Theodora Boutsikou

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.

Associations of novel adipocytokines with bone biomarkers in intra uterine growth-restricted fetuses/neonates at term

Abstract Objective: To prospectively investigate the potential associations of the novel adipocytokines resistin, apelin and visfatin (recently implicated in bone metabolism) with bone biomarkers in fetal and neonatal blood from intra uterine growth restricted (IUGR, associated with low bone mass at birth) and appropriate for gestational age (AGA) pregnancies. Methods: Circulating concentrations of resistin, apelin and visfatin were correlated with concentrations of markers of bone formation [osteocalcin (OC), bone-specific alkaline phosphatase (BALP)] and resorption [osteoprotegerin (OPG), soluble receptor activator of nuclear factor-κB ligand (sRANKL) and cross-linked N-telopeptide of type I collagen (NTx)] in 20 IUGR and 20 AGA full-term fetuses and neonates on postnatal day 1-(N1) and 4-(N4). Results: In the AGA group, fetal resistin and N1 visfatin concentrations negatively correlated with respective NTx ones (r ≥ −0.472, p ≤ 0.036 in both cases). In the IUGR group, fetal and N4 resistin concentrations negatively correlated with sRANKL concentrations (r ≥ −0.583, p ≤ 0.007 in both cases). Furthermore, fetal apelin and visfatin concentrations positively correlated with fetal BALP ones (r ≥ 0.471, p ≤ 0.042, in both cases). Conclusions: All three adipocytokines may exert a positive effect on fetal/neonatal bone metabolism, either by inhibiting bone resorption or promoting bone formation in both normal and IUGR pregnancies. Although the mechanisms behind these correlations are unclear, a modulation of perinatal bone metabolism by these adipocytokines may be suggested.

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.

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.

Cord blood netrin-1 and -4 concentrations in term pregnancies with normal, restricted and increased fetal growth

Abstract Objective: To determine levels of the possible angioregulatory molecules netrin-1 and -4, in intrauterine-growth-restricted (IUGR), large for gestational age (LGA) (both groups characterized by altered angiogenic mechanisms) and appropriate-for-gestational-age (AGA) pregnancies. Methods: Cord blood (UC) netrin-1 and -4 concentrations were measured in 30 IUGR, 30 LGA and 20 AGA infants and their mothers (MS). Results: Netrin-1 and -4 concentrations did not differ in all groups. UC netrin-4 increased with gestational age (b = 0.075, 95% CI 0.029–0.121, p = 0.002). In the IUGR group, MS netrin-4 decreased as birth-weight centiles increased [b = −0.058, 95% CI −0.112 to −0.004, p = 0.036]. In the LGA group, MS netrin-1 decreased with advanced gestational age [b = −0.063, 95% CI −0.105 to −0.022, p = 0.004]. In all cases, MS netrin-1 positively correlated with MS netrin-4 (r = 0.299, p = 0.007), while UC netrin-1 negatively correlated with UC netrin-4 (r = −0.239, p = 0.033). Conclusions: Increased UC netrin-4 levels with advancing gestational age may reflect its effect on fetal development. Decreased maternal netrin-1 levels in the LGA group possibly represent a negative feedback mechanism against increased angiogenesis. Increased maternal netrin-4 levels in IUGR neonates may reflect in utero hypoxia, while the negative correlations between fetal netrin-1 and -4 levels may exert the dynamic balance between their angio- and anti-angiogenic properties.

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.

Relationships between maternal novel adipocytokines and bone biomarkers in complicated by gestational hypertensive disorders and normal pregnancies.

Abstract Objective: To investigate possible associations of the novel adipocytokines resistin, apelin and visfatin (implicated in the complex control of bone biology) with several biochemical determinants of bone turnover in maternal blood from normal pregnancies and pregnancies complicated by gestational hypertensive disorders (preeclampsia or pregnancy-induced hypertension). Methods: Circulating maternal concentrations of resistin, apelin and visfatin were correlated with circulating markers of bone formation [osteocalcin (OC), bone-specific alkaline phosphatase (BALP)] and resorption [osteoprotegerin (OPG), soluble receptor activator of nuclear factor-κB ligand (sRANKL) and cross-linked N-telopeptide of type I collagen (NTx)] in full-term pregnancies (20 normal and 20 complicated by gestational hypertensive disorders). Results: In normal pregnancies, no correlation was recorded between maternal concentrations of adipocytokines and the above bone biomarkers. In pregnancies with gestational hypertensive disorders, maternal apelin concentrations negatively correlated with NTx ones (r = −0.489, p = 0.034), while maternal visfatin concentrations positively correlated with OPG ones (r = 0.464, p = 0.039). Conclusions: No associations were found between maternal concentrations of all three studied adipocytokines and respective concentrations of bone biomarkers in normal pregnancies. By contrast, in pregnancies with gestational hypertensive disorders, maternal concentrations of apelin and visfatin correlated with respective concentrations of indices of bone turnover. Further prospective studies are needed to clarify these relationships.