Wingren Carl Johan, Agardh Daniel, Merlo Juan
Department of Clinical Sciences, Faculty of Medicine, Lund University, Unit for Social Epidemiology, Malmö, Sweden.
Scand J Gastroenterol. 2012 Jun;47(6):632-9. doi: 10.3109/00365521.2012.661760. Epub 2012 Mar 19.
An association between small for gestational age (SGA) and risk for celiac disease (CD) in childhood has previously been reported. However, this association may reflect residual confounding by genetic or environmental factors. For example, presence of subclinical CD in the mother might be a common cause of both SGA and CD in the offspring. We investigate whether SGA is causally associated with CD before age six years by applying both conventional population-based regression models and sibling analysis that investigates the association in siblings discordant for SGA.
Using the Swedish Medical Birth Registry, we identified all singleton children born in Sweden during 1987-1993 (792,401). Of these we included 681,954 children in the study and identified 2641 cases of CD using the Swedish National In-Hospital Registry. We applied both conventional Cox regression analysis and a quasi-experimental sibling design that to some extent simulates a counterfactual situation of exposure, reducing possible confounding effects of genetic and shared environmental factors.
We identified an increased risk of CD in both boys (hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.25-2.32) and girls (HR 1.30, 95% CI 0.99-1.70) using conventional Cox regression models. Using sibling analysis, the association between SGA and CD was confirmed in boys (HR 4.23, 95% CI 1.19-15.04) but not in girls (HR 1.00, 95% CI 0.45-2.20).
Our results support a causal association between SGA and CD risk in boys but not in girls, although the mechanisms underlying this difference are still unclear.
此前已有报道称小于胎龄儿（SGA）与儿童乳糜泻（CD）风险之间存在关联。然而，这种关联可能反映了遗传或环境因素导致的残余混杂。例如，母亲存在亚临床CD可能是后代SGA和CD的共同原因。我们通过应用传统的基于人群的回归模型和同胞分析来研究SGA与6岁前CD是否存在因果关联，同胞分析旨在研究SGA不一致的同胞之间的关联。
利用瑞典医学出生登记处的数据，我们确定了1987 - 1993年在瑞典出生的所有单胎儿童（792,401名）。其中，我们将681,954名儿童纳入研究，并通过瑞典国家住院登记处确定了2641例CD病例。我们应用了传统的Cox回归分析和一种准实验性同胞设计，该设计在一定程度上模拟了暴露的反事实情况，减少了遗传和共同环境因素可能产生的混杂效应。
使用传统的Cox回归模型，我们发现男孩（风险比（HR）1.70，95%置信区间（CI）1.25 - 2.32）和女孩（HR 1.30，95% CI 0.99 - 1.70）患CD的风险均增加。通过同胞分析，在男孩中证实了SGA与CD之间的关联（HR 4.23，95% CI 1.19 - 15.04），但在女孩中未得到证实（HR 1.00，95% CI 0.45 - 2.20）。
我们的结果支持SGA与男孩CD风险之间存在因果关联，但在女孩中不存在，尽管这种差异背后的机制仍不清楚。
