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 相似文献   

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.     

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 相似文献   

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 ≤ 0.049). In both groups, NT-proBNP levels were similar in MS and higher in N1 (p ≤ 0.001). In AGA, MS NT-proBNP correlated positively with UC. Conclusions: Fetal and neonatal NT-proBNP levels are lower in IUGR compared with AGA, probably due to blood flow redistribution in IUGR and NT-proBNP placental transport in AGA. NT-proBNP levels peak on N1.     

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 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.     

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.     

Adropin concentrations in term pregnancies with normal,restricted and increased fetal growth

Objective: To determine levels of adropin (implicated in insulin resistance and endothelial dysfunction) in intrauterine growth restricted (IUGR), large (LGA) and appropriate for gestational age (AGA) pregnancies.

Methods: Cord-blood (UC) adropin and insulin concentrations were measured in 30 IUGR, 30 LGA and 20 AGA full-term infants and their mothers (MS).

Results: No significant differences in adropin concentrations were observed between the three groups. In the IUGR group MS adropin was significantly decreased when neonates had higher birth weights [b?= ?0.003, 95% CI??0.006 to 0.0, p?=?0.043]. In all groups, MS adropin levels were positively correlated with UC ones (r?=?0.282, p?=?0.011) and were significantly increased in female neonates [b?=?0.977, 95% CI 0.122–1.832, p?=?0.026]. In the LGA group, MS insulin was negatively correlated with UC adropin (r?= ?0.362 p?=?0.049).

Conclusions: Increased maternal adropin levels in severe IUGR cases might represent a regulatory feedback mechanism against endothelial placental dysfunction. The positive correlation between maternal and umbilical cord adropin levels implies its transplacental transfer. Increased maternal adropin levels in female neonates could be attributed to interaction of adropin with fetal estrogens through vascular endothelial growth factor (VEGF). The negative correlation between maternal insulin and fetal adropin levels in the LGA group is probably attributed to their respective insulin resistance.     

Angiopoietin-2 in the perinatal period and the role of intrauterine growth restriction

BACKGROUND: Angiopoietin-2, an angiogenic factor, causing destabilization and postnatal remodeling of blood vessels, is upregulated by hypoxia. We hypothesized that circulating Angiopoietin-2 levels might differ in intrauterine growth restricted and appropriate for gestational age fetuses and neonates, as the former have restricted growth and development and suffer from in utero hypoxia. METHODS: This is a prospective, controlled study, including forty asymmetric, mainly due to hypertension or pre-eclampsia intrauterine growth restricted (0-9 customized centiles, corrected for gestational age, sex, maternal weight, height, ethnic group, and parity), and 20 appropriate for gestational age (42-82 customized centiles) full-term infants, as well as their mothers. Blood samples were drawn from mothers, from the doubly clamped umbilical cord (mixed arteriovenous blood, representing fetal state), and from neonates on days 1 (N1) and 4 (N4) of life (representing transition and stabilization to extrauterine life, respectively). Circulating angiopoietin-2 levels were measured by enzyme immunoassay and the statistical analysis involved t-test and Pearson correlation. RESULTS: Angiopoietin-2 levels were significantly higher in intrauterine growth restricted cases only in N4 (p = 0.04). No dependence on the mode of delivery and gender was documented. CONCLUSIONS: These findings may suggest that intrauterine hypoxia possibly does not upregulate circulating angiopoietin-2 levels in intrauterine growth restricted fetuses and day 1 neonates; however, increased angiopoietin-2 on N4, after stabilization to extrauterine life, might signify initiation of catch-up growth-related angiogenesis and stimulation of angiogenic factors, granted that angiopoietin-2 is critically involved in postnatal vascular remodeling.     

Maternal and neonatal circulating visfatin concentrations in patients with pre-eclampsia and a small-for-gestational age neonate

Objective.?Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age (AGA) neonate or in those with pre-eclampsia. It has been proposed that enhanced transfer of visfatin from the foetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: (1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of pre-eclamptic mothers; and (2) to assess the relationship between maternal and foetal circulating visfatin concentrations in patients with an SGA neonate and those with pre-eclampsia.

