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Objective: To investigate possible alterations in cord blood levels of adipokines, chemerin and obestatin (secreted by adipose tissue and associated with later development of insulin resistance/metabolic syndrome), as well as insulin, in large for gestational age (LGA) and appropriate for gestational age (AGA) pregnancies, granted that these groups differ in body fat mass and metabolic/endocrine mechanisms., Methods: Cord blood chemerin, obestatin, and insulin concentrations were prospectively measured in 40 LGA (9 born from diabetic and 31 from nondiabetic mothers) and 40 AGA singleton full-term infants., Results: Cord blood chemerin concentrations were significantly higher in LGA compared with AGA neonates (b = 38.91, SE 9.29, p < 0.001). In contrast, no significant differences in obestatin concentrations were observed between groups. Insulin levels were significantly elevated as customized centiles increased (b = 0.003, SE = 0.001, p = 0.032)., Conclusions: Higher chemerin concentrations in LGA neonates possibly reflect the increased adipose tissue in this group. Lack of difference between the two groups in circulating levels of obestatin-possibly a sensitive marker of insulin resistance-might be due to development of metabolic disorders later in life.

Background: Intrauterine growth restriction (IUGR) has been associated with low bone mass in infancy and increased risk for osteoporosis development in adult life. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) are main determinants of bone resorption., Objectives: To investigate OPG and soluble RANKL (sRANKL) concentrations in maternal, fetal and neonatal serum of IUGR patients and appropriate for gestational age (AGA) pregnancies. Additionally, plasma intact parathormone (PTH) concentrations were evaluated., Methods: Circulating OPG, sRANKL and PTH concentrations were measured in 40 mothers and their singleton full-term fetuses-neonates (AGA: n = 20, and IUGR: n =20) on postnatal days 1 (N1) and 4 (N4)., Results: No significant differences in OPG, sRANKL or PTH concentrations were observed between AGA and IUGR groups. In both groups, maternal OPG concentrations were elevated compared with fetal, and N1 and N4 concentrations (p < or = 0.045 in all cases). N4 sRANKL concentrations were elevated compared with maternal, fetal and N1 ones (p < or = 0.01 in all cases). Fetal and N1 sRANKL concentrations correlated positively with PTH levels (r = 0.642, p = 0.024 and r = 0.584, p = 0.046, respectively)., Conclusions: The lack of a difference in circulating OPG, sRANKL or PTH concentrations between IUGR cases and AGA controls suggests that the low bone mass of IUGR infants may not be related to higher bone resorption rates. The increased maternal, compared with fetal/neonatal, OPG concentrations may suggest their placental origin. The lower OPG and higher sRANKL concentrations in fetuses and neonates could represent high bone resorption rates., (Copyright 2009 S. Karger AG, Basel.)

Objective: To investigate circulating concentrations of human fetuin-A (important fetal glycoprotein, involved in vascular pathology and bone metabolism) in mothers, fetuses and neonates from intrauterine-growth-restricted (IUGR, associated with low bone mass at birth and metabolic syndrome in adult life) and appropriate-for-gestational-age (AGA) pregnancies., Methods: Serum fetuin-A concentrations were prospectively measured in 40 mothers, the doubly-clamped umbilical cords (representing fetal state) and their 20 IUGR and 20 AGA full-term neonates on postnatal day 1 (N1) and 4 (N4)., Results: No significant differences in fetuin-A concentrations were observed between groups, or between maternal, fetal and neonatal samples in both groups. In the AGA group, maternal fetuin-A concentrations positively correlated with fetal and N1 ones (r = 0.599, p = 0.005 and r = 0.469, p = 0.037, respectively). In the IUGR group, maternal fetuin-A concentrations positively correlated with N4 ones (r = 0.541, p = 0.014)., Conclusion: Serum fetuin-A concentrations do not differ between IUGR cases and AGA controls. Maternal and fetal fetuin-A concentrations are similar and positively correlated, indicating the likelihood of passive transplacental transfer of this substance.

Background: The adipocytokine resistin inhibits adipogenesis and induces insulin resistance. Intrauterine growth-restricted (IUGR) neonates have reduced fat mass and changes of endocrine/metabolic mechanisms, predisposing to insulin resistance and metabolic syndrome in adult life., Objectives: To investigate plasma resistin concentrations in maternal, fetal and neonatal samples from IUGR and appropriate-for-gestational-age (AGA) pregnancies and correlate them with respective insulin concentrations., Methods: Plasma resistin and insulin concentrations were determined in 40 mothers and their 20 IUGR and 20 AGA singleton full-term fetuses and neonates on postnatal day 1 (N1) and day 4 (N4)., Results: No significant differences in resistin concentrations were observed between AGA and IUGR groups. In the AGA group, maternal resistin concentrations were significantly lower compared to fetal, N1 and N4 ones (p = 0.003, p = 0.017 and p = 0.039, respectively). Maternal resistin concentrations positively correlated with fetal ones (r = 0.527, p = 0.02). In the IUGR group, maternal resistin concentrations were significantly lower compared to N1 (p < 0.001) and positively correlated with N4 concentrations (r = 0.626, p = 0.007). In both groups, the effect of gender, mode of delivery, parity and adjusted birth weight (customized centiles) on resistin concentrations was not significant. No correlation between resistin and insulin concentrations was documented., Conclusions: Lack of difference in resistin concentrations between IUGR and AGA groups, and lack of correlation between resistin and insulin concentrations as well as customized centiles, possibly suggests that resistin may not be directly involved in the regulation of insulin sensitivity and adipogenesis in the perinatal period. Mode of delivery and parity are not associated with circulating resistin concentrations., (Copyright (c) 2007 S. Karger AG, Basel.)

