Stavroula Baka

Blood visfatin concentrations in normal full-term pregnancies

Aim: To prospectively investigate blood visfatin concentrations during the perinatal period in normal pregnancies.

Omentin-1 and vaspin are present in the fetus and neonate, and perinatal concentrations are similar in normal and growth-restricted pregnancies

The aim of this study was to investigate circulating concentrations of omentin-1 and vaspin (adipocytokines predominantly secreted by visceral adipose tissue and not yet investigated in perinatal life) in maternal, fetal, and neonatal samples from intrauterine growth-restricted (IUGR; associated with altered development of adipose tissue) and appropriate-for-gestational-age (AGA) pregnancies and to correlate them with the respective insulin concentrations. Serum omentin-1 and vaspin concentrations were determined by enzyme immunoassay 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). Both hormones were detectable in fetal and neonatal blood (omentin-1 [mean ± SD, in nanograms per milliliter]: AGA vs IUGR group--fetal: 11.32 ± 1.88 vs 10.47 ± 1.30, N1: 10.74 ± 1.42 vs 10.46 ± 1.54, and N4: 10.90 ± 2.72 vs 11.35 ± 3.92; vaspin [median, minimum-maximum; in nanograms per milliliter]: AGA vs IUGR group--fetal: 0.39 [0.04-19.06] vs 0.40 [0.05-1.34], N1: 0.40 [0.04-16.70] vs 0.44 [0.23-3.34], and N4: 0.49 [0.02-8.89] vs 0.55 [0.06-3.92]). No significant differences in omentin-1 or vaspin concentrations were observed between IUGR and AGA groups, whereas fetal and N1 insulin concentrations were lower in the former (P = .025 and P = .027, respectively). In both groups, fetal omentin-1 concentrations were higher (P ≤ .018), whereas vaspin concentrations were lower (P ≤ .001), than maternal ones. Furthermore, maternal vaspin concentrations were higher in cases of cesarean delivery (P = .024). Omentin-1 and vaspin concentrations did not correlate with the respective insulin ones. In conclusion, omentin-1 and vaspin are present in the fetus and neonate. Perinatal concentrations of omentin-1 and vaspin are similar in IUGR cases and AGA controls--despite lower insulin concentrations in the former--and do not correlate with the respective insulin concentrations. Higher omentin-1 concentrations in the fetus may be crucial to enhance a growth-promoting effect, whereas lower maternal vaspin concentrations in cases of vaginal delivery may be attributed to spontaneous term delivery inflammation.

Circulating apelin concentrations in mother/infant pairs at term

Aim: To prospectively investigate circulating concentrations of the adipokine and angiogenic factor apelin in mother/infant pairs and correlate them with respective insulin concentrations.

Fetal concentrations of the growth factors TGF-α and TGF-β1 in relation to normal and restricted fetal growth at term

Transforming growth factor-α (TGF-α) and TGF-β1 are major anti-inflammatory cytokines and substantially contribute to normal pregnancy outcome. TGF-α stimulates placental mitosis, whereas TGF-β1 is a critical regulator of trophoblast invasion and fetal growth. We aimed to study cord blood TGF-α and TGF-β1 concentrations in intrauterine-growth-restricted (IUGR, usually associated with abnormal trophoblast invasion, uteroplacental vascular insufficiency and enhanced inflammation) and appropriate-for-gestational-age-(AGA) pregnancies, and investigate possible correlations of the above concentrations with several demographic parameters of infants at birth. Plasma TGF-α and TGF-β1 concentrations were determined by ELISA in 154 mixed arterio-venous cord blood samples from IUGR (n=50) and AGA (n=104) singleton full-term infants. After controlling for possible confounding factors (gender, birth-weight, gestational age, maternal age and parity), cord blood TGF-α and TGF-β1 concentrations were significantly higher in IUGR than AGA group (b=0.402, SE=0.179, p=0.027 and b=0.152, SE=0.061, p=0.014, respectively). Delivery mode had an effect on cord blood TGF-α and TGF-β1 concentrations, both being elevated in cases of vaginal delivery (b=-0.282, SE=0.117, p=0.018 and b=-0.123, SE=0.059, p=0.038, respectively). In conclusion, higher cord blood TGF-α and TGF-β1 concentrations may represent a compensatory response to the inflammatory process characterizing the IUGR state. Additionally, higher cord blood TGF-β1 concentrations in IUGRs could be attributed to increased shear stress, resulting from abnormal blood flow in IUGR fetal blood vessels. Finally, vaginal delivery-associated cytokine release may account for elevated TGF-α and TGF-β1 concentrations.

Perinatal role of hepcidin and iron homeostasis in full-term intrauterine growth–restricted infants

To prospectively investigate iron homeostasis in full‐term intrauterine growth–restricted (IUGR) and appropriate‐for‐gestational‐age (AGA) infants at birth, by evaluating cord blood concentrations of hepcidin (a bioactive molecule, principal regulator of iron metabolism, downregulated by hypoxia/iron deficiency and upregulated by inflammation), erythropoietin (EPO, a marker of prolonged fetal hypoxia), soluble transferrin receptor (sTfR, a marker of increased erythropoiesis and tissue iron deficiency), iron, ferritin, and unsaturated iron‐binding capacity (UIBC).

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.

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.

Cord blood copeptin concentrations in fetal macrosomia

BACKGROUND/AIM Excessive fetal growth is associated with increased adiposity and reduced insulin sensitivity at birth. Copeptin, a surrogate marker of arginine vasopressin (AVP) secretion, is upregulated in states of hyperinsulinemia and is considered one of the mediators of insulin resistance. We aimed to investigate cord blood concentrations of copeptin (C-terminal fragment of AVP pro-hormone) in healthy large-for-gestational-age (LGA) infants at term. METHODS This prospective study was conducted on 30 LGA (n=30) and 20 appropriate-for-gestational-age (AGA, n=20) singleton full-term healthy infants. Cord blood copeptin and insulin concentrations were determined by ELISA and IRMA, respectively. Infants were classified as LGA or AGA, based on customized birth-weight standards adjusted for significant determinants of fetal growth. RESULTS Cord blood copeptin concentrations were similar in LGA cases, compared to AGA controls, after adjusting for delivery mode. However, in the LGA group, cord blood copeptin concentrations positively correlated with birth-weight (r=0.422, p=0.020). In the AGA group, cord blood copeptin concentrations were elevated in cases of vaginal delivery vs elective cesarean section (p=0.003). Cord blood insulin concentrations were higher in LGA cases, compared to AGA controls (p=0.036). No association was recorded between cord blood copeptin concentrations and maternal age, parity, gestational age or fetal gender in both groups. CONCLUSIONS Cord blood copeptin concentrations may not be up-regulated in non-distressed LGA infants. However, the positive correlation between cord blood copeptin concentrations and birth-weight in the LGA group may point to the documented association between AVP release and increased fat deposition. Vaginal delivery vs elective cesarean section is accompanied by a marked stress-related increase of cord blood copeptin concentrations.