Maternal iron status during pregnancy and respiratory and atopic outcomes in the offspring: a Mendelian randomization approach

Abstract

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 randomization (MR) can potentially provide unconfounded estimates of causal effects by using genes as instrumental variables. In the large population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), we used MR to determine whether maternal iron status during pregnancy is likely to be causally associated with atopy, current doctor-diagnosed asthma, wheezing, eczema, hay fever, serum total IgE and lung function at 7-9 years of age (n=6,002). A maternal genotypic risk score was constructed by summing the total number of risk alleles (associated with lower iron status) across six single nucleotide polymorphisms (SNPs) known to be associated with serum iron concentrations. After controlling for iron supplementation there was weak evidence for positive associations between the genotypic risk score and childhood atopy and asthma (per score category odds ratio [95% CI]: 1.06 [1.00-1.13] and 1.08 [1.01-1.16]; p for trend: 0.06 and 0.03, respectively). When we repeated these analyses, excluding a SNP that was in Hardy Weinberg disequilibrium from the risk score, these associations were attenuated (OR [95% CI]: 1.04 [0.97-1.11] and 1.06 [0.98-1.14]; p for trend: 0.25 and 0.17, respectively). No association was found with other childhood outcomes. Using MR we have not found convincing evidence to suggest that low maternal iron status during pregnancy is causally associated with childhood respiratory and atopic outcomes.