Neonatal Fat Mass Research Articles

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy

Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. ClinicalTrials.gov Identifier: NCT02932475.

Excessive Gestational Weight Gain Alters DNA Methylation and Influences Foetal and Neonatal Body Composition.

Changes in body weight are associated with the regulation of DNA methylation (DNAm). In this study, we investigated the associations between maternal gestational weight gain-related DNAm and foetal and neonatal body composition. Brazilian pregnant women from the Araraquara Cohort Study were followed up during pregnancy, delivery, and after hospital discharge. Women with normal pre-pregnancy BMI were allocated into two groups: adequate gestational weight gain (AGWG, n = 45) and excessive gestational weight gain (EGWG, n = 30). Foetal and neonatal body composition was evaluated via ultrasound and plethysmography, respectively. DNAm was assessed in maternal blood using Illumina Infinium MethylationEPIC BeadChip arrays. Linear regression models were used to explore the associations between DNAm and foetal and neonatal body composition. Maternal weight, GWG, neonatal weight, and fat mass were higher in the EGWG group. Analysis of DNAm identified 46 differentially methylated positions and 11 differentially methylated regions (DMRs) between the EGWG and AGWG groups. Nine human phenotypes were enriched for these 11 DMRs located in 13 genes (EMILIN1, HOXA5, CPT1B, CLDN9, ZFP57, BRCA1, POU5F1, ANKRD33, HLA-B, RANBP17, ZMYND11, DIP2C, TMEM232), highlighting the terms insulin resistance, and hyperglycaemia. Maternal DNAm was associated with foetal total thigh and arm tissues and subcutaneous thigh and arm fat, as well as with neonatal fat mass percentage and fat mass. The methylation pattern in the EGWG group indicated a risk for developing chronic diseases and involvement of maternal DNAm in foetal lean and fat mass and in neonatal fat mass.

Physical activity and sedentary time across pregnancy and associations with neonatal weight, adiposity and cord blood parameters: a secondary analysis of the DALI study.

Obesity during pregnancy is associated with neonatal adiposity, which is a risk factor for childhood obesity. Maternal physical activity (PA) and sedentary behaviours during pregnancy might modify this risk. We therefore studied associations between maternal PA and sedentary time (ST) during pregnancy and neonatal anthropometry and cord blood parameters and investigated whether associations differed by offspring sex. Participants of the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention (DALI) study with a BMI ≥ 29 kg/m2 were analysed as a cohort. Maternal moderate-to-vigorous PA (MVPA) and ST were measured repeatedly with accelerometers across pregnancy. Associations between mean levels and changes in MVPA and ST and birthweight, neonatal adiposity (fat mass (FM)%) and cord blood parameters, including C-peptide, leptin and lipids, were analysed in 213 mother-child pairs with Bayesian multilevel models. Interactions with offspring sex were considered. Almost all women decreased MVPA levels and increased ST throughout gestation. Both higher maternal mean MVPA and increasing MVPA were associated with lower offspring FM% in males (-0.520%; 95% CI: -1.011%, -0.031% and -4.649%; -7.876%, -1.432% respectively). In female offspring, mean ST was associated with lower cord blood C-peptide (-0.145 µg/l; -0.279 µg/l, -0.005 µg/l). No associations were found with birthweight or other cord blood parameters. Maternal MVPA is associated with neonatal fat mass, but not birthweight, in male offspring. Our findings underline the importance of physical activity throughout pregnancy.

1189-P: The Project Wellness Pilot Feasibility Randomized Controlled Trial, a Behavioral Physical Activity Intervention for Gestational Glucose Intolerance and Gestational Diabetes

