Maternal Marijuana Use and Adverse Perinatal Outcomes

项目摘要 大麻是怀孕期间最常用的药物，估计使用率为7%，以及 在高危人群中高达25%。大麻成分和代谢物穿过胎盘 可能会影响产妇和新生儿的结局。最近，美国国家科学院发现了大量 将产前使用大麻与降低出生体重联系在一起的证据，以及评估其他 妊娠结局。这些发现突显了一个关键的知识鸿沟。随着毒品合法化程度的提高， 在美国，关于怀孕期间使用大麻风险的更高质量的数据是 迫切需要。 以前的研究都受到依赖自我报告而不是生物抽样的限制，而且缺乏对 重要的混杂因素。其结果是，关于大麻使用对围产儿的影响仍存在不确定性 结果。这项拟议的观察性研究使用了现有的数据和来自全国范围内的 NICHD赞助的准妈妈监测网络(NuMoM2B)。我们假设大麻的使用在 怀孕将与不良围产期结局的增加有关，不依赖于烟草，其他 吸毒和社会人口学因素。我们的具体目标是：(1)确定接触大麻是否 与不良的围产期结局有关。我们将使用现有的数据和9260份保存的样本 未分娩妇女参加nuMoM2B，通过自我报告和连续生物学来确定大麻使用情况 取样。我们将对怀孕期间储存的尿样进行大麻生物标志物的检测。 暴露、可替宁和其他药物。我们的主要结果是负面结果的组合，反映了 胎盘功能不全：胎儿生长受限、医学指征早产、死产和高血压 疾病包括先兆子痫和妊娠期高血压。(2)评估是否存在关键窗口 与不良围产期结局相关的暴露剂量或阈值暴露剂量。我们将使用 先进的统计模型，以澄清大麻暴露对结果的每个组成部分的影响， 并评估暴露的关键窗口。我们将分别检查我们的结果之间的关联 以及四个量化的大麻暴露生物标志物，使用一种新的脐带检测。(3)评估 产前使用大麻的不同措施之间的一致性，包括脐带检测、连续尿液 化验和母亲自我报告。 随着大麻合法化的扩大，迫切需要像这样的严格的观察性研究来 了解围产期使用大麻的影响。这些发现可以立即用于临床实践。 就产前使用大麻的预期影响向妇女提供咨询。这些目标合在一起将会回答 关于大麻暴露和围产期结局的关键问题，使用高度杠杆的现有数据和 因此，克服了以前阻碍这一领域研究的限制。

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 hindered research in this area.