leptin and Fetal-Macrosomia

Gestational diabetes mellitus (GDM) is the most frequent pathophysiological state of pregnancy, which in many cases produces fetuses with macrosomia, requiring increased nutrient transport in the placenta. Recent studies by our group have demonstrated that leptin is a key hormone in placental physiology, and its expression is increased in placentas affected by GDM. However, the effect of leptin on placental nutrient transport, such as transport of glucose, amino acids, and lipids, is not fully understood. Thus, we aimed to review literature on the leptin effect involved in placental nutrient transport as well as activated leptin signaling pathways involved in the expression of placental transporters, which may contribute to an increase in placental nutrient transport in human pregnancies complicated by GDM. Leptin appears to be a relevant key hormone that regulates placental transport, and this regulation is altered in pathophysiological conditions such as gestational diabetes. Adaptations in the placental capacity to transport glucose, amino acids, and lipids may underlie both under- or overgrowth of the fetus when maternal nutrient and hormone levels are altered due to changes in maternal nutrition or metabolic disease. Implementing new strategies to modulate placental transport may improve maternal health and prove effective in normalizing fetal growth in cases of intrauterine growth restriction and fetal overgrowth. However, further studies are needed to confirm this hypothesis.

Topics: Amino Acids; Diabetes, Gestational; Female; Fetal Macrosomia; Glucose; Humans; Leptin; Lipids; Membrane Transport Proteins; Nutrients; Placenta; Pregnancy

Leptin is highly expressed in the placenta, mainly by trophoblastic cells, where it has an important autocrine trophic effect. Moreover, increased leptin levels are found in the most frequent pathology of pregnancy: gestational diabetes, where leptin may mediate the increased size of the placenta and the fetus, which becomes macrosomic. In fact, leptin mediates the increased protein synthesis, as observed in trophoblasts from gestational diabetic subjects. In addition, leptin seems to facilitate nutrients transport to the fetus in gestational diabetes by increasing the expression of the glycerol transporter aquaporin-9. The high plasma leptin levels found in gestational diabetes may be potentiated by leptin resistance at a central level, and obesity-associated inflammation plays a role in this leptin resistance. Therefore, the importance of anti-inflammatory nutrients to modify the pathology of pregnancy is clear. In fact, nutritional intervention is the first-line approach for the treatment of gestational diabetes mellitus. However, more nutritional intervention studies with nutraceuticals, such as polyphenols or polyunsaturated fatty acids, or nutritional supplementation with micronutrients or probiotics in pregnant women, are needed in order to achieve a high level of evidence. In this context, the Mediterranean diet has been recently found to reduce the risk of gestational diabetes in a multicenter randomized trial. This review will focus on the impact of maternal obesity on placental inflammation and nutrients transport, considering the mechanisms by which leptin may influence maternal and fetal health in this setting, as well as its role in pregnancy pathologies.

Topics: Anti-Inflammatory Agents; Diabetes, Gestational; Diet, Mediterranean; Female; Fetal Macrosomia; Humans; Leptin; Nutrition Therapy; Nutritional Status; Obesity; Placenta; Pregnancy; Pregnancy Complications; Trophoblasts

Diabetes mellitus complicates 1-2% of all pregnancies but is associated with high perinatal morbidity and mortality. Gestational diabetes affects up to 4% of pregnancies and is associated with fetal macrosomia (large for dates). Fetal growth is a complex process influenced by determinants such as genetics, maternal factors, uterine environment and maternal and fetal hormones. Infants of pre-gestational diabetic mothers have an additional influence of maternal fluctuations in glycaemia. The purpose of this paper is to review maternal and fetal growth factors, including insulin, in the aetiology of macrosomia in diabetic pregnancy. Placental Growth Hormone is the major growth hormone secreted during human pregnancy. Leptin may have a role in satiety. Resistin was originally proposed as the link between obesity and diabetes but is now thought to have a more complex role. These hormones and their actions on human in-utero growth are reviewed in depth with particular reference to both pre-gestational (type 1 and type 2 diabetes) and gestational diabetes. Previously increased fetal weight in infants of diabetic mothers was thought to be as a result of maternal hyperglycaemia. It is now evident that control of fetal growth, in normal as well as diabetic pregnancies, is far more complex than previously thought.

Topics: Adult; Birth Weight; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Fetal Macrosomia; Fetus; Growth Hormone; Humans; Hyperglycemia; Infant; Insulin; Leptin; Placental Hormones; Pregnancy; Pregnancy in Diabetics; Resistin

C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration.. For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration.. In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 - 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 - 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 - 0.42, p < 0.001; and Coef.= 0.34, 95% CI: 0.06 - 0.63, p = 0.02, respectively).. UC blood concentration of C-peptide is significantly associated with the incidence of maternal GDM and neonatal macrosomia. Using stratification for maternal BMI and gestational weight gain (GWG) and investigating molecular markers like Leptin and IGF-1 in the future might lay the ground to better understand the link between metabolic disturbances of pregnancy and UC blood C-peptide concentration.

Topics: Birth Weight; Body Mass Index; C-Peptide; Cesarean Section; Child; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Iran; Leptin; Pregnancy; Pregnancy Outcome; Weight Gain

This is a secondary analysis of 621 women in ROLO study, a randomized control trial of low glycemic index (GI) diet in pregnancy to prevent the recurrence of macrosomia, which aims to assess the effect of the diet on maternal and fetal insulin resistance, leptin, and markers of inflammation. In early pregnancy and at 28 weeks, serum was analyzed for insulin, leptin, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6). At delivery, cord blood concentrations of leptin, TNF-α, IL-6, and C-peptide were recorded. We found no difference between those who did or did not receive low GI advice with respect to the concentrations of any marker in early pregnancy, at 28 weeks or in cord blood. Women in the intervention arm of the study did have a lower overall rise in insulin concentrations from early pregnancy to 28 weeks gestation, P = .04. Of the women in the intervention arm, 20% were in the highest quartile for insulin change (28-week insulin - insulin at booking) compared to 29% of controls (P = .02). In conclusion, a low GI diet in pregnancy has little effect on leptin and markers of inflammation although an attenuated response to the typical increase in insulin resistance seen in pregnancy with advancing gestation was seen in those who received the low GI advice.

