Role of FGF-19, FGF-21 and FGF-23 in Fetal and Neonatal Growth

Background: The Fibroblast Growth Factor (FGF) 19 subfamily plays a key role in the regulation of metabolic and growth processes, and their dysregulation can lead to fetal growth disorders, such as small for gestational age (SGA) and large for gestational age (LGA), as well as to pathogenesis and development of gestational diabetes and gestational hypertension. Methods: We conducted a narrative review using the PRISMA2020 statement. Two electronic databases were searched: PubMed and Web of Science until October 2024. The search terms were as follows: (FGF-21 OR fibroblast growth factor-21 OR FGF-23 OR fibroblast growth factor-23 OR FGF-19 OR fibroblast growth factor-19) AND (human fetus development OR fetal growth OR infancy). We only included original papers that analysed the effect of FGF-19,21,23 on pre- and postnatal development. Results: Only 6 out of 203 studies met the inclusion criteria. There were higher concentrations of FGF-21 among patients with gestational diabetes mellitus (GDM) compared to healthy females, but no differences were found in FGF-21 values in newborn's umbilical cord blood. Interestingly, higher FGF-21 concentrations were observed in females than males born to patients with GDM. FGF-19 was linked to fetal development by its association with chronic insulin secretion levels during fetal life, particularly in female newborns, but no significant correlation with GDM was found. The evaluation of the role of FGF-23 has shown that its low level could be related to gestational hypertension and fetal growth restriction. Conclusions: In conclusion, all the studies discussed suggest that FGF-19 subfamily factors may play an important role in fetal and neonatal growth and development, particularly in pregnancies complicated by metabolic disorders, such as gestational diabetes or gestational hypertension. Differences in FGF-19 and FGF-21 concentrations based on gender and gestational disorders suggest the need for further research in order to fully understand the effects of these proteins and their potential clinical applications.