Cord blood galectin-1 and -3 concentrations in term pregnancies with normal restricted and increased fetal growth.

OBJECTIVE: To determine levels of galectins (gal)-1 and -3 (implicated in angiogenesis/immunologic mechanisms) in intrauterine growth restricted (IUGR), large (LGA) and appropriate for gestational age (AGA) pregnancies, as these groups differ in fat mass, angiogenic patterns and immune responses. METHODS: Cord-blood (UC) gal-1 and -3 concentrations were measured in 30 IUGR, 30 LGA and 20 AGA singleton full-term infants and their mothers (MS). RESULTS: IUGR, LGA and AGA groups did not differ in gal-1 and -3 concentrations. UC gal-1 levels were lower when mothers were older [b=-0.651, CI 95% -1.186 (-0.116), P=0.018] and UC gal-3 levels were increased when mothers presented gestational diabetes [b=9.836, CI 95% 3.833- (15.839), P=0.002]. In IUGRs MS gal-3 and in LGAs UC gal-1 were decreased in multiparas [b=-5.372, CI 95% -9.584- (-1.161), P=0.014], and [b=-7.540, CI 95% -14.606- (-0.473), P=0.037], respectively. No correlations were found between MS or UC gal-1 and gal-3 concentrations. CONCLUSIONS: Lower UC gal-1 levels, when mothers were older, and increased UC gal-3 levels in cases of gestational diabetes, possibly reflect angiogenic activity. In multiparas, decreased MS gal-3 and UC gal-1 levels in IUGR/LGA, respectively, might imply inflammatory response against immunosuppression expected in subsequent pregnancies, as compared to the first one.

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 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 ß-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.

Perinatal changes of circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) in normal and intrauterine-growth-restricted pregnancies.

OBJECTIVE: To investigate changes in NT-proBNP in intrauterine-growth-restricted (IUGR) and appropriate-for-gestational-age (AGA) pregnancies. METHODS: NT-proBNP levels were measured in 40 mothers (MS), umbilical cords (UC), and their 20 IUGR/ 20 AGA neonates on day 1 (N1) and day 4 (N4). RESULTS: UC, N1, and N4 NT-proBNP was lower in IUGR pregnancies (p

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-for-gestational-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 > or = .498, P < or = .025 in all cases in the AGA and r > or = .615, P < or = .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 netrin-1 and -4 concentrations in term pregnancies with normal, restricted and increased fetal growth.

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.

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.

Perinatal collagen turnover markers in intrauterine growth restriction.

OBJECTIVE: To investigate bone and connective tissue collagen turnover in intrauterine growth restricted (IUGR) pregnancies, by determining circulating markers of type I collagen synthesis (carboxy-terminal propeptide of type I procollagen [PICP], representing bone formation) and degradation (cross-linked telopeptide of type I collagen [ICTP], representing bone resorption) as well as type III collagen synthesis (N-terminal propeptide of type-III procollagen [PIIINP], reflecting growth and tissue maturity). METHODS: Plasma PICP, ICTP and PIIINP concentrations were measured in 40 mothers and their 20 asymmetric IUGR and 20 appropriate for gestational age (AGA) full-term fetuses and neonates on postnatal day 1-(N1) and 4-(N4). RESULTS: Fetal PICP, fetal and N4 ICTP, as well as fetal, N1 and N4 PIIINP concentrations were higher in the IUGR group (p ≤ 0.038, in all cases). In both groups, maternal PICP, ICTP and PIIINP concentrations were lower than fetal, N1 and N4 ones (p<0.001, in each case). CONCLUSIONS: Type I collagen turnover is enhanced in IUGR than AGA fetuses/neonates. Similarly, fetal/neonatal PIIINP concentrations are elevated in IUGR, probably due to stress, responsible for induction of tissue maturation, and/or to impaired excretory renal function, leading to reduced protein clearance. Fetal/neonatal PICP, ICTP and PIIINP concentrations are higher than maternal concentrations, possibly reflecting increased skeletal growth and collagen turnover in the former.

Circulating osteoprotegerin and sRANKL concentrations in the perinatal period at term. The impact of intrauterine growth restriction.

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-kappaB 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 < or = 0.045 in all cases). N4 sRANKL concentrations were elevated compared with maternal, fetal and N1 ones (p < or = 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.

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.

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.

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 < or = 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 beta-cell mass and/or impaired beta-cell function.

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 (or= 0.376 and P

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.