Large For Gestational Age Newborns Research Articles

High level of γH2AX phosphorylation in the cord-blood cells of large-for-gestational-age (LGA) newborns

Newborns can experience adverse effects as a consequence of maternal or in utero exposure, altered growth of the fetus, or placental dysfunctions. Accurate characterization of gestational age allows monitoring of fetal growth, identification of deviations from the normal growth trajectory, and classification of babies as adapted, small, or large for gestational age (AGA, SGA, or LGA). The aim of this work was to evaluate nuclear and oxidative damage in umbilical cord-blood cells of newborns (sampled at birth), by applying the γH2AX assay and the fluorescent probe BODIPY581/591 C11, to detect DNA DSB and cell membrane oxidation, respectively. No statistically significant differences were observed in the proportion of oxidized cord-blood cells among the groups of newborns, although the LGA group showed the highest value. With regard to genome damage, elevated levels of γH2AX foci were detected in the cell nuclei from LGA newborns as compared to AGA or SGA babies, whose values did not differ from each other. Considering that the observed DNA damage, although still repairable, can represent a risk factor for obesity, metabolic diseases, or other pathologies, monitoring genome and cell integrity at birth can provide useful information for prevention of diseases later in life.

Association of maternal socio-demographic factors, maternal anthropometric measurements, and foetal sex with LGA newborns in Sri Lanka

Introduction: There is an increased trend of delivering large for gestational age (LGA) newborns globally, which has already caused significant impact on health, nutrition, economics, and social aspects. LGA newborns are more vulnerable for complications developed from intrauterine life to adulthood and it is becoming additional burden to the health care and economic state of the country. However, we lack published data on incidence, trend and factors affecting LGA newborns in Sri Lanka. Determination of risk factors associated with LGA newborns would help to formulate and implement effective preventive measures. Method: A case control study was carried out at obstetrics and gynaecology unit, Teaching Hospital Kandy from 01.01.2016 to 31.12.2016. Systematic sample technique was used, and study sample was consisted of 44 cases and 132 controls. Pretested interviewer administered questionnaire was used for data collection. Significance of associations between dependent and independent variables was estimated using probit regression model. Probit coefficient was estimated to assess the significance and respective marginal effects were estimated to assess the magnitude of significance. STATA software was used for analysis. Ethical clearance was obtained from ethical review committee, Teaching Hospital Kandy. Results: According to probit regression estimates of socio-demographic factors, maternal parity of two (Coefficient 1.89: 95% CI 0.75-3.03: P <0.05) or more (Coefficient 2.37: 95% CI 0.92-3.82: P <0.05), Monthly family income of more than 30,000/= rupees (Coefficient 2.28: 95% CI 0.92-3.63: P<0.05) and Tamil ethnicity (Coefficient 2.10: 95% CI 0.69-3.52: P<0.05) were statistically significant risk factor. In the analysis, maternal age (Coefficient 0.09: 95% CI -0.05-0.23: P>0.05), mother’s occupation (Coefficient 0.08: 95% CI -1.01-1.17: P>0.05) and maternal educational level (Coefficient 1.68: 95% CI -0.30-3.66: P>0.05) were not significant risk factors at 5% significance level. Considering the maternal anthropometric measurements, maternal weight gain during pregnancy (Coefficient 0.77: 95% CI 0.50-1.03: P<0.05) was a significant risk factor. Maternal BMI at booking visit (Coefficient 1.76: 95% CI -0.34-3.85: P>0.05), maternal weight at booking visit (Coefficient -0.63: 95% CI -1.5-0.26: P>0.05) and maternal height (Coefficient 0.56: 95% CI -0.08-1.2: P>0.05) were not significant risk factors in the analysis at 5% significance level. Foetal sex (Coefficient -0.69: 95% CI -1.5-0.13: P>0.05) was not a significant causative factor at 5% significance level. Conclusions: Among maternal socio-demographic factors, high monthly family income, parity of 2 or more and Tamil ethnicity were determined as statistically significant risk factors for LGA newborns. Among maternal anthropometric measurements, increased weight gain during pregnancy was determined as significant modifiable risk factor for LGA newborns. Maternal weight gain during pregnancy should be monitored throughout the antenatal period from the booking visit to identify mothers at risk. Effective interventions should be designed to minimize the negative impact on mothers at risk.

