Man Kenneth K C, Chan Esther W, Ip Patrick, Coghill David, Simonoff Emily, Chan Phyllis K L, Lau Wallis C Y, Schuemie Martijn J, Sturkenboom Miriam C J M, Wong Ian C K
Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
BMJ. 2017 May 31;357:j2350. doi: 10.1136/bmj.j2350.
To assess the potential association between prenatal use of antidepressants and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Population based cohort study. Data from the Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System. 190 618 children born in Hong Kong public hospitals between January 2001 and December 2009 and followed-up to December 2015. Hazard ratio of maternal antidepressant use during pregnancy and ADHD in children aged 6 to 14 years, with an average follow-up time of 9.3 years (range 7.4-11.0 years). Among 190 618 children, 1252 had a mother who used prenatal antidepressants. 5659 children (3.0%) were given a diagnosis of ADHD or received treatment for ADHD. The crude hazard ratio of maternal antidepressant use during pregnancy was 2.26 (P<0.01) compared with non-use. After adjustment for potential confounding factors, including maternal psychiatric disorders and use of other psychiatric drugs, the adjusted hazard ratio was reduced to 1.39 (95% confidence interval 1.07 to 1.82, P=0.01). Likewise, similar results were observed when comparing children of mothers who had used antidepressants before pregnancy with those who were never users (1.76, 1.36 to 2.30, P<0.01). The risk of ADHD in the children of mothers with psychiatric disorders was higher compared with the children of mothers without psychiatric disorders even if the mothers had never used antidepressants (1.84, 1.54 to 2.18, P<0.01). All sensitivity analyses yielded similar results. Sibling matched analysis identified no significant difference in risk of ADHD in siblings exposed to antidepressants during gestation and those not exposed during gestation (0.54, 0.17 to 1.74, P=0.30). The findings suggest that the association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by confounding by indication of antidepressants. If there is a causal association, the size of the effect is probably smaller than that reported previously.
评估孕期使用抗抑郁药与后代注意力缺陷多动障碍（ADHD）风险之间的潜在关联。基于人群的队列研究。数据来自香港基于人群的电子病历临床数据分析与报告系统。190618名在2001年1月至2009年12月期间于香港公立医院出生并随访至2015年12月的儿童。计算孕期母亲使用抗抑郁药与6至14岁儿童患ADHD之间的风险比，平均随访时间为9.3年（范围7.4 - 11.0年）。在190618名儿童中，1252名儿童的母亲在孕期使用过抗抑郁药。5659名儿童（3.0%）被诊断患有ADHD或接受过ADHD治疗。孕期母亲使用抗抑郁药的粗风险比为2.26（P<0.01），而未使用者为参照。在调整了包括母亲精神疾病和其他精神药物使用等潜在混杂因素后，调整后的风险比降至1.39（95%置信区间1.07至1.82，P = 0.01）。同样，在比较孕前使用抗抑郁药的母亲的孩子与从未使用者的孩子时也观察到了类似结果（1.76，1.36至2.30，P<0.01）。即使母亲从未使用过抗抑郁药，患有精神疾病的母亲的孩子患ADHD的风险也高于没有精神疾病的母亲的孩子（1.84，1.54至2.18，P<0.01）。所有敏感性分析均得出类似结果。同胞匹配分析发现，孕期接触抗抑郁药的同胞与未接触抗抑郁药的同胞患ADHD的风险无显著差异（0.54，0.17至1.74，P = 0.30）。研究结果表明，孕期使用抗抑郁药与后代患ADHD风险之间的关联可能部分由抗抑郁药的指征性混杂因素所解释。如果存在因果关联，其效应大小可能比之前报道的要小。
