TOPLINE:

Antenatal corticosteroid (ACS) courses administered before delivery in pregnancies at high risk for preterm birth were associated with a reduced risk for moderate-to-severe bronchopulmonary dysplasia (BPD) in very preterm infants, with complete courses offering greater protection.

METHODOLOGY:

• Researchers conducted a prospective, multicenter cohort study to evaluate the association between ACS exposure and BPD in very preterm infants and to assess the potential mediating effects of respiratory distress syndrome and invasive mechanical ventilation.
• They enrolled 1097 preterm infants (median gestational age, 28.71 weeks; 44% girls among those with known sex) who were admitted to an NICU within 24 hours of birth and hospitalized for more than 2 weeks.
• ACS exposure was classified as a complete course (two doses of betamethasone or four doses of dexamethasone administered ≥ 24 hours before delivery), an incomplete course (1-2 doses of betamethasone or 1-4 doses of dexamethasone given < 24 hours before delivery), or no ACS.
• The primary outcome was moderate-to-severe BPD at 36 weeks’ corrected gestational age, as per standard BPD severity criteria; BPD was defined as oxygen dependence for ≥ 28 days.
• Secondary outcomes were severe respiratory distress syndrome and the duration ofinvasive mechanical ventilation.

TAKEAWAY:

• Complete ACS courses were associated with a lower risk for moderate-to-severe BPD than no ACS (adjusted risk ratio [aRR], 0.68; P = .02); incomplete ACS courses showed a smaller protective association (aRR, 0.78; P = .04).
• Compared with no ACS, complete ACS courses were linked with a lower risk for severe respiratory distress syndrome (aRR, 0.67; P = .002) and with a reduction in the duration of invasive mechanical ventilation (beta-coefficient = -2.003; P < .001).
• The protective association of complete ACS courses was strongest among singleton infants (P = .004), those born at 28+0 to 28+6 weeks’ gestation (P = .01), and those delivered vaginally (P = .01).
• Mediation analysis indicated that ACS reduced the risk for BPD through both a direct pathway (62%) and indirect pathways (38%) — by lowering the risk for severe respiratory distress syndrome or reducing the duration of invasive mechanical ventilation and through a combined pathway linking both.

IN PRACTICE:

“Emphasizing the importance of timely ACS completion and postnatal airway management may help optimize neonatal pulmonary outcomes,” the authors wrote.

“[The study] provides, however, a significant contribution in clarifying the mechanisms of action of ACS at a population level (the why),” experts wrote in a commentary accompanying the journal article.

SOURCE:

This study was led by Liang Gao, MM, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China. It was published online on November 26, 2025, in JAMA Network Open.

LIMITATIONS:

Residual confounding from unmeasured factors may have persisted despite adjustment. The observational design precluded causal inference, even with mediation analyses. The small number of extremely preterm infants may have masked ACS effects in this high-risk group.

DISCLOSURES:

This study was supported by multiple organizations, including the Guidance Project of Xiamen Science and Technology Plan, the Fujian Provincial Natural Science Foundation of China, the Fujian Provincial Health Technology Project, and the Key Project of Xiamen Science and Technology Plan. Two authors reported receiving grants from these funders.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.