Endocrine Abstracts

Fibroblast growth factor-23 (FGF23), a phosphate-regulating hormone is elevated in hypophosphataemic syndromes and is a predictor of mortality in patients with kidney disease. Recent findings demonstrate iron deficiency as a potential mediator of FGF23 expression and murine studies have shown in utero effects of maternal iron deficiency on FGF23 and phosphate (P) metabolism and bone formation (Clinkenbeard, JBMR, 2013).

The aim of the current study was to investigate the impact of maternal iron status on infant mineral metabolites in humans over the first two years of life. Infants born to mothers with normal (NI n=25) and low (LI n=25) iron status during pregnancy, from a mother-infant trial ISRCTN49285450 from rural Gambia, West Africa, had blood and plasma samples analysed at 12, 24, 52, 78 and 104 weeks of life for circulating haemoglobin (Hb), C-terminal (C-FGF23; Immutopics, USA) and intact-FGF23 (I-FGF23; Kainos, Japan), P, total alkaline phosphatase (TALP) and cystatin C (Cys C) (Kone Analyser 20i, Finland). Circulating I-FGF23, P, TALP and Hb decreased and estimated glomerular filtration rate (eGFR; 74.835/(cys C (mg/l)^1.333) increased over time (mean (S.D.) I-FGF23: 49.1 (13.1) to 34.3 (10.9) pg/ml, P: 1.86 (0.13) to 1.69 (0.17) mmol/l, TALP: 406 (133) to 318 (135) U/l, Hb: 10.7 (1.6) to 9.4 (1.6) g/dl and eGFR: 59.9 (11.2) to 94.5 (23.4) ml/min all P≤0.0001)). C-FGF23 did not change significantly over time (402 (218) to 487 (502) RU/ml, P=0.15). C-FGF23 and TALP were significantly higher in LI compared with NI from 52 weeks for C-FGF23 (52 weeks: 732 (702) vs 334 (225), 78 weeks: 702 (827) vs 417 (754) and 104 weeks: 628 (628) vs 347 (283) RU/ml) and from 24 weeks for TALP (24 weeks: 373 (153) vs 306 (77), 78 weeks: 310 (106) vs 258 (66), 104 weeks: 340 (162) vs 289 (93) U/l). Adjusted for timepoint Hb was the strongest negative predictor of C-FGF23 concentration (Beta coefficient (S.E.) −104.1 (27.28) RU/ml, P≤0.0002; group difference P=0.03) and P the strongest positive predictor of I-FGF23 (31.4 (3.9) pg/ml, P≤0.0001, group difference P=0.8) and I-FGF23 did not predict C-FGF23 (−2.68 (3.56) RU/ml, P=0.45, group difference P=0.03). In conclusion, this study suggests that poor maternal iron status leads to an increased infant C-FGF23 and TALP concentration in humans. Further studies are required to investigate the role of maternal iron status in the regulation of offspring FGF23 status and mineral metabolism.

Disclosure: This research was jointly funded by the UK Medical Research Council (MRC) & the Department for International Development (DFID) under the MRC/DFID Concordat agreement. MRC programmes: U105960371, U123261351 & MC-A760-5QX00.