Impaired Fetal Growth Mediates the Association Between Hypertensive Disorders of Pregnancy and Neurodevelopment in Extremely Preterm Infants

Abstract Objective: To evaluate the association between hypertensive disorders of pregnancy (HDP) and neurodevelopmental outcomes in extremely preterm (EPT) infants and determine whether fetal growth mediates this relationship. Study Design: Retrospective multicenter cohort study of infants born at 22 0⁄7–26 6⁄7 weeks’ gestation within the NICHD Neonatal Research Network (2012–2019). HDP was defined as maternal hypertension before/during pregnancy. Primary outcome was Bayley-3 cognitive composite score at 22–26 months corrected age; secondary outcomes included language, motor, and composite death/neurodevelopmental impairment (NDI). Multivariable regression adjusted for maternal, perinatal, and socioeconomic confounders. Mediation analyses evaluated mediating role of birth weight Z-scores and gestational age. Results: Among 4,712 infants, 1,178 (25%) were HDP-exposed. HDP exposure was associated with lower cognitive, language, and motor scores, and higher odds of death/NDI. Birth weight Z-scores mediated ~65% of this relationship. Conclusions: HDP exposure was associated with adverse neurodevelopment in EPT infants, largely mediated through impaired fetal growth.