Liu Xiaoqin, Agerbo Esben, Ingstrup Katja G, Musliner Katherine, Meltzer-Brody Samantha, Bergink Veerle, Munk-Olsen Trine
National Center for Register-based Research, Aarhus University, Aarhus, Denmark
National Center for Register-based Research, Aarhus University, Aarhus, Denmark.
BMJ. 2017 Sep 6;358:j3668. doi: 10.1136/bmj.j3668.
To investigate the association between in utero exposure to antidepressants and risk of psychiatric disorders. Population based cohort study. Danish national registers. 905 383 liveborn singletons born during 1998-2012 in Denmark and followed from birth until July 2014, death, emigration, or date of first psychiatric diagnosis, whichever came first. The children were followed for a maximum of 16.5 years and contributed 8.1×10 person years at risk. Children were categorised into four groups according to maternal antidepressant use within two years before and during pregnancy: unexposed, antidepressant discontinuation (use before but not during pregnancy), antidepressant continuation (use both before and during pregnancy), and new user (use only during pregnancy). First psychiatric diagnosis in children, defined as first day of inpatient or outpatient treatment for psychiatric disorders. Hazard ratios of psychiatric disorders were estimated using Cox regression models. Overall, psychiatric disorders were diagnosed in 32 400 children. The adjusted 15 year cumulative incidence of psychiatric disorders was 8.0% (95% confidence interval 7.9% to 8.2%) in the unexposed group, 11.5% (10.3% to 12.9%) in the antidepressant discontinuation group, 13.6% (11.3% to 16.3%) in the continuation group, and 14.5% (10.5% to 19.8%) in the new user group. The antidepressant continuation group had an increased risk of psychiatric disorders (hazard ratio 1.27, 1.17 to 1.38), compared with the discontinuation group. In utero exposure to antidepressants was associated with increased risk of psychiatric disorders. The association may be attributable to the severity of underlying maternal disorders in combination with antidepressant exposure in utero. The findings suggest that focusing solely on a single psychiatric disorder among offspring in studies of in utero antidepressant exposure may be too restrictive.
为研究子宫内接触抗抑郁药与精神疾病风险之间的关联。基于人群的队列研究。丹麦国家登记处。1998年至2012年期间在丹麦出生的905383例活产单胎婴儿,从出生起随访至2014年7月、死亡、移民或首次精神疾病诊断日期(以先到者为准)。这些儿童最长随访16.5年,共产生8.1×10人年的风险暴露时间。根据母亲在怀孕前两年及怀孕期间使用抗抑郁药的情况,将儿童分为四组:未暴露组、抗抑郁药停药组(怀孕前使用但怀孕期间未使用)、抗抑郁药持续使用组(怀孕前和怀孕期间均使用)和新使用者组(仅在怀孕期间使用)。儿童的首次精神疾病诊断定义为因精神疾病住院或门诊治疗的第一天。使用Cox回归模型估计精神疾病的风险比。总体而言,32400名儿童被诊断患有精神疾病。未暴露组经调整的15年精神疾病累积发病率为8.0%(95%置信区间7.9%至8.2%),抗抑郁药停药组为11.5%(10.3%至12.9%),持续使用组为13.6%(11.3%至16.3%),新使用者组为14.5%(10.5%至19.8%)。与停药组相比,抗抑郁药持续使用组患精神疾病的风险增加(风险比1.27,1.17至1.38)。子宫内接触抗抑郁药与精神疾病风险增加有关。这种关联可能归因于潜在母亲疾病的严重程度以及子宫内接触抗抑郁药。研究结果表明,在子宫内抗抑郁药暴露研究中仅关注后代中的单一精神疾病可能过于局限。