Antenatal Corticosteroids and Bronchopulmonary Dysplasia in Very Preterm Infants

Abstract

Importance: The impact of antenatal corticosteroids (ACS) on bronchopulmonary dysplasia (BPD) in very preterm infants remains controversial, with limited evidence on causal mediation pathways.

Objective: To evaluate the association between ACS and BPD in very preterm infants and assess whether respiratory distress syndrome (RDS) and invasive mechanical ventilation (IMV) have mediating roles.

Design, setting, and participants: This prospective multicenter cohort study included preterm infants from 28 tertiary centers in China between September 1, 2019, and December 31, 2020. Inclusion criteria were gestational age (GA) less than 30 weeks, admission to the neonatal intensive care unit with 24 hours of birth, and neonatal hospitalization for more than 2 weeks. Analysis was done from April 1 to May 1, 2025.

Exposure: Complete or incomplete ACS courses (vs no ACS).

Main outcomes and measures: The primary outcome was moderate-to-severe BPD (using National Institute of Child Health and Human Development 2001 criteria) assessed at corrected GA of 36 weeks. Secondary outcomes were severe RDS (grade 3-4) and IMV duration. Regression models adjusted for demographic, pregnancy, and birth characteristics.

Results: A total of 1097 preterm infants were enrolled, with median gestational age of 28.71 weeks (IQR, 27.71-29.29 weeks), median birth weight of 1150 g (IQR, 1000-1310 g), and median IMV duration of 2.0 days (IQR, 0.0-7.0 days). Of 1075 infants with available sex data, 599 (56%) were males. A total of 1069 infants had known ACS data; ACS were given in 832 cases (78%), with 518 (48%) receiving complete courses. Moderate-to-severe BPD occurred in 309 of 1097 infants (28%) and severe RDS in 237 of 1085 (22%). Complete ACS courses showed negative associations with risk of moderate-to-severe BPD (adjusted risk ratio [ARR], 0.68; 95% CI, 0.55-0.84), severe RDS (ARR, 0.67; 95% CI, 0.51-0.88), and IMV duration (β, -2.003; 95% CI, -3.391 to -0.614). Significant associations with lower BPD risk were observed in infants with GA of 28 weeks to 28 weeks 6 days (ARR, 0.47; 95% CI, 0.29-0.74), singletons (ARR, 0.67; 95% CI, 0.50-0.88), and vaginal deliveries (ARR, 0.62; 95% CI, 0.46-0.83). Mediation analysis suggested that ACS was associated with reduced risk of BPD (β, -0.050; 95% CI, -0.081 to -0.017) through direct (β, -0.031; 95% CI, -0.061 to -0.001) and indirect (β, -0.019; 95% CI, -0.032 to -0.007) effects, with the latter comprising both single and serial mediation pathways.

Conclusions and relevance: In this cohort study of preterm infants, complete ACS courses in high-risk pregnancies were associated with a reduction in neonatal BPD, potentially mediated through multifactorial pathways. Emphasizing the importance of timely ACS completion and postnatal airway management may help optimize neonatal pulmonary outcomes.

Figure 1.. Mediation Analysis of Association Between Antenatal Corticosteroids and Bronchopulmonary Dysplasia

The directed acyclic graph illustrates the mediation pathway for the association of antenatal corticosteroids (exposure) with bronchopulmonary dysplasia (outcome), mediated through respiratory distress syndrome (RDS) and duration of invasive mechanical ventilation (IMV). Total effect size represents the overall association, partitioned into direct effect (exposure to the outcome independent of mediators) and indirect effect (exposure to the outcome mediated through RDS and IMV duration). GA indicates gestational age; GD, gestational diabetes; HDCP, hypertensive disorder complicating pregnancy; SGA, small for gestational age.

Figure 2.. Association of Incomplete and Complete Courses of Antenatal Corticosteroids (ACS) With Bronchopulmonary Dysplasia (BPD) in Very Preterm Infants Stratified by Demographic Variables

The reference category was no ACS. 95% CIs are presented without adjustment for multiple comparisons. P values were adjusted using the Hochberg step-up procedure to control the false discovery rate across 9 prespecified subgroup tests (singleton pregnancy, GA of 28 weeks to 28 weeks 6 days, vaginal delivery, female sex, GA of 29 weeks to 29 weeks 6 days, male sex, plurality pregnancy, cesarean delivery, and GA less than 28 weeks). ARR indicates adjusted risk ratio.