The effect of antenatal iron supplementation on fibroblast growth factor-23 concentration in mothers and infants: a randomised controlled trial in rural Kenya

Abstract

Objectives: Murine studies have shown that iron deficiency during pregnancy can cause abnormal phosphate and bone metabolism in offspring by elevating concentrations of fibroblast growth factor-23 (FGF23). FGF23 exists in plasma as an intact phosphate-and vitamin D-regulating hormone and its C-terminal fragment, a cleavage product that possibly antagonises the intact hormone. These findings are pertinent to low-income countries, where the prevalence of iron deficiency in pregnant women often exceeds 50%, and rickets is the most common non-communicable disorder of children. We aimed to determine the effect of antenatal oral iron supplementation on maternal and infant FGF23 and bone mineral metabolites. Methods: Pregnant women in rural Kenya (n= 470) were randomised to daily supplementation with iron (60 mg, as ferrous fumarate) or placebo from 13–23 weeks gestation until 1 month post-partum. We collected EDTA blood samples at delivery in mothers and infants (cord blood), and measured haemoglobin concentration and plasma markers of iron status (ferritin, hepcidin), inflammation (C-reactive protein), bone metabolism (FGF23; parathyroid hormone; 25-hydroxyvitamin D [25OHD], total alkaline phosphatase, phosphate) and renal function (cystatin C). For FGF23, we used assays that measured either its intact form (I-FGF23), or both intact FGF23 together with its C-terminal fragment (C-FGF23). Results: Iron supplementation improved maternal iron status (as seen by effects on haemoglobin and ferritin concentrations), and increased ferritin concentrations in infants (medians: 130 μg/l vs 108 μg/l, P= 0.008). In addition …