Dimitrios Gourgiotis

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.

Immunoassay‐Based Serum Hepcidin Reference Range Measurements in Healthy Children: Differences Among Age Groups

Hepcidin is a peptide hormone that plays a key role in regulating iron absorption from the small intestine and body iron distribution. Alterations in hepcidin concentrations have been associated with chronic inflammatory conditions or inherited diseases of iron metabolism. The aim of our study was to evaluate healthy children in order to define normal reference range of serum hepcidin concentrations. The universal use of a reliable commercial ELISA kit gives the ability to compare our results with those from previous studies.

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).

Midtrimester amniotic fluid concentrations of angiogenic factors in relation to maternal, gestational and neonatal characteristics in normal pregnancies

Objective: To describe associations among maternal/gestational/neonatal characteristics and midpregnancy amniotic fluid concentrations of the main angiogenic markers vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Methods: In a cohort of 206 normal full-term pregnancies, midpregnancy amniotic fluid VEGF and PlGF reference values were recorded. Possible associations among the above concentrations and various parameters, such as maternal age and body mass index, race, parity, smoking, gestational age, delivery mode, birth-weight and fetal gender were investigated. Results: Midpregnancy amniotic fluid concentrations of both VEGF and PlGF increased with increasing gestational age (r = 0.173, p = 0.013 and r = 0.255, p < 0.001, respectively), whereas PlGF concentrations positively correlated with birth-weight (r = 0.154, p = 0.027). The effect of the other above-mentioned parameters on VEGF and PlGF concentrations was not significant. Conclusions: In normal pregnancies, midgestation amniotic fluid VEGF and PlGF concentrations positively correlate with gestational age. Furthermore, midgestation amniotic fluid PlGF concentrations may be a predictor of neonatal birth weight.

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.

Soluble Fas Antigen and Soluble Fas Ligand in Intrauterine Growth Restriction

Background: The Fas-Fas ligand (FasL) pathway of apoptosis contributes to immune tolerance at the fetomaternal interface and has been ascribed a role in implantation and placental development. Intrauterine growth restriction (IUGR) may be associated with impaired maternal-fetal tolerance, resulting in increased trophoblast apoptosis and uteroplacental vascular insufficiency. Objectives: To investigate soluble Fas (sFas) and FasL (sFasL) concentrations in maternal, fetal and neonatal serum of IUGR and appropriate-for-gestational-age (AGA) pregnancies. Methods: Circulating sFas and sFasL concentrations were determined in 40 mothers and their 20 IUGR (due to several etiologies) and 20 AGA singleton full-term fetuses and neonates on postnatal day 1 (N1) and 4 (N4). Results: No significant differences in sFas and sFasL concentrations were observed between groups. In both groups, maternal sFas concentrations were increased compared to fetal, N1 and N4 ones (p≤0.005 in AGA and p < 0.001 in IUGR, in all cases). On the other hand, maternal sFasL concentrations were lower compared to fetal, N1 and N4 ones (p < 0.001 in all cases). Fetal sFasL concentrations were increased compared to maternal, but lower compared to N4 sFasL ones (p < 0.001 in AGA and p ≤ 0.020 in IUGR, in all cases). N4 sFasL concentrations were elevated compared to N1 ones (p < 0.001). Conclusions: Circulating maternal, as well as fetal sFas and sFasL concentrations do not differ between AGA controls and IUGR cases, irrespectively of the etiology of the latter. Furthermore, the results of this study imply an acceleration of Fas-FasL-mediated apoptosis during delivery and a respective decrease postpartum in both normal and IUGR pregnancies.

Biochemical markers of bone resorption are present in human milk: implications for maternal and neonatal bone metabolism

This study investigated breast milk and maternal serum concentrations of biochemical markers of bone resorption, which may be implicated in both maternal and neonatal bone metabolism.