Can prenatal conditions impact the effect of omega-3 on bronchopulmonary dysplasia in very preterm infants? A secondary analysis of a randomized controlled trial.

To explore whether prenatal conditions (i.e. chorioamnionitis, preeclampsia or small-for-gestational age (SGA)) affect the very preterm infant's response to docosahexaenoic acid (DHA) on bronchopulmonary dysplasia (BPD), according to mode of delivery, an independent factor shown to modulate this association. Secondary exploratory analysis of the MOBYDIck randomized controlled trial (NCT02371460) evaluating the effect of a neonatal high-dose DHA supplementation through maternal breastmilk compared to placebo. Population was preterm infants born before 29 weeks of gestation in sixteen Canadian neonatal intensive care units. Primary outcome was physiological BPD based on pulse oximetry assessment. Secondary outcomes included "death or BPD"; "moderate-or-severe" BPD; severe BPD; death from any causes. Heterogeneity in the effect of DHA on outcomes was assessed by prenatal conditions and mode of delivery using generalized estimating equation logistic regression models. The trial intended to enroll 800 mothers but was stopped early for safety, likely making subgroup analysis underpowered. 230 mothers (271 infants) were included in DHA group and 226 mothers (252 infants) in placebo group. The association between high-dose DHA and BPD differed by chorioamnionitis status (heterogeneity P=0.04). In infants exposed to chorioamnionitis and vaginal delivery, DHA supplementation was associated with a reduced risk of physiological BPD (adjusted odds ratio, 0.18 [95% CI, 0.05 to 0.62], P=0.007). No heterogeneity was found by maternal preeclampsia (heterogeneity P=0.44) nor SGA status (heterogeneity P=0.17).

Conclusion: This secondary analysis generated hypotheses for a potential differential effect of neonatal enteral high-dose DHA supplementation on BPD in very preterm infants according to chorioamnionitis exposure.

What is known: • The MOBYDIck trial reported a potential protective effect of docosahexaenoic acid (DHA) supplementation on bronchopulmonary dysplasia (BPD) in infants born vaginally, but not in those born via cesarean section. • Placenta pathologies are associated with inflammation in the infants and could affect the very preterm infant's response to a high-dose DHA supplementation on BPD according to the mode of delivery.

What is new: • This study suggests that, in infants born very preterm before 29 weeks of gestation, the association between enteral high-dose DHA supplementation in neonatal period and BPD at 36 weeks' postmenstrual age differ according to the maternal status for chorioamnionitis at delivery.