Comparative assessment of the health status of large for gestational age newborns

Our aim was to conduct a comparative assessment of the health status of large for gestational age (LGA) newborns. 348 full-term neonates who were born at the Republican Scientific and Practical Center “Mother and Child” were examined. The main group 1 (Gr1) consisted of 58 LGA newborns from mothers with diabetes mellitus (DM) type 1, the main group 2 (Gr2) consisted of 66 LGA babies from mothers without carbohydrate and lipid metabolism disorders, the main group 3 (Gr3) included 65 LGA babies from mothers with pregravid overweight or obesity, the control group (Gr4) had 159 newborns with the anthropometric parameters corresponding to the gestational age (AGA) from mothers without carbohydrate and lipid metabolism disorders. The negative impact of the mothers’ metabolic disorders on the newborns’ health status, functional state, and neuropsychological development was established. Babies born with macrosomia from mothers with DM were diagnosed with hypoglycemia, congenital pneumonia, hyperbilirubinemia, and neonatal encephalopathy much more often (p < 0.001). LGA babies from obese women were characterized by polycythemia, hyperbilirubinemia, and neonatal encephalopathy. Polycythemia, hyperbilirubinemia, and toxic erythema were often noted in Gr2 patients. The cases of brachial plexus injuries and limb fractures were not registered. A slower rate of neuropsychological development was noted in large neonates in the analyzed groups, and was more pronounced in infants from mothers with diabetes mellitus and obesity. LGA newborns from mothers with DM had a high hospitalization rate at the intensive care unit, followed by the separation of mother and child and a lower breastfeeding rate in the neonatal period. Large newborns from mothers with DM and from women with obesity had a higher probability of adverse neonatal outcomes and a reduced health status in the neonatal period.

Late-Pregnancy Dysglycemia After Negative Testing for Gestational Diabetes and Risk of the Large-for-Gestational-Age Newborns: A Nest Case-Control Study Based on the Xi'an Longitudinal Mother-Child Cohort Study.

BackgroundThe implications of gestational diabetes mellitus (GDM) on the short- and long-term health outcomes of both mother and child have been extensively studied. However, studies related to negative Oral Glucose Tolerance Test (OGTT) results in the second trimester but dysglycemia in late pregnancy on maternal and infant pregnancy outcomes are rare.MethodsWe conducted a nest case-control study within the Xi'an Longitudinal Mother-Child Cohort study (XAMC) to investigate the risk of adverse pregnancy outcomes in mothers and children with maternal negative mid-pregnancy OGTT results but high glycated hemoglobin (HbA1c) levels (≥5.7%) in late pregnancy. All target women who delivered from January 1st, 2017 to December 31st, 2018 in Northwest Women's and Children's Hospital in Xi'an were enrolled as the case group (HbA1c ≥ 5.7%). Others with HbA1c < 5.7% but without GDM were selected as the control group (HbA1c < 5.7%) by matching with the same delivery period. The logistic regression models were used to find out the risk factors of adverse pregnancy outcomes in the target population.ResultsA total of 2,116 and 1,907 women were finally enrolled in the case and control groups, respectively. Compared to the control group, more newborns with macrosomia (9.2% vs 4.1%, P < 0.001) and large for gestational age (LGA) (23.7% vs. 13.5%, P < 0.001), but less small for gestational age (SGA) (4.4% vs. 6.1%, P = 0.017) were found in the case group. The differences in other outcomes were not statistically significant. The multiple logistic regression analysis showed that gestational age, fetal length, prenatal HbA1c, and total cholesterol (TG) were independent risk factors for newborns with large-for-gestational-age (LGA). The case group had a 2.516-fold (95% CI, 1.692–3.739) risk of delivering LGA newborns compared to the control group.ConclusionThe glycemic management during the late pregnancy of non-GDM women should be given special consideration to reduce the risk of overweight offspring at birth.

Birth Size and Maternal, Social, and Environmental Factors in the Province of Jujuy, Argentina.

