Impact of in utero Marijuana Exposure on Neurodevelopment, Behavior and Mental Health: A Longitudinal Birth Cohort Study

摘要 在美国，怀孕期间使用大麻的人数正在迅速增加。合法化的传播与成长 怀孕期间对大麻的接受、可及性和使用引发了对以下方面的重要公共卫生问题 孕妇作为我们对儿童发育、行为和心理健康影响的理解 在子宫内暴露于大麻是令人震惊的不足。为了解决这一关键的研究差距，我们提出了一种 凯撒永久医院2010-2021年间出生的42万多名儿童的纵向出生队列研究 北加州(KPNC)医院。我们将利用来自KPNC全面电子健康的数据 记录(EHR)和独特的普遍产前药物使用筛查计划，筛查40,000名妇女 每年通过“黄金标准”自我报告和尿毒学检测大麻和其他物质的使用情况。AS 作为标准护理的一部分，所有儿童在探视健康儿童时都会普遍接受发育迟缓筛查，并作为 随着年龄的增长，普遍的心理健康筛查可以捕捉到抑郁症和药物使用障碍。 将提供有关儿童神经发育、行为和心理健康筛查结果和诊断的信息 从KPNC的EHR并通过与加州发展服务部的联系确定。我们 将确定有关重要混杂因素的信息(例如，产妇精神健康、产妇年龄、烟草和 其他药物使用、早产)来自KPNC的EHR。单胎妊娠妇女所生子女 那些接受产前大麻和其他物质使用筛查的人将被包括在内。我们将评估 出生前接触大麻与神经发育障碍风险之间的关系 行为障碍和从出生到13岁的心理健康结果，在考虑了潜在的 混血儿。我们还将测试这些关联中的性别差异。其他分析将评估 母亲仅在怀孕期间对大麻筛查呈阳性的儿童的影响(即没有其他 产前物质使用)。拟议的研究利用了不同的人群，并具有高度的概括性， 将是迄今为止最大的一次。研究结果将对公共卫生和临床产生重大影响，并可用于 妇女在知情的情况下作出怀孕期间使用大麻的决定。此外，这项研究队列 将是未来研究产前使用大麻对健康的长期影响的宝贵资源 儿童健康。

ABSTRACT Marijuana use during pregnancy is increasing rapidly in the US. The spreading legalization and growing acceptance, accessibility, and use of marijuana during pregnancy raise important public health concerns for pregnant women as our understanding of the developmental, behavior, and mental health impacts on children exposed to marijuana in utero is alarmingly inadequate. To address this critical research gap, we propose a longitudinal birth cohort study of over 420,000 children born between 2010-2021 at Kaiser Permanente Northern California (KPNC) hospitals. We will leverage data from KPNC's comprehensive electronic health records (EHR) and unique universal prenatal drug use screening program which screens 40,000 women annually via “gold standard” self-report and urine toxicology tests for marijuana and other substance use. As part of standard care, all children are universally screened for developmental delays at well-child visits and as they grow older universal mental health screening captures depression and substance use disorders. Information on child neurodevelopment, behavior and mental health screening outcomes and diagnoses will be ascertained from KPNC's EHR and through linkage to California's Department of Developmental Services. We will ascertain information on important confounders (e.g., maternal mental health, maternal age, tobacco and other substance use, preterm delivery) from KPNC's EHR. Children born to women with singleton gestations who are screened for prenatal marijuana and other substance use will be included. We will evaluate associations between prenatal marijuana exposure and the risk of neurodevelopmental impairments, behavioral disorders, and mental health outcomes from birth to 13 years of age, after accounting for potential confounders. We will also test for sex differences in these associations. Additional analyses will assess the effects in children whose mothers screened positive for marijuana only during pregnancy (i.e., no other prenatal substance use). The proposed study leverages a diverse population, and with high generalizability, will be the largest to date. Findings will have significant public health and clinical implications and can be used by women to make informed decisions about marijuana use during pregnancy. Additionally, the study cohort will be a valuable resource for future research on the longer-term impact of prenatal marijuana use on children's health.