Demetrios Hassiakos

Leptin and adiponectin concentrations in intrauterine growth restricted and appropriate for gestational age fetuses, neonates, and their mothers.

OBJECTIVE Leptin and adiponectin are two adipocytokines that play a critical role in the control of energy balance and metabolism as well as in conditions, such as insulin resistance, inflammation, and the development of the metabolic syndrome in adult life. Leptin has been associated with asymmetric intrauterine growth restriction (IUGR). The aim of this study was to investigate the perinatal implication of leptin and adiponectin in IUGR. Design Leptin and adiponectin were measured in the plasma of 40 mothers, in the umbilical cord (UC) blood of their 20 appropriate for gestational age (AGA) and 20 IUGR singleton, full-term fetuses, and neonates on day 1 (d1) and day 4 (d4) of life postnatally. METHODS Serum leptin and adiponectin levels were measured by RIA. Serum cortisol levels were measured with an electrochemiluminescence immunoassay. RESULTS Leptin and adiponectin serum levels were higher and lower respectively in IUGR (mean+/-s.e.m., 32.5+/-3.8 and 5.4+/-0.9 mug/l respectively) compared with AGA (20.4+/-2.1 and 11.8+/-1.3 mug/l respectively) mothers (P<0.05), although body mass index did not differ between these two groups. Leptin levels positively correlated with adiponectin levels in the AGA (r=0.547, P<0.05) but not in the IUGR mothers. UC, d1, and d4 leptin and adiponectin levels did not differ between IUGR and AGA groups. UC were significantly higher than d1 leptin levels (P<0.05) in the IUGR group but not in the AGA group. CONCLUSIONS The increased UC leptin levels compared with d1 in IUGR fetuses might be directly and/or indirectly related to the subsequent development of insulin resistance in these neonates. This pathologic situation seems to be related to a specific profile of increased leptin and decreased adiponectin levels in IUGR mothers indicating a genetic predisposition for the development of insulin resistance.

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.

Elevated placental growth factor concentrations at 11–14 weeks of gestation to predict gestational diabetes mellitus

OBJECTIVE To examine maternal serum concentrations of placental growth factor (PlGF) at 11-14 gestational weeks in pregnancies that developed gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. METHODS Case control study including 40 GDM cases and 94 controls. PlGF, biophysical and biochemical markers and maternal-pregnancy characteristics were analyzed. RESULTS Log10 transformed PlGF (log10 PlGF) was not related to maternal factors. Log10 PlGF was increased (p=0.008) in the GDM group compared to the control group. Log10 PlGF was associated with fasting glucose levels (p=0.04) in the oral glucose tolerance test. Log10 PlGF had a strong relation with birth weight adjusted for gestational age in the control but not in the GDM group. Maternal weight and maternal age were the only predictors of GDM among the maternal factors [area under the curve (AUC)=0.73, p<0.001]. Log10 PlGF alone was a significant predictor of GDM (AUC=0.63, p<0.001). Combination of maternal weight, maternal age and log10 PlGF resulted in an improved prediction (DR=71.4%, for 25% FPR, AUC=0.78, Model R(2)=0.17, p<0.001). CONCLUSION At 11-14weeks in pregnancies that develop GDM, the maternal serum levels of PlGF are increased. Measurement of serum PlGF at 11-14weeks improves the performance of early screening for GDM provided by maternal factors alone.

Circulating Levels of Inflammatory Markers in Intrauterine Growth Restriction

We aimed to investigate possible alterations in circulating levels of the perinatal stress markers high sensitivity (hs)-CRP, PAI-1, and S100B—probably reflecting brain and adipose tissue inflammation—in intrauterine growth-restricted-(IUGR) and appropriate-for-gestational-age-(AGA) pregnancies, given that these groups differ in fat mass and metabolic mechanisms involving aseptic inflammation. Serum hs-CRP, PAI-1, and S100B levels were measured in 40 mothers, and their 20 AGA and 20 IUGR full-term fetuses and neonates on postnatal days 1 and 4. hs-CRP, PAI-1, and S100B levels did not differ at all time points between AGA and IUGR groups. We conclude that the lack of difference in hs-CRP, PAI-1 and S100B levels, between IUGR and AGA fetuses/neonates—despite the lower birth weight, reflecting reduced fat mass in the former—might indicate more intense adipose tissue and nervous system inflammation in IUGRs. However, implication of other inflammation-related mechanisms, common in the IUGR state (e.g. preeclampsia), cannot be excluded.

Cord Blood Ischemia-Modified Albumin Levels in Normal and Intrauterine Growth Restricted Pregnancies

Ischemia-modified albumin (IMA) is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR) may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals—“brain sparing effect”). Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA) full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035), and offspring of multigravidas (P = .021). In conclusion, “brain sparing effect” is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas.