Introduction: birth size is affected by diverse maternal, environmental, social, and economic factors. Aim: analyze the relationships between birth size—shown by the indicators small for gestational age (SGA) and large for gestational age (LGA)—and maternal, social, and environmental factors in the Argentine province of Jujuy, located in the Andean foothills. Methods: data was obtained from 49,185 mother-newborn pairs recorded in the Jujuy Perinatal Information System (SIP) between 2009 and 2014, including the following: newborn and maternal weight, length/height, and body mass index (BMI); gestational age and maternal age; mother’s educational level, nutritional status, marital status and birth interval; planned pregnancy; geographic-linguistic origin of surnames; altitudinal place of birth; and unsatisfied basic needs (UBN). The dataset was split into two groups, SGA and LGA, and compared with adequate for gestational age (AGA). Bivariate analysis (ANOVA) and general lineal modeling (GLM) with multinomial distribution were employed. Results: for SGA newborns, risk factors were altitude (1.43 [1.12–1.82]), preterm birth (5.33 [4.17–6.82]), older maternal age (1.59 [1.24–2.05]), and primiparous mothers (1.88 [1.06–3.34]). For LGA newborns, the risk factors were female sex (2.72 [5.51–2.95]), overweight (1.33 [1.22–2.46]) and obesity (1.85 [1.66–2.07]). Conclusions: the distribution of birth size and the factors related to its variability in Jujuy are found to be strongly conditioned by provincial terrain and the clinal variation due to its Andean location.

ОЦЕНКА СОСТОЯНИЯ СЕРДЕЧНО-СОСУДИСТОЙ СИСТЕМЫ У КРУПНОВЕСНЫХ И МАЛОВЕСНЫХ К СРОКУ ГЕСТАЦИИ НОВОРОЖДЕННЫХ ДЕТЕЙ

The aim of the study was to assess the cardiovascular status of large-forgestational-age (LGA) and small-for-gestational-age (SGA) full-term newborns. A survey of 192 newborns was carried out on the basis of the Republican Scientific and Practical Center “Mother and Child”. Group 1 (Gr1) consisted of 54 large-for-gestational-age newborns, group 2 (Gr2) – 43 small-for-gestational-age newborns, group 3 (Gr3) – 95 newborns with physical development corresponding to gestational age (appropriate for gestational age). Echocardiographic parameters were compared between study groups, as corrected to body surface area. Morphometric assessment of heart structures in the course of Echo-CG in Gr1 patients showed a statistically significant thickening of the heart walls with predominant localization in the posterior wall of the left ventricle (LV) and interventricular septum (IVS). Significant differences were found in all derivatives of echocardiographic indicators in the examined groups of newborns. In Gr2, signs of diastolic myocardial dysfunction were revealed reflecting an impairment of the age-related evolution of myocardial relaxation processes. The intragroup analyses of LGA and SGA neonates (subgrouped according to the birth weight percentile) revealed no statistically significant differences in the direct and derived echocardiographic parameters analyzed. The frequency of detection of open foramen ovale (PFO), IVS thickness of 5.0 mm and more in LGA newborns had greater as compared with the group of conditionally healthy infants (р = 0.038, р = 0.001). Fetal communications in SGA newborns occurred significantly more often (PFO – р = 0.031, patent ductus arteriosus – р = 0.026) than in newborns with normal weight. LGA and SGA newborns are characterized by the specific cardiovascular status. The revealed changes make it possible to assign infants with large and small birth weight to the risk group for the development of cardiovascular pathology, which requires dynamic observation as well as therapeutic and prophylactic measures.

ОСОБЕННОСТИ АДИПОЦИТОКИНОВОГО СТАТУСА И ЛИПИДНОГО СПЕКТРА КРУПНОВЕСНЫХ НОВОРОЖДЕННЫХ ДЕТЕЙ

The purpose of the study was to analyze the characteristics of the adipocytokine status and lipid spectrum in large for gestational age (LGA) in the dynamics of the neonatal period, to assess the influence of the metabolic status of mothers on the analyzed indicators of their infants. 348 full­term newborns were examined. 3 groups of LGA were distinguished, taking into account the presence of type 1 diabetes mellitus in the mother (Gr1), overweight or obesity (Gr3) or the absence of disorders of carbohydrate and fat metabolism (Gr2). Group 4 (Gr4) – normal weight from mothers without changes in carbohydrate­lipid metabolism. The content of adipocytokines, lipids, glucose and vitamin D was studied in the “mother­child” dyads, blood serum of children in the dynamics of the neonatal period. An adipocytokine imbalance and hyperlipidemia were revealed in mothers of the examined groups of LGA, more pronounced with overweight and obesity. The TG/HDL ratio was significantly higher in Gr3. The influence of metabolic disorders in women on indicators of physical development, parameters of hormonal status and lipid profiles of children was established. Leptin levels at birth were significantly higher in LGA of all three groups compared to normal­weight children (p &lt; 0.001, p = 0.002, p &lt; 0.001). In the dynamics of the early neonatal period, a statistically significant decrease in leptin was observed against the background of an increase in total serum cholesterol. Maternal HDL, leptin, and cord blood IGF­1 levels were associated with neonatal size. The identified perinatal hormonal and metabolic patterns have a pronounced effect not only on the condition and anthropometric status of LGA newborns, but also program the pace of physical development in the neonatal period.

