Heparin-Binding Angiogenic Factors (Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor) in Early Neonatal Life

Abstract

This study investigated whether serum levels of the potent angiogenic factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), which are abundantly produced in utero by the placenta and fetal tissues, change after birth at term, consequent to diminished angiogenic but increased adaptational demands in extrauterine life. Moreover, whether serum levels of the above factors correlate with sex, birth weight, or mode of delivery was also evaluated. One milliliter of blood was drawn from 30 healthy, appropriate for gestational age, full-term infants on d 1 (N1) and 4 (N4) postnatally. In 10 of the above cases maternal and umbilical cord blood samples were also drawn. Serum was analyzed by enzyme immunoassays, using commercial kits. Levels of bFGF and VEGF were significantly lower in maternal serum than in umbilical cord (p = 0.02 and 0.036, respectively) or N1 (p = 0.009 and 0.006, respectively) and N4 serum (p = 0.009 and 0.006, respectively). Levels of bFGF in umbilical cord serum did not differ significantly from those in N1 and N4. In contrast, levels of VEGF rose in N1, differing significantly from levels in umbilical cord serum (p = 0.008). Both factors did not change from N1 to N4. Neither bFGF nor VEGF serum levels depended on sex, mode of delivery, or birth weight. In conclusion, bFGF levels in neonates do not differ from levels in fetuses, possibly reflecting diminished angiogenesis in extrauterine life, which already has started in utero. On the contrary, neonatal levels of VEGF rise significantly after birth, possibly signifying adaptation demands, in addition to angiogenesis, as VEGF is also considered a regulator of normal function.

Vascular Endothelial Growth Factor and Angiogenin Levels during Fetal Development and in Maternal Diabetes

“…A marked increase in plasma VEGF has occurred in term infants postnatally [19]. Similarly, a rapid postnatal increase has been reported in circulatory angiogenin levels during the first postnatal days [20]; moreover, this increase in angiogenin levels has been shown to continue until adulthood [21].…”

“…In what is, to our knowledge, the first study to compare VEGF concentrations between preterm and term fetuses, we discovered correlations between gestational age and both VEGF and angiogenin concentrations in umbilical cord plasma; previously no correlations seem to have been noted between gestational age and pulmonary VEGF levels in preterm infants nor between gestational age and circulatory VEGF levels in term infants [18,19]. A marked increase in plasma VEGF has occurred in term infants postnatally [19].…”

VEGF increases engraftment of bone marrow-derived endothelial progenitor cells (EPCs) into vasculature of newborn murine recipients

“…In contrast, disruption of VEGF Ϸ4 weeks after birth had no effect on mortality and only minor effects on tissue vascularity, suggesting a developmental switch in VEGF-mediated new blood vessel formation. Another group reported that VEGF levels increased dramatically after birth in human neonates (27). These findings suggest that neovascularization in the immediate postnatal period, in contrast to the adult animal, may be sensitive to VEGF.…”

“…Newborn serum VEGF levels increase sharply after birth and are higher than adult levels (27). Because VEGF is known to increase circulating BM-EPCs (28), the relative numbers of circulating BM-EPCs may be higher in the newborn period.…”

Angiogenic Growth Factors in Patients with Cyanotic Congenital Heart Disease and in Normal Children.

“…Ariadne and colleagues reported that the plasma level of VEGF rose significantly in early neonatal life compared with the levels in umbilical cord blood [21]. Increase of VEGF in the early neonatal period may reflect the physiological development of vessels in the neonatal period [22].…”