Maternal iron status during pregnancy and respiratory and atopic outcomes in the offspring: a Mendelian randomisation study.

Introduction: Limited evidence from birth cohort studies suggests that lower prenatal iron status may be a risk factor for childhood respiratory and atopic outcomes, but these observational findings may be confounded. Mendelian randomisation (MR) can potentially provide unconfounded estimates of causal effects by using common genetic variants as instrumental variables. We aimed to study the relationship between prenatal iron status and respiratory and atopic outcomes in the offspring using MR. Methods: In the Avon Longitudinal Study of Parents and Children birth cohort, we constructed four maternal genotypic risk scores by summing the total number of risk alleles (associated with lower iron status) across single nucleotide polymorphisms known to be associated with at least one of four iron biomarkers (serum iron, ferritin, transferrin and transferrin saturation). We used MR to study their associations with respiratory and atopic outcomes in children aged 7-9 years (n=6002). Results: When analyses were restricted to mothers without iron supplementation during late pregnancy, negative associations were found between the maternal transferrin saturation score and childhood forced expiratory volume in 1 s and forced vital capacity (difference in age, height and gender-adjusted SD units per SD increase in genotypic score: -0.05 (-0.09, -0.01) p=0.03, and -0.04 (-0.08, 0.00) p=0.04, respectively). Conclusion: Using MR we have found weak evidence suggesting that low maternal iron status during pregnancy may cause impaired childhood lung function