LGA Groups Research Articles

Comparison of anthropometric, metabolic, and body compositional abnormalities in Korean children and adolescents born small, appropriate, and large for gestational age: a population-based study from KNHANES V (2010-2011).

The impacts of growth restriction and programming in the fetal stage on metabolic and bone health in children and adolescents are poorly understood. Moreover, there is insufficient evidence for the relationship between current growth status and metabolic components. Herein, we compared the growth status, metabolic and body compositions, and bone mineral density in Korean children and adolescents based on birth weight at gestational age. We studied 1,748 subjects (272 small for gestational age [SGA], 1,286 appropriate for gestational age [AGA], and 190 large for gestational age [LGA]; 931 men and 817 women) aged 10-18 years from the Korean National Health and Nutrition Examination Survey (KNHANES) V (2010-2011). Anthropometric measurements, fasting blood biochemistry, and body composition data were analyzed according to birth weight and gestational age. The prevalence of low birth weight (14.7% vs. 1.2% in AGA and 3.2% in LGA, p<0.001) and current short stature (2.237 [1.296-3.861] compared to AGA, p=0.004) in SGA subjects was greater than that in other groups; however, the prevalence of overweight and obesity risks, metabolic syndrome (MetS), and MetS component abnormalities was not. Moreover, no significant differences were found in age- and sex-adjusted lean mass ratio, fat mass ratio, truncal fat ratio, bone mineral content, or bone density among the SGA, AGA, and LGA groups in Korean children and adolescents. Our data demonstrate that birth weight alone may not be a determining factor for body composition and bone mass in Korean children and adolescents. Further prospective and longitudinal studies in adults are necessary to confirm the impact of SGA on metabolic components and bone health.

Nontargeted metabolomics reveals the potential mechanism underlying the association between birthweight and metabolic disturbances

AimsThe aim of this study was to characterize the metabolites associated with small- and large-gestational-age newborns in maternal and cord blood, and to investigate potential mechanisms underlying the association between birthweight and metabolic disturbances.Research design and methodsWe recorded detailed anthropometric data of mother-offspring dyads. Untargeted metabolomic assays were performed on 67 pairs of cord blood and maternal fasting plasma samples including 16 pairs of small-for-gestational (SGA, < 10th percentile) dyads, 28 pairs of appropriate-for-gestational (AGA, approximate 50 percentile) dyads, and 23 pairs of large-for-gestational (LGA, > 90th percentile) dyads. The association of metabolites with newborn birthweight was conducted to screen for metabolites with U-shaped and line-shaped distributions. The association of metabolites with maternal and fetal phenotypes was also performed.ResultsWe found 2 types of metabolites that changed in different patterns according to newborn birthweight. One type of metabolite exhibited a “U-shaped” trend of abundance fluctuation in the SGA-AGA-LGA groups. The results demonstrated that cuminaldehyde level was lower in the SGA and LGA groups, and its abundance in cord blood was negatively correlated with maternal BMI (r = -0.352 p = 0.009) and weight gain (r = -0.267 p = 0.043). 2-Methoxy-estradiol-17b 3-glucuronide, which showed enrichment in the SGA and LGA groups, was positively correlated with homocysteine (r = 0.44, p < 0.001) and free fatty acid (r = 0.42, p < 0.001) in maternal blood. Serotonin and 13(S)-HODE were the second type of metabolites, denoted as “line-shaped”, which both showed increasing trends in the SGA-AGA-LGA groups in both maternal and cord blood and were both significantly positively correlated with maternal BMI before pregnancy. Moreover, cuminaldehyde, serotonin, 13(S)-HODE and some lipid metabolites showed a strong correlation between maternal and cord blood.ConclusionsThese investigations demonstrate broad-scale metabolomic differences associated with newborn birthweight in both pregnant women and their newborns. The U-shaped metabolites associated with both the SGA and LGA groups might explain the U-shaped association between birthweight and metabolic dysregulation. The line-shaped metabolites might participate in intrauterine growth regulation. These observations might help to provide new insights into the insulin resistance and the risk of metabolic disturbance of SGA and LGA babies in adulthood and might identify potential new markers for adverse newborn outcomes in pregnant women.

