Rationale: Associations between fetal growth restriction and lung function impairment could be due to gestational age as well as shared (familial) genetic and environmental factors.
Objectives: To study the association between fetal growth and lung function in childhood while taking gestational age and familial factors into account.
Methods: First, full-cohort analyses of twins were performed to study the association between birth weight, gestational age, fetal growth, and lung function (FEV1, FVC, and FEV1/FVC) in z-scores before (n = 520) and after (n = 539) bronchodilator treatment. Second, to control for gestational age and familial factors, within-twin-pair analyses were performed.
Results: Regarding full-cohort post-bronchodilator treatment, FEV1 was significantly associated with a decrease in birth weight (-0.16 z-score per 500 g; 95% confidence interval [CI], -0.28 to -0.04) and fetal growth (-0.15 z-score per 1 SD decrease; 95% CI, -0.26 to -0.04), and similar and significant associations for FVC with birth weight and fetal growth were also seen. Nonsignificant associations for FEV1 and FVC with gestational age were found. The direction of effect was similar in pre-bronchodilator analyses, although with somewhat less strong and nonsignificant effect estimates for both FEV1 and FVC with fetal growth. No associations were found between any of the exposure variables and FEV1/FVC either pre- or post-bronchodilator. In the within-twin-pair analyses, the direction of effect appeared similar to that of the whole cohort, but the CIs were wider.
Conclusions: Our results suggest that there is a significant association between restricted fetal growth and post-bronchodilator FEV1 and FVC, but not FEV1/FVC, in childhood that may be independent of gestational age and shared familial factors.
Keywords: asthma; bronchodilator; confounding; spirometry; twins.