Introduction: Animal evidence suggests that maternal exercise improves metabolic health in the offspring. The offspring of individuals with gestational glucose intolerance (GGI) or gestational diabetes mellitus (GDM) are at increased risk for large for gestational age, shoulder dystocia, obesity, and diabetes. Maternal physical activity (PA) is indicated for these pregnancies, though PA levels tend to be suboptimal and decline over pregnancy. This pilot feasibility randomized controlled trial explored the effects of a behavioral counseling intervention on late pregnancy maternal PA and neonatal anthropometrics. Methods: Twenty individuals with GGI or GDM were enrolled. Those randomized to the behavioral PA intervention met weekly with a lifestyle coach via Zoom for at least 5 sessions (10-20 minutes per session). Participants completed surveys and wore ActiGraph CentrePoint PA monitoring devices on their dominant wrist for a 7-day period, at both baseline and follow-up. The TwoRegressions algorithm estimated minute by minute metabolic equivalents of task (METs) for periods in which the devices were worn, and minutes per day at ≥ 3.0 METs, indicative of moderate to vigorous intensity PA (MVPA), were totaled. Neonatal measurements (n = 17) occurred within 3 days of birth. Results: Those in the PA intervention decreased MVPA less than controls [i.e., -4.0 minutes per day (95% CI -14.5, 6.5) vs. -23.5 minutes per day (95% CI -34.9, -12.1), P = .02]. Neonates born to those in the PA intervention were smaller than control neonates, however no difference attained statistical significance (e.g., weight, neonatal fat mass, total skinfolds). There was the suggestion of significant effect on subscapular skinfold (P = .07). Conclusion: A behavioral PA counseling intervention mitigated late pregnancy declines in PA in GGI or GDM, and could reduce upper-trunk adiposity in their neonates. Disclosure S.F.Ehrlich: None. B.G.Rand: None. N.Zite: Other Relationship; Merck &amp; Co., Inc. K.B.Fortner: Other Relationship; Pfizer Inc. A.M.Paudel: None. S.E.Crouter: None. J.M.Maples: None. Funding National Institutes of Health (K01DK105106)

Novel Metabolic Subtypes in Pregnant Women and Risk of Early Childhood Obesity in Offspring

The in utero metabolic milieu is associated with offspring adiposity. Standard definitions of maternal obesity (according to prepregnancy body mass index [BMI]) and gestational diabetes (GDM) may not be adequate to capture subtle yet important differences in the intrauterine environment that could be involved in programming. To identify maternal metabolic subgroups during pregnancy and to examine associations of subgroup classification with adiposity traits in their children. This cohort study included mother-offspring pairs in the Healthy Start prebirth cohort (enrollment: 2010-2014) recruited from University of Colorado Hospital obstetrics clinics in Aurora, Colorado. Follow-up of women and children is ongoing. Data were analyzed from March to December 2022. Metabolic subtypes of pregnant women ascertained by applying k-means clustering on 7 biomarkers and 2 biomarker indices measured at approximately 17 gestational weeks: glucose, insulin, Homeostatic Model Assessment for Insulin Resistance, total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, free fatty acids (FFA), HDL-C:triglycerides ratio, and tumor necrosis factor α. Offspring birthweight z score and neonatal fat mass percentage (FM%). In childhood at approximately 5 years of age, offspring BMI percentile, FM%, BMI in the 95th percentile or higher, and FM% in the 95th percentile or higher. A total of 1325 pregnant women (mean [SD] age, 27.8 [6.2 years]; 322 [24.3%] Hispanic, 207 non-Hispanic Black [15.6%], and 713 [53.8%] non-Hispanic White), and 727 offspring with anthropometric data measured in childhood (mean [SD] age 4.81 [0.72] years, 48% female) were included. We identified the following 5 maternal metabolic subgroups: reference (438 participants), high HDL-C (355 participants), dyslipidemic-high triglycerides (182 participants), dyslipidemic-high FFA (234 participants), and insulin resistant (IR)-hyperglycemic (116 participants). Compared with the reference subgroup, women in the IR-hyperglycemic and dyslipidemic-high FFA subgroups had offspring with 4.27% (95% CI, 1.94-6.59) and 1.96% (95% CI, 0.45-3.47) greater FM% during childhood, respectively. There was a higher risk of high FM% among offspring of the IR-hyperglycemic (relative risk, 8.7; 95% CI, 2.7-27.8) and dyslipidemic-high FFA (relative risk, 3.4; 95% CI, 1.0-11.3) subgroups; this risk was of greater magnitude compared with prepregnancy obesity alone, GDM alone, or both conditions. In this cohort study, an unsupervised clustering approach revealed distinct metabolic subgroups of pregnant women. These subgroups exhibited differences in risk of offspring adiposity in early childhood. Such approaches have the potential to refine understanding of the in utero metabolic milieu, with utility for capturing variation in sociocultural, anthropometric, and biochemical risk factors for offspring adiposity.

