Rai Dheeraj, Lee Brian K, Dalman Christina, Newschaffer Craig, Lewis Glyn, Magnusson Cecilia
Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol, UK
Avon and Wiltshire Partnership NHS Mental Health Trust, Bristol, UK.
BMJ. 2017 Jul 19;358:j2811. doi: 10.1136/bmj.j2811.
To study the association between maternal use of antidepressants during pregnancy and autism spectrum disorder (ASD) in offspring. Observational prospective cohort study with regression methods, propensity score matching, sibling controls, and negative control comparison. Stockholm County, Sweden. 254 610 individuals aged 4-17, including 5378 with autism, living in Stockholm County in 2001-11 who were born to mothers who did not take antidepressants and did not have any psychiatric disorder, mothers who took antidepressants during pregnancy, or mothers with psychiatric disorders who did not take antidepressants during pregnancy. Maternal antidepressant use was recorded during first antenatal interview or determined from prescription records. Offspring diagnosis of autism spectrum disorder, with and without intellectual disability. Of the 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar results. The results of a sibling control analysis were in the same direction, although with wider confidence intervals. In a negative control comparison, there was no evidence of any increased risk of autism in children whose fathers were prescribed antidepressants during the mothers' pregnancy (1.13, 0.68 to 1.88). In all analyses, the risk increase concerned only autism without intellectual disability. The association between antidepressant use during pregnancy and autism, particularly autism without intellectual disability, might not solely be a byproduct of confounding. Study of the potential underlying biological mechanisms could help the understanding of modifiable mechanisms in the aetiology of autism. Importantly, the absolute risk of autism was small, and, hypothetically, if no pregnant women took antidepressants, the number of cases that could potentially be prevented would be small.
研究孕期母亲使用抗抑郁药与后代自闭症谱系障碍(ASD)之间的关联。采用回归方法、倾向得分匹配、同胞对照和阴性对照比较的观察性前瞻性队列研究。瑞典斯德哥尔摩县。254610名年龄在4至17岁的个体,其中包括5378名自闭症患者,他们于2001年至2011年生活在斯德哥尔摩县,其母亲未服用抗抑郁药且无任何精神疾病、孕期服用抗抑郁药的母亲或孕期未服用抗抑郁药的患有精神疾病的母亲所生。在首次产前检查时记录母亲使用抗抑郁药的情况,或从处方记录中确定。后代自闭症谱系障碍的诊断,伴有或不伴有智力障碍。在孕期接触抗抑郁药的3342名儿童中,4.1%(n = 136)被诊断为自闭症,而在其母亲有精神疾病史但未接触抗抑郁药的12325名儿童中,患病率为2.9%(n = 353)(调整后的优势比为1.45,95%置信区间为1.13至1.85)。倾向得分分析得出了类似结果。同胞对照分析的结果方向相同,尽管置信区间更宽。在阴性对照比较中,没有证据表明母亲孕期父亲被开抗抑郁药的儿童患自闭症的风险有任何增加(1.13,0.68至1.88)。在所有分析中,风险增加仅涉及无智力障碍的自闭症。孕期使用抗抑郁药与自闭症之间的关联,尤其是无智力障碍的自闭症,可能不仅仅是混杂因素的副产品。对潜在的生物学机制进行研究可能有助于理解自闭症病因中可改变的机制。重要的是,自闭症的绝对风险很小,假设没有孕妇服用抗抑郁药,可能预防的病例数也会很少。