Preeclampsia, Fetal Growth Restriction, and 24-Month Neurodevelopment in Very Preterm Infants

Importance Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized. Objective To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants. Design, Setting, and Participants In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care units (NICUs). Eligible infants were born before 30 weeks’ gestation. Infants were excluded for any major congenital anomalies and for maternal age younger than 18 years or cognitive impairment impacting the ability to provide informed consent. Data analysis was performed from November 2023 to January 2024. Exposure Maternal preeclampsia and FGR in very preterm infants. Main Outcomes and Measures The Bayley-III cognition, motor, and language scores less than 85 (−1 SD) indicated developmental delay. Child Behavior Checklist/Preschool 1.5-5 T-scores greater than or equal to 64 for internalizing, externalizing, or total problems indicated clinical importance. Results Of 704 infants enrolled, 529 (mean [SD] gestational age, 27.0 [1.9] weeks; 287 male [54.3%]) were studied at 24-month follow-up. A total of 94 infants’ mothers had preeclampsia (23.2%), and 46 infants (8.7%) had FGR. In adjusted models, preeclampsia was not associated with Bayley-III (cognitive, B = 3.43 [95% CI, −0.19 to 6.66]; language, B = 3.92 [95% CI, 0.44 to 7.39]; motor, B = 1.86 [95% CI, −1.74 to 5.47]) or Child Behavior Checklist/Preschool 1.5-5 (internalizing, B = −0.08 [95% CI, −2.58 to 2.73]; externalizing, B = 0.69 [95% CI, −1.76 to 3.15]; total, B = 0.21 [95% CI, −2.48 to 2.91]) outcomes. FGR was associated with significantly lower Bayley-III scores (cognitive, B = −8.61 [95% CI, −13.33 to −3.89]; language, B = −8.29 [95% CI, −12.95 to −3.63]; motor, B = −7.60 [95% CI, −12.40 to −2.66]), regardless of preeclampsia status. Conclusions and Relevance In this cohort study of preterm infants, preeclampsia was not associated with developmental and/or behavioral outcomes, but infants with FGR may be prone to developmental delays. These findings suggest future areas of research for understanding the roles of preeclampsia and FGR separately and together in early child development for preterm infants.