Topics: Biomarkers; C-Peptide; Diet, Carbohydrate-Restricted; Female; Fetal Blood; Fetal Macrosomia; Gestational Age; Glycemic Index; Humans; Inflammation Mediators; Insulin Resistance; Interleukin-6; Leptin; Maternal Nutritional Physiological Phenomena; Nutritional Status; Pregnancy; Tumor Necrosis Factor-alpha

The present study is a secondary analysis of the ROLO study, a randomised control trial of a low-glycaemic index (GI) diet in pregnancy to prevent the recurrence of fetal macrosomia. The objectives of the present study were to identify which women are most likely to respond to a low-GI dietary intervention in pregnancy with respect to three outcome measures: birth weight; maternal glucose intolerance; gestational weight gain (GWG). In early pregnancy, 372 women had their mid-upper arm circumference recorded and BMI calculated. Concentrations of glucose, insulin and leptin were measured in early pregnancy and at 28 weeks. At delivery, infant birth weight was recorded and fetal glucose, C-peptide and leptin concentrations were measured in the cord blood. Women who benefited in terms of infant birth weight were shorter, with a lower education level. Those who maintained weight gain within the GWG guidelines were less overweight in both their first and second pregnancies, with no difference being observed in maternal height. Women who at 28 weeks of gestation developed glucose intolerance, despite the low-GI diet, had a higher BMI and higher glucose concentrations in early pregnancy with more insulin resistance. They also had significantly higher-interval pregnancy weight gain. For each analysis, women who responded to the intervention had lower leptin concentrations in early pregnancy than those who did not. These findings suggest that the maternal metabolic environment in early pregnancy is important in determining later risks of excessive weight gain and metabolic disturbance, whereas birth weight is mediated more by genetic factors. It highlights key areas, which warrant further interrogation before future pregnancy intervention studies, in particular, maternal education level and inter-pregnancy weight gain.

Topics: Adiposity; Adult; Birth Weight; Body Mass Index; Cohort Studies; Diet, Carbohydrate-Restricted; Educational Status; Female; Fetal Blood; Fetal Macrosomia; Glucose Intolerance; Glycemic Index; Humans; Insulin; Insulin Resistance; Leptin; Maternal Nutritional Physiological Phenomena; Patient Education as Topic; Pregnancy; Pregnancy Complications; Secondary Prevention; Weight Gain

Topics: Adiponectin; Birth Weight; Body Mass Index; East Asian People; Fatty Acids, Nonesterified; Female; Fetal Macrosomia; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Triglycerides

Fetal overgrowth "programs" an elevated risk of obesity and type 2 diabetes in adulthood. Plausibly, adipokines may be involved in programming metabolic health.. This work aimed to evaluate whether large-for-gestational-age (LGA), an indicator of fetal overgrowth, is associated with altered circulating leptin and adiponectin levels in infancy, and assess the determinants.. In the Canadian 3D birth cohort, we studied 70 LGA (birth weight > 90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) infants matched by maternal ethnicity, smoking, and gestational age at delivery. The primary outcomes were fasting leptin, and total and high-molecular-weight (HMW) adiponectin concentrations at age 2 years.. LGA infants had higher body mass index (BMI) than OGA infants. However, there were no significant differences in leptin, and total and HMW adiponectin concentrations. Leptin concentrations were positively associated with female sex, weight (z score) gain 0 to 24 months, current BMI, and the sum of triceps and subscapular skinfold thickness, and negatively associated with maternal age and White ethnicity. Female sex was associated with lower total and HMW adiponectin concentrations. Weight (z score) gain 0 to 24 months and current BMI were positively correlated with total and HMW adiponectin concentrations in LGA infants only.. This study is the first to demonstrate that LGA does not matter for circulating leptin and adiponectin concentrations in infancy, and there may be LGA-specific positive associations between weight gain or current BMI and adiponectin concentrations in infancy, suggesting dysfunction in establishing the adiposity-adiponectin negative feedback loop in LGA individuals.

Topics: Adiponectin; Adiposity; Birth Weight; Canada; Case-Control Studies; Child, Preschool; Female; Fetal Macrosomia; Follow-Up Studies; Gestational Age; Humans; Infant; Infant, Newborn; Insulin Resistance; Leptin; Male; Sex Factors; Weight Gain

Fetal overgrowth "programs" an elevated risk of type 2 diabetes in adulthood. Epigenetic alterations may be a mechanism in programming the vulnerability. We sought to characterize genome-wide alterations in placental gene methylations in fetal overgrowth and the associations with metabolic health biomarkers including leptin, adiponectin and fetal growth factors.. Comparing genome-wide placental gene DNA methylations in large-for-gestational-age (LGA, an indicator of fetal overgrowth, n = 30) versus optimal-for-gestational-age (OGA, control, n = 30) infants using the Illumina Infinium Human Methylation-EPIC BeadChip, we identified 543 differential methylation positions (DMPs; 397 hypermethylated, 146 hypomethylated) at false discovery rate < 5% and absolute methylation difference > 0.05 after adjusting for placental cell-type heterogeneity, maternal age, pre-pregnancy BMI and HbA1c levels during pregnancy. Twenty-five DMPs annotated to 20 genes (QSOX1, FCHSD2, LOC101928162, ADGRB3, GCNT1, TAP1, MYO16, NAV1, ATP8A2, LBXCOR1, EN2, INCA1, CAMTA2, SORCS2, SLC4A4, RPA3, UMAD1,USP53, OR2L13 and NR3C2) could explain 80% of the birth weight variations. Pathway analyses did not detect any statistically significant pathways after correcting for multiple tests. We validated a newly discovered differentially (hyper-)methylated gene-visual system homeobox 1 (VSX1) in an independent pyrosequencing study sample (LGA 47, OGA 47). Our data confirmed a hypermethylated gene-cadherin 13 (CDH13) reported in a previous epigenome-wide association study. Adiponectin in cord blood was correlated with its gene methylation in the placenta, while leptin and fetal growth factors (insulin, IGF-1, IGF-2) were not.. Fetal overgrowth may be associated with a large number of altered placental gene methylations. Placental VSX1 and CDH13 genes are hypermethylated in fetal overgrowth. Placental ADIPOQ gene methylations and fetal circulating adiponectin levels were correlated, suggesting the contribution of placenta-originated adiponectin to cord blood adiponectin.

