Maternal antiepileptic drug use during pregnancy and offspring birth defects and neurodevelopmental disorders

母亲妊娠期间使用抗癫痫药物及后代出生缺陷和神经发育障碍

• 批准号: 10051330
• 负责人: Kelsey Kathleen Wiggs
• 金额: $ 3.31万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2021-07-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10051330
• 关键词: Animal Model; Animals; Antiepileptic Agents; Attention deficit hyperactivity disorder; Basic Science; Behavior; Benefits and Risks; Birth; Brain; Carbamazepine; Characteristics; Child; Clinical; Congenital Abnormality; Data Set; Development; Diagnosis; Drug Exposure; Drug usage; Environmental Risk Factor; Epidemiologic Methods; Epilepsy; Ethics; Etiology; Evidence based intervention; Exposure to; Fetal health; Fetus; Functional disorder; Genetic; Genetic Risk; Goals; Guidelines; Human; Individual; Investigation; Link; Maternal Health; Measures; Mental disorders; Methods; Modeling; Mothers; Neurodevelopmental Disorder; Observational Study; Outcome; Perinatal; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacotherapy; Physicians; Placenta; Population; Population Registers; Practice Guidelines; Pregnancy; Pregnant Women; Process; Research; Resources; Risk; Risk Estimate; Risk Factors; Rodent; Role; Sampling; Seizures; Socioeconomic Factors; Sweden; Testing; Training; Weighing patient; Woman; Women' s Health; Work; adverse outcome; autism spectrum disorder; base; career; clinical care; clinical practice; clinically relevant; cohort; comparative safety; comparison group; conditioning; design; fetus at risk; genetic risk factor; high dimensionality; high risk; improved; lamotrigine; maternal condition; migration; nervous system disorder; neuronal growth; neuropsychopharmacology; offspring; premature; prenatal exposure; safety study; sociodemographic factors; socioeconomics; treatment guidelines; valproate

Project Summary Several observational studies have linked antiepileptic (AED) use during pregnancy to offspring birth defects (BDs) and neurodevelopmental disorders (NDDs), including attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Research in humans and animals suggest the associations might be causal, as there is evidence that AEDs cross the human placenta and animal models show aberrant brain development and behavior following exposure. However, important non-causal explanations for associations need to be ruled out before we can conclude that the association in humans is causal. Specifically, maternal indications for AED use (e.g., epilepsy), genetic factors (e.g., common to BDs, NDDs, and seizures), other environmental factors (e.g., socioeconomic resources), or a combination of these factors may explain the increased risk for BDs and NDDs in offspring after exposure to AED use. Understanding whether associations are causal is important for doctors and patients weighing the potential risks and benefits of AED use during pregnancy. Specifically, although AED exposure may harm the fetus, AED use is the primary treatment for epilepsy, and seizures during pregnancy put fetus and mother at risk. The objective of this proposal is to test the hypothesis that prenatal exposure to AEDs causes these outcomes. I will accomplish the objective of this proposal through the analysis of a large, national dataset from Sweden and pursuing two aims: (1) estimate the risk of BDs following AED use during pregnancy, and (2) estimate the risk of NDDs following AED use during pregnancy independent of confounding. In aim 1, I will leverage the largest sample to date to examine associations between AEDs and offspring BDs. I will do this by comparing exposed and unexposed offspring of women with epilepsy, while adjusting for many measured covariates that previous research has not accounted for. In aim 2, I will use marginal models (e.g., propensity score matching) and several comparison groups to help rule out alternative explanations for the associations. This proposal is significant because it will inform basic research investigating mechanisms for BDs and NDDs and best-practice guidelines for treatment during pregnancy. I am uniquely equipped to answer the question in this proposal because I will analyze the largest study to date (n = ~2.1 million), have access to combined Swedish registers with predictors spanning multiple domains and levels of analysis, and will use multiple advanced designs to test causal inferences. This proposal also weaves together my previous work in which I have investigated pre- and perinatal risk factors for NDDs and used pharmaco-epidemiologic approaches to investigate the risks for seizures. This project will facilitate my long-term training goal to develop a career researching risk factors for NDDs, including extensive training in epidemiologic methods, women’s health and neuropsychopharmacology, the etiology and assessment of NDDs, and professional development (e.g., training in ethics and dissemination).

项目总结

项目成果

A nationwide study of initiation of antidepressant pharmacotherapy and the risk of seizures.

一项关于开始抗抑郁药物治疗和癫痫发作风险的全国性研究。

• DOI: 10.1016/j.eplepsyres.2023.107134
• 发表时间: 2023
• 期刊: Epilepsy research
• 影响因子: 2.2
• 作者: Wiggs,KelseyK;Lagerberg,Tyra;Quinn,PatrickD;Öberg,ASara;Larsson,Henrik;Chang,Zheng;D'Onofrio,BrianM
• 通讯作者: D'Onofrio,BrianM

Antiseizure medication use during pregnancy and risk of ASD and ADHD in children.

• DOI: 10.1212/wnl.0000000000010993
• 发表时间: 2020-12-15
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Wiggs KK;Rickert ME;Sujan AC;Quinn PD;Larsson H;Lichtenstein P;Oberg AS;D'Onofrio BM
• 通讯作者: D'Onofrio BM

Maternal Serotonergic Antidepressant Use in Pregnancy and Risk of Seizures in Children.

孕产妇血清素能在妊娠中使用抗抑郁药和儿童癫痫发作的风险。

• DOI: 10.1212/wnl.0000000000200516
• 发表时间: 2022-06-06
• 期刊: Neurology
• 影响因子: 9.9