Study design.?This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: (1) 44 normal pregnant women at term and their AGA neonates; (2) 22 normotensive pregnant women and their SGA neonates; (3) 22 women with pre-eclampsia and their neonates; and (4) 22 preterm neonates delivered following spontaneous preterm labour without funisitis or histologic chorioamnionitis, matched for gestational age with infants of pre-eclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses.

Results.?(1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and pre-eclampsia groups (p?<?0.001 for all comparisons); (2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with pre-eclampsia and their gestational-age-matched preterm AGA neonates; (3) maternal and cord blood visfatin concentrations correlated only in the normal term group (r?=?0.48, p?=?0.04).

Conclusion.?Circulating visfatin concentrations are lower in the foetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the foetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate.     

Endocrine regulation in asymmetric intrauterine fetal growth retardation.

OBJECTIVE: The ponderal index (PI) is a widely accepted measure of disproportionate growth or asymmetrical growth retardation by pediatricians worldwide. Identification of disproportionately grown small for gestational age (SGA) neonates by using the ponderal index as a measure of the nutritional status at birth, is important because they constitute a high-risk group among SGA neonates. Poor nutritional status of the mother could have a direct effect on the organs of the developing fetus and/or affect the endocrine milieu in the maternal feto-placental unit resulting in an increased incidence of intrauterine growth-retarded (IUGR)/SGA births. IUGR is a significant risk factor for adult disease. In this study, we have investigated the endocrine adaptation by the fetus to overcome the growth disadvantage caused due to poor nutritional status of the mother. MATERIALS AND METHODS: We examined the quantitative variations in hormonal and growth factor profiles in paired maternal and cord blood samples obtained from mothers and their neonates who were classified based on their growth status into SGA and appropriate for gestational age (AGA). RESULTS: (1) A total of 24.7% neonates had a PI < 2, indicating a high incidence of asymmetric IUGR in the population studied. (2) Anthropometric parameters measured in the mothers indicate that the mothers giving birth to neonates with a PI < 2 had poor nutritional status, both prior to and during pregnancy. (3) We observed increased levels of placental lactogen and prolactin and decreased levels of insulin in the cord blood of neonates with PI < 2, while lower levels of insulin-like growth factor 1 (IGF-1) and higher levels of epidermal growth factor (EGF) were observed in their mothers. CONCLUSION: Poor maternal nutritional status results in fetal adaptation to a growth restricted environment via the modulation of the pituitary-thyroid axis thereby altering the endocrine milieu, thus affecting fetal growth.     

胎盘肥胖基因表达与胎儿宫内生长发育相关性研究

目的　探讨胎盘肥胖基因表达与脐血瘦素水平和胎儿宫内生长发育的关系。　方法　采用逆转录定量聚合酶链反应 (RT- PCR)检测 40例胎盘肥胖基因 m RNA相对表达水平 ,采用放射免疫法检测脐血肥胖基因蛋白 (瘦素 )水平 ,采用 Ponderal指数 [PI=10 0×体重 (g) /身长 (cm) 3 ]估测新生儿营养状态。　结果　胎盘组织肥胖基因呈现高效表达 ,表达水平与孕母脂肪组织肥胖基因表达水平相似 ;13例小于胎龄儿胎盘组织瘦素 - m RNA相对表达水平为 0 .44 9± 0 .0 2 6 ,显著低于 15例适于胎龄儿的表达水平 [0 .487± 0 .0 42 (P<0 .0 5 ) ];12例大于胎龄儿胎盘组织瘦素 - m RNA相对表达水平为 0 .5 2 5± 0 .0 2 9,显著高于适于胎龄儿 (P<0 .0 5 )。胎盘肥胖基因 m RNA相对表达水平与脐血瘦素水平显著相关 (r=0 .6 1,P<0 .0 5 ) ,与新生儿出生体重和 Ponderal指数显著相关 (r=0 .6 0和0 .5 6 ,P<0 .0 5 )。　结论　胎盘是脐血瘦素重要来源 ,胎盘瘦素可能对胎儿宫内生长发育有促进作用     