Type 2 diabetes in pregnancy: effect of metformin added to insulin on neonatal outcome

Optimal management of type 2 diabetes mellitus in pregnancy is uncertain. Our objective was to estimate the effect of metformin added to insulin for maternal type 2 diabetes treatment on composite adverse neonatal outcome. In this multicenter trial, we randomly assigned patients with pre-gestational type 2 diabetes or diabetes diagnosed < 22 weeks’ gestation to insulin/placebo or insulin/metformin until delivery. The primary outcome was a composite of perinatal death or severe neonatal complications; principal secondary outcomes were maternal hypoglycemia and neonatal fat mass at birth. Pre-specified subgroup analyses included patients with BMI > 30 kg/m2 and pre-gestational diabetes. Logistic regression controlling for site, timing of diabetes diagnosis, BMI, and gestational age at enrollment estimated the adjusted odds ratio (aOR) and 95% CI of composite adverse neonatal outcome. 397 were randomized to insulin/placebo and 397 to insulin/metformin. The primary outcome occurred in 71% of infants in the insulin/placebo group and 69% in the insulin/metformin group [relative risk 0.96; 95% CI 0.82-1.12]. Frequency of maternal hypoglycemia was similar between groups. Compared to insulin/placebo, the insulin/metformin group had lower odds of delivery of a large for gestational age (LGA) infant [aOR 0.66, 95%CI 0.50-0.92], but no significance difference in cesarean delivery. There were no significant differences in composite adverse neonatal outcome in subgroup analyses for BMI > 30 kg/m2 or pre-gestational diabetes. There were also no significant differences in maternal/neonatal adverse events or delivery of an SGA infant. Adding metformin to insulin to treat type 2 diabetes in pregnancy did not reduce composite adverse neonatal outcome, reduce maternal hypoglycemia, or infant fat mass. Metformin reduced frequency of an LGA infant without effecting mode of delivery. While the addition of metformin did not demonstrate a decrease in adverse composite neonatal outcome, the reduction in LGA suggests additional studies are needed to measure long term infant metabolic outcomes.

ODP413 Impact of Gestational Weight Gain according to 2009 IOM Recommendations on Neonatal Anthropometrics in Asians: A Pilot Study from Malaysia

Abstract Introduction Gestational Weight Gain (GWG) modulates pregnancy outcomes and long-term offspring metabolic health [1,2]. Thus far, the widely used 2009 Institute of Medicine (IOM) recommendations on GWG have largely been evaluated in Caucasian populations and some monoethnic East Asian cohorts. We designed this study to determine if IOM GWG thresholds are applicable in a multi-ethnic Asian cohort of Malaysian mothers. Methods In this prospective observational study, 875 mothers were recruited from a Malaysian tertiary urban center during screening for gestational diabetes. Amongst data collected were Total GWG (maternal weight at delivery – self-reported pre-gravid weight) and neonatal anthropometrics. BMI was stratified by Caucasian (overweight ≥25kg/m 2, obese ≥30 kg/m 2) and Asian (overweight ≥23kg/m 2, obese ≥27.5kg/m 2) thresholds, and patients categorized by 2009 IOM GWG recommendations. Results This study included 67% Malay, 23% Chinese and 10% Indian mothers. There was a high prevalence of overweight/obesity regardless of cut-offs used (Asian 56.9% vs Caucasian 44%). When Asian BMI cut-offs were used, excessive GWG prevalence increased (34.1% → 40.6%) whilst inadequate GWG declined (30% → 24.9%). Prevalence of LGA, macrosomia, Birth Weight(BW)/Neonatal Fat Mass(NFM)/Sum of Skinfold Thickness(SSFT) &amp;gt;90th centile was highest (p&amp;lt;0. 05) in those with excess GWG whether stratified by Caucasian or Asian BMI cut-offs. Upon multivariate analysis adjusting for age, parity, race, GDM, Ln HOMA2%S and baby gender, excessive GWG (by Asian BMI categories) was associated only with increased risk of SSFT &amp;gt;90th centile (aOR 5.7, 95% CI 2.33–14. 03). Excessive GWG (by Caucasian BMI categories) was associated with increased risk of macrosomia (aOR 8.65, 95% CI 1. 07–70. 01), NFM &amp;gt;90th centile (aOR 2.14, 95% CI 1. 02–4.45) and SSFT &amp;gt;90th centile (aOR 3.88, 95% CI 1.77–8.51). SGA status was associated with insufficient GWG by both Caucasian (aOR 4.26, 95% CI 2.46–7.38) and Asian BMI cut-offs (aOR 3.55, 95% CI 2. 07–6.10). Conclusion The 2009 IOM recommendations, using either Caucasian or regional Asian BMI thresholds, are applicable in our multi-ethnic Asian cohort in terms of predicting increased neonatal adiposity and SGA status.

