Demetrios Gourgiotis

Perinatal Circulating Visfatin Levels in Intrauterine Growth Restriction

OBJECTIVE. The objective of this study was to investigate possible alterations in circulating levels of the adipocytokine visfatin in intrauterine growth-restricted and normal pregnancies, given that these groups differ considerably in fetal nutrition, body fat mass, and metabolic/endocrine mechanisms. METHODS. Serum visfatin levels were prospectively measured by enzyme immunoassay in 40 mothers and their 40 singleton term fetuses and neonates on postnatal days 1 and 4. Twenty neonates had intrauterine growth restriction (birth weight ≤3rd customized centile, adjusted for parameters that influence growth potential), and 20 were appropriate for gestational age. RESULTS. Circulating maternal visfatin levels were significantly elevated in pregnancies with intrauterine growth restriction compared with control pregnancies with appropriate-for-gestational-age infants and negatively correlated with customized centiles in the group with intrauterine growth restriction. Postnatal day-1 and -4 visfatin levels were significantly higher in neonates with intrauterine growth restriction compared with neonates who were appropriate for gestational age. Postnatal-day-1 prefeeding insulin levels were significantly lower in neonates with intrauterine growth restriction. CONCLUSIONS. Pathologic conditions in pregnancy that lead to intrauterine growth restriction could be responsible for elevated maternal visfatin levels. Higher visfatin levels in neonates with intrauterine growth restriction may serve as an early marker with prognostic value for later development of insulin resistance or type 2 diabetes, whereas lower insulin levels may indicate reduced β-cell mass and/or impaired β-cell function.

Perinatal changes of plasma resistin concentrations in pregnancies with normal and restricted fetal growth.

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.

Circulating Osteoprotegerin and sRANKL Concentrations in the Perinatal Period at Term

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-κB 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 ≤ 0.045 in all cases). N4 sRANKL concentrations were elevated compared with maternal, fetal and N1 ones (p ≤ 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.

Perinatal Changes of Cardiac Troponin-I in Normal and Intrauterine Growth-Restricted Pregnancies

Intrauterine growth restriction (IUGR) implies fetal hypoxia, resulting in blood flow redistribution and sparing of vital organs (brain, heart). Serum cardiac Troponin-I (cTnI), a well-established marker of myocardial ischaemia, was measured in 40 mothers prior to delivery, the doubly clamped umbilical cords (representing fetal state), and their 20 IUGR and 20 appropriate-forgestational-age (AGA) neonates on day 1 and 4 postpartum. At all time points, no differences in cTnI levels were observed between the AGA and IUGR groups. Strong positive correlations were documented between maternal and fetal/neonatal values (r ≥ .498, P ≤ .025 in all cases in the AGA and r ≥ .615, P ≤ .009 in all cases in the IUGR group). These results may indicate (a) normal heart function, due to heart sparing, in the IUGR group (b) potential crossing of the placental barrier by cTnI in both groups.

Cord blood chemerin and obestatin levels in large for gestational age infants

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.

Cord blood nesfatin-1 in large for gestational age pregnancies

OBJECTIVE To investigate possible alterations in cord blood levels of adipokine nesfatin-1 (secreted by adipose tissue and pancreatic β-cells and implicated in glucose metabolism and insulin resistance), as well as insulin, in large (LGA) and appropriate for gestational age (AGA) pregnancies, granted that these groups differ in body fat mass and metabolic/endocrine mechanisms. MATERIALS AND METHODS Cord blood nesfatin-1 and insulin concentrations were prospectively measured in 40 LGA (9 born from diabetic and 31 from non-diabetic mothers) and 20 AGA singleton full-term infants as well as their mothers. RESULTS Cord blood nesfatin-1 concentrations were significantly lower in LGA compared to AGA neonates (b=-0.206, SE 0.07, p=0.005). However, cord blood nesfatin-1 concentrations were elevated in infants born from mothers with gestational diabetes mellitus (GDM), compared to those born from non-diabetic mothers, after controlling for group (b=0.190, SE 0.10, p=0.05). Finally, cord blood nesfatin-1 concentrations were lower in cases of vaginal delivery (b=0.11, SE 0.05, p=0.042). Insulin levels were significantly elevated, as customized centiles increased (b=0.004, SE=0.002, p=0.016). No significant correlation was found between insulin and nesfatin-1 in maternal and umbilical cord levels. CONCLUSIONS In this study nesfatin-1 levels are decreased in LGA compared to AGA fetuses. Fetal nesfatin-1 concentrations are higher in cases of GDM and cord blood nesfatin-1 concentrations are lower in cases of vaginal delivery.

Serum fetuin-A/alpha2-HS-glycoprotein in human pregnancies with normal and restricted fetal growth

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.