Role of visfatin, insulin-like growth factor-I and insulin in fetal growth

OBJECTIVE: IGF-I and insulin are the main regulators of intrauterine and postnatal growth. Adipose tissue secreted cytokines are implicated in intrauterine growth. The relevant function of the adipocytokine visfatin is unknown. MATERIALS AND METHODS: Serum visfatin, IGF-I and insulin levels were measured by enzyme immunoassays in 40 singleton full-term fetuses and neonates on postnatal days 1(N1) and 4 (N4). RESULTS: No significant correlations exist between visfatin and IGF-I or insulin. N1 and N4 visfatin positively correlated with customized (adjusted) birth weight centiles (r=0.511, P=0.021, and r=0.597, P=0.005, respectively). Fetal and N1 IGF-I positively correlated with customized centiles (r=0.608, P<0.001 and r=0.485, P=0.006, respectively). Fetal insulin positively correlated with customized centiles (r=0.654, P=0.021). CONCLUSIONS: Potential implication of visfatin in fetal growth is probably not mediated by IGF-I or insulin. Although a more active role cannot be excluded, visfatin may simply represent a marker of fat accumulation.     

Indicative markers of cell proliferation and apoptosis during the perinatal period

Tissue polypeptide-specific antigen (TPS), an indicative marker of cell proliferation and soluble Fas (sFas), an antiapoptotic molecule were determined in neonatal serum (day 1-N1 and day 4-N4 of life), compared with maternal serum (MS) and umbilical cord serum (UC) to study changes of these markers during the perinatal period. Serum TPS and sFas concentrations were measured in 33 healthy, termed neonates, their mothers and 25 healthy nonpregnant controls (CS), age-matched to the mothers. TPS serum concentrations were significantly elevated in N1 and N4 as compared to CS (p < 0.0001 and p < 0.0003), increasing significantly from UC to N1 (p < 0.0001) and decreasing thereafter in N4 (p < 0.0002). MS serum concentrations, being significantly higher than CS (p < 0.0001), UC (p < 0.0001) and N4 (p < 0.003), but lower than N1 (p < 0.02) were strongly depended on the mode of delivery (p < 0.001). Serum concentrations of sFas, being lower in UC than in MS or CS (p < 0.0001), increased significantly in N4 samples (p < 0.01). A strong correlation was found between sFas serum concentrations in N1 and N4 (r = 0.65; p < 0.001). Our results demonstrate significant perinatal changes in TPS and sFas serum concentrations, possibly indicating gradual decrease of proliferation and apoptosis in early postnatal life.     

胎儿胰岛素样生长因子-Ⅰ的检测及意义

目的评估胰岛素样生长因子Ⅰ（ＩＧＦⅠ）在胎儿、胎盘生长发育中的作用。方法用放射免疫分析法（ＲＩＡ）测定大于胎龄儿（ＬＧＡ）组３０例,适于胎龄儿（ＡＧＡ）组３６例及小于胎龄儿（ＳＧＡ）组３６例的脐血清ＩＧＦⅠ的水平。用线性相关分析法分析各组变量之间的相关关系。结果３组胎儿脐血清ＩＧＦⅠ与胎龄、胎儿体重、胎盘重量均呈显著正相关（ｒ＝０．３２,Ｐ＜０．００１;ｒ＝０．６８,Ｐ＜０．００１;ｒ＝０．７５,Ｐ＜０．０１）,其中与胎盘重量呈高度正相关。脐血清ＩＧＦⅠ水平,ＡＧＡ组为１４４５９±４６．７３μｇ／Ｌ;ＳＧＡ组为９０．８０μｇ／Ｌ（ｔ＝４．７,Ｐ＜０．００１）,ＬＧＡ组为２０９１７μｇ／Ｌ（ｔ＝７．９７,Ｐ＜０．００１）。结论ＩＧＦⅠ是胎儿、胎盘生长发育的重要调节因子,对巨大儿、小于胎龄儿的形成有重要作用。     