Role of first trimester screening test in predicting the perinatal outcomes in low risk term pregnancies

Objective: This study aims to investigate the relationship between the nuchal translucency (NT) values measured in the first trimester and the well-being of the newborn. Methods: The study was planned as a retrospective cross-sectional study and was conducted between January 2018 and January 2020. A total of 2394 patients who had a combined test and delivered at our university hospital were included in the study. The demographic data of the pregnant women were recorded. NT MoM values, PAPP-A and β-hCG MoM values, birth weight, gender, need for neonatal intensive care (NICU), and Apgar scores were evaluated. Results: It was found that NT (MoM) values were similar among the SGA, AGA, and LGA groups (p=0.159). PAPP-A (MoM) values were similar in the SGA group compared to AGA and LGA infant groups (p=0.947). It was also found that β-hCG (MoM) values were similar in the AGA group compared to SGA and the LGA infant groups (p=0.694). When compared with those with NICU and non-NICU, the NT, PAPP-A, β-hCG, and birth weight values were again not found to be statistically significant (p&gt;0.05). The NT, PAPP-A, β-hCG, and male gender factors were evaluated in the Binary Logistic Regression Analysis, in which being an SGA baby was considered as a risk. It was found that a 1 mm increase in NT values increased the risk of having an SGA baby 2.63 times at a statistically significant level (OR=2.636, p=0.009, 95% CI: 1.277–5.440). PAPP-A, β-hCG levels, and having a male gender were not related to the risk of having an SGA baby. Furthermore, NT, PAPP-A, β-hCG levels, and having a male gender were not associated with the risk of NICU hospitalization. Conclusion: In conclusion, we could not predict the birth weight with increased NT MoM values that were detected in the first trimester combined test in this study; however, we found that the risk of having an SGA fetus increases with a weak rise in NT value.

Does low gonial angle affect the Amount of Bone Loss Around implant in the posterior mandible?

Background: The purpose of this study was to investigate whether there is a role of the low gonial angle on marginal bone resorption around the implants placed in the posterior mandible. Methods: This retrospective study, including 20 patients with 46 implants followed 36 months were inserted in the toothless posterior area. Patients without systemic disease were included in this study. The gonial angle was measured on a panoramic x-ray; Patients with a gonial angle of more than 1250were classified as high gonial angle, and those with less than 1200 were classified as a low gonial angle group. Mesial and distal marginal bone resorption and implant angulation with the occlusal plane were measured via Image J software (National Institutes of Health; version 1.5i, USA). Independent samples t-test was used to compare measured variables between high and low gonial angle groups. Results: The mean marginal bone resorption (MBL) was 0.27±0.16 mm for the mesial side and 0.27±0.13mm for the distal side in the LGA group. In the HGA group, MBL was 0.77±0.28mm for the mesial side and 0.71±0.27mm for the distal side. There was no statistical significance between HGA and LGA groups regarding marginal bone resorption. However, implant angulation with the occlusal plane was correlated with marginal bone resorption in the HGA group. Conclusion: The result of this study is that a low gonial angle is not directly a risk factor for marginal bone resorption around the dental implant. However, implants should be placed perpendicular to the occlusal plane as possible in the HGA group.

Neurodevelopmental outcomes of singleton large for gestational age infants

To compare neurodevelopmental outcomes of large and appropriate for gestational age (LGA, AGA) infants <29 weeks' gestation at 18-24 months of corrected age. Retrospective cohort study using the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network databases. Primary outcome was a composite of death or significant neurodevelopmental impairment (NDI), defined as severe cerebral palsy, Bayley III cognitive, language and motor scores of <70, need for hearing aids or cochlear implant and bilateral visual impairment. Univariate and multivariable logistic analyses were applied for outcomes. The study cohort comprised 170 LGA and 1738 AGA infants. There was no difference in significant NDI or individual components of the Bayley III between LGA and AGA groups. LGA was associated with the increased risk of death by follow-up, 44/170 (25.9%) vs. 320/1738 (18.4%) (aOR: 1.60 95% CI: 1.00-2.54). Risk of NDI was similar between LGA and AGA infants.

