Background Preeclampsia complicates approximately 3% to 5% of pregnancies and remains a major cause of maternal and neonatal morbidity and mortality. It shares pathogenic similarities with adult cardiovascular disease as well as many risk factors. Pravastatin, a hydrophilic, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, has been shown in preclinical studies to reverse various pathophysiological pathways associated with preeclampsia, providing biological plausibility for its use for preeclampsia prevention. However, human trials are lacking. Objective As an initial step in evaluating the utility of pravastatin in preventing preeclampsia, and after consultation with the U.S. Food and Drug Administration, we undertook a pilot randomized controlled trial with the objective to determine pravastatin safety and pharmacokinetic parameters when used in pregnant women at high risk of preeclampsia. Study Design We conducted a pilot, multicenter, double-blind, placebo-controlled, randomized trial of women with singleton, non-anomalous pregnancies at high risk for preeclampsia. Women between 120/7 and 166/7 weeks gestation were assigned to daily pravastatin 10 mg or placebo orally until delivery. Primary outcomes were maternal-fetal safety and pharmacokinetic parameters of pravastatin during pregnancy. Secondary outcomes included rates of preeclampsia and preterm delivery, gestational age at delivery, birthweight, and maternal and cord blood lipid profile (Clinicaltrials.gov Identifier NCT01717586). Results Ten women assigned to pravastatin and ten to placebo completed the trial. There were no differences between the two groups in rates of study drug side effects, congenital anomalies, or other adverse or serious adverse events. There was no maternal, fetal, or neonatal death. Pravastatin renal clearance was significantly higher in pregnancy compared to postpartum. Four subjects in the placebo group developed preeclampsia compared to none in the pravastatin group. Although pravastatin reduced maternal cholesterol concentrations, umbilical cord cholesterol concentrations and infant birthweight were not different between the groups. The majority of umbilical cord and maternal pravastatin plasma concentrations at time of delivery were below the lower limit of quantification of the assay. Conclusions This study provides preliminary safety and pharmacokinetic data regarding the use of pravastatin for preventing preeclampsia in high-risk pregnant women. Although the data are preliminary, no identifiable safety risks were associated with pravastatin use in this cohort. This favorable risk-benefit analysis justifies using pravastatin in a larger clinical trial with dose escalation.

In April 2016, the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited experts to a workshop to address numerous knowledge gaps and to review the evidence for the screening and management of opioid use in pregnancy and neonatal abstinence syndrome. The rising prevalence of opioid use in pregnancy has led to a concomitant dramatic fivefold increase in neonatal abstinence syndrome over the past decade. Experts from diverse disciplines addressed research gaps in the following areas: 1) optimal screening for opioid use in pregnancy; 2) complications of pregnancy associated with opioid use; 3) appropriate treatments for pregnant women with opioid use disorders; 4) the best approaches for detecting, treating, and managing newborns with neonatal abstinence syndrome; and 5) the long-term effects of prenatal opioid exposure on children. Workshop participants identified key scientific opportunities to advance the understanding of opioid use disorders in pregnancy and to improve outcomes for affected women, their children, and their families. This article provides a summary of the workshop presentations and discussions.

(Abstracted from Obstet Gynecol 2017;130(1):10–28) This article provides a summary of the “Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes” workshop convened by the Eunice Kennedy Shriver National Institute of Child Health and Human Development on April 4 and 5, 2016, and cosponsored by the American College of Obstetricians and Gynecologists (ACOG), the American Academy of Pediatrics, the Society for Maternal-Fetal Medicine, the Centers for Disease Control and Prevention, and the March of Dimes. Expert speakers from diverse fields and workshop participants identified scientific opportunities to advance the understanding of opioid use disorders in pregnancy and to improve outcomes for affected women, their children, and their families.