Boukhris Takoua, Sheehy Odile, Bérard Anick
Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
Research Center, CHU Sainte-Justine, Montreal, Quebec, Canada.
Paediatr Perinat Epidemiol. 2017 Jul;31(4):363-373. doi: 10.1111/ppe.12378. Epub 2017 Jun 22.
The association between antidepressant (AD) use during pregnancy and the risk of attention deficit with or without hyperactivity disorder (ADHD) in children is debated. We investigated the risk of ADHD associated with overall and class-specific antidepressant exposure in utero.
We designed a register-based cohort study using the Quebec Pregnancy/Children Cohort (QPC). A total of 144 406 singleton full-term live-born from 1998 to 2009 were included. Cox proportional hazards regression models were used to estimate unadjusted and adjusted hazard ratio with 95% confidence interval (CI).
During 542 897 person-years of follow-up, 4564 (3.2%) infants were identified with ADHD. The mean age at first ADHD diagnosis was 6.3 ± 2.3 years (range 0-11 years), and the mean age at first ADHD medication use was 7.0 ± 1.5 years. Adjusting for potential confounders, including maternal history of depression/anxiety and ADHD, AD use during the 2nd or 3rd trimester of pregnancy was associated with an increased risk of (HR 1.3, 95% CI 1.0, 1.6; 134 exposed cases). More specifically, tricyclic use was associated with an increased risk of ADHD (HR 1.8, 95% CI 1.0, 3.1; 16 exposed cases); SSRI and SNRI use were not associated with increased ADHD risk.
This study suggests that AD use during the 2nd and 3rd trimester of pregnancy, specifically tricyclics, is an independent risk factor for ADHD in children above and beyond the risk associated with maternal depression/anxiety or ADHD. However, residual confounding by indication severity could not be completely ruled out.
孕期使用抗抑郁药（AD）与儿童注意力缺陷伴或不伴多动障碍（ADHD）风险之间的关联存在争议。我们调查了子宫内总体及特定类别抗抑郁药暴露与ADHD风险的关系。
我们利用魁北克妊娠/儿童队列（QPC）设计了一项基于登记的队列研究。纳入了1998年至2009年期间出生的144406名单胎足月活产儿。采用Cox比例风险回归模型估计未调整和调整后的风险比及95%置信区间（CI）。
在542897人年的随访期间，4564名（3.2%）婴儿被诊断为ADHD。首次ADHD诊断的平均年龄为6.3±2.3岁（范围0 - 11岁），首次使用ADHD药物治疗的平均年龄为7.0±1.5岁。在调整了包括母亲抑郁/焦虑和ADHD病史等潜在混杂因素后，孕期第二或第三个月使用AD与ADHD风险增加相关（风险比1.3，95%CI 1.0，1.6；134例暴露病例）。更具体地说，三环类药物的使用与ADHD风险增加相关（风险比1.8，95%CI 1.0，3.1；16例暴露病例）；选择性5-羟色胺再摄取抑制剂（SSRI）和5-羟色胺与去甲肾上腺素再摄取抑制剂（SNRI）的使用与ADHD风险增加无关。
本研究表明，孕期第二和第三个月使用AD，特别是三环类药物，是儿童ADHD的一个独立危险因素，超出了与母亲抑郁/焦虑或ADHD相关的风险。然而，不能完全排除因适应症严重程度导致的残余混杂因素。