788 Can urinary metabolite markers at 12-20 weeks’ gestation be used to predict birthweight?

To examine if urinary metabolites are predictive of birthweight. Urine samples were collected at 12-20 weeks’ from 126 women participating in the Mothers, Omega 3 & Mental Health Study, a double blind, placebo-controlled randomized controlled trial of omega-3 fatty acid supplementation for pregnant women identified at high risk for depression. Delivery birthweights were available for 112 of the participants and classified as small for gestational age (SGA, n=9), appropriate for gestational age (AGA, n=84) and large for gestational age (LGA, n=19). Urine samples underwent ion pairing reverse phase LC-MS analysis for 49 metabolites. Principle component analysis (PCA) was used to determine if there was a relationship between individual metabolites and weight classification. Means of each metabolite were calculated for each birthweight group and were statistically compared using T tests. In the SGA group, we found increased mean concentrations of urinary gluconate (P=0.046), inosine (P=0.020), and a-hydroxyisobutyrate (P=0.043) as well as decreased concentration of hypoxanthine (P=0.021) when compared with the mean urinary concentrations of these metabolites among mothers who gave birth to AGA infants. There were no significant differences between mean metabolite concentrations in the LGA and AGA groups. Our exploratory study found four early pregnancy urinary metabolites (gluconate, inosine, a-hydroxyisobutyrate, hypoxanthine) to be correlated with later SGA birthweight. Further research is warranted to evaluate whether these markers may identify women at risk of delivering SGA neonates. Earlier detection may impact pregnancy care and antenatal fetal surveillance. This may be particularly important for gravid woman at risk for developing depressive symptoms.

Maternal serum uric acid levels in pregnancy and fetal growth

Objective: Studies of maternal serum uric acid (UA) in pregnancy focus primarily on high levels of UA, however, both low and high UA levels can be markers of oxidative stress, a biological state potentially linked to fetal growth. We therefore aimed to test whether low and high maternal serum UA levels during pregnancy are associated with atypical fetal growth (unusually small or large) measured as birthweight (BW) for gestational age.Methods: The Pregnancy Outcomes and Community Health Study enrolled 3019 pregnant women between their 16th–27th week of pregnancy from 52 clinics in five Michigan communities (1998–2004). Maternal UA levels were measured in blood collected at enrollment among a subcohort of 1291 participants. Infant BW and gestational age were used to calculate gestational age-specific BW Z-score. Infants were grouped as small (SGA = BW < 10th percentile), appropriate (AGA = BW 10th–90th percentile), or large (LGA) = BW > 90th percentile) for their gestational age. Analyses considered multiple potential confounders. Linear spline or multiple linear regression models were applied to evaluate the relationship between maternal UA levels and BW Z-score overall and within SGA, AGA, and LGA groups. Model robustness was tested through bootstrap, sensitivity analysis, and cross-validation techniques.Results: The relation between maternal UA levels and BW Z-score varied by infant group. Among SGA infants, the relation was nonlinear (J-shape): both extremes of UA had lower BW Z-score with a breakpoint of 0.267 mmol/L UA (adjusted regression coefficient β = 2.32, p = .01 for lower UA; adjusted β = −37.38, p < .01 for higher UA). Among AGA infants, there was no significant association, and among LGA infants, the relation was linear (adjusted β = 2.86, p = .03).Conclusions: Future research on maternal UA levels in pregnancy may benefit from considering both very low and high levels, and identifying in utero conditions associated with the two extremes.

Enhanced neuronal and blunted hemodynamic reactivity to cocaine in the prefrontal cortex following extended cocaine access: optical imaging study in anesthetized rats.

Cocaine addiction is associated with dysfunction of the prefrontal cortex (PFC), which facilitates relapse and compulsive drug taking. To assess if cocaine's effects on both neuronal and vascular activity contribute to PFC dysfunction, we used optical coherence tomography and multi-wavelength laser speckle to measure vascularization and hemodynamics and used GCaMP6f to monitor intracellular Ca2+ levels ([Ca2+ ]in ) as a marker of neuronal activity. Rats were given short (1hour; ShA) or long (6hours; LgA) access cocaine self-administration. As expected, LgA but not ShA rats escalated cocaine intake. In naïve rats, acute cocaine decreased oxygenated hemoglobin, increased deoxygenated hemoglobin and reduced cerebral blood flow in PFC, likely due to cocaine-induced vasoconstriction. ShA rats showed enhanced hemodynamic response and slower recovery after cocaine, versus naïve. LgA rats showed a blunted hemodynamic response, but an enhanced PFC neuronal [Ca2+ ]in increase after cocaine challenge associated with drug intake. Both ShA and LgA groups had higher vessel density, indicative of angiogenesis, presumably to compensate for cocaine's vasoconstricting effects. Cocaine self-administration modified the PFC cerebrovascular responses enhancing it in ShA and attenuating it in LgA animals. In contrast, LgA but not ShA animals showed sensitized neuronal reactivity to acute cocaine in the PFC. The opposite changes in hemodynamics (decreased) and neuronal responses (enhanced) in LgA rats indicate that these constitute distinct effects and suggest that the neuronal and not the vascular effects are associated with escalation of cocaine intake in addiction whereas its vascular effect in PFC might contribute to cognitive deficits that increase vulnerability to relapse.

Perinatal sclerostin concentrations in abnormal fetal growth: the impact of gestational diabetes

Objective: To prospectively evaluate maternal and cord blood concentrations of sclerostin – an osteocyte-secreted factor, inhibiting osteoblast differentiation and bone formation and associated with adverse metabolism – in pregnancies with normal and abnormal fetal growth. Methods: Plasma sclerostin concentrations were determined by ELISA in 80 maternal and 80 cord blood samples from asymmetric intrauterine-growth-restricted (IUGR, n = 30), large-for-gestational-age (LGA, n = 30), and appropriate-for-gestational-age (AGA, n = 20) singleton full-term pregnancies. Fourteen out of 30 mothers with LGA offspring presented with gestational diabetes mellitus (GDM). Results: Maternal and fetal sclerostin concentrations did not differ among LGA, IUGR, and AGA groups. Fetal concentrations were higher than maternal. In LGA group, maternal concentrations were elevated in cases of GDM (b = 13.009, 95%CI 1.425–24.593, p = .029). In a combined group and the IUGR group, maternal concentrations were elevated in older mothers (b = 0.788, 95%CI 0.190–1.385, p = .010, and b = 0.740, 95%CI 0.042–1.438, p = .039, respectively). Conclusions: Maternal and fetal sclerostin concentrations may not be differentially regulated in pregnancies complicated by abnormal fetal growth. Circulating maternal levels are higher in cases of GDM, probably implying reduced bone formation. Sclerostin up-regulation with aging may be one of the molecular pathways responsible for the observed age-related decline in bone synthesis, leading to accelerated bone loss in humans.

Small for gestational age as an independent risk factor for long-term pediatric gastrointestinal morbidity of the offspring

Objective: The concept of neonatal programming has begun to emerge as an important component of adult health. Scarce data exist regarding perinatal risk factors for long-term gastrointestinal (GI) morbidity of the offspring. We aimed to evaluate the association between birthweight (BW) at term and long-term pediatric GI morbidity.Study design: A population-based cohort analysis was performed, comparing the risk of long-term GI morbidity (up to the age of 18 years) in children delivered at term according to their BW. The study included all term deliveries occurring between 1991 and 2014 at a single regional tertiary medical center. Multiple gestations and fetuses with congenital malformations were excluded. BW was subdivided into: small for gestational age (small for gestational age (SGA) – BW ≤ 5th centile), appropriate for gestational age (AGA −5th centile < BW < 95th centile), and large for gestational age (LGA – BW ≥95th centile). Hospitalizations up to the age of 18 years involving GI morbidity were evaluated, using a predefined set of ICD-9 codes, as recorded in the hospital files. A Kaplan–Meier survival curve was used to compare cumulative GI morbidity incidence. A Cox proportional hazards model was constructed to control for confounders.Results: During the study period, 225,600 term singleton deliveries met the inclusion criteria. Of them, 4.6% (n = 10,415) were SGA and 4.3% (n = 9796) were LGA. During the 18-years follow-up period, 11,791 (5.2%) children were hospitalized with GI morbidity. Hospitalizations were significantly more common in the SGA group, as compared with the AGA and LGA groups (6.6 versus 5.2 versus 4.5%, respectively, p < .001) Specifically, inflammatory bowel disease, celiac, hernia, hepatitis, and cholecystitis, were more common in the SGA group. The Kaplan–Meier survival curve demonstrated a significantly higher cumulative incidence of gastrointestinal morbidity in the SGA group (log rank p < .001). In the Cox proportional hazards model, controlled for relevant clinical confounders, SGA BW was found to be an independent risk factor for long-term GI morbidity (adjusted HR = 1.23, 95%CI 1.14–1.33, p < .001).Conclusions: SGA offspring are at an increased and independent risk for long-term pediatric GI morbidity.

