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. Objective 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 six years. In this unique "case-control design" the smaller twin represents the case, and the co-twin the almost identical counterpart. They performed spirometry, body plethysmography, multiple-breath washout (MBW), and magnetic resonance imaging (MRI). We compared lung function and MRI outcomes between the smaller twins and their co-twins by paired t-tests, and 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 270-1130). Mean forced expiratory volume in 1 second (FEV1) z-score was -0.64 (95% CI -0.98 to -0.30) and forced vital capacity (FVC) z-score -0.55 (95% CI -0.92 to -0.18) lower in the smaller twins compared to their co-twins. Both were associated with birth weight: per 500 g birth weight, FEV1 z-score increased by 0.50 (95% CI 0.35-0.65, P <0.001) and FVC z-score by 0.44 (95% CI 0.31-0.57, P <0.001). Sacin from MBW, as a marker for ventilation inhomogeneity of acinar airways, was elevated in the smaller twins, and associated with low birth weight. There was no difference for MRI outcomes. Results remained similar after adjustment for study height. Conclusion 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.
