Long-Term Neurodevelopmental Follow-up of Children Exposed to Pravastatin in-Utero

Document Type

Journal Article

Publication Date



American journal of obstetrics and gynecology




fetal programming; neonatal safety; neurobehavior; neurodevelopment; neuromotor; pravastatin; preeclampsia


BACKGROUND: Preeclampsia, especially when preterm, increases 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-Obstetrics Fetal Pharmacology Research Centers Network support the safety and utility of pravastatin to prevent preeclampsia. OBJECTIVE: To determine the effect of antenatal pravastatin treatment in high-risk pregnant individuals on their child's health, growth, and neurodevelopment. STUDY DESIGN: We conducted an ancillary follow-up cohort study of children born to mothers who participated in the Obstetrics 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 assessment using validated tools. Given the small numbers of individuals in the studies, the 10 and 20mg of pravastatin were combined into one group and compared with those in the placebo group. RESULTS: Out of the 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 [2.5-6.9] years, was not different between those in the pravastatin or placebo groups. There were no differences in child's body mass index percentiles per sex and corrected age, rates of extremes of body mass index percentiles or the report of any other medical or developmental complications between the two groups. No child born in the pravastatin group had any limitation in motor assessment compared with two (13.3%) children who walked with difficulty and four (26.7%) children who had reduced manual abilities in the placebo group. Moreover, children born to mothers who received pravastatin had non-significant higher general mean conceptual ability score (98.2 ± 16.7 vs. 89.7 ± 11.0, p=0.13) and a non-significant lower frequency (15.4% vs. 35.7%, p=0.38) of having a score below 85 (i.e., one standard deviation lower than the mean) compared with those in the placebo group. Lastly, there no significant differences in the parents' report on the Child Behavior Checklist between the two groups. CONCLUSIONS: To our knowledge, this is the first report on the long-term neuromotor, cognitive, and behavioral outcomes among children exposed to pravastatin in-utero during the 2 and 3 trimesters of pregnancy. Although the data are 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.