Cerebral maturation in IUGR and appropriate for gestational age preterm babies

Intrauterine growth restriction (IUGR) is associated with increased risk of perinatal morbidity and mortality, as well as long-term neurological deficits. However, neurostructural correlations with observed developmental disabilities have not yet been established. Magnetic resonance imaging (MRI) could prove useful for assessing brain development in the early neonatal period. We evaluated cerebral lesions and morphological maturation by MRIs in 59 preterm neonates, in order to verify the hypothesis that IUGR interferes on human brain development. A total of 26 pregnancies were complicated by IUGR and 33 pregnancies delivered preterm at a comparable gestational age with appropriate for gestational age (AGA). Magnetic resonance examination was performed at the completion of 41 weeks' gestation. White matter disease studied with MR included periventricular cavitations and punctuate lesions characterized by increased signal on T1-weighted and decreased signal on T2-weighted images. Cerebral maturation was defined by the total maturation score, on the basis of 4 morphological parameters of cerebral maturation: myelination (M), cortical infolding (C), germinal matrix distribution (GM), and glial cell migration pattern (G). No difference in brain lesions and in the level of cerebral maturation was found between preterm AGA and IUGR neonates. However, myelination was significantly reduced in IUGR neonates with brain sparing compared to IUGR neonates with normal Doppler of middle cerebral artery. Our study could not demonstrate any major significant difference between preterm AGA and IUGR neonates in terms of lesion occurrence and cerebral maturation. We observed, however, a mild delay in myelination in IUGR with brain sparing in utero. The relevance of this finding needs to be investigated with long-term follow-up.     

Chemokines Rantes and interleukin-8 in the perinatal period: changes in serum concentrations

Chemokines, a superfamily of polypeptide mediators, are a key component of immune surveillance and are implicated in the initiation of the inflammatory cascade. This study investigated whether serum concentrations of the chemokines regulated upon activation, normal T-cell expressed and presumably secreted (RANTES) and interleukin-8 (IL-8) change in the perinatal period because of the transition from intra- to extrauterine life, and compared determined values in mothers (MS) (n = 30) with those in their fetuses (UC), neonates (day of life 1 [N1] and 4 [N4]), and controls (CS) (n = 20). RANTES serum concentrations were higher in MS than in UC ( p < 0.006), N1 ( p < 0.0001), N4 ( p < 0.0001), and CS ( p < 0.0001). IL-8 serum concentrations in MS and UC, respectively, were significantly lower than in N1 ( p < 0.0002 and p < 0.0007) and N4 ( p < 0.0001 and p < 0.0001). Thus, after birth, neonatal serum concentrations of RANTES decrease, possibly because of elimination of the placenta (probable production site), and neonatal serum concentrations of IL-8 increase, possibly triggered by environmental antigenic stimuli to which the neonate is exposed.     

Endocrine regulation in asymmetric intrauterine fetal growth retardation

Objective. The ponderal index (PI) is a widely accepted measure of disproportionate growth or asymmetrical growth retardation by pediatricians worldwide. Identification of disproportionately grown small for gestational age (SGA) neonates by using the ponderal index as a measure of the nutritional status at birth, is important because they constitute a high-risk group among SGA neonates. Poor nutritional status of the mother could have a direct effect on the organs of the developing fetus and/or affect the endocrine milieu in the maternal feto-placental unit resulting in an increased incidence of intrauterine growth-retarded (IUGR)/SGA births. IUGR is a significant risk factor for adult disease. In this study, we have investigated the endocrine adaptation by the fetus to overcome the growth disadvantage caused due to poor nutritional status of the mother.

Materials and methods. We examined the quantitative variations in hormonal and growth factor profiles in paired maternal and cord blood samples obtained from mothers and their neonates who were classified based on their growth status into SGA and appropriate for gestational age (AGA).