Serum Cystatin C in Pregnancies With Normal and Restricted Fetal Growth

The objective of this study was to investigate circulating levels of cystatin C (an important endogenous marker of renal function) in mothers, fetuses, and neonates from intrauterine growth–restricted (IUGR; characterized by impaired nephrogenesis) and appropriate-for-gestational-age (AGA) pregnancies. Serum cystatin C levels were measured by enzyme immunoassay in 40 parturients and their 20 IUGR (≤3rd customized centile, due to gestational pathology) and 20 AGA fetuses and neonates on postnatal day 1 (N1) and 4 (N4). Comparatively, creatinine and urea concentrations were determined in the same samples. Fetal cystatin C levels were higher in the AGA than the IUGR group (P = .001). In both groups, maternal cystatin C levels were lower than fetal (P < .001), N1 (P < .001), and N4 (P < .001) levels. Fetal levels were higher than N1 (P < .001) and N4 (P < .001), and N1 levels were higher than N4 (P = .007) ones. In both groups, no correlation existed between maternal and fetal levels, but positive correlations were found between cystatin C, creatinine, and urea levels in maternal and neonatal samples (in all cases, r ≥ 0.376 and P ≤ .045). Cystatin C levels did not correlate with gestational age and did not differ between males and females. Fetal cystatin C serum levels are lower in the IUGR group, significantly decrease after birth, and do not correlate with maternal levels in both groups. In addition, serum cystatin C levels positively correlate with respective creatinine and urea levels in the perinatal period.

N-terminal parathyroid hormone-related protein levels in human intrauterine growth restricted pregnancies

Background. N‐terminal parathyroid hormone‐related protein has a vital role in regulating cell growth and differentiation, uteroplacental vasodilatation, uterine muscle relaxation, and placental transport. These functions are compromised in intrauterine growth restriction. We aimed to investigate N‐terminal parathyroid hormone‐related protein concentrations in maternal, fetal, and neonatal plasma of intrauterine‐growth‐restricted and appropriate for gestational age pregnancies. Methods. Plasma N‐terminal parathyroid hormone‐related protein levels were determined in 40 mothers and their 20 intrauterine‐growth‐restricted and 20 appropriate for gestational age singleton full‐term fetuses and neonates on postnatal days 1 and 4. Results. Fetal N‐terminal parathyroid hormone‐related protein levels were significantly lower in the intrauterine growth restriction group (b = 1.166, 95%CI: 0.430–1.902, p = 0.003) and correlated with the customized centiles of the infants (r = 0.407, p = 0.009). In the appropriate for gestational age group, neonatal day 1 N‐terminal parathyroid hormone‐related protein levels were significantly lower compared to maternal (p<0.001) and fetal (p = 0.022) ones. Fetal and neonatal day 1 levels were significantly lower in males (b = −1.303, 95%CI: −2.508 to −0.097, p = 0.036, and b = −0.802, 95%CI: −1.5 to −0.105, p = 0.027, respectively). In the intrauterine growth restriction group, maternal N‐terminal parathyroid hormone‐related protein levels were significantly increased compared to fetal (p<0.001) and neonatal day 1 (p = 0.001) levels. Conclusions. The reduced fetal N‐terminal parathyroid hormone‐related protein concentrations in intrauterine growth restriction may reflect compromised placental function and impaired fetal growth, suggesting that N‐terminal parathyroid hormone‐related protein may be involved in the pathogenesis of intrauterine growth restriction.

Adipokines vaspin and omentin-1 are up-regulated in large for gestational age infants at term.

OBJECTIVE Large- (LGA) and appropriate-for-gestational age (AGA) infants differ in body fat mass and metabolic/endocrine mechanisms. We aimed to investigate in LGA and AGA infants possible alterations in cord blood levels of insulin and the adipokines vaspin and omentin-1 which are secreted by the adipose tissue and are implicated in insulin resistance/metabolic syndrome. METHODS Cord blood vaspin, omentin-1 and insulin levels were prospectively measured in 61 LGA and 36 AGA singleton full-term infants. Of the LGA group 13 infants were born from diabetic and 48 from non-diabetic mothers. RESULTS Cord blood vaspin and omentin-1 levels were significantly higher in LGA compared with AGA neonates (p = 0.021 and b = 0.115, SE 0.037, p = 0.002, respectively). Umbilical cord omentin-1 levels were significantly decreased in neonates delivered vaginally (b = -0.075, SE 0.031, p = 0.016), after controlling for group. Insulin levels increased in proportion to the customized centiles of the infants (b = 0.004, SE = 0.001, p = 0.009). Finally, in the LGA group vaspin levels correlated with omentin-1 serum levels (r = 0.318, p = 0.013). CONCLUSIONS The increased levels of vaspin observed in LGA infants compared with AGA ones, possibly represent a defensive mechanism against insulin/glucose dysregulation, commonly seen in the former. In addition, the increased omentin-1 levels in the LGA group could possibly reflect the amount of developing adipose tissue in the early stages of life in this group. Alternatively, these levels could reflect the growth-promoting effect of omentin-1 in the fetus. The inflammation associated with vaginal deliveries may account for the lower cord blood omentin-1 levels in neonates delivered by this mode.