Levels of asymmetric dimethylarginine throughout normal pregnancy and in pregnancies complicated with preeclampsia or had a small for gestational age baby

Objective: The aim of this study was to investigate maternal asymmetric dimethylarginine (ADMA) concentrations at the three trimesters of pregnancy in uncomplicated pregnancies and in women who developed preeclampsia or had small for gestational age infants (SGA) without preeclampsia. Methods: ADMA concentrations were retrospectively determined in the first, second and third trimester of pregnancy in 41 uncomplicated pregnancies, 10 pregnancies complicated with preeclampsia and 14 pregnancies that delivered a SGA baby. ADMA was measured with an ELISA kit. Results: Mean (±SD) concentrations of ADMA (µmol/L) in uncomplicated l pregnancies were: 0.51 ± 0.14; 0.52 ± 0.13; 0.58 ± 0.16 in the three trimesters, respectively. ADMA concentrations in SGA pregnancies were significantly lower in each trimester compared to uncomplicated pregnancies: (0.40 ± 0.10, p = 0.005 1st trim; 0.42 ± 0.10, p = 0.007 2nd trim; 0.45 ± 0.10, p = 0.007 3rd trim). Although pregnancies that developed preeclampsia had higher ADMA concentration in all trimesters compared to uncomplicated pregnancies (0.58 ± 0.10; 0.63 ± 0.14; 0.68 ± 0.11), the difference was statistically significant only in the 2nd trimester (p = 0.02). Conclusions: Maternal serum ADMA concentration tends to increase during normal pregnancy. Pregnancies with SGA infants had significantly lower ADMA levels in all trimesters of pregnancy. ADMA concentrations in the 2nd trimester was significantly elevated in pregnancies that later developed preeclampsia.

Elevated Second Trimester Amniotic Fluid Interferon γ-Inducible T-Cell α Chhemoattractant Concentrations as a Possible Predictor of Preterm Birth

Objective: To determine and correlate midtrimester amniotic fluid concentrations of interferon γ-inducible T-cell α chemoattractant (ITAC, a chemokine directing the migration of activated T lymphocytes toward inflammation sites) and C-reactive protein (CRP) in women undergoing amniocentesis and subsequently delivering pre-or full-term infants. Methods: Among 312 women undergoing midtrimester transabdominal amniocentesis, 13 progressed to spontaneous delivery at less than 37 gestational weeks (GW). Subjects were matched for maternal age, parity, and GW at amniocentesis with 21 controls who delivered at greater than 37 GW. Amniotic fluid ITAC and CRP levels were determined by enzyme-linked immunosorbent assay (ELISA) and by nephelometry, respectively. Results: Both ITAC and CRP values were significantly higher (P = .005 and P = .04, respectively) in the amniotic fluid of women delivering at less than 37 GW. A statistically significant correlation between amniotic fluid ITAC and CRP concentrations was also found (r = .366 P <.05). The receiver operator curve (ROC) analysis of delivery at less than 37 GW gave the best cutoff point for ITAC at a concentration of 44 PG/mL AND for CRP at a concentration of 0.16 mg/dL. Positive and negative predictive values for ITAC were 82% and 85%, respectively, and for CRP, 55% and 76%, respectively. Conclusions: Present data indicate that from the second trimester of pregnancy elevated amniotic fluid concentrations of ITAC are found in women delivering at less than 37 GW, as compared to women delivering at term. Therefore, ITAC in combination with other cytokines or CRP could possibly serve as predictor of preterm delivery.

Detection of congenital heart defects throughout pregnancy; impact of first trimester ultrasound screening for cardiac abnormalities.

Objective: To evaluate prospectively the efficacy to screen for congenital heart defects (CHD) during the first trimester nuchal translucency (NT) ultrasound examination by assessing the four chambers’ view of fetal heart. Methods: Pregnancies that were examined prospectively by ultrasound in the first trimester (11th–14th week), the second (19th–24th week) and third trimester were included in the study. 3774 fetuses were examined and fetal heart was assessed during the NT scan by examining the four chambers view. Detailed echocardiography was performed during the anomaly and growth scans. Diagnosis of congenital heart defects (CHD) was further confirmed by a fetal cardiologist. Results: The four chambers view was obtained in 99.52% of the cases. CHD were diagnosed in 29 fetuses (0.77%). Thirteen cases (44.8%) were detected during the 11–13 weeks’ scan, 14 cases (48.3%) during the anomaly scan, 1 CHD (3.5%) during the third trimester scan and 1 case (3.5%) postpartum. Conclusion: Assessment of the four chambers of fetal heart early in pregnancy was feasible and allowed the detection of 45% of CHD. Additional parameters of fetal cardiac anatomy during the NT scan may further improve the detection rate providing pregnancy management information early in the first trimester.

Investigation of Midtrimester Amniotic Fluid Factors as Potential Predictors of Term and Preterm Deliveries

Aims. Our aim is to investigate, in 13 cases (delivering preterm) and 21 matched (for age, parity, and gestational age) controls (delivering at term), whether midtrimester amniotic fluid concentrations of elastase, secretory leukocyte proteinase inhibitor (SLPI), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule predict asymptomatic intra-amniotic inflammation/infection and preterm labor. Results. Concentrations of all substances were not statistically different among mothers, delivering preterm or at term. SLPI concentrations significantly increased in women, going into labor without ruptured membranes, irrespective of pre- or term delivery (P < .007, P < .001, resp) and correlated with elastase (r = 0.508, P < .002). Conclusions. Midtrimester amniotic fluid SLPI concentrations significantly decrease when membrane rupture precedes pre- or full-term labor. However, none of the investigated substances predict preterm delivery.