Bone Abstracts

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, antenatal iron supplementation led to reduced C-FGF23 concentrations in mothers (medians: 105 relative units (RU)/ml vs 399 RU/ml, P=0.0001) and infants (means: 491 RU/ml vs 570 RU/ml, P=0.05); increased I-FGF23 in infants (medians: 7.3 μg/l vs 5.8 μg/l, P=0.04); and reduced concentrations of 25OHD in mothers (means: 93 nmol/l vs 100 nmol/l, P=0.01). There were no evident effects on I-FGF23 in mothers, 25OHD in infants, or other markers.

Conclusions: These findings suggest that iron may play a role on maternal and infant skeletal health through its complex effects on FGF23 expression and downstream catabolism, and its effect on maternal vitamin D metabolism. Mechanisms for these actions require further investigation.

Funded through a Royal Society Project Grant and MRC programmes U105960371, U123261351, MC-A760-5QX00 and DfID under the MRC/DfID Concordat.

Disclosure: The authors declared no competing interests.