Association Between Umbilical Cord Levels of Glypican-1, Glypican-3, Syndecan-1, WISP1, Leptin and Birth Weight of Small, Appropriate, and Large for Gestational Age Infants

Background:Many factors are affecting intrauterine growth. The role of Wingless-type (Wnt) inducible signaling pathway protein-1 (WISP1), a novel adipokine and placental proteoglycans in intrauterine growth, is not known. We aimed to measure umbilical cord blood levels of glucose, insulin, leptin, WISP1, and placental proteoglycans [glypican-1 (GPC1), glypican-3 (GPC3), and syndecan-1 (SDC1)] which are thought to have an important role in fetal growth and investigate their relation with birth weight.Methods:Full-term neonates were included in this prospective, cross-sectional study and classified as appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA) according to their birth weight. Umbilical cord blood levels of glucose, insulin, leptin, WISP1, GPC1, GPC3, and SDC1 were measured.Results:Leptin levels were higher in LGA newborns compared to AGA and SGA newborns, while WISP1, GPC1, GPC3, and SDC1 levels were not different between the three groups. Leptin and GPC1 levels were higher in infants of mothers with gestational diabetes mellitus compared to infants of non-diabetic mothers, while WISP1, GPC3, and SDC1 were not different between the groups. Leptin was positively correlated with insulin, birth weight, and maternal weight. While there was a strong correlation between the WISP1, GPC1, GPC3, and SDC1 levels; there was no correlation between the birth weight, maternal weight, glucose, insulin, and WISP1, GPC1, GPC3, and SDC1 levels.Conclusion:Umbilical cord blood levels of GPC1, GPC3, SDC1, and WISP1 were not different between SGA, AGA, and LGA infants. The significance of serum levels of these adipokines and proteoglycans remains to be elucidated.

Obstetric consequences of a false‐positive diagnosis of large‐for‐gestational‐age fetus

ObjectiveTo compare delivery outcomes between true‐positive (TP) and false‐positive (FP) large‐for‐gestational‐age (LGA) fetuses, appropriate‐for‐gestational‐age (AGA) fetuses, and false‐negative (FN) LGA fetuses.MethodsRetrospective cohort study of singleton pregnancies at risk for macrosomia without contraindication to vaginal delivery, receiving an ultrasound scan at 34–37 weeks of pregnancy.ResultsIn all, 430 pregnancies were included: 155 TP LGA, 87 FP LGA, 177 AGA and 11 FN LGA newborns. Cesarean section rate during labor was significantly higher in FP LGA than in AGA (19% vs. 8.7%) but not significantly different between FP LGA and TP LGA (19% vs. 32.4%). Median birth weight z score was significantly higher in TP LGA (1.9) compared with the FP LGA and AGA (0.91 and 0.84, respectively), whereas no significant differences were found between FP LGA and AGA. Admission to a neonatal intensive care unit was significantly more frequent in TP LGA than AGA, whereas shoulder dystocia, postpartum hemorrhage, and third‐ to fourth‐degree perineal tears were similar between the different groups.ConclusionA false‐positive diagnosis of LGA fetus is associated with a significant increase of cesarean section during labor. Therefore, a suspicious ultrasound may result in reduction of the clinical threshold for the diagnosis of abnormal labor.

The mediating role of gestational diabetes mellitus in the associations of maternal prepregnancy body mass index with neonatal birth weight.

