Association between Use of Prophylactic Indomethacin and the Risk for Bronchopulmonary Dysplasia in Extremely Preterm Infants

Abstract

Objective: To assess the association between prophylactic indomethacin and bronchopulmonary dysplasia (BPD) in a recent, large cohort of extremely preterm infants.

Study design: Retrospective cohort study using prospectively collected data for infants with gestational ages < 29 weeks or birth weights of 401-1000 g born between 2008 and 2012 at participating hospitals of the National Institute of Child Health and Human Development Neonatal Research Network. Infants treated with indomethacin in the first 24 hours of life were compared with those who were not. Study outcomes were BPD, defined as use of supplemental oxygen at 36 weeks postmenstrual age among survivors to that time point, death, and the composite of death or BPD. Prespecified subgroup analyses were performed.

Results: Prophylactic indomethacin use varied by hospital. Treatment of a patent ductus arteriosus after the first day of life was less common among 2587 infants who received prophylactic indomethacin compared with 5244 who did not (21.0% vs 36.1%, P < .001). After adjustment for potential confounders, use of prophylactic indomethacin was not associated with higher or lower odds of BPD (OR 0.89, 95% CI 0.72-1.10), death (OR 0.80, 95% CI 0.64-1.01), or death or BPD (OR 0.87, 95% CI 0.71-1.05). The only evidence of subgroup effects associated with prophylactic indomethacin were lower odds of death among infants with birth weights above the 10th percentile and those who were not treated for a patent ductus arteriosus after the first day of life.

Conclusions: Prophylactic indomethacin was not associated with either reduced or increased risk for BPD or death.

Trial registration: ClinicalTrials.gov: NCT00063063.

Keywords: bronchopulmonary dysplasia; extreme prematurity; indomethacin; prophylaxis.

Figure 1

Flow diagram of the infants included in the analysis and those alive at 36 weeks postmenstrual age (PMA) and assessed for the primary study outcome.

Figure 2

Proportion of infants treated with prophylactic indomethacin at each of the 35 study hospitals.

Figure 3. BPD among survivors to 36 weeks postmenstrual age

Unadjusted rates and risk-adjusted odds ratios for the full cohort and 5 infant subgroups are shown. n indicates the number of infants with the outcome and N indicates the total number of infants in each group. OR indicates odds ratio. CI indicates confidence interval. Odds ratios were determined with adjustment for hospital as a random affect and birth weight, gestational age, sex, birth weight < 10^th percentile for sex and gestational age, maternal gestational hypertension, antenatal antibiotic exposure, antenatal corticosteroid exposure, rupture of amniotic membranes for greater than 18 hr, cesarean delivery, intubation or cardiopulmonary resuscitation in the delivery room, and invasive mechanical ventilation at 24hr of life as fixed effects.