Project Summary Marijuana is the most commonly used drug during pregnancy with an estimated use prevalence of 7%, and reaching as high as 25% in high risk groups. Marijuana components and metabolites cross the placenta and may impact maternal and neonatal outcomes. Recently, the National Academy of Sciences found substantial evidence linking prenatal marijuana use to lower birth weight and insufficient evidence to evaluate other pregnancy outcomes. These findings highlight a critical knowledge gap. With increasing legalization of marijuana in the United States, higher quality data about the risks of marijuana use during pregnancy are desperately needed. Prior studies are limited both by reliance on self-report rather than biologic sampling, and lack of adjustment for important confounders. The result is ongoing uncertainty regarding the effect of marijuana use on perinatal outcomes. The proposed observational study uses existing data and biospecimens from the nationwide NICHD-sponsored Monitoring Mothers-to-Be Network (nuMOM2b). We hypothesize that marijuana use during pregnancy will be associated with an increase in adverse perinatal outcomes independent of tobacco, other drug use, and sociodemographic factors. Our specific aims are to: (1) Determine if exposure to marijuana is associated with adverse perinatal outcomes. We will use existing data and banked specimens from 9,260 nulliparous women enrolled in nuMoM2b to ascertain marijuana use by both self-report and serial biological sampling. We will assay stored urine samples from throughout pregnancy for biomarkers of marijuana exposure, cotinine and other drugs. Our primary outcome is a composite of adverse outcomes reflecting placental insufficiency: fetal growth restriction, medically-indicated preterm birth, stillbirth and hypertensive disorders including preeclampsia and gestational hypertension. (2) Evaluate whether there is a critical window of exposure or a threshold “dose” of exposure associated with adverse perinatal outcomes. We will use advanced statistical modeling to clarify the effects of marijuana exposure on each component of the outcome, and evaluate for critical windows of exposure. We will separately examine associations between our outcomes and four quantified biomarkers of marijuana exposure, using a novel umbilical cord assay. (3) Evaluate the agreement between different measures of prenatal marijuana use including umbilical cord assay, serial urine assays and maternal self-report. As marijuana legalization expands, rigorous observational studies such as this are urgently needed to understand the impact of perinatal marijuana use. These findings could immediately be used in clinical practice to counsel women regarding the anticipated effects of prenatal marijuana use. Together these aims will answer key questions regarding marijuana exposure and perinatal outcomes using highly leveraged existing data and biospecimens, thereby overcoming limitations that have previously h...