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

Abstract

IntroductionLimited 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.MethodsIn 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).ResultsWhen 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).ConclusionUsing MR we have found weak evidence suggesting that low maternal iron status during pregnancy may cause impaired childhood lung function.

The Role of the Status of Selected Micronutrients in Shaping the Immune Function

“…Iron deficiency affects Th1 lymphocytes to a higher degree than their Th2 counterparts due to larger and less labile iron stores in Th2 cells that render them more resilient to the effects of iron chelators and anti-transferrin receptor antibodies [ 26 ]. This finding is in accordance with a higher prevalence of allergies in iron- deficient children and adolescents [ 27 ] and a higher risk for atopic disease development in children of mothers having a low iron status during pregnancy [ 28 ].…”

Atopic Disease and Anemia in Korean Patients: Cross-Sectional Study with Propensity Score Analysis

“…However, it can be explained that the inflammatory status of food allergy increases the prevalence of anemia based on the study that patients with food allergies have a high risk of atopic disease and food allergy is also one of atopic diseases [41]. In addition, some studies have suggested a correlation between the maternal iron levels during pregnancy and her baby's atopic disease including asthma or lung function [42][43][44]. Meanwhile, a recent study had shown that hemoglobin levels during the mother's pregnancy were associated with respiratory and allergic diseases in childhood [45].…”

Maternal iron supplementation in pregnancy and asthma in the offspring: follow-up of a randomised trial in Finland

“…Animal experiments have implicated iron in fetal airway development 3 . In two UK population-based birth cohorts, using different approaches, we have found evidence suggesting that lower maternal iron levels in pregnancy may increase the risk of wheezing, atopy and lower lung function in the offspring [4][5][6][7] . However, the possibility that unmeasured or residual confounding might explain these observational findings cannot be ruled out.…”