Results. (1) A total of 24.7% neonates had a PI < 2, indicating a high incidence of asymmetric IUGR in the population studied. (2) Anthropometric parameters measured in the mothers indicate that the mothers giving birth to neonates with a PI < 2 had poor nutritional status, both prior to and during pregnancy. (3) We observed increased levels of placental lactogen and prolactin and decreased levels of insulin in the cord blood of neonates with PI < 2, while lower levels of insulin-like growth factor 1 (IGF-1) and higher levels of epidermal growth factor (EGF) were observed in their mothers.

Conclusion. Poor maternal nutritional status results in fetal adaptation to a growth restricted environment via the modulation of the pituitary–thyroid axis thereby altering the endocrine milieu, thus affecting fetal growth.     

Differential expression of cord blood neurotrophins in gestational diabetes: the impact of fetal growth abnormalities

Objective: Gestational diabetes mellitus (GDM) may induce fetal macrosomia or growth restriction and is associated with later offspring neurodevelopmental disorders. We aimed to determine whether neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-4 (NT-4) are differentially expressed in cord blood samples at birth in large-for-gestational-age (LGA), intrauterine-growth-restricted (IUGR) and appropriate-for-gestational-age (AGA) offspring of diabetic mothers, as compared to AGA controls from non-diabetic mothers.

Methods: BDNF, NGF and NT-4 concentrations were prospectively determined in 80?cord blood samples from LGA (n?=?15), IUGR (n?=?12) and AGA (n?=?33) diabetic, as well as from AGA normal (controls, n?=?20) singleton full-term pregnancies.

Results: Fetal BDNF concentrations considerably decreased in GDM, as compared with normal pregnancies [(b?=??2.836, 95%CI ?5.067 to (?0.604), p?=?0.013)] and were higher in females (b?=?2.298, 95%CI 0.357–4.238, p?=?0.021). Cord blood NGF concentrations were lower in IUGR than AGA infants (p?=?0.038).

Conclusions: BDNF is down-regulated in the fetus exposed to GDM, independently of the fetal growth pattern, probably representing a candidate mechanism underlying the association between maternal diabetes and later psychopathology. IUGR fetuses born to diabetic mothers present with NGF deficiency, which may contribute to their long-term neurodevelopmental sequelae. Gender-dependent differences in fetal BDNF may partly explain the higher prevalence of adverse neurodevelopmental outcomes following brain insults in male infants.     

The effect of intrauterine growth on leukocyte telomere length at birth

Abstract

Objective: Telomeres are specialized nucleoprotein structures located at the ends of chromosomes, which play a crucial role in genomic stability. Telomere shortening has been proposed as a biomarker for the onset of age-related diseases. This study aimed to determine whether restricted or increased intrauterine growth affects leukocyte telomere length (LTL) at birth.

Materials and methods: One hundred sixty-five (n?=?165) full-term neonates participated in the study. Fetuses were classified as intrauterine growth restriction (IUGR, n?=?21), large-for-gestational-age (LGA, n?=?15), or appropriate-for-gestational-age (AGA, n?=?129), based on customized birth-weight standards. Mixed arteriovenous cord blood samples were collected for isolation of leukocyte DNA. The LTL was measured using multiplex monochrome quantitative real-time PCR and telomeric restriction fragments through Southern blot analysis (terminal restriction fragment [TRF]).

Results: Despite differences among groups in birth weight, length and head circumference, LTL did not differ among AGA (6.78?±?0.58), IUGR (10.54?±?1.80), and LGA (11.95?±?2.42) neonates (p?=?.098). Cord blood IGF-1 and IGFBP-3 concentrations were higher in the LGA group. LTL positively correlated with birth length (r?=?0.176, p?=?.032).

Conclusions: Intrauterine growth does not seem to affect LTL at birth. Further studies, comprising a larger sample size of IUGR, LGA, and AGA neonates, are required to determine whether growth at birth influences LTL.