Low Birth Weight and Impaired Later Lung Function: Results from a Monochorionic Twin Study

Rationale: Fetal growth restriction (FGR) and resulting low birth weight are risk factors for impaired lung development. However, both are often correlated with other factors, especially prematurity. Therefore, the question whether lung function changes in individuals with FGR are driven by gestational age, fetal growth, or both often remains unanswered. Objectives: To examine the association of birth weight with lung function in monochorionic twins with selective FGR in one twin. Methods: We included 20 monochorionic twin pairs with selective FGR and subsequent discordant birth weight with a minimum age of 6 years. In this unique case-control design, the smaller twin represents the case and the cotwin the almost identical counterpart. They performed spirometry and underwent body plethysmography, multiple-breath washout, and magnetic resonance imaging (MRI). We compared lung function and MRI outcomes between the smaller twins and their cotwins by paired t tests, and we used mixed linear models to assess the association between birth weight and outcomes. Results: Mean study age was 18.4 years (range, 7.5-29.4), and mean difference in birth weight within the twin pairs was 575 g (range, 270-1,130). The mean difference of forced expiratory volume in 1 second z-score was -0.64 (95% confidence interval [CI], -0.98 to -0.30), and -0.55 (95% CI, -0.92 to -0.18) of forced vital capacity z-score between the smaller twins and their cotwins. Both were associated with birth weight: per 500 g of birth weight, forced expiratory volume in 1 second z-score increased by 0.50 (95% CI, 0.35-0.65; P < 0.001) and forced vital capacity z-score increased by 0.44 (95% CI, 0.31-0.57; P < 0.001). S_acin from multiple-breath washout, as a marker for ventilation inhomogeneity of acinar airways, was elevated in the smaller twins and was associated with low birth weight. There was no difference for MRI outcomes. The results remained similar after adjustment for study height. Conclusions: Low birth weight was associated with reduced large and small airway function independent of gestational age and body growth. Our findings suggest that intrauterine impairment of lung development induced by FGR has significant consequences on lung function until early adulthood.