Maternal respiratory health and intrauterine exposure-driven birthweight: a two-sample Mendelian randomization study

Background: Observationally, poorer maternal respiratory health is associated with poorer birth outcomes, possibly confounded by socioeconomic position and other maternal attributes. We used multivariable Mendelian randomization (MR) to obtain unconfounded estimates of effect of maternal lung function on birthweight, independent of maternal height. Methods: Single nucleotide polymorphisms (SNPs) for forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in women were obtained from publicly available summary statistics from the UK Biobank. SNPs for asthma were obtained from the Trans-National Asthma Genetic consortium. SNPs for height in women were obtained from the Genetic Investigation of Anthropometric Traits consortium and the genetic estimates were obtained the UK Biobank. The genetic associations with maternally-driven birthweight were obtained from the Early Growth Genetics consortium. Multivariable MR estimates were obtained using inverse variance weighting with multivariable MR-Egger as sensitivity analysis. Results: Maternal lung capacity, as indicated by FVC, was positively associated with maternally-driven birthweight (0.08 per standard deviation, 95% confidence interval 0.01 to 0.15) independent of maternal height, whereas no clear such associations were shown for maternal airway function, indicated by FEV1 and peak expiratory flow, or for asthma, on maternally-driven birthweight. Similar findings were shown using MR-Egger. Conclusions: These findings suggest that maternal lung function, especially lung capacity independent of maternal height, is directly associated with maternally-driven birthweight, and highlights the importance of maternal respiratory health in fetal growth.