Topics: Adiponectin; Adult; Carrier Proteins; Diabetes Mellitus, Type 2; Diabetes, Gestational; DNA Methylation; Female; Fetal Blood; Fetal Development; Fetal Macrosomia; Gestational Age; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Membrane Proteins; Placenta; Pregnancy

To determine predictors of neonatal adiposity and differences in associations by fetal sex in women with gestational diabetes mellitus (GDM), normal-weight and overweight (BMI ≥ 25 kg/m. Skinfold thickness was measured in 576 newborns, and cord blood leptin, c-peptide and lipids in 327 newborns in a multi-centric prospective cohort study.. Compared to neonates of normal-weight NGT women (327), neonates of women with GDM (97) were more often large-for-gestational age (LGA) (16.5% vs 8.6%, p = 0.024) ,but the macrosomia rate (8.2% vs 5.8%, p = 0.388), sum of skinfolds (13.9 mm ± 2.9 vs 13.3 mm ± 2.6, p = 0.067), neonatal fat mass (1333.0 g ± 166.8 vs 1307.3 g ± 160.9, p = 0.356), and cord blood biomarkers were not significantly different. Compared to neonates of normal-weight NGT women, neonates of overweight NGT women (152) had higher rates of macrosomia (12.5% vs 5.8%, p = 0.012), LGA (17.1% vs 8.6%, p = 0.006), higher sum of skinfolds (14.3 mm ± 2.6 vs 13.2 mm ± 2.6, p < 0.001), neonatal fat mass (1386.0 g ± 168.6 vs 1307.3 g ± 160.9, p < 0.001), % neonatal fat mass > 90th percentile (15.2% vs 7.1%, p < 0.001), without significant differences in cord blood biomarkers. Maternal BMI, fasting glycemia, triglycerides, gestational weight gain, cord blood leptin ,and cord blood triglycerides were independent predictors for neonatal adiposity. Gestational weight gain was positively associated with adiposity in boys only.. Compared to neonates of normal-weight NGT women, neonates of GDM women have higher LGA rates but similar adiposity, while neonates of overweight NGT women have increased adiposity. Limiting gestational weight gain might be especially important in the male fetus to reduce neonatal adiposity.

Topics: Adiposity; Adolescent; Adult; Belgium; Birth Weight; C-Peptide; Cohort Studies; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Fetus; Humans; Infant, Newborn; Leptin; Lipids; Male; Middle Aged; Pregnancy; Pregnancy Outcome; Prognosis; Prospective Studies; Sex Characteristics; Skinfold Thickness; Young Adult

We previously demonstrated an association between placental leptin (LEP) methylation levels and macrosomia without gestational diabetes mellitus (non-GDM). This study further explored the association between LEP methylation in cord blood and non-GDM macrosomia.. We carried out a case-control study of 61 newborns with macrosomia (birth weight ≥4000 g) and 69 newborns with normal birth weight (2500-3999 g). Methylation in the LEP promoter region was mapped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.. Average cord blood LEP methylation levels were lower in macrosomia newborns than in control newborns (P < 0.001). Eleven CpG sites were associated with macrosomia. Multivariate logistic regression revealed that low LEP methylation levels [adjusted odds ratio (AOR) = 2.84, 95% confidence interval (CI): 1.72-4.17], high pre-pregnancy body mass index (AOR = 7.44, 95% CI: 1.99-27.75), long gestational age (AOR = 3.18, 95% CI: 1.74-5.79), high cord blood LEP concentration (AOR = 2.25, 95% CI: 1.34-3.77), and male newborn gender (AOR = 3.91, 95% CI: 1.31-11.69) significantly increased the risk of macrosomia.. Lower cord blood LEP methylation levels and certain maternal and fetal factors are associated with non-GDM macrosomia.

Topics: Adult; Birth Weight; Case-Control Studies; China; DNA Methylation; Female; Fetal Blood; Fetal Macrosomia; Genotype; Humans; Infant, Newborn; Leptin; Male; Maternal Age; Multivariate Analysis; Polymorphism, Single Nucleotide; Pregnancy; Pregnancy Complications

We have shown that some markers of oxidative stress were higher in women with gestational diabetes mellitus (GDM). This study examines the relationship between adipokines and oxidative stress and their potential effects in pregnant women.. Three markers of oxidative stress (malondialdehyde, 8-isoprostane and xanthine oxidase) and three adipokines (leptin, adiponectin and resistin) were measured in maternal plasma, cord plasma and placenta of 208 pregnant women.. Among all these women, 105 were diagnosed with GDM while the other 103 were controls. Leptin, resistin, malondialdehyde, xanthine oxidase and 8-isoprostane in maternal plasma, cord plasma and placenta were significantly higher while maternal adiponectin significantly lower in women with GDM (P < 0.05). Adipokines in maternal plasma, cord plasma and placenta were positively correlated with markers of oxidative stress. Both markers of oxidative stress and adipokines were correlated inversely with homeostasis model assessment of insulin resistance whereas positively with quantitative insulin sensitivity check index (P < 0.01). Adiponectin is negatively correlated with leptin and resistin. Placental/cord leptin and cord resistin levels were higher in the macrosomia while maternal adiponectin level was lower (P < 0.05) than normal birthweight newborns. Both markers of oxidative stress and adipokines in maternal and cord plasma are negatively correlated with newborn birthweight (P < 0.05).. Adipokines interact with markers of oxidative stress, both of which lead to insulin resistance, GDM and macrosomia. It has long been known that placenta involves in the development of GDM. Adipokines might participate in this process and need to be confirmed by further studies.

