Antipsychotic use in pregnancy and risk of attention/deficit-hyperactivity disorder and autism spectrum disorder: a Nordic cohort study.

IF 11.4 2区医学 Q1 PSYCHIATRY

Evidence Based Mental Health Pub Date : 2022-05-01 Epub Date: 2021-11-22 DOI:10.1136/ebmental-2021-300311

Óskar Hálfdánarson, Jacqueline M Cohen, Øystein Karlstad, Carolyn E Cesta, Marte-Helene Bjørk, Siri Eldevik Håberg, Kristjana Einarsdóttir, Kari Furu, Mika Gissler, Vidar Hjellvik, Helle Kieler, Maarit K Leinonen, Mette Nørgaard, Buket Öztürk Essen, Sinna Pilgaard Ulrichsen, Johan Reutfors, Helga Zoega

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引用次数: 6

Abstract

Background: Antipsychotics are increasingly used among women of childbearing age and during pregnancy.

Objective: To determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), accounting for maternal diagnoses of bipolar, psychotic and other psychiatric disorders. Design Population-based cohort study, including a sibling analysis. Setting Nationwide data on all pregnant women and their live-born singletons in Denmark (1997-2017), Finland (1996-2016), Iceland (2004-2017), Norway (2004-2017), and Sweden (2006-2016). Participants 4 324 086 children were eligible for inclusion to the study cohort. Intervention Antipsychotic exposure in utero, assessed by pregnancy trimester, type of antipsychotic, and varying patterns of use. Main outcome measures Non-mutually exclusive diagnoses of ADHD and ASD. We used Cox proportional hazard models to calculate hazard ratios (HRs) controlling for maternal psychiatric disorders and other potential confounding factors.

Findings: Among 4 324 086 singleton births, 15 466 (0.4%) were exposed to antipsychotics in utero. During a median follow-up of 10 years, we identified 72 257 children with ADHD and 38 674 children with ASD. Unadjusted HRs were raised for both outcomes but shifted substantially towards the null after adjustment; 1.10 (95%CI 1.00 to 1.27) for ADHD and 1.12 (0.97 to 1.29) for ASD. Adjusted HRs remained consistent by trimester of exposure and type of antipsychotic. Comparing in utero exposure with pre-pregnancy use yielded HRs of 0.74 (0.62 to 0.87) for ADHD and 0.88 (0.70 to 1.10) for ASD. Sibling analyses yielded HRs of 1.14 (0.79 to 1.64) for ADHD and 1.34 (0.75 to 2.39) for ASD.

Discussion: Our findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics.

Clinical implications: Results regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy.

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妊娠期使用抗精神病药物与注意/缺陷-多动障碍和自闭症谱系障碍的风险:北欧队列研究

背景:抗精神病药物越来越多地用于育龄妇女和怀孕期间。目的:考虑到母亲诊断为双相情感障碍、精神病和其他精神疾病，确定在子宫内暴露于抗精神病药物的儿童患注意力缺陷/多动障碍(ADHD)或自闭症谱系障碍(ASD)的风险是否增加。设计基于人群的队列研究，包括兄弟姐妹分析。丹麦(1997-2017年)、芬兰(1996-2016年)、冰岛(2004-2017年)、挪威(2004-2017年)和瑞典(2006-2016年)所有孕妇及其活产单胎的全国数据。4 324 086名儿童符合纳入研究队列的条件。干预措施:子宫内抗精神病药物暴露，根据妊娠三个月、抗精神病药物类型和不同的使用模式进行评估。主要结果测量ADHD和ASD的非互斥诊断。我们使用Cox比例风险模型来计算控制产妇精神疾病和其他潜在混杂因素的风险比(hr)。结果:在4 324 086例单胎分娩中，15 466例(0.4%)在子宫内接触过抗精神病药物。在中位随访10年期间，我们确定了72 257名ADHD儿童和38 674名ASD儿童。两种结果的未经调整的hr均有所提高，但调整后显著向零转移;ADHD为1.10 (95%CI 1.00 ~ 1.27)， ASD为1.12 (95%CI 0.97 ~ 1.29)。调整后的hr在暴露的三个月和抗精神病药物类型之间保持一致。将子宫内暴露与孕前使用相比，ADHD的hr为0.74(0.62至0.87)，ASD的hr为0.88(0.70至1.10)。兄弟姐妹分析显示ADHD的hr为1.14 (0.79 - 1.64)，ASD的hr为1.34(0.75 - 2.39)。讨论:我们的研究结果表明，在子宫内暴露于抗精神病药物后，儿童ADHD或ASD的风险很少或没有增加。临床意义:关于儿童神经发育的研究结果让怀孕期间需要抗精神病药物的妇女感到放心。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Evidence Based Mental Health PSYCHIATRY-

CiteScore

18.10

自引率

7.70%

发文量

期刊介绍： Evidence-Based Mental Health alerts clinicians to important advances in treatment, diagnosis, aetiology, prognosis, continuing education, economic evaluation and qualitative research in mental health. Published by the British Psychological Society, the Royal College of Psychiatrists and the BMJ Publishing Group the journal surveys a wide range of international medical journals applying strict criteria for the quality and validity of research. Clinicians assess the relevance of the best studies and the key details of these essential studies are presented in a succinct, informative abstract with an expert commentary on its clinical application.Evidence-Based Mental Health is a multidisciplinary, quarterly publication.