Relationship of ANGPTL6 With Neonatal Glucose Homeostasis and Fat Mass Is Disrupted in Gestational Diabetic Pregnancies.

Angiopoietin-like protein 6 (ANGPTL6) is a hepatokine, which, in animal studies, improves insulin sensitivity and increases energy expenditure to counteract insulin resistance. Evaluate in a human population, the role of serum ANGPTL6 in gestational diabetes mellitus (GDM) or its presence in fetal circulation. A total of 190 women (115 controls and 75 GDM) and their offspring were studied. Insulin, glucose, ANGPTL6, retinol binding protein 4 (RBP4), and retinol, as well as leptin and adiponectin, were determined in maternal serum obtained at term and from umbilical artery blood at delivery. At term, pregnant women with GDM showed higher serum concentrations of ANGPTL6, insulin, homeostatic model assessment, and apo-RBP4 (free RBP4) than controls but not of glucose, which remained similar in both groups. Also, in arterial cord serum, ANGPTL6 concentration was increased in GDM neonates with respect to the control group (201 ± 12 ng/mL vs 119 ± 8 ng/mL, respectively). No effect of maternal insulin treatment of some GDM mothers in neonates of either sex on ANGPTL6 levels was observed. In GDM, circulating ANGPTL6 showed no correlation with glucose or insulin concentration or with neonatal adiposity. However, in control pregnancies, the variation in glucose concentration was positively correlated with ANGPTL6 concentration, both in maternal and in cord samples, and cord ANGPTL6 was negatively correlated with neonatal fat mass. Furthermore, in control pregnant women, serum concentrations of ANGPTL6 and apo-RBP4 were negatively correlated. Serum ANGPTL6 levels are associated with maternal glucose homeostasis and fetal adiposity in normal pregnancy. ANGPTL6 levels in maternal and cord serum GDM pregnancy at term are increased, although its mechanism and physiological role are unknown yet.

Cord blood leptin level and a common variant of its receptor as determinants of the BMI trajectory: The EDEN mother-child cohort.

Cord blood leptin is an indicator of neonatal fat mass and could shape postnatal adiposity trajectories. Investigating genetic polymorphisms of the leptin receptor gene (LEPR) could help understand the mechanisms involved. We aimed to investigate the association of cord blood leptin level and the LEPR rs9436303 polymorphism, with body mass index (BMI) at adiposity peak (AP) and age at adiposity rebound (AR). In the EDEN cohort, BMI at AP and age at AR were estimated with polynomial mixed models, for 1713 and 1415 children, respectively. Multivariable linear regression models allowed for examining the associations of cord blood leptin level and LEPR rs9436303 genotype with BMI at AP and age at AR adjusted for potential confounders including birth size groups. We also tested interactions between cord blood leptin level and rs9436303 genotype. Increased leptin level was associated with reduced BMI at AP and early age at AR (comparing the highest quintile of leptin level to the others). Rs9436303 G-allele carriage was associated with increased BMI at AP and later age at AR but did not modulate the association with leptin level. These results illustrate the role of early life body composition and the intrauterine environment in the programming of adiposity in childhood.