Topics: Adiponectin; Adult; Diabetes, Gestational; Dinoprost; Female; Fetal Blood; Fetal Macrosomia; Humans; Infant, Low Birth Weight; Infant, Newborn; Leptin; Male; Malondialdehyde; Placenta; Pregnancy; Resistin; Xanthine Oxidase

Fetuses exposed to an obese intrauterine environment are more likely to be born large-for-gestational age (LGA) and are at increased risk of obesity in childhood and cardiovascular disease and/or type 2 diabetes mellitus as adults, but which factors that influence the intrauterine environment is less clear.. To investigate the association between circulating levels of leptin and adiponectin, measured multiple times during pregnancy, and birth weight and prevalence of LGA or small-for-gestational-age infants. The association between birth weight and messenger RNA (mRNA) expression of adiponectin receptors and genes involved in nutrient transport in the placenta was also investigated.. Population-based prospective cohort [substudy of the STORK study (STORe barn og Komplikasjoner, translated as Large Babies and Complications)] from 2001 to 2008.. University hospital. Patients or other participants: 300 women.. Oral glucose tolerance test was performed twice along with adiponectin and leptin levels measured four times during pregnancy.. Circulating adiponectin was lower in mothers who gave birth to LGA offspring or had fetuses with high intrauterine abdominal circumference late in pregnancy. Adiponectin decreased most from early to late pregnancy in mothers who gave birth to LGA offspring, and the decrease was an independent predictor of birth weight. Adiponectin receptor 2 and system A amino acid transporter mRNA expression in placentas was negatively correlated with birth weight and was lower in placentas from LGA infants.. Our findings suggest that maternal adiponectin may be an important predictor of fetal growth and birth weight, independent of body mass index and insulin resistance.

Topics: Adiponectin; Adult; Birth Weight; Cohort Studies; Female; Fetal Development; Fetal Macrosomia; Gestational Age; Glucose Tolerance Test; Hospitals, University; Humans; Infant, Newborn; Insulin Resistance; Leptin; Male; Pregnancy; Pregnancy Outcome; Receptors, Adiponectin; Retrospective Studies

The etiology of childhood obesity and the associated morbidity is multifactorial. Recently, data suggesting a prenatal programming towards later childhood obesity and metabolic deregulation through the intrauterine environment has emerged. This study explored the concentrations of adipokines and their mutual relationship at birth in children born to non-diabetic mothers.. Adiponectin, leptin and sOB-R were measured using ELISA-based commercial kits in umbilical cord blood from 60 neonates (30 born large for gestational age [LGA] and 30 born appropriate for gestational age [AGA]). Children exposed to maternal diabetes, chronic disease and preeclampsia were excluded.. The LGA group exhibited significantly elevated concentrations of leptin (p<0.001) and of free leptin index (p<0.001) and decreased sOB-R concentrations (p=0.005) when compared to the AGA group, which persisted in multiple regression analysis after taking the gestational age into account (p=0.048, p<0.001 and p<0.001, respectively). Only a trend towards a difference in adiponectin was demonstrated (p=0.057) regardless of adjustment (p=0.150). However, the leptin/adiponectin ratio was elevated in the LGA group (p=0.008), regardless of adjustment (p=0.039).. The data indicate a disturbance of adipokines in macrosomic newborns and that the mutual ratios between adipokines may provide a more sensitive marker of metabolic disturbance than any isolated adipokine.

Topics: Adipokines; Adult; Birth Weight; Body Mass Index; Female; Fetal Blood; Fetal Macrosomia; Fetal Monitoring; Gestational Age; Humans; Infant, Newborn; Leptin; Male; Pregnancy; Young Adult

The present study examined the placental leptin (LEP) DNA methylation and mRNA levels in macrosomic infants from normal pregnancies. In total, 49 neonates with macrosomia, i.e., high birth weights of ≥ 4,000 g, and 52 neonates with normal birth weights between 2,500 g and 4,000 g were recruited from The Second Affiliated Hospital of Wenzhou Medical University (Wenzhou, Zhejiang) in China. Placental LEP promoter methylation and LEP transcript levels were determined by Sequenom MassARRAY and quantitative PCR, respectively. LEP promoter methylation and mRNA levels were not significantly different between the individuals with macrosomia and the controls. However, stratification revealed that individual CpG dinucleotides were hypermethylated in macrosomia (P<0.05) in primiparous females and at 39 weeks of gestation (P<0.05). Variations in methylation did not affect placental LEP expression. It was concluded that the methylation of the placental LEP promoter was altered during a specific gestational period in macrosomia following a normal pregnancy and under certain conditions. However, placental LEP expression was not affected.

Topics: Adolescent; Adult; CpG Islands; Demography; DNA Methylation; Female; Fetal Macrosomia; Gestational Age; Humans; Infant, Newborn; Leptin; Male; Placenta; Pregnancy; Promoter Regions, Genetic; RNA, Messenger; Young Adult

Children born large for gestational age (LGA) may be at risk for development of obesity and insulin resistance (IR). The reciprocal relationship of adipokines and proinflammatory cytokines is suggested to play a putative role in fine tuning of insulin secretory dynamics. To evaluate serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, insulin-like growth factor-1 (IGF-1), and IGF-binding protein-1 (IGFBP-1) concentrations in idiopathic LGA-born children to appropriate for gestational age (AGA) and idiopathic LGA-born children at prepubertal ages and investigate their associations with IR, evaluated by homeostasis model assessment-IR (HOMA-IR), we conducted a cross-sectional study to compare 40 (19 females) idiopathic LGA-born prepubertal children [mean ± SD age 6.1 ± 2.5 years] and 49 (25 females) (5.4 ± 1.8 years) AGA-born BMI-matched peers with respect to anthropometric and laboratory data. Both groups were further divided into subgroups as being obese/overweight (OW) and non-OW, and the analyses were repeated. LGA-born children were taller and heavier than AGA-born children (p < 0.001). Fasting insulin, HOMA-IR, and leptin were higher in LGA-born children than in AGA-born counterparts (p < 0.001). Serum TNF-α levels were lower and IL-6 levels were significantly higher in LGA- than in AGA-born children (p < 0.001). In the LGA group, TNF-α was correlated with HOMA-IR (r = -0.49, p = 0.002). LGA-born non-OW children had higher serum insulin concentrations and HOMA-IR than AGA-born counterparts. Multivariate regression analysis revealed that HOMA-IR was best explained by (R (2) = 0.517) birth weight SDS (β = +0.418, p = 0.002), leptin (β = +0.620, p = 0.000), and TNF-α (β = -0.374, p = 0.003) in LGA-born children. Idiopathic LGA-born children have significantly lower TNF-α and higher IL-6 levels than AGA-born children. Reduced TNF-α levels are associated with increased IR.

Topics: Birth Weight; Child; Cross-Sectional Studies; Female; Fetal Macrosomia; Gestational Age; Humans; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Male; Tumor Necrosis Factor-alpha

Low vitamin D [25(OH)D] levels have been associated with type-2 diabetes mellitus. Children born large for gestational age (LGA) may exhibit increased indices of insulin resistance early in life.. This study aims to prospectively examine serum 25(OH)D and parathormone (iPTH) levels in LGA and appropriate for gestational age (AGA) prepubertal children, in relation to the severity of macrosomia and insulin resistance.. Children were examined at age 5-7.5 years, 38 born LGA and 39 AGA, matched for age, gender, body weight, height and body mass index (BMI). Twenty-one LGA had birth weights in the 90th-97th percentile and 17 >97th percentile. Fasting serum levels of glucose, insulin, 25(OH)D, and iPTH were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was estimated.. The insulin resistance indices were higher in the LGA >97th percentile subgroup than in the AGA group: HOMA-IR 1.53±0.66 vs. 1.04±0.53 and fasting insulin 6.92±3.1 vs. 4.78±2.2 μIU/mL (but similar to the AGA group), and in the LGA 90th-97th percentile subgroup: HOMA-IR 1.17±0.61 and insulin 5.53±2.2. There was no difference in 25(OH)D among the three subgroups. The iPTH was higher in the LGA >97th percentile subgroup than in the AGA group (26.8±7.6 and 22.6±7.2 pg/mL, respectively, p<0.05), although it was not correlated with insulin resistance indices. Birth weight was correlated negatively with fasting insulin and HOMA-IR in the entire cohort, independent of age, sex, waist circumference, and BMI (β=0.37, p<0.01 and β=0.30, p<0.05, respectively), while waist circumference was positively correlated with HOMA-IR (R=0.40, p<0.001).. Birth weight and current body composition appear to affect glucose homeostasis in LGA prepubertal children, while the serum levels of 25(OH)D and iPTH appear to be uninvolved.

Topics: Biomarkers; Birth Weight; Body Mass Index; Case-Control Studies; Child; Child, Preschool; Female; Fetal Macrosomia; Follow-Up Studies; Gestational Age; Humans; Insulin; Insulin Resistance; Leptin; Male; Parathyroid Hormone; Prognosis; Prospective Studies; Vitamin D

The sample of women with physiologic pregnancy consisting of 40 females with fetus normosomia and 8 females with fetus macrosomia were examined. The examination covered the evaluation of changes in concentration of ghrelin, somatotropin, insulin-like growth factor-I, insulin, leptin and thyroid hormones in mother and umbilical blood. In females with fetus macrosomia the changes in concentration of hormones regulating trophism, energy balance and anabolic processes in organisms of mother and fetus were detected

Topics: Biomarkers; Case-Control Studies; Female; Fetal Blood; Fetal Macrosomia; Ghrelin; Human Growth Hormone; Humans; Immunoenzyme Techniques; Insulin; Insulin-Like Growth Factor I; Leptin; Peptide Hormones; Pregnancy; Thyroid Hormones

Evidence for a role of vitamin D in maintaining normal glucose homeostasis is inconclusive. We sought to clarify the relationship between maternal and fetal insulin resistance and vitamin D status. This is a prospective cohort study of 60 caucasian pregnant women. Concentrations of 25-hydroxyvitamin D (25-OHD), glucose, insulin, and leptin were measured in early pregnancy and at 28 weeks. Ultrasound at 34 weeks assessed fetal anthropometry including abdominal wall width, a marker of fetal adiposity. At delivery birth weight was recorded and fetal 25-OHD, glucose, C-peptide, and leptin measured in cord blood. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA) equation. We found that those with lower 25-OHD in early pregnancy had higher HOMA indices at 28 weeks, (r = -.32, P = .02). No significant relationship existed between maternal or fetal leptin and 25-OHD, or between maternal or fetal 25-OHD and fetal anthropometry or birth weight. The incidence of vitamin D deficiency was high at each time point (15%-45%). These findings lend support to routine antenatal supplementation with vitamin D in at risk populations.

Topics: Adiposity; Biomarkers; Blood Glucose; Female; Fetal Blood; Fetal Development; Fetal Macrosomia; Gestational Age; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Longitudinal Studies; Pregnancy; Prospective Studies; Risk Factors; Vitamin D; Vitamin D Deficiency

The delivery of excess maternal nutrients to the fetus is known to increase the risk of macrosomia, even among infants of women without gestational diabetes mellitus. With the current obesity epidemic, maternal adiposity and its associated effects on circulating adipokines and inflammatory proteins may now have a greater impact on fetal growth. We sought to evaluate the independent effects of maternal glycemia, lipids, obesity, adipokines and inflammation on infant birth weight.. We included 472 women who underwent an oral glucose tolerance test in late pregnancy and were found not to have gestational diabetes; 104 (22.0%) had gestational impaired glucose tolerance. We also measured fasting levels of insulin, low-and high-density lipoprotein cholesterol, triglycerides, leptin, adiponectin and C-reactive protein. Obstetric outcomes were assessed at delivery.. The mean birth weight was 3481 g (standard deviation 493 g); 68 of the infants were large for gestational age. On multiple linear regression analysis, positive determinants of birth weight were length of gestation, male infant, weight gain during pregnancy up to the time of the oral glucose tolerance test, body mass index (BMI) before pregnancy and impaired glucose tolerance in pregnancy. Leptin, adiponectin and C-reactive protein levels were each negatively associated with birth weight. On logistic regression analysis, the significant metabolic predictors of having a large-for-gestational-age infant were BMI before pregnancy (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05-1.27, per 1 kg/m(2) increase), weight gain during pregnancy up to the time of the oral glucose tolerance test (OR 1.12, 95% CI 1.05-1.19, per 1 kg increase) and leptin level (OR 0.50, 95% CI 0.30-0.82, per 1 standard deviation change).. Among women without gestational diabetes, maternal adiposity and leptin levels were the strongest metabolic determinants of having a large-for-gestational-age infant rather than glucose intolerance and lipid levels.

Topics: Adipokines; Adiposity; Adult; Birth Weight; Body Mass Index; Body Weight; C-Reactive Protein; Female; Fetal Macrosomia; Glucose Intolerance; Humans; Leptin; Lipids; Logistic Models; Mothers; Pregnancy

Improved glycaemic control during pregnancy in mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) has resulted in a marked reduction of perinatal mortality and morbidity, but the prevalence of macrosomia is usually high.. We used non-invasive anthropometric methods to estimate the body composition and the thickness of the interventricular heart septum in 18 infants of mothers with well-controlled T1DM, 10 infants of mothers with GDM and 28 infants of healthy control mothers matched for gestational age and mode of delivery.. Skinfold measurements were obtained with a Harpenden calliper within 48 h after delivery. Echocardiography was also performed to measure the thickness of the interventricular septum. Cord blood was sampled for assays of C-peptide, leptin and IGF-I.. The rates of macrosomia (gestational age-adjusted birth weight >2 standard deviation score, SDS) were 56 and 30% in infants of mothers with T1DM and GDM, respectively, compared to 10% in control infants. The body fat content was 40% (0.2 kg) higher and the interventricular heart septum thickness was increased by 20% in both groups of infants of diabetic mothers. We found no associations between maternal levels of HbA1c during pregnancy and body composition or interventricular heart septum thickness. Cord levels of C-peptide and leptin were significantly higher in infants of T1DM mothers than in control infants. Cord leptin level was associated with birth weight SDS and percent body fat in infants of T1DM mothers. IGF-I was associated with percent body fat in infants of GDM mothers and control mothers. A multiple-regression analysis showed that 50% of the variation in body weight SDS could be determined, with IGF-I, leptin and C-peptide as independent variables.. Both fat mass and cardiac septal thickness are increased in newborn infants of women with T1DM and GDM in spite of efforts to achieve good glycaemic control during pregnancy.

Topics: Adipose Tissue; Adult; Blood Glucose; Body Composition; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Fetal Macrosomia; Glycated Hemoglobin; Heart Septum; Humans; Hypertrophy; Infant, Newborn; Insulin-Like Growth Factor I; Leptin; Pregnancy; Prevalence; Regression Analysis

Maternal diabetes is associated with polycythaemia and thrombocytopaenia in the offspring; however, the relationship with fetal hormones is unknown. We assessed the association of maternal glycaemic control, birthweight and fetal hormones with haematological indices in pregnancies complicated by maternal diabetes.. Prospective study using cord blood samples from 89 offspring of mothers with Type 1 diabetes (OT1DM) and 34 control offspring. Full blood count, insulin, leptin, adiponectin, cortisol, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3, intercellular adhesion molecule 1 and C-reactive protein were measured in the umbilical vein at birth.. Haematocrit was higher in OT1DM (OT1DM 0.55 +/- 0.17%, control offspring 0.51 +/- 0.06%; P = 0.02). The difference in platelets count was not statistically significant [OT1DM 214 x 10(9)/l (173-259); control offspring 253 x 10(9)/l (180-310), P = 0.06]. Maternal glycated haemoglobin (HbA(1c)) showed a moderate positive correlation with fetal haematocrit (r = 0.30, P = 0.02). Cord platelet counts were negatively associated with birthweight in OT1DM (r = -0.27, P = 0.01). In multivariate models, cord insulin was not associated with haematocrit, but cord leptin was negatively associated with platelets in control offspring (P < 0.001) and OT1DM (P = 0.046), with additional contributions from male sex (P = 0.08) in OT1DM, and IGF-1 (P = 0.04) and insulin (P = 0.04) in control offspring.. Fetal haematocrit is increased in response to diabetes in pregnancy and is related to maternal glycaemic control. Fetal hyperinsulinism, hyperleptinaemia or macrosomia, although readily demonstrable in this cohort, do not emerge as determinants of raised fetal haematocrit in OT1DM. Both increased birthweight and fetal leptin are negatively associated with platelet count.

Topics: Biomarkers; Diabetes Mellitus, Type 1; Female; Fetal Blood; Fetal Macrosomia; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Leptin; Male; Polycythemia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy in Diabetics; Prospective Studies

It has been suggested that hyperleptinemia could be caused by hyperinsulinemia in infants of diabetic mothers (IDMs).. To compare leptin, insulin, and glucose levels in large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) infants.. A cross-sectional study was conducted in IDMs, infants of non-diabetic mothers (INDM) and AGA infants.. Seventy-seven newborns were studied (11 IDM, 16 INDM, and 50 AGA infants). Leptin levels were significantly higher in LGA infants than in the AGA group and a trend for higher levels in IDM than NIDM was observed. Insulin levels and insulin resistance were significantly higher in IDMs. Glucose levels were lower in both groups of LGA infants.. We found insulin resistance, hyperinsulinism and hyperleptinemia in IDMs, and the trend of higher leptin levels in IDMs than INDMs shows that leptin could be related to insulin resistance in these infants.

Topics: Birth Weight; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus; Female; Fetal Macrosomia; Gestational Age; Humans; Hyperinsulinism; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Insulin Resistance; Leptin; Male; Obesity; Pregnancy; Pregnancy in Diabetics

Exposure to diabetes in utero has been established as a significant risk factor for some of the components of metabolic syndrome, and was associated with increased levels of maternal, placental, and fetal insulin-like growth factors and leptin. The atherogenic effects of leptin and insulin-like growth factor-I (IGF-I) have been extensively described. The present study was therefore designed to investigate relationships between abdominal aortic intima-media thickness (aIMT), serum IGF-I, IGF binding protein-3 (IGFBP-3) and leptin levels in macrosomic newborns.. Neonates whose birth weights exceed 90th percentile for gestational age and gender are termed macrosomic. Abdominal aortic intima-media thickness was measured in 30 macrosomic neonates of diabetic mothers (group A), 30 macrosomic neonates of healthy mothers (group B) and 30 healthy neonates (group C). Serum IGF-I, IGFBP-3 and leptin levels were determined in all infants and their mothers. Stepwise logistic regression analysis was used to determine independent risk factors for aortic intima-media thickness.. Mean aortic intima-media thickness was significantly higher in groups A and B (0.489+/-0.015,0.466+/-0.019 mm, respectively) than in controls (0.375+/-0.024 mm, p<0.0001). Weight-adjusted aortic intima-media thickness was significantly higher in-group A than in groups B (p=0.004) and C (p=0.048). Serum leptin concentration in-group B (37.4+/-10.7 ng/ml) was significantly greater than in-group C (23.5+/-7.1 ng/ml, p<0.0001), but significantly lower than in-group A (46.6+/-14.1 ng/ml, p<0.0001). Serum IGF-I levels of the infants were significantly lower in-group C (113.2+/-33.1 ng/ml) than in groups A and B (205.2+/-60.1 and 179.3+/-55.1 ng/ml respectively, p<0.0001). Serum IGF-I, IGFBP-3 and leptin levels of the infants were positively correlated with mean (p<0.0001) and weight-adjusted aortic intima-media thickness measurements (p=0.003, p=0.006 and p=0.001, respectively).. Macrosomic neonates of diabetic mothers have significantly increased aortic intima-media thickness with higher serum IGF-I, IGFBP-3 and leptin concentrations than those of controls. It might be speculated that these changes may exaggerate the atherosclerotic process later in life.

