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.
- lung function
- Mendelian randomisation
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JH and SS are joint senior authors.
Contributors AB and SOS conceived the study and drafted the manuscript. All authors were involved in the analysis strategy. SJL and SB gave advice on the genetic analyses, and AB performed the statistical analyses. AJH was responsible for all clinical respiratory and allergy data collection. All authors participated in the interpretation of the findings, reviewed the manuscript and revised it critically before submission. All authors have seen and approved the final version of the manuscript.
Funding The UK Medical Research Council, the Wellcome Trust (grant ref: 102215/2/13/2) and the University of Bristol currently provide core support for ALSPAC. AB is funded by a European Respiratory Society Long-Term Research Fellowship (Fellowship ID LTRF 2015-5838).
Disclaimer The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Competing interests None declared.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval ALSPAC Ethics and Law Committee (IRB 00003312) and the Local NHS Research Ethics Committees.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The data sets generated and/or analysed during the current study are available in the ALSPAC repository (http://www.bristol.ac.uk/alspac/researchers/access/). ALSPAC operates managed access to the data, which can be obtained by application to ALSPAC according to the term of the access policy available on the website.
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