The impact of excessive maternal weight on the nutritional status of the fetus - the role of leptin.

IntroductionAssessment of leptin concentration in the blood of pregnant women (leptin concentration – Lc) and in their newborns, according to their nutritional status.Material and methodsPregnant women (n = 42) were divided into normal body mass (NBM) and excessive body mass (EBM) groups. Neonates were divided into AGA (eutrophic) and LGA (macrosomic) groups. Leptin concentraction was studied in 4 subgroups: NBM/AGA, NBM/LGA, EBM/AGA, EBM/LGA.ResultsMothers: A significant correlation was found between maternal Lc and body mass index (BMI) (r = 0.75, p < 0.001). Maternal Lc was 3 times higher than neonatal Lc (p < 0.00001). The NBM mothers showed lower Lc compared to EBM mothers (p = 0.000018). Leptin concentration values in NBM/LGA and NBM/AGA mothers were similar (p = 0.6775). Newborns: Correlations were found between Lc and ponderal index (PI) (r = 0.67, p < 0.001), weight (r = 0.43, p = 0.004) and placental weight (r = 0.56, p < 0.001). Girls presented higher Lc than boys (p = 0.0338). In LGA groups, newborns born to EBM mothers presented higher Lc than those born to NBM mothers (p = 0.0013). In both AGA groups, Lc was similar (AGA/EBM vs. AGA/NBM p = 0.1619). The highest Lc and the largest placentas were found in the group of LGA newborns born to EBM mothers.ConclusionsLeptin concentration positively correlates with BMI in pregnant women, with PI and female sex in newborns as well as with placental weight. The nutritional status of fetuses does not affect the Lc of their non-obese mothers. The LGA neonates born to EBM women demonstrate higher Lc than LGA neonates born to NBM mothers, whereas Lc of AGA neonates is similar regardless of the nutritional status of their mothers.

Relationship between folate transporters expression in human placentas at term and birth weights

BackgroundAdequate folate levels are essential for successful pregnancy outcomes. We aimed to study the relationship between placental mRNA and protein levels of folate transporters to birth weight. MethodsPlacental folate transporters (FOLR1, RFC1 and HCP1/PCFT) mRNA and protein levels in basal (BP) and chorionic plate (CP) of small (SGA), appropriate (AGA) and large (LGA) for gestational age term infants (≥37 weeks gestation, n = 111) were determined by real-time PCR and Western blot respectively. ResultsFOLR1 and HCP1/PCFT mRNA were lower in both plates of SGA and LGA placentas compared to AGA (p < 0.01) and RFC1 mRNA was lower only in CP (p < 0.02). RFC1 protein levels were lower in BP of SGA (p < 0.05) and LGA (p < 0.01), and FOLR1 protein levels were lower in CP of SGA (p < 0.02) and LGA (p < 0.01) groups compared to AGA. HCP1/PCFT protein levels remained unchanged in all groups. ConclusionPlacentas of SGA and LGA groups showed a reduced mRNA expression and protein levels of folate transporters, with some differences depending on the location within the placenta (BP or CP). This suggests the presence of specific placental regulation mechanisms in gene expression that may be associated to birth weight.

C1q and tumor necrosis factor-related protein 3 is present in human cord blood and is associated with fetal growth

BackgroundTo determine the presence of C1q and tumor necrosis factor-related protein 3 (CTRP3) in cord blood and its relationship with fetal growth among Chinese newborns. MethodsThis pilot study recruited 126 infants (small for gestational age [SGA], n=34; appropriate for gestational age [AGA], n=60; large for gestational age [LGA], n=32); cord blood CTRP3 levels were measured, and fetal growth parameters were collected. ResultsMedian (25–75th percentile) CTRP3 levels in the SGA, AGA, and LGA groups were 297.2 (236.4–360.2), 297.5 (261.0–369.9), and 368.6 (298.5–507.1) ng/ml, respectively (P=0.01). LGA infants had higher CTRP3 levels than AGA infants (multiple linear regression analysis; P=0.01). The CTRP3 levels were positively correlated with birth weight (r=0.25, P<0.01), Ponderal index (r=0.28, P<0.01), and placental weight (r=0.20, P=0.03) in the total study population. In the subgroup analysis, CTRP3 levels were negatively correlated with birth length z scores (r=−0.39, P=0.03) and were positively correlated with the Ponderal index (r=0.43, P=0.02) only in the SGA group; no other significant correlations were observed. The CTRP3 levels were similar between the sexes (P=NS). ConclusionsCTRP3 is present in cord blood and might be involved in fetal growth.