Topics: Aorta, Abdominal; Birth Weight; Female; Fetal Macrosomia; Humans; Infant, Newborn; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Male; Mothers; Tunica Intima; Ultrasonography

Intrauterine exposure to maternal diabetes and large size at birth are known risk factors for the subsequent development of insulin resistance and metabolic syndrome. Although Hispanic youth have been shown to have a high prevalence of metabolic syndrome, it is unknown whether metabolic abnormalities and a predisposition for glucose intolerance are present at birth.. The objective of the study was to determine whether abnormalities in insulin sensitivity exist at or soon after birth in large-for-gestational-age neonates born to Hispanic women with and without gestational diabetes. DESIGN/PATIENTS/SETTING: Forty-two term Hispanic neonates were enrolled for cross-sectional studies at 24-48 h after birth and included nine large-for-gestational-age neonates delivered of women with gestational diabetes (large-for-gestational-age-IDM), 12 large-for-gestational-age but not IDM neonates, 11 poorly grown (at the fifth to 10th percentile), and 10 appropriate-for-gestational-age neonates. Insulin sensitivity and secretion were measured by shortened fasting iv glucose tolerance test.. Insulin sensitivity index was measured within 48 h of birth.. Neonates were studied at 36 +/- 11 h postnatally, and all groups were euglycemic at the time of study. However, insulin sensitivity was significantly lower (P < 0.05, ANOVA) in large-for-gestational-age-IDM [3.0 +/- 0.7 (sem) mU/liter.min] and large-for-gestational-age-non-IDM (2.2 +/- 0.4 mU/liter.min) cohorts in comparison with poorly grown (5.0 +/- 0.7 mU/liter.min) and appropriate-for-gestational-age controls (5.4 +/- 0.8 mU/liter.min). Insulin secretion did not differ between groups.. Reduced insulin sensitivity is present soon after birth in Hispanic large-for-gestational-age neonates born to mothers with and without gestational diabetes, demonstrating the onset of insulin resistance before birth and evidence of altered fetal programming.

Topics: Adult; Birth Weight; Blood Glucose; Cross-Sectional Studies; Diabetes, Gestational; Female; Fetal Macrosomia; Gestational Age; Hispanic or Latino; Humans; Infant, Newborn; Insulin; Insulin Resistance; Leptin; Lipids; Male; Pregnancy; Prevalence; Risk Factors

Not much is known about the implication of adipokines and different cytokines in gestational diabetes mellitus (GDM) and macrosomia. The purpose of this study was to assess the profile of these hormones and cytokines in macrosomic babies, born to gestational diabetic women.. A total of 59 women (age, 19-42 yr) suffering from GDM with their macrosomic babies (4.35 +/- 0.06 kg) and 60 healthy age-matched pregnant women and their newborns (3.22 +/- 0.08 kg) were selected.. Serum adipokines (adiponectin and leptin) were quantified using an obesity-related multiple ELISA microarray kit. The concentrations of serum cytokines were determined by ELISA.. Serum adiponectin levels were decreased, whereas the concentrations of leptin, inflammatory cytokines, such as IL-6 and TNF-alpha, were significantly increased in gestational diabetic mothers compared with control women. The levels of these adipocytokines were diminished in macrosomic babies in comparison with their age-matched control newborns. Serum concentrations of T helper type 1 (Th1) cytokines (IL-2 and interferon-gamma) were decreased, whereas IL-10 levels were significantly enhanced in gestational diabetic mothers compared with control women. Macrosomic children exhibited high levels of Th1 cytokines and low levels of IL-10 compared with control infants. Serum IL-4 levels were not altered between gestational diabetic mothers and control mothers or the macrosomic babies and newborn control babies.. GDM is linked to the down-regulation of adiponectin along with Th1 cytokines and up-regulation of leptin and inflammatory cytokines. Macrosomia was associated with the up-regulation of Th1 cytokines and the down-regulation of the obesity-related agents (IL-6 and TNF-alpha, leptin, and adiponectin).

Topics: Adiponectin; Adult; Blood Glucose; Cytokines; Diabetes, Gestational; Female; Fetal Macrosomia; Humans; Infant, Newborn; Insulin; Interferon-gamma; Interleukin-2; Interleukin-4; Interleukin-6; Leptin; Lipids; Male; Pregnancy; Tumor Necrosis Factor-alpha

To investigate whether mitochondrial DNA (mtDNA) content may be associated with clinical features, anthropometric variables, and laboratory findings in both extremes of abnormal fetal growth: small and large size for gestational age.. Eighty-eight pregnant women and their infants were included in a cross-sectional study. According to the offspring birthweight, normalized by sex and gestational age, there were 57 newborns with appropriate weight for gestational age (AGA) and 31 with abnormal weight for gestational age: 17 small for gestational age (SGA) and 14 large for gestational age (LGA). mtDNA quantification using nuclear DNA as a reference was measured by a real-time quantitative polymerase chain reaction method.. The mothers' pregestational BMI was associated with the weight of their offspring: SGA infants had lean mothers (BMI, 21.4 +/- 0.7), and LGA infants had overweight mothers (BMI, 26.7 +/- 1.4) in comparison with AGA infants (BMI, 23.0 +/- 0.7) (p < 0.003). Newborn leptin levels were associated with birthweight after adjustment for sex and gestational age (SGA, 7.0 +/- 1.1 ng/mL; AGA, 15.2 +/- 1.6 ng/mL; and LGA, 25.6 +/- 4.1 ng/mL) (p < 0.002). Conversely, mtDNA/nuclear DNA ratio was significantly lower in both extremes of abnormal fetal growth, SGA (18 +/- 6) and LGA (9 +/- 2), at birth in comparison to AGA-weight infants (28 +/- 4) (p < 0.03).. Our findings show that mtDNA content is decreased in newborns with abnormal weight in comparison with AGA infants. On the basis of a cumulative body of evidence, we speculate that mtDNA depletion is one of the putative links between abnormal fetal growth and metabolic and cardiovascular complications in later life.