A secondary analysis of maternal ultra-processed food intake in women with overweight or obesity and associations with gestational weight gain and neonatal body composition outcomes.

BackgroundThis study is an observational secondary analysis of the Lifestyle Intervention for Two (LIFT) randomised controlled trial data. There is a paucity of data related to mechanisms of health effects and dietary intake of ultra-processed foods (UPF). Earlier studies demonstrate associations between greater UPF intake and weight gain. The purpose of the study was to describe associations among maternal UPF intake with gestational weight gain (GWG) and neonatal body composition.Material and methodsWomen with overweight or obesity (n=156) and offspring (n=126) with complete energy intake, anthropometrics and body composition measures were selected. Maternal weights and diet recalls (Automated Self-Administered 24) were measured at weeks 14 and 35 gestational age (GA). Body composition was assessed by infant quantitative magnetic resonance (infant-QMR) and air displacement plethysmography (ADP) at birth. Dependent variables were GWG and neonatal fat mass, fat-free mass, and lean mass at birth; covariates were dietary, socioeconomic and biological. Stepwise linear regressions were used to test associations.ResultsHighest quartile of percentage of energy intake from UPF (PEI-UPF) was not significantly correlated with maternal GWG (p=0.215), infant QMR fat (p=0.816) and lean mass (p=0.423) or ADP fat (p=0.482) or fat-free mass (p=0.835).ConclusionsWhile no significant associations with UPF were observed in this smaller size cohort, further investigations would be justified in larger cohorts on the relationships of maternal UPF intake and GWG and offspring outcomes. Clinical Trial NCT01616147

Gestational weight gain in women with type 2 diabetes and perinatal outcomes: A secondary analysis of the metformin in women with type 2 diabetes in pregnancy (MiTy) trial

AimsOur study assesses perinatal outcomes among women with type 2 diabetes, with gestational weight gain (GWG) within and outside of US Institute of Medicine (IOM) guidelines, by conducting a secondary analysis of the Metformin in Type 2 Diabetes in Pregnancy (MiTy) trial. Methods460 participants were classified into three cohorts by total and weekly GWG (excessive, appropriate vs. restricted according to IOM). The primary outcome was birthweight z score, and secondary outcomes included both maternal and fetal outcomes. ResultsWomen with restricted (total and weekly) GWG had lower birthweight z score, lower fetal birthweight, and lower neonatal body fat mass. Women with restricted weekly GWG had fewer LGA, extreme LGA, and lower neonatal body fat mass infants, but more SGA and preterm births. Women with excessive (total and weekly) GWG had higher maternal total insulin doses in the third trimester. Women with excessive weekly GWG had more preeclampsia and higher SGA. ConclusionsRestricted GWG among women with type 2 diabetes is associated with both benefits and harms. Both must be considered when counseling patients.

Longitudinal Associations of Plasma Phospholipid Fatty Acids in Pregnancy with Neonatal Anthropometry: Results from the NICHD Fetal Growth Studies-Singleton Cohort.

Despite increasing interest in the health effects of polyunsaturated FAs (PUFAs), their roles in fetal and neonatal growth remain understudied. Within the NICHD Fetal Growth Studies—Singleton Cohort, we prospectively investigated the associations of individual and subclasses of plasma phospholipid PUFAs at gestational weeks (GW) 10–14, 15–26, 23–31, and 33–39 with neonatal anthropometric measures as surrogates for fetal growth among 107 women with gestational diabetes mellitus (GDM) and 214 non-GDM controls. Multivariable weighted linear regression models estimated the associations between plasma phospholipid PUFAs and neonatal anthropometric measures. Adjusted beta coefficients for phospholipid docosahexaenoic acