Ullemar V, Lundholm C, Almqvist C
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Lung and Allergy Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Clin Exp Allergy. 2015 Aug;45(8):1328-36. doi: 10.1111/cea.12547.
Children born with low gestational age (GA) or low birthweight (BW) are at increased risk of asthma. Twins as compared to singletons are on average more likely to be born with lower GA and BW and have been hypothesized to comprise a high-risk population for asthma. Many previous studies have not accounted for potential confounders or mediators.
To investigate the association between twinship and childhood asthma or early life wheeze and identify potential mediators, such as GA/BW.
The study population consisted of two cohorts including all children born in Sweden from 1 January 1993 to 1 June 2001 (n = 756,363 singletons, n = 22,478 twins) and 1 July 2005 to 31 December 2009 (n = 456,239 singletons, n = 12,872 twins). Asthma was defined using validated register-based outcomes of diagnosis or medication. The data were analysed using logistic (older cohort) and Cox regression (younger cohort). Adjusted models incorporated potential confounding or mediating factors including gestational age and birthweight.
In the younger cohort, the crude hazard ratio (HR) of asthma medication after 1.5 years of age was 1.12 (95% CI 1.01-1.23), and fully adjusted HR was 0.80, 95% CI 0.72-0.89. Crude HR of asthma diagnosis in the same age group was 1.14 (95% CI 0.99-1.30), fully adjusted 0.78 (0.68-0.98). Adjusted analyses in the older group yielded similar results.
Twins were at significantly higher unadjusted risk of asthma or early life wheeze compared to singletons in the younger, but not in the older cohort. Associations attenuated following adjustment for GA/BW, suggesting that GA/BW mediates the effect of twinship on asthma risk. After adjustments, twins were at lower risk of asthma outcomes, possibly due to unmeasured confounding.
低胎龄（GA）或低出生体重（BW）出生的儿童患哮喘的风险增加。与单胎相比，双胞胎平均更有可能以较低的GA和BW出生，并且被假设为哮喘的高危人群。许多先前的研究没有考虑潜在的混杂因素或中介因素。
研究双胞胎与儿童哮喘或早期喘息之间的关联，并确定潜在的中介因素，如GA/BW。
研究人群包括两个队列，分别为1993年1月1日至2001年6月1日在瑞典出生的所有儿童（n = 756,363名单胎，n = 22,478对双胞胎）以及2005年7月1日至2009年12月31日在瑞典出生的所有儿童（n = 456,239名单胎，n = 12,872对双胞胎）。哮喘通过基于登记的经过验证的诊断或用药结果来定义。数据使用逻辑回归（较年长队列）和Cox回归（较年轻队列）进行分析。调整后的模型纳入了潜在的混杂或中介因素，包括胎龄和出生体重。
在较年轻的队列中，1.5岁后哮喘用药的粗危险比（HR）为1.12（95%CI 1.01 - 1.23），完全调整后的HR为0.80，95%CI 0.72 - 0.89。同一年龄组哮喘诊断的粗HR为1.14（95%CI 0.99 - 1.30），完全调整后为0.78（0.68 - 0.98）。较年长组的调整分析得出了类似的结果。
与单胎相比，在较年轻队列中，双胞胎患哮喘或早期喘息的未调整风险显著更高，但在较年长队列中并非如此。在对GA/BW进行调整后，这种关联减弱，表明GA/BW介导了双胞胎身份对哮喘风险的影响。调整后，双胞胎患哮喘的风险较低，可能是由于未测量的混杂因素。
