were reported as early as 2 hours following administration of the first dose, with an ARR of 0.83. An ARR of 0.56 highlighted a plateau 12 hours after exposure.

For the first 2 weeks after exposure, the reduction in neonatal mortality risk remained stable, but gradually decreased after this period. After 4 weeks, no association was observed. Similar patterns were reported for secondary outcomes, highlighting reduced neonatal morbidity among preterm infants with ACS exposure.

“These findings may have important clinical implications for practice, including the administration of ACS even when preterm birth is imminent, and the decision and timing of a repeat course of ACS in centers where repeat courses are considered,” wrote investigators.

References

1. Melamed N, Murphy KE, Pylypjuk C, et al. Timing of antenatal corticosteroid administration and neonatal outcomes. JAMA Netw Open. 2025;8(5):e2511315. doi:10.1001/jamanetworkopen.2025.11315
2. Crowley PA. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol. 1995;173(1):322-35. doi:10.1016/0002-9378(95)90222-8