Association of time of first corticosteroid treatment with bronchopulmonary dysplasia in preterm infants

Abstract

Objective: To evaluate the association between the time of first systemic corticosteroid initiation and bronchopulmonary dysplasia (BPD) in preterm infants.

Study design: A multi-center retrospective cohort study from January 2010 to December 2016 using the Children's Hospitals Neonatal Database and Pediatric Health Information System database was conducted. The study population included preterm infants <32 weeks' gestation treated with systemic corticosteroids after 7 days of age and before 34 weeks' postmenstrual age. Stepwise multivariable logistic regression was used to assess the association between timing of corticosteroid initiation and the development of Grade 2 or 3 BPD as defined by the 2019 Neonatal Research Network criteria.

Results: We identified 598 corticosteroid-treated infants (median gestational age 25 weeks, median birth weight 760 g). Of these, 47% (280 of 598) were first treated at 8-21 days, 25% (148 of 598) were first treated at 22-35 days, 14% (86 of 598) were first treated at 36-49 days, and 14% (84 of 598) were first treated at >50 days. Infants first treated at 36-49 days (aOR 2.0, 95% CI 1.1-3.7) and >50 days (aOR 1.9, 95% CI 1.04-3.3) had higher independent odds of developing Grade 2 or 3 BPD when compared to infants treated at 8-21 days after adjusting for birth characteristics, admission characteristics, center, and co-morbidities.

Conclusions: Among preterm infants treated with systemic corticosteroids in routine clinical practice, later initiation of treatment was associated with a higher likelihood to develop Grade 2 or 3 BPD when compared to earlier treatment.

Keywords: CHNC; chronic lung disease; dexamethasone; hydrocortisone; prematurity.

Figure 1.. Flow of participants.

Figure 2.. Breakdown of corticosteroid use in each steroid initiation group.

Hydrocortisone use (shown in orange) was most common in the 8–21 days group and decreased in frequency with subsequent steroid initiation groups. Dexamethasone (shown in blue) was less commonly used at 8–21 days but was increasingly utilized in subsequent postnatal age groups.

Figure 3.. BPD rates between steroid initiation groups.

Stacked column plot comparing BPD rates between different steroid initiation groups broken down by severity. Grade 2 BPD (shown in blue) was lower in the 22–35 days group compared to the 36–49 days group (23% vs 46%, P<0.001), while Grade 3 BPD (shown in orange) was lower in the 8–21 days group compared to the ≥50 days group (13% vs 27%, P=0.004). Bonferonni-corrected alpha level of 0.008 (0.5/6) was used to determine significance.

Figure 4.. Comparison of BPD rates, ventilator days, and steroid initiation by center.

Shown are scatter plots of center proportion for steroid initiation after 35 days of life plotted against (A) center proportion of Grade 2 or 3 BPD and (B) center median ventilator days. Each bubble represents a center, and the size of the bubble is representative of the number of infants from that center.