Familial Factors Do not Confound the Association Between Birth Weight and Childhood Asthma

Abstract

Studies have found associations between low birth weight and asthma. However, this association could be due to familial confounding. Our objective was to investigate whether fetal growth and birth weight affect the risk of asthma in childhood, controlling for gestational age (GA), and shared (familial) environment and genetic factors. Information on asthma, zygosity, birth characteristics, and potential confounders was collected for all 9- and 12-year-old twins through the Swedish Twin Register and Medical Birth Register. To obtain an overall effect of birth weight on risk of asthma, we performed cohort analyses on all twins (N = 10918). To address genetic and shared environmental confounding, we performed a co-twin control analysis by using the 157 monozygotic and 289 dizygotic same-sex twin pairs who were discordant for asthma. The overall rate of asthma ever was 13.7%. In the cohort analysis, the adjusted odds ratio (OR) for asthma in relation to a 1000-g decrease in birth weight was 1.57 (95% confidence interval [CI]: 1.38-1.79), and for each reduced gestational week the OR was 1.10 (95% CI: 1.07-1.13). In the co-twin control analyses, a 1000-g decrease in birth weight corresponded to an OR of 1.25 (95% CI: 0.74-2.10) for dizygotic same-sex twins and 2.42 (95% CI: 1.00-5.88) for monozygotic twins. There is an association between fetal growth and childhood asthma that is independent of GA and shared (familial) environment and genetic factors, which indicates that fetal growth restriction affects lung development, supporting additional studies on the early metabolic and physiologic mechanisms of childhood asthma.