Aim: To prospectively investigate circulating concentrations of the adipokine and angiogenic factor apelin in mother/infant pairs and correlate them with respective insulin concentrations., Methods: Plasma apelin concentrations were determined in 40 mothers and their singleton full-term foetuses and neonates on day 1 (N1) and 4 (N4) of life., Results: Maternal apelin concentrations were lower compared to foetal, N1 and N4 ones (p<0.001 in all cases). N1 apelin concentrations were lower compared to foetal and N4 ones (p=0.002 and p=0.005, respectively). Maternal apelin concentrations positively correlated with foetal, N1 and N4 concentrations (r=0.663, p<0.001, r=0.486, p=0.003, r=0.484, p=0.003, respectively). Foetal apelin concentrations positively correlated with N1 and N4 ones (r=0.337, p=0.044 and r=0.574, p<0.001, respectively). N1 apelin concentrations positively correlated with N4 ones (r=0.513, p=0.001). No association was found between apelin concentrations and birthweight, gender, parity or mode of delivery. No significant correlations were observed between apelin and insulin concentrations., Conclusions: Concentrations of apelin are high in the foetus, possibly suggesting its potential role in intrauterine development. Apelin expression in placental tissue could account for its higher foetal concentrations and for its down-regulation soon after birth. The postnatal increase of apelin concentrations could presumably point to a gradual initiation of ex utero angiogenesis.

Aim: To prospectively investigate blood visfatin concentrations during the perinatal period in normal pregnancies., Methods: Visfatin concentrations were determined in maternal, umbilical cord (representing the foetal state) and neonatal blood on day 1 (N1) and 4 (N4)., Results: Maternal and foetal visfatin concentrations were similar (18.83+/-4.27 and 19.35+/-4.90 ng/mL, respectively). There were significant correlations between maternal and foetal (r=0.742, p<0.001), as well as between N1 and N4 (r=0.487, p=0.029) visfatin concentrations. Foetal concentrations were significantly elevated compared to N1 (p=0.032). There was no difference between N1 and N4 concentrations. However, there was a correlation between birth weight and neonatal visfatin concentrations: there was a mean increase in N1 and N4 visfatin concentrations by 0.221 ng/mL and 0.292 ng/mL, respectively, for every unit increase in customized centile (adjusted birth weight) (p=0.021 and p=0.005, respectively). No association was found between serum visfatin concentrations and gender, parity or mode of delivery., Conclusions: Expression in foetal membranes and placental transfer could be responsible for higher blood visfatin concentrations during intrauterine life. Customized centiles seem to be independent predictor variables for postnatal visfatin concentrations. This finding could be attributed to the production of visfatin in adipose tissue, a main contributor to birth weight and consequently to customized centiles.

Neurotrophins (NTs), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 are of major importance in prenatal and postnatal brain development, due to their neuroprotective action. Developmental changes alter the neuronal responsiveness to certain NTs, which subsequently are variously expressed, to properly balance their action. The following study aimed at examining the pattern of perinatal changes of the four NTs--NGF, BDNF, NT-3, and NT-4 in 30 appropriate for gestational age (AGA) full-term fetuses and neonates by determining their circulating levels at characteristic time points. This study show a gradual decrease of circulating levels of the NTs, NT-3 and NT-4 from umbilical cord (UC) to neonates day 4 (N4), while circulating levels of NGF and BDNF present the opposite pattern: an increase from UC to N4. These patterns of perinatal changes differ according to their impact on the process of neuronal development and their reaction to perinatal stress. NT3 and NT4 have been documented to act at early stages of neuronal development and to decrease after hypoxia-ischemia, while NGF and BDNF to increase. Further studies should investigate these patterns in premature or full-term infants, presenting various pathological conditions in the perinatal period.

Background: Angiogenesis, a critical process for growth and development is altered in intrauterine growth restriction (IUGR). Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1, soluble (s) VEGFR-1 and VEGFR-2 represent a regulatory system, essential for both physiological and pathological angiogenesis., Aim: To study the implication of sVEGFR-1-a VEGF antagonist-in IUGR., Study Design: Prospective study., Methods: Twenty-five IUGR and 15 appropriate for gestational age (AGA) full-term fetuses and neonates with their mothers were included in the study., Outcome Measures: sVEGFR-1 levels were determined by enzyme immunoassay in the serum of: mothers (MS), umbilical cords (UC)-representing fetal state - and neonates on day 1 (N1) and 4 (N4) of life., Results: MS, UC, N1 and N4 sVEGFR-1 levels in IUGR were significantly higher compared to respective AGA cases (p = 0.005, p = 0.026, p = 0.005 and p = 0.017, respectively). In IUGR and AGA groups, maternal sVEGFR-1 levels were significantly higher than fetal and neonatal levels (p in all cases < 0.001). The latter presented in both IUGR and AGA groups a significant decrease from UC to N4 (p in all cases < 0.01). MS, N1 and N4 sVEGFR-1 levels negatively correlated with the infants' customized centiles [(r = -0.489, p = 0.001), (r = -0.440, p = 0.004), (r = -0.431, p = 0.006), respectively]., Conclusions: Higher sVEGFR-1 levels in the IUGR as compared to the AGA group possibly reflect the predominance of antiangiogenic mechanisms present in IUGR. The decrease of sVEGFR-1 levels from UC to N4 may represent ex utero initiation of growth and development and therefore, prevalence of angiogenic mechanisms.