Maternal Smoking During Pregnancy and Childhood Obesity: linear association or threshold effect? An IPD Meta-Analysis

母亲在怀孕期间吸烟和儿童肥胖：线性相关还是阈值效应？

• 批准号: 269758285
• 负责人: Professor Dr. Rüdiger von Kries
• 金额: --
• 依托单位: Institut für Biometrie und Epidemiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/269758285?language=en
• 关键词: Maternal; Smoking; During; Pregnancy; Childhood

In a recent state of the art paper Gillman MW and Ludwig DS (NEJM, 2013) suggested that 7% of the probability of obesity at 7 to 10 years of age could be explained by maternal smoking in pregnancy. This empirical evidence for a causal association between intrauterine exposure to nicotine and overweight in the offspring has been questioned, however, because of potential residual confounding. Major concerns regarding possible residual confounding were based on the observation that children who were exposed to paternal or second-hand smoking while in utero or after pregnancy also had an increased risk of being overweight, although smaller than for maternal smoking. Is this a reflection of a linear dose effect relation? Or are both effects are reflection of residual confounding by unknown family factors? A linear dose effect relation might appear possible in face of some overlap in cotinine concentrations in the newborns hair between newborns exposed to maternal or paternal smoking in pregnancy. The reported data on the dose effect of maternal smoking in pregnancy are equivocal, however: some suggesting a threshold effect with a steep increase related to small doses while others suggest a linear association. These equivocal findings may reflect artefacts due to reporting effects by dose categories. The original data of most studies, however, ascertained maternal smoking exposure by number of cigarettes smoked. An IPD meta-analysis of these data will therefore allow to elucidate the true nature of the dose effect of maternal smoking in pregnancy. The authors of 16 studies have expressed their interest in a collaborative IPD study allowing to study the association in more than 300 000 mother infant pairs. These data will provide a clue for understanding potential causality of the association between maternal smoking in pregnancy and obesity in the offspring. In case of a linear association the additional effects observed for paternal smoking in pregnancy might be explained by a dose effect. In case of a threshold effect with a steep increase related to small numbers of cigarettes the effect of both maternal and paternal smoking would be more likely to reflect residual confounding related to shared family environment.

在最近的最新论文中，Gillman MW和Ludwig DS（NEJM，2013）表明，7至10岁肥胖的概率中有7%可以解释为母亲在怀孕期间吸烟。然而，由于潜在的残留混杂，宫内暴露于尼古丁和后代超重之间因果关系的经验证据受到质疑。关于可能的残留混杂因素的主要担忧是基于以下观察结果，即在子宫内或怀孕后暴露于父亲或二手吸烟的儿童也有超重的风险增加，尽管小于母亲吸烟的风险。这是否反映了线性剂量效应关系？或者这两种效应都是未知家族因素的残余混杂的反映？在妊娠期暴露于母亲或父亲吸烟的新生儿之间，新生儿头发中可替宁浓度存在一定重叠，因此可能出现线性剂量效应关系。然而，报告的关于孕妇吸烟剂量效应的数据是模棱两可的：一些数据表明与小剂量相关的阈值效应急剧增加，而另一些数据则表明线性关联。这些模棱两可的结果可能反映了由于按剂量类别报告效应而产生的伪影。然而，大多数研究的原始数据通过吸烟数量确定了母亲的吸烟暴露。因此，IPD对这些数据的荟萃分析将有助于阐明妊娠期母亲吸烟剂量效应的真实性质。16项研究的作者表达了他们对IPD合作研究的兴趣，该研究允许在超过30万对母婴中研究这种关联。这些数据将为理解母亲在怀孕期间吸烟与后代肥胖之间的潜在因果关系提供线索。在线性关联的情况下，可以通过剂量效应来解释妊娠期父亲吸烟的额外影响。在阈值效应与少量香烟相关的急剧增加的情况下，母亲和父亲吸烟的影响更可能反映与共享家庭环境相关的残留混杂。