Impact of placental pathology on the risk of bronchopulmonary dysplasia in preterm infants: The role of gestational age and sex.

To analyze the impact of placental histological findings on the development of bronchopulmonary dysplasia (BPD) in preterm infants, this prospective, observational, single-center study included infants born before 32 weeks of gestation between 2012 and 2023. Perinatal variables were collected and correlated with mortality at hospital discharge and the diagnosis of grade 2-3 BPD at 36 weeks postmenstrual age (PMA). Placental histology was categorized into three groups: inflammatory pathology, vascular malperfusion, and no pathology. A total of 1128 preterm infants were enrolled, with placental histology results available for 899 cases. Inflammatory placental pathology was associated with a lower gestational age (GA) at birth (- 1.4 weeks, 95% CI - 1.74 to - 1.11). The increased mortality linked to placental inflammation was no longer significant after adjusting for GA. In preterm infants born at 27 weeks' GA or later, the effect of vascular malperfusion on BPD showed sexual dimorphism. In males, placental malperfusion was associated with a 2.25-fold increased risk of developing BPD (95% CI 1.10 to 4.57), independent of GA and exposure to mechanical ventilation. No significant differences were observed in females born at 27 weeks or later.

Conclusions: The impact of placental histological abnormalities on BPD development is influenced by gestational age and sex. While placental inflammation increases mortality by triggering extremely preterm birth, it does not appear to increase respiratory morbidity compared to cases with normal placental histology at similar GAs. In males, however, placental malperfusion appears to affect lung development and contributes to BPD independently of GA and exposure to mechanical ventilation.

What is known: • Bronchopulmonary dysplasia (BPD) is a common respiratory complication among preterm infants, strongly influenced by prenatal events. • The placenta plays a crucial role in fetal lung development, and its analysis provides objective insight into antenatal conditions.

What is new: • Placental malperfusion affects lung development in a sex-specific manner, with male infants born at or after 27 weeks of gestation being more specifically affected and showing a higher susceptibility to BPD, independent of gestational age or mechanical ventilation. • These findings highlight the importance of considering sex differences in BPD pathophysiology and the role of placental pathology.