Farah N Ali1, Jami Josefson1, Armando J Mendez1, Karen Mestan1, Myles Wolf1. 1. Department of Pediatrics (F.N.A., J.J., K.M.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611; Center for Translational Metabolism and Health (F.N.A., M.W.), Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Department of Medicine (A.J.M.), Division of Endocrinology, Diabetes and Metabolism, and The Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida 33021; Division of Nephrology and Hypertension (M.W.), Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
Abstract
CONTEXT: Elevated levels of the phosphate-regulating hormone, fibroblast growth factor-23 (FGF-23) are associated with skeletal and cardiovascular disease. Levels of FGF-23 are elevated in neonates, but the mechanisms are poorly understood. Iron deficiency is a recently described stimulus for FGF-23 production. OBJECTIVE: To test the hypothesis that lower fetal iron status, as measured by lower cord blood ferritin, is independently associated with elevated FGF-23 levels in neonates. DESIGN AND PARTICIPANTS: This is a cross-sectional study of 64 full-term, healthy neonates. SETTING: This study took place in a university-based, tertiary care center. MAIN OUTCOME MEASURES: Plasma levels of second generation C-terminal FGF-23 (cFGF-23) and intact FGF-23 (iFGF-23). RESULTS: Levels of cFGF-23 ranged from 108 to 7508 reference units (RU)/ml (median, 824 RU/ml), and iFGF-23 from undetectable (<8.5) to 135.4 pg/ml (median, <8.5 pg/mL). Ferritin ranged from 58 to 719 ng/ml (mean, 203 ng/ml). Lower cord blood ferritin levels were associated with higher cFGF-23 (r = −0.320; P = .014), but not iFGF-23 levels (r = −0.222; P = .082). In multivariate analyses adjusted for glycemic indices, maternal race, and parity, lower ferritin levels remained independently associated with higher cFGF-23 levels (B = −0.261, P = .01). In the full models, higher cord blood glucose and C-peptide levels were also independently associated with higher cFGF-23 levels. CONCLUSIONS: cFGF-23, but not iFGF-23 levels, are elevated in cord blood of healthy term neonates and independently associated with lower serum ferritin and higher glycemic indices.
CONTEXT: Elevated levels of the phosphate-regulating hormone, fibroblast growth factor-23 (FGF-23) are associated with skeletal and cardiovascular disease. Levels of FGF-23 are elevated in neonates, but the mechanisms are poorly understood. Iron deficiency is a recently described stimulus for FGF-23 production. OBJECTIVE: To test the hypothesis that lower fetal iron status, as measured by lower cord blood ferritin, is independently associated with elevated FGF-23 levels in neonates. DESIGN AND PARTICIPANTS: This is a cross-sectional study of 64 full-term, healthy neonates. SETTING: This study took place in a university-based, tertiary care center. MAIN OUTCOME MEASURES: Plasma levels of second generation C-terminal FGF-23 (cFGF-23) and intact FGF-23 (iFGF-23). RESULTS: Levels of cFGF-23 ranged from 108 to 7508 reference units (RU)/ml (median, 824 RU/ml), and iFGF-23 from undetectable (<8.5) to 135.4 pg/ml (median, <8.5 pg/mL). Ferritin ranged from 58 to 719 ng/ml (mean, 203 ng/ml). Lower cord blood ferritin levels were associated with higher cFGF-23 (r = −0.320; P = .014), but not iFGF-23 levels (r = −0.222; P = .082). In multivariate analyses adjusted for glycemic indices, maternal race, and parity, lower ferritin levels remained independently associated with higher cFGF-23 levels (B = −0.261, P = .01). In the full models, higher cord blood glucose and C-peptide levels were also independently associated with higher cFGF-23 levels. CONCLUSIONS: cFGF-23, but not iFGF-23 levels, are elevated in cord blood of healthy term neonates and independently associated with lower serum ferritin and higher glycemic indices.
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