Skoglund Charlotte, Chen Qi, D'Onofrio Brian M, Lichtenstein Paul, Larsson Henrik
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
J Child Psychol Psychiatry. 2014 Jan;55(1):61-8. doi: 10.1111/jcpp.12124. Epub 2013 Jul 30.
Maternal Smoking During Pregnancy (SDP) has consistently been associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring, but recent studies indicate that this association might be due to unmeasured familial confounding.
A total of 813,030 individuals born in Sweden between 1992 and 2000 were included in this nationwide population-based cohort study. Data on maternal SDP and ADHD diagnosis were obtained from national registers and patients were followed up from the age of 3 to the end of 2009. Hazard Ratios (HRs) were estimated using stratified Cox regression models. Cousin and sibling data were used to control for unmeasured familial confounding.
At the population level maternal SDP predicted ADHD in offspring (HR(ModerateSDP) = 1.89; HR(HighSDP)= 2.50). This estimate gradually attenuated toward the null when adjusting for measured confounders (HR(ModerateSDP)= 1.62; HR(HighSDP)= 2.04), unmeasured confounders shared within the extended family (i.e., cousin comparison) (HR(ModerateSDP)= 1.45; HR(HighSDP)= 1.69), and unmeasured confounders within the nuclear family (i.e., sibling comparison) (HR(ModerateSDP)= 0.88; HR(HighSDP)= 0.84).
Our results suggest that the association between maternal SDP and offspring ADHD are due to unmeasured familial confounding.
孕期母亲吸烟（SDP）一直与后代患注意力缺陷多动障碍（ADHD）的风险增加有关，但最近的研究表明，这种关联可能是由于未测量的家族混杂因素所致。
这项基于全国人群的队列研究纳入了1992年至2000年在瑞典出生的813,030人。母亲SDP和ADHD诊断的数据来自国家登记处，对患者从3岁开始随访至2009年底。使用分层Cox回归模型估计风险比（HRs）。利用堂兄弟姐妹和兄弟姐妹的数据来控制未测量的家族混杂因素。
在人群水平上，母亲SDP可预测后代患ADHD（HR（中度SDP）= 1.89；HR（高度SDP）= 2.50）。在对测量的混杂因素进行调整后（HR（中度SDP）= 1.62；HR（高度SDP）= 2.04），这种估计值逐渐向零衰减，在大家庭中共享的未测量混杂因素（即堂兄弟姐妹比较）（HR（中度SDP）= 1.45；HR（高度SDP）= 1.69），以及核心家庭中的未测量混杂因素（即兄弟姐妹比较）（HR（中度SDP）= 0.88；HR（高度SDP）= 0.84）。
我们的结果表明，母亲SDP与后代ADHD之间的关联是由于未测量的家族混杂因素所致。