The growth hormone receptor exon 3 polymorphism is not associated with height or metabolic traits in healthy young adults

ContextThe GHR polymorphisms contribution to the interindividual variability in prenatal and postnatal growth as well as to metabolic traits is controversial. ObjectiveThe aim of this study is to analyze the association of the GHRfl/d3 polymorphism with prenatal and postnatal growth and metabolic outcomes in adult life and to compare the genotype distribution in different populations. Design385 community healthy subjects followed from birth to adult life (23–25years old) were grouped according to birth size: small—SGA (n=130, 62 males), appropriate—AGA (n=162, 75 males) and large for gestational age—LGA (n=93, 48 males). GHRfl/d3 genotype distribution and its potential association with anthropometric (at birth, childhood and adult life) and metabolic features (in adult life) were analyzed and compared with data obtained from a systematic review of GHRfl/d3 association studies (31 articles). ResultsThe frequency of the GHR d3/d3 genotype was lower in the LGA (χ2 p=0.01); SGA and AGA subjects exhibited an increased chance of the d3/d3 genotype (OR=3.58; 95%CI: 1.55; 8.24) and (OR=2.39; 95%CI: 1.02; 5.62), respectively. Despite the different prevalence among different birth size groups, in adults, GHRfl/d3 genotype was not associated with height, plasma IGF1 levels or metabolic phenotype and cardiovascular risk. GHRfl/d3 genotype distributions in AGA, SGA and LGA groups were comparable with those found in subjects of European origin but not with those of Asian ancestry. ConclusionsThe GHRd3 genotype was negatively associated with birth size but it was not associated with adult height or weight, plasma IGF1, metabolic phenotype or any marker of increased cardiovascular risk in young adults.

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

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. 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). 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. 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.

Cord blood C-peptide, insulin, HbA1c, and lipids levels in small- and large-for-gestational-age newborns.

BackgroundSmall- and large-for-gestational-age (SGA, LGA) newborns are associated with metabolic syndrome in their later life. Cord blood C-peptide, insulin, glycosylated hemoglobin (HbA1c), and lipids levels may be altered in SGA and LGA newborns; however, the results are conflicting. Therefore, this study aimed to determine the effect of cord blood markers on SGA and LGA newborns.Material/MethodsThis was a prospective cohort study and included 2873 term newborns of non-diabetic women. Among these newborns, 83 (2.9%) were SGA, 2236 (77.8%) were appropriate-for-gestational-age (AGA), and 554 (19.3%) were LGA newborns. Cord blood C-peptide, insulin, HbA1c, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. The chi-square, Kruskal-Wallis, and Mann-Whitney tests were used to analyze categorical variables and continuous variables, respectively. Multinomial logistic regression analysis was used to determine the independent effect of these variables on SGA and LGA newborns.ResultsCord serum TG level was significantly higher in the SGA group than in AGA and LGA groups (p<0.05). The LGA group had significantly higher cord serum insulin level than AGA and SGA groups (p<0.05). After adjustment for confounding variables, including maternal age, parity, pre-pregnancy body mass index (BMI), education, annual household income, pregnancy-induced hypertension (PIH), mode of delivery, and newborn sex, high TG and insulin levels remained significantly associated with SGA and LGA newborns, respectively (p<0.05).ConclusionsHigh cord serum TG and insulin levels are independently associated with SGA and LGA newborns, respectively.

Different Adaptations in AMPA Receptor Transmission in the Nucleus Accumbens after Short vs Long Access Cocaine Self-Administration Regimens

Ca(2+)-permeable AMPA receptors (CP-AMPARs) accumulate in the nucleus accumbens (NAc) after ∼1 month of withdrawal from a long-access cocaine self-administration regimen (6 h/d, 10d). This is functionally significant because CP-AMPARs mediate the 'incubated' cue-induced cocaine craving produced by this regimen. Our present goal was to determine if other commonly employed cocaine self-administration regimens also elicit CP-AMPAR accumulation. We compared four regimens, named according to whether sessions were short-access (ShA, 2 h) or long-access (LgA, 6 h) and the total number of sessions: LgA/10d (already shown to elicit CP-AMPAR accumulation), ShA/11d, ShA/20-24d, and LgA/20-24d. In the latter regimens, rats began with 10 days of ShA and then entered a differential phase (10-14 days) in which ShA sessions either continued or switched to LgA. Controls self-administered saline. After >40 days of withdrawal, whole-cell patch-clamp recordings were performed in NAc core medium spiny neurons to assess the contribution of CP-AMPAR transmission, based on the magnitude of synaptic suppression elicited by bath application of the selective CP-AMPAR antagonist naspm (100 μM). Naspm produced a non-significant (∼10%) attenuation of electrically evoked local excitatory postsynaptic current in the saline and ShA groups. By contrast, a significant naspm-induced synaptic attenuation (25-30%) was observed in both the LgA groups. Further analyses indicate that this emergence of CP-AMPAR transmission in the LgA groups is associated with increased baseline responsiveness of MSN to excitatory drive. Together with data on cocaine infusions in each group, our results show that CP-AMPAR accumulation and enhanced glutamate transmission is associated with longer sessions (6 h), rather than the number of sessions or cocaine infusions.

220 Cord Blood Chemerin and Obestatin in Large for Gestational Age Infants

Background and aimsIncreased neonatal adiposity is associated with childhood obesity and subsequent development of adult diseases. Chemerin was recently introduced as a novel adipocytokine inducing insulin resistance and regulating maternal-fetal...

Escalation of methamphetamine self-administration in adolescent and adult rats

BackgroundMethamphetamine (METH) use has increased substantially in the last 10 years and poses a serious health concern, especially for young populations. Drug abuse primarily begins during adolescence, when uninhibited and excessive and drug intake is a common occurrence; thus, understanding the developmental patterns of addiction during this critical period is an essential step in its prevention. In the present study, the effect of age on the vulnerability to METH abuse was examined using a rat model of bingeing (i.e., escalation). MethodsAdolescent and adult rats were compared during short (ShA, 2-h) and long-access (LgA, 6-h) to METH self-administration. On postnatal (PN) days 23 (adolescents) and 90 (adults), rats were implanted with i.v. catheters and trained to lever press for infusions of METH (0.05mg/kg) during 2-h sessions. Once the rats reached a steady rate of METH self-administration, they were divided into ShA or LgA groups and allowed to self-administer METH for 15 additional days. ResultsResults indicated that adolescent rats earned significantly more infusions than adults under the LgA condition, but the age groups did not differ during ShA. Adolescents, but not adults, also significantly increased (i.e., escalated) METH self-administration across the 15 days of testing under the LgA condition. Further analysis indicated excessive responding during infusions in the LgA METH-exposed adolescents compared to the other groups, suggesting elevated impulsivity or motivation for drug. ConclusionThese results demonstrate that adolescents are more vulnerable to the escalation of METH than adults during LgA.

Caspase-3 mediates apoptosis of striatal cells in GA I rat model

In previous study, glutaric acid (GA) induced apoptosis of primary striatal neuron in vitro. In order to investigate the neurotoxic effects of GA on neonatal rat corpus striatum and the possible mechanism, 34 male pups were randomly assigned to NS group, low dose GA (LGA, 5 μmol GA/g body weight) group and high dose GA (HGA, 10 μmol GA/g body weight) group. These pups were subcutaneously administered with three injections from postnatal day 3 to 22 at 7:30 am, 15:00 pm and 22:30 pm and killed 12 h after the last injection. Microscopic pathology in corpus striatum was evaluated by HE staining. The apoptotic cells were identified by TUNEL staining. The transcript levels of caspase-3, 8, 9, Bax, Bcl-2 were detected by using real-time PCR and the protein levels of procaspase-3 and the active fraction were evaluated by Western blotting. In LGA and HGA groups, ventricle collapse, cortical atrophy by a macroscope and interstitial edema, vacuolations, widened perivascular space of bilateral striatum by a microscope were observed. TUNEL assay revealed that the apoptotic cells were increased in LGA and HGA groups. The transcript of caspase-3 was up-regulated to 2.5 fold, accompanied by the up-regulation of caspase-9, Bax and down-regulation of Bcl-2. The protein levels of procaspase-3 and the active fraction were up-regulated in LGA and HGA groups. The rat model for GA I showed mitochondrial apoptotic pathway may be involved in the GA-induced striatal lesion. Further studies should be taken to investigate the underlying mechanisms.