Topics: Adult; Anthropometry; Birth Weight; Body Mass Index; Cross-Sectional Studies; DNA, Mitochondrial; Female; Fetal Macrosomia; Humans; Infant, Newborn; Infant, Small for Gestational Age; Leptin; Male; Obesity; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications

To investigate the frequency of macrosomia in an homogeneous cohort of type 1 diabetic mothers and to analyze the influence of maternal factors and glycemic control on the incidence of fetal macrosomia.. Fifty-five consecutive type 1 diabetic first-pregnancies were prospectively studied. Macrosomia was defined by a ponderal index above the 90(th) percentile. Venous cord blood levels of insulin, C peptide and leptin were measured at delivery. The influence of HbA1c levels and other maternal variables on the occurrence of macrosomia and on the ponderal index was assessed using a stepwise regression logistic model.. The mean (+/- SD) birth weight was 3482 (+/- 497) g at 37.4 +/- 1.0 weeks gestation. Macrosomia occurred in 29 cases (53.7%). Fetal insulin, C peptide and leptin levels were significantly higher in macrosomic than in non macrosomic infants. Maternal age, duration of diabetes, pregravid body mass index, parity, weight gain during pregnancy, presence of a microangiopathy, nephropathy, smoking habits, gestational hypertension or preeclampsia, and HbA1c levels throughout pregnancy did not differed between mothers of macrosomic and non macrosomic infants. In the stepwise analysis none of these covariates was explanatory of the ponderal index.. The frequency of macrosomia remains very high in infants of type 1 diabetic mothers despite a reasonable degree of glycemic control. The variability of the fetal growth response to mild hyperglycemia prompts for the identification of other factors involved in the modulation of fetal growth.

Topics: Adult; Birth Weight; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Embryonic and Fetal Development; Female; Fetal Macrosomia; Gestational Age; Glycated Hemoglobin; Humans; Hypoglycemia; Infant, Newborn; Insulin; Leptin; Maternal Age; Placenta; Pregnancy; Pregnancy in Diabetics; Prospective Studies; Reference Values

To determine the relationships among serum leptin, insulin-like growth factor-I, and insulin levels in large for gestational age (LGA) infants.. Serum samples were collected from maternal veins and umbilical arteries of 52 consecutive, term, LGA neonates of nondiabetic mothers. Maternal and neonatal serum samples were analyzed for levels of leptin, insulin-like growth factor-I, and insulin by specific radioimmunoassays. Multiple regression analysis was used to determine independent risk factors for fetal macrosomia.. The independent risk factor significantly associated with fetal macrosomia was umbilical cord leptin concentration (P <.01, beta = 0.59). There was a statistically significant correlation between umbilical cord leptin and insulin-like growth factor-I levels and birth weight (r = 0.51, P <.01; r = 0.37, P <.01; respectively). The correlation between umbilical cord insulin levels and birth weight was not statistically significant (r = 0.06, P =.63), nor was that between maternal body mass index and birth weight (r = 0.09, P =.50).. Our data showed that umbilical cord leptin concentration was an independent risk factor for fetal macrosomia.

Topics: Adult; Birth Weight; Female; Fetal Blood; Fetal Macrosomia; Humans; Infant, Newborn; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Pregnancy; Risk Factors

We sought to reanalyze the concept of fetal macrosomia with regard to the ponderal index and to investigate the role of insulin, insulinlike growth factor I, leptin, and maternal factors on birth size in a population of infants with nondiabetic mothers.. Venous cord blood levels of insulin, insulinlike growth factor I, insulinlike growth factor binding protein 3, and leptin were measured in 28 large-for-gestational-age and 21 appropriate-for-gestational-age newborns.. Large-for-gestational-age newborns can be divided into symmetric and asymmetric subtypes according to the ponderal index. Mean leptin concentrations in cord blood were significantly higher in asymmetric than in symmetric large-for-gestational-age newborns (P =.01). A positive correlation was observed between leptin and the ponderal index (r = 0.53, P =.001) and between leptin and insulin concentrations in cord blood (r = 0.53, P =.008).. Our results strongly suggest that macrosomia should not be classified on the basis of birth weight and gestational age alone. We also show that asymmetric macrosomic infants with nondiabetic mothers have abnormal leptin and insulin concentrations.

Topics: Embryonic and Fetal Development; Female; Fetal Blood; Fetal Macrosomia; Gestational Age; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Proteins; Umbilical Veins

The hormone leptin, produced in the adipose tissue, is involved in the regulation of body weight. The release of the hormone is increased in obese adults and decreased after fasting in human adults. This study investigated whether the plasma leptin level was related to the infant's birth weight and whether the level was reduced in connection with the physiological weight loss during the neonatal period.. We measured the plasma leptin level in cord blood from infants who were large for gestational age (LGA) (n = 15), small for gestational age (SGA) (n = 16), and appropriate for gestational age (AGA) (n = 38). AGA infants (n = 120), who were exclusively breastfed, were also studied during their first 4 postnatal days in a cross-sectional method. One blood sample was collected before breastfeeding from each infant. Plasma leptin concentrations were determined by radioimmunoassay.. The median (range) concentration of leptin from cord blood was increased in LGA infants and decreased in SGA infants compared with the level in AGA infants. There was a positive correlation between the log of the plasma leptin level in cord blood and both the infant's birth weight (r = 0.76; n = 69) and the body mass index (r = 0.63; n = 69). The normal 3% to 6% weight reduction that occurs during the first 4 postnatal days was associated with a 26% decrease in the plasma leptin level in healthy breastfed infants.. The plasma leptin level is highly correlated to the size of adipose tissue mass and decreases in connection with the initial physiological weight loss in newborn infants. These data provide evidence that leptin is highly related to the nutritional status already during the fetal and neonatal periods.

Topics: Adipose Tissue; Body Mass Index; Breast Feeding; Cross-Sectional Studies; Female; Fetal Macrosomia; Humans; Infant, Newborn; Infant, Small for Gestational Age; Leptin; Male; Proteins; Weight Loss