Purpose: Fibroblast Growth Factor 23 (FGF23) is a hormone produced by osteocytes that targets the heart leading to cardiovascular remodeling and the kidney affecting phosphate homeostasis. Biologically active intact FGF23 (iFGF23) undergoes cleavage into N- terminal and C-terminal FGF23 (cFGF23) which inactivates it. Elevated FGF23 is associated with cardiovascular, renal, metabolic, and bone disease in adults. Levels measured at birth in cord blood may serve as important indicators of fetal programming mechanisms that give rise to these diseases. An important mediator may be intrauterine growth restriction, and therefore the interrelationships between gestational age (GA) and birth weight (BW) with FGF23 at birth require investigation. Methods: Umbilical cord blood samples were collected from an ongoing prospective longitudinal cohort study. 152 infants were included with GA distribution as shown in Table 1, ranging from < 32 weeks preterm to 40+ weeks full term. Umbilical cord blood was collected at delivery, and samples were centrifuged for 10 minutes at 3000rpm and plasma stored at -80°C until assay. Commercially available EIA kits were used to measure plasma iFGF23, cFGF23, and phosphorous. The cFGF23 assay recognizes both iFGF23 (active form) and cFGF23 fragments. Ratios of iFGF23 to cFGF23 (i/c ratio) were calculated for each patient. BW-for-GA percentiles were determined using Fenton growth curves with IUGR defined as BW < 10th percentile for GA. Results: iFGF23 and phosphorus increased with increasing GA, while cFGF23 and i/c ratio did not vary by GA (Table 1). cFGF23 was increased with IUGR, while phosphorus and iFGF23 were not significantly different from the non-IUGR group (Table 2). The i/c ratio showed relatively high cFGF23 to low iFGF23 with IUGR (median ratio < 0.01), indicating that circulating FGF23 is almost completely in the cleaved form in cord blood of the IUGR infants. Conclusion: Cord blood iFGF23 and phosphorus increase with gestational maturity, likely due to phosphorus accretion. In IUGR infants, cFGF23 is significantly elevated with no difference in iFGF23. Higher cFGF23 in lower BW-for-GA infants suggest increased production and cleavage of FGF23 with IUGR. Cleaved FGF23 is thought to act as an mRNA signal to produce more FGF23, and iFGF23 is the active circulating form. One potential mechanism is that chronic fetal hypoxia of IUGR upregulates cFGF23. This increased cleavage may act to conserve phosphorus in the developing fetus, preserving fetal growth as FGF23 contributes to renal phosphorus wasting. Postnatally, cleavage may decrease, leading to increased iFGF23 with persistently high cFGF23. Our findings support a potential mechanistic link between IUGR and later onset metabolic and growth outcomes of low birthweight infants. Cord blood FGF23 may serve as a marker of future cardiovascular and metabolic disease mediated by IUGR.
Cord Blood Cleaved Fibroblast Growth Factor 23 (cFGF23) is Increased with Intrauterine Growth Restricted (IUGR)
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Andrew Franklin, Karen Mestan, Juanita Saqibuddin; Cord Blood Cleaved Fibroblast Growth Factor 23 (cFGF23) is Increased with Intrauterine Growth Restricted (IUGR). Pediatrics May 2018; 142 (1_MeetingAbstract): 162. 10.1542/peds.142.1MA2.162
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