Zuccolo Luisa, DeRoo Lisa A, Wills Andrew K, Davey Smith George, Suren Pål, Roth Christine, Stoltenberg Camilla, Magnus Per
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Sci Rep. 2016 Dec 23;7:39535. doi: 10.1038/srep39535.
Although microcephaly is a feature of Fetal Alcohol Syndrome, it is currently unknown whether low-to-moderate prenatal alcohol exposure affects head circumference. Small magnitude associations reported in observational studies are likely to be misleading due to confounding and misclassification biases. Alternative analytical approaches such as the use of family negative controls (e.g. comparing the effects of maternal and paternal exposure) could help disentangle causal effects. We investigated the association of maternal and paternal alcohol drinking before and early in pregnancy with infant head circumference, using data from 68,244 mother-father-offspring trios from the Norwegian Mother and Child Cohort Study (MoBa) (1999-2009). In analyses adjusted for potential confounders, we found no consistent pattern of association between maternal or paternal alcohol intake before or during pregnancy and offspring head circumference modelled as a continuous outcome. However, we found higher odds of microcephaly at birth for higher paternal, but not maternal, alcohol consumption before pregnancy, and similar but weaker effect estimates for first trimester drinking. Associations with paternal drinking before pregnancy were unexpected and should be regarded as hypothesis generating, until independently replicated, although potentially important given the absence of guidelines on safe drinking levels for men in couples trying for a pregnancy.
虽然小头畸形是胎儿酒精综合征的一个特征,但目前尚不清楚低至中度的产前酒精暴露是否会影响头围。观察性研究中报告的小幅度关联可能会因混杂和错误分类偏差而产生误导。诸如使用家庭阴性对照(例如比较母亲和父亲暴露的影响)等替代分析方法可能有助于理清因果效应。我们利用挪威母婴队列研究(MoBa)(1999 - 2009年)中68244对母婴 - 父亲 - 后代三人组的数据,调查了怀孕前及孕早期母亲和父亲饮酒与婴儿头围之间的关联。在对潜在混杂因素进行调整的分析中,我们发现,将后代头围作为连续结果进行建模时,怀孕前或怀孕期间母亲或父亲的酒精摄入量与后代头围之间没有一致的关联模式。然而,我们发现,怀孕前父亲而非母亲的酒精消费量较高时,婴儿出生时患小头畸形的几率更高,孕早期饮酒的效应估计相似但较弱。怀孕前父亲饮酒的关联出乎意料,在独立重复验证之前应视为产生假设,尽管鉴于备孕夫妇中男性安全饮酒水平尚无指南,这一关联可能具有重要意义。