Long-term neurodevelopmental follow-up of children exposed to pravastatin in utero

BACKGROUND: Preeclampsia, especially before term, increases the risk of child neurodevelopmental adverse outcomes. Biological plausibility, preclinical studies, and pilot clinical trials conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Obstetric-Fetal Pharmacology Research Centers Network support the safety and use of pravastatin to prevent preeclampsia.

OBJECTIVE: This study aimed to determine the effect of antenatal pravastatin treatment in high-risk pregnant individuals on their child's health, growth, and neurodevelopment.

STUDY DESIGN: This was an ancillary follow-up cohort study of children born to mothers who participated in the Obstetric-Fetal Pharmacology Research Centers Network pilot trials of pravastatin vs placebo in individuals at high risk of preeclampsia (ClinicalTrials.gov; identifier NCT01717586). After obtaining written informed consent (and assent as appropriate), the parent was instructed to complete the Child Behavior Checklist. To assess the child's motor, cognitive, and developmental outcomes, a certified and blinded study psychologist completed child motor, cognitive, emotional, and behavioral assessments using validated tools. Given the small number of individuals in the studies, the 10- and 20-mg pravastatin groups were combined into 1 group, and the results of the pravastatin group were compared with that of the placebo group.

RESULTS: Of 40 children born to mothers in the original trial, 30 (15 exposed in utero to pravastatin and 15 to placebo) were enrolled in this follow-up study. The time of follow-up, which was 4.7 years (interquartile range, 2.5-6.9), was not different between children in the pravastatin group and children in the placebo group. There was no difference in the child's body mass index percentiles per sex and corrected age, the rates of extremes of body mass index percentiles, or the report of any other medical or developmental complications between the 2 groups. No child born in the pravastatin group had any limitation in motor assessment compared with 2 children (13.3%) who walked with difficulty and 4 children (26.7%) who had reduced manual abilities in the placebo group. Moreover, children born to mothers who received pravastatin had a higher general mean conceptual ability score (98.2±16.7 vs 89.7±11.0; P=.13) and a lower frequency (15.4% vs 35.7%; P=.38) of having a score of <85 (ie, 1 standard deviation lower than the mean) compared with those in the placebo group. Finally, there was no difference in the parents' report on the Child Behavior Checklist between the 2 groups.

CONCLUSION: This study reported on the long-term neuromotor, cognitive, and behavioral outcomes among children exposed to pravastatin in utero during the second and third trimesters of pregnancy. Although the data were limited by the original trial's sample size, no identifiable long-term neurodevelopmental safety signal was evident with the use of pravastatin during pregnancy. This favorable neonatal risk-benefit analysis justifies continued research using pravastatin in clinical trials.