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

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\u27s 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\u27s 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\u27s 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\u27 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\u27s 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

The moderating role of the built environment in prenatal lifestyle interventions

This study examined whether the neighborhood built environment moderated gestational weight gain (GWG) in LIFE-Moms clinical trials. Participants were 790 pregnant women (13.9 weeks’ gestation) with overweight or obesity randomized within four clinical centers to standard care or lifestyle intervention to reduce GWG. Geographic information system (GIS) was used to map the neighborhood built environment. The intervention relative to standard care significantly reduced GWG (coefficient = 0.05; p = 0.005) and this effect remained significant (p \u3c 0.03) after adjusting for built environment variables. An interaction was observed for presence of fast food restaurants (coefficient = −0.007; p = 0.003). Post hoc tests based on a median split showed that the intervention relative to standard care reduced GWG in participants living in neighborhoods with lower fast food density 0.08 [95% CI, 0.03,0.12] kg/week (p = 0.001) but not in those living in areas with higher fast food density (0.02 [−0.04, 0.08] kg/week; p = 0.55). Interaction effects suggested less intervention efficacy among women living in neighborhoods with more grocery/convenience stores (coefficient = −0.005; p = 0.0001), more walkability (coefficient −0.012; p = 0.007) and less crime (coefficient = 0.001; p = 0.007), but post-hoc tests were not significant. No intervention x environment interaction effects were observed for total number of eating establishments or tree canopy. Lifestyle interventions during pregnancy were effective across diverse physical environments. Living in environments with easy access to fast food restaurants may limit efficacy of prenatal lifestyle interventions, but future research is needed to replicate these findings