Neonatal outcomes of preterm infants with pulmonary hypertension: clustering based on prenatal risk factors.

Background: To investigate association of prenatal risk factors and neonatal outcomes of preterm infants with pulmonary hypertension (PH).

Methods: A prospective cohort study of very-low-birth-weight infants born at 22-29 weeks' gestation who received PH-specific treatment during hospitalization. Infants were classified using a two-step cluster analysis based on gestational age (GA), small-for-gestational-age (SGA), exposure to antenatal corticosteroids (ACS), histologic chorioamnionitis (HCA), and oligohydramnios.

Results: Among 910 infants, six clusters were identified: cluster A (HCA, n = 240), cluster B (oligohydramnios, n = 79), cluster C (SGA, n = 74), cluster D (no-ACS, n = 109), cluster E (no dominant parameter, n = 287), and cluster F (HCA and oligohydroamnios, n = 121). Cluster A was used as a reference group for comparisons among clusters. Compared to cluster A, cluster C (aHR: 1.63 [95% CI: 1.17-2.26]) had higher risk of overall in-hospital mortality. Clusters B (aHR: 1.52 [95% CI: 1.09-2.11]), D (aHR: 1.71 [95% CI: 1.28-2.30]), and F (aHR: 1.51 [95% CI: 1.12-2.03]) had higher risks of receiving PH-specific treatment within the first week of birth compared to cluster A.

Conclusion: These findings may provide a better understanding of prenatal risk factors contributing to the development of PH.

Impact: Pulmonary hypertension (PH), presenting as hypoxic respiratory failure, has complex etiologies in preterm infants. Although multifactorial risks for the development of PH in preterm infants are known, few studies have classified infants with similar etiologies for PH. Each cluster has distinct patterns of prenatal condition and neonatal outcome.