Norwegian Institute of Public Health, Oslo, Norway.
Department of Psychology.
Int J Epidemiol. 2017 Oct 1;46(5):1633-1640. doi: 10.1093/ije/dyx067.
Maternal alcohol use during pregnancy has repeatedly been associated with development of attention-deficit hyperactivity disorder (ADHD) in the offspring. It is, however not known whether this reflects a direct casual intra-uterine effect or a non-causal relationship due to confounding. We used three different approaches to control for measured and unmeasured confounding: statistical adjustment for covariates, negative control comparison against maternal pre-pregnancy alcohol use, and comparison among differentially exposed siblings.
The sample comprised 114 247 children (34 283 siblings) from 94 907 mothers, recruited to the Norwegian Mother and Child Birth Cohort Study between 1999 and 2008. Self-reported measurements of alcohol use were obtained in week 30 during the pregnancy. Mothers rated offspring ADHD symptoms at 5 years on two measures. Clinical ADHD diagnoses were obtained from the Norwegian Patient Registry.
We found an overall positive association between maternal alcohol use during pregnancy and offspring ADHD symptoms, which was only marginally attenuated after inclusion of measured covariates. Both the negative control and the sibling comparison analysis further attenuated the estimated association, but it remained greater than zero [β = 0.017, 95% confidence interval (CI) = 0.005-0.030). No association was found between maternal alcohol use during pregnancy and offspring ADHD diagnosis.
For offspring ADHD symptoms we found a weak, but possibly causal association with maternal alcohol use during pregnancy, but no such effect was observed for clinical ADHD diagnosis.
母体在怀孕期间饮酒与后代注意力缺陷多动障碍(ADHD)的发生反复相关。然而,尚不清楚这是否反映了宫内的直接因果关系,还是由于混杂因素导致的非因果关系。我们使用了三种不同的方法来控制已测量和未测量的混杂因素:对协变量进行统计调整、与母亲怀孕前饮酒进行负面对照比较,以及对不同暴露程度的兄弟姐妹进行比较。
该样本包括来自 94907 位母亲的 114247 名儿童(34283 对兄弟姐妹),这些母亲于 1999 年至 2008 年期间参加了挪威母婴队列研究。在怀孕期间的第 30 周,通过自我报告的方式测量了酒精的使用情况。母亲在孩子 5 岁时通过两种测量方法对其 ADHD 症状进行了评估。临床 ADHD 诊断是通过挪威患者登记处获得的。
我们发现母体在怀孕期间饮酒与后代 ADHD 症状之间存在总体上的正相关关系,而纳入已测量的混杂因素后,这种相关性仅略有减弱。负面对照和兄弟姐妹比较分析进一步减弱了估计的相关性,但仍大于零[β=0.017,95%置信区间(CI)=0.005-0.030]。母体在怀孕期间饮酒与后代 ADHD 诊断之间未发现关联。
对于后代的 ADHD 症状,我们发现与母体在怀孕期间饮酒存在微弱但可能是因果关系,但对于临床 ADHD 诊断则没有观察到这种效应。