BackgroundBoth prepregnancy obesity and gestational diabetes mellitus (GDM) have been linked to adverse neonatal birth weight. However, the mediating role of GDM between prepregnancy obesity and neonatal birth weight is unclear.MethodThe cohort study included 17 260 singleton pregnant women and their newborns. Participants' demographic characteristics, disease history, family history of the disease, and the perinatal outcomes were recorded. The association between maternal prepregnancy body mass index (BMI) status and small for gestational age (SGA) or large for gestational age (LGA) neonates was analyzed using logistic regressions, before and after adjusting for covariates and GDM. The potential mediation of GDM on the association between prepregnancy BMI and adverse birth weight was examined.ResultMultivariate logistic regression demonstrated that prepregnancy underweight women were more likely to deliver SGA neonates compared to those who had normal weights, whereas prepregnancy obese pregnant women were more likely to have LGA neonates. The RMediation analyses illustrated that the mediation effect of GDM on the maternal prepregnancy BMI (continuous variable) and the risk of SGA was not significant, whereas the association between prepregnancy BMI and LGA was statistically mediated by GDM (95%CI of a*b: 0.009‐0.051). The Iacobacci (2012) method indicated that the impact of maternal prepregnancy overweight (Zmediation = 2.418, P = .015) and obesity (Zmediation = 2.165, P = .030) on LGA was partially mediated by GDM, with an indirect effect of 16.3% and 13.1%, respectively.ConclusionPrepregnancy BMI was observed to be associated with SGA and LGA. The association of prepregnancy overweight and obesity with LGA was found to be partially mediated by GDM.

The risk of small and large for gestational age newborns in women with gestational diabetes according to pre-gestational body mass index and weight gain

Aim To explore the effects of pregestational body mass index (BMI) and gestational weight gain (GWG) on maternal and neonatal outcomes of women with gestational diabetes mellitus (GDM). Methods We conducted retrospective cohort analyses of outcomes among women with GDM who delivered at Shamir Medical Center, Israel (2017–2018). Results We included 673 women with GDM in our analysis, 217 (32.24%) with appropriate GWG (aGWG), 247 (36.7%) with excessive GWG (eGWG), and 209 (31%) with insufficient GWG (iGWG). Cesarean section (CS) was less prevalent among women with iGWG (19.6%), compared with women with eGWG (31.2%) and aGWG (31.1%) (p = .008). Small for gestational weight (SGA) newborns were more prevalent in women with iGWG 9.1%, compared with 2% and 0.9% for women with eGWG and aGWG, respectively (p<.001). Large for gestational age (LGA) newborns were significantly more prevalent in women with eGWG 17.4% compared with 4.8% and 9.7% in patients with iGWG and aGWG women, respectively (p<.001). SGA and LGA newborns were more prevalent in women with iGWG and e-GWG across all pre-gestational BMI groups >18.5 kg/m2. Conclusions A complex interplay exists between pregestational weight, GWG, and GDM and pregnancy outcomes, specifically SGA and LGA newborns. A strict follow-up considering the pregestational BMI, GWG, blood glucose levels, treatment modality, and fetal abdominal circumference could assist in managing the complex interplay of patients with GDM for better neonatal outcomes.

Vaginal birth after cesarean in women with no prior vaginal delivery carrying a large for gestational age baby.

To study the factors associated with successful labor after cesarean (LAC) among women with no prior vaginal delivery, delivering a large for gestational age (LGA) baby. A retrospective case-control study at two tertiary medical centers in Israel, including all women undergoing LAC with no prior vaginal delivery during 2010-2020, delivering a singleton LGA newborn. Factors associated with successful vaginal delivery were examined by a multivariable analysis. Overall, 323/505 (64.0%) had a successful LAC. Arrest of labor as the indication for previous CD was less common in the LAC success group [39 (12.1%) vs. 58 (31.9%), P<.001]. The rate of epidural analgesia was higher in the LAC success group [249 (77.1%) vs. 122 (67.0%), P=.014]. The rate of weight centile ≥97th was lower in the LAC success group [64 (19.8%) vs. 51 (28.0%), P=.035], as well as the rate of higher LAC birthweight than previous cesarean birthweight [264 (81.7%) vs. 162 (89.0%), P=.030]. In a multivariable logistic regression analysis, maternal height (aOR [95% CI]:1.09 (1.01, 1.17), P=.014) and epidural anesthesia (aOR [95% CI]:3.68 (1.31, 10.32), P=.013) were the only independent factors associated with LAC success. Among primiparous women undergoing LAC carrying LGA newborns, the vaginal delivery rate is acceptable; however, uterine rupture risk is increased. Epidural administration is a modifiable factor and should be taken into consideration during LAC management.

