Exploring the relationship between maternal iron status and offspring’s blood pressure and adiposity: a Mendelian randomization study

Nisreen A Alwan,¹ Debbie A Lawlor,² Harry J McArdle,³ Darren C Greenwood,⁴ Janet E Cade<sup>1

1</sup>Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK; ²MRC Centre for Causal Analyses in Translational Research, University of Bristol, Bristol; ³Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen; ⁴Biostatistics Unit, Leeds Institute for Health, Genetics and Therapeutics, University of Leeds, Leeds, UK

Background: Iron deficiency is the most common micronutrient deficiency worldwide. Experimental animal studies suggest that mothers deficient in iron during pregnancy are more likely to have offspring who become obese with high blood pressure. C282Y mutation carriers are more likely to have higher iron stores.
Methods: We undertook an instrumental variable (IV) analysis, using maternal C282Y as an indicator for the mother’s iron status, to examine its association with offspring blood pressure (BP), waist circumference (WC), and body mass index (BMI), and compared the results to that of ordinary least squares (OLS) regression. Offspring of a sub-cohort of mothers from the UK Women’s Cohort Study (UKWCS) were recruited in 2009–2010 (n = 348, mean age = 41 years). Their blood pressure, height, and weight were measured at their local general medical practice, and they were asked to self-measure their waist circumference. About half were offspring of C282Y carriers. Maternal ferritin was used as a biomarker of maternal iron status.
Results: Maternal C282Y was strongly associated with maternal ferritin (mean difference per allele = 84 g/L, 95% confidence interval: 31–137, P = 0.002). Using IV analyses, maternal ferritin was not linked to offspring’s BP, BMI, or WC. The first stage F-statistic for the strength of the instrument was 10 (Kleibergen–Paap rk LM P = 0.009). Maternal ferritin was linked to offspring diastolic BP, WC, and BMI in univariable, but not in multivariable OLS analysis. There was no difference between the OLS and the IV models coefficients for any of the outcomes considered.
Conclusion: We found no association between maternal iron status and adult offspring’s BP and adiposity using both multivariable OLS and IV modeling. To our knowledge, this is the first study examining this relationship. Further exploration in larger studies that have genetic variation assessed in both mother and offspring should be considered.

Keywords: iron, pregnancy, developmental origins, Mendelian randomization