Differences of DNA methylation patterns in the placenta of large for gestational age infant

To investigate the molecular mechanisms of later metabolic health changes in large for gestational age (LGA) newborns by analyzing deoxyribonucleic acid (DNA) methylation patterns in the placenta of LGA and appropriate for gestational age (AGA) newborns.A total of 6 placentas of LGA and 6 placentas of AGA newborns were enrolled as LGA group and AGA group. DNA methylation was analyzed using the Illumina Infinium Human MethylationEPIC BeadChip microarrays and verified via pyrosequencing and reverse transcription-quantitative real-time polymerase chain reaction. Functional enrichment analysis were constructed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis based on the differentially methylated regions between LGA and AGA groups.Clinical investigation showed that LGA newborns had significantly lower hemoglobin and blood glucose compared to AGA newborns. Birth weight was negatively correlated to hemoglobin and blood glucose. Genome-wide DNA methylation analysis identified 17 244 methylation variable positions achieving genome-wide significance (adjusted P < .05). 34% methylation variable positions were located in the gene promoter region. A total of 117 differentially methylated regions were revealed by bump hunting analysis, which mapped to 107 genes. Function analysis showed 13 genes enriched in adhesion and infection process, endocrine and other factor-regulated calcium reabsorption, calcium signaling pathway and transmembrane transport. Four genes linked to type II diabetes mellitus. Among the 13 genes, we selected GNAS and calcium voltage-gated channel subunit alpha1 G for independent verification of pyrosequencing, and the messenger ribonucleic acid levels of guanine nucleotide binding protein, calcium voltage-gated channel subunit alpha1 G, DECR1, and FK506 binding protein 11 were verified by reverse transcription-quantitative real-time polymerase chain reaction.DNA methylation variation and gene expression differences in placental samples were associated with LGA newborns, which linking the effect of intrauterine environment to regulation of the offspring's gene expression. Furthermore, pathway analysis suggested that intrauterine environment affecting fetal growth might had a functional impact on multiple signaling pathways involved in fetal growth, metabolism, and inflammation. Further studies were required to understand the differences of methylation patterns.

Novel Continuous Glucose Monitoring Metrics and Large-for-Gestational-Age Risk: An Exploratory Retrospective Cohort Study in Pregnancies with Type 1 Diabetes

Background: Continuous glucose monitoring (CGM) improves pregnancy outcomes in patients with type 1 diabetes (T1D). We aimed to assess the between-group differences in glycated hemoglobin (HbA1c) and the incidence of large-for-gestational-age (LGA) neonates in CGM and glucometer users and analyze the potential association of novel CGM metrics with LGA risk in T1D pregnancies. Materials and Methods: Our retrospective study cohort included 134 women with T1D treated with insulin pumps-75 of them used CGM and 59 patients measured their glucose concentrations using glucometers only. As part of our study, we matched the CGM users and patients who preferred the self-monitoring of blood glucose (SMBG) according to their baseline HbA1c and White's diabetes class at a 1:1 ratio. After the matching, both groups included 42 pregnancies. Results: We did not find any difference in changes in HbA1c and perinatal outcomes between CGM and SMBG users; however, we achieved a limited statistical power, and there were more cases of diabetic nephropathy in the SMBG group. Mothers of LGA infants had higher first-trimester HbA1c, time above target, and mean glucose concentrations in each trimester of pregnancy. Other CGM metrics reflecting glucose fluctuations attributed to hyperglycemia were associated with an increased risk of LGA. Despite optimal maternal HbA1c, 39% of neonates demonstrated LGA. Conclusions: Although participants reached the target HbA1c concentrations, mothers of LGA newborns had higher first-trimester HbA1c, as well as higher time above target range, higher mean glucose concentrations, and more glycemic fluctuations, suggesting that several CGM metrics associated with maternal hyperglycemia are associated with LGA in pregnancies with T1D.

Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus.

Background To investigate the association between free fatty acid (FFA) level at mid-pregnancy and large-for-gestational-age (LGA) newborns in women with gestational diabetes mellitus (GDM).Methods We enrolled 710 pregnant women diagnosed with GDM from February 2009 to October 2016. GDM was diagnosed by a ‘two-step’ approach with Carpenter and Coustan criteria. We measured plasma lipid profiles including fasting and 2-hour postprandial FFA (2h-FFA) levels at mid-pregnancy. LGA was defined if birthweights of newborns were above the 90th percentile for their gestational age.Results Mean age of pregnant women in this study was 33.1 years. Mean pre-pregnancy body mass index (BMI) was 22.4 kg/m2. The prevalence of LGA was 8.3% (n=59). Levels of 2h-FFA were higher in women who delivered LGA newborns than in those who delivered non-LGA newborns (416.7 μEq/L vs. 352.5 μEq/L, P=0.006). However, fasting FFA was not significantly different between the two groups. The prevalence of delivering LGA newborns was increased with increasing tertile of 2h-FFA (T1, 4.3%; T2, 9.8%; T3, 10.7%; P for trend <0.05). After adjustment for maternal age, pre-pregnancy BMI, and fasting plasma glucose, the highest tertile of 2h-FFA was 2.38 times (95% confidence interval, 1.11 to 5.13) more likely to have LGA newborns than the lowest tertile. However, there was no significant difference between groups according to fasting FFA tertiles.Conclusion In women with GDM, a high 2h-FFA level (but not fasting FFA) at mid-pregnancy is associated with an increasing risk of delivering LGA newborns.

Metabolic biomarkers of small and large for gestational age newborns

BackgroundSmall for gestational age (SGA) and large for gestational age (LGA) newborns are at increased risk for developmental, metabolic and cardiovascular morbidities. AimsTo compare the metabolic biomarkers of SGA and LGA infants with those of appropriate for gestational age (AGA) newborns in order to shed more light on a possible pathogenesis of those morbidities. Study designAn observational retrospective study. Subjects70,809 term newborns divided into AGA, SGA, LGA, and severe subcategories (<3rd percentile or ≥97th percentile). Outcome measures18 metabolites were measured by dried blood tandem mass spectrometry and compared in between groups in univariate and multivariate logistic regression. ResultsSGA newborns had a significant likelihood for elevated methionine, proline, free carnitine, and reduced valine levels compared to AGA newborns (P < .0001). Severe SGA showed more apparent trends including elevated leucine. LGA newborns had a significant likelihood for low citrulline, glutamine, proline, tyrosine, and elevated leucine levels (P ≤ .0033). Severe LGA newborns showed the same trends, with the exception of citrulline and glutamine. ConclusionsSGA and LGA newborns demonstrate distinct metabolic biomarkers in newborn screening. Most of the altered metabolites in the SGA group were elevated while those in the LGA group were decreased in comparison to AGA newborns. These trends were more apparent in the severe SGA subgroup while they mostly remained the same in the severe LGA subgroup. Whether these metabolic changes are involved with or can predict long-term outcome awaits further trials.

Prediabetes and pregnancy: Early pregnancy HbA1c identifies Australian Aboriginal women with high-risk of gestational diabetes mellitus and adverse perinatal outcomes

AimsTo assess whether early pregnancy HbA1c can predict gestational diabetes mellitus (GDM) and adverse birth outcomes in Australian women. MethodsProspective study of 466 women without diabetes, aged ≥16-years at first antenatal presentation. Recruitment was from 27 primary healthcare sites in rural and remote Australia from 9-January 2015 to 31-May 2018. HbA1c was measured with first antenatal investigations (<20-weeks gestation). Primary outcome measure was predictive value of HbA1c for GDM, by routine 75 g oral glucose tolerance test (OGTT; ≥24-weeks gestation), and for large-for-gestational-age (LGA) newborn. ResultsOf 396 (129 Aboriginal) women with routine OGTT, 28.8% had GDM (24.0% Aboriginal). HbA1c ≥5.6% (≥38 mmol/mol) was highly predictive (71.4%, 95% CI; 47.8–88.7%) for GDM in Aboriginal women, and in the total cohort increased risk for LGA newborn (RR 2.04, 95% CI; 1.03–4.01, P = 0.040). There were clear differences between Aboriginal and non-Aboriginal women: 16.3% v 5.2% (P < 0.001) had elevated HbA1c whereas 12.4% v 29.6% (P < 0.001) developed hyperglycemia during pregnancy. ConclusionsEarly pregnancy HbA1c ≥5.6% (≥38 mmol/mol) identifies Aboriginal women with apparent prediabetes and elevated risk of having an LGA newborn. Universal HbA1c at first antenatal presentation could facilitate earlier management of hyperglycemia and improved perinatal outcome in this high-risk population.

Third trimester HbA1c and the association with large-for-gestational-age neonates in women with gestational diabetes.

To evaluate the association between HbA1c levels measured in the third trimester and the risk for large for gestational age (LGA) in neonates of mothers affected by gestational diabetes mellitus (GDM). Secondarily, we aimed to identify an ideal cut-off for increased risk of LGA amongst pregnant women with GDM. Observational retrospective review of singleton pregnant women with GDM evaluated in a diabetes and pregnancy clinic of a tertiary and academic hospital. From January/2011 to December/2017, 1,085 pregnant women underwent evaluation due to GDM, of which 665 had an HbA1c test in the third trimester. A logistic regression model was performed to evaluate predictors of LGA. A receiver-operating-characteristic (ROC) curve was used to evaluate the predictive ability of third trimester HbA1c for LGA identification. A total of 1,085 singleton pregnant women were evaluated during the study period, with a mean age of 32.9 ± 5.3 years. In the multivariate analysis, OGTT at 0 minutes (OR: 1.040; CI 95% 1.006-1.076, p = 0.022) and third trimester HbA1c (OR: 4.680; CI 95% 1.210-18.107, p = 0.025) were associated with LGA newborns. Using a ROC curve to evaluate the predictive ability of third trimester HbA1c for LGA identification, the optimal HbA1c cut-off point was 5.4% where the sensitivity was 77.4% and the specificity was 71.7% (AUC 0.782; p < 0.001). Few studies in the Mediterranean population have evaluated the role of HbA1c in predicting neonatal complications in women with GDM. A third trimester HbA1c > 5.4% was found to have good sensitivity and specificity for identifying the risk of LGA.

Accuracy of Third Trimester Ultrasound for Predicting Large-for-Gestational Age Newborn in Women with Gestational Diabetes Mellitus

Objective: To determine the accuracy of ultrasonography for predicting a large-for-gestational-age (LGA) newborn in women with gestational diabetes mellitus (GDM).Materials and Methods: Singleton pregnancy, diagnosed with GDM were recruited. They underwent ultrasonography at 32-36 weeks’ gestation for fetal biometry. Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). Estimated fetal weight (EFW) was derived from these 4 parameters by Hadlock formula. Delivery of an LGA newborn in women with the ultrasound finding of LGA fetus was the primary outcome.Results: Of 345 studied women, 107 (31%) had an LGA newborn. EFW of ≥ 90 th percentile at third trimester ultrasonography was found in 13 women, all of whom had an LGA newborn. It had a positive predictive value (PPV), specificity, sensitivity and negative predictive value (NPV) of 100%, 100%, 12.1% and 71.7% respectively to predict LGA at birth. Considering each fetal parameter individually, AC &gt; 90 th percentile and HC &gt; 90 th percentile had odds ratios (OR) with 95% confidence intervals of the newborn being LGA of 6.5 (3.3-12.8) and 2.0 (1.0-4.0) respectively while EFW &gt; 85 th percentile had the highest OR of 9.3 (1.1-77.9). Lowering cutoff values of EFW to 80 th and 70 th percentile increased the sensitivity and NPV for prediction of LGA at birth while reducing the PPV and specificity slightly.Conclusion: EFW derived from the third trimester ultrasonography in GDM had high PPV and specificity with low to moderate sensitivity and NPV to predict an LGA newborn in GDM.

Maternal lipid levels in pregnant women without complications in developing risk of large for gestational age newborns: a study of meta-analysis.

Background: Circulating into foetal circulation across the placental barrier, abnormal maternal serum lipids predispose neonates to metabolic dysfunction and thereafter affect the steroid metabolism and functions of extra-embryonic foetal tissues. Methods: A systematic review was conducted by searching PubMed-MEDLINE and the Cochrane library between January 2010 and January 2020. The included studies were English case control studies that described original data on at least one raw lipid measurement during pregnancy in healthy women who delivered large for gestational age (LGA) newborns and in healthy women with non-LGA newborns. The data extracted from 12 studies were pooled, and the weighted mean difference (WMD) in lipid levels was calculated using random effects models. A meta-analysis was performed to identify sources of heterogeneity and to describe the significant value of the collected studies. Results: Of 649 published articles identified, a total of 12 met the inclusion criteria . Compared with women who had non-LGA newborns, those who had LGA newborns had significantly higher triglyceride (TG) levels (WMD = 0.28, 95% CI -0.02 to 0.54) and lower high density lipoprotein cholestrol (HDL-C) levels (WMD = 0.08, 95% CI -0.13 to -0.03), but not have significantly lower high-density lipoprotein cholesterol (LDL-C) levels. Moreover, the levels of total cholesterol, low-density lipoprotein cholesterol, and very low density lipoprotein cholesterol (VLDL-C) were inconsistent between both groups. Conclusions: High levels of TG and low levels of HDL-C could cause births of LGA newborns whereas maternal serum of TC, LDL-C and VLDL-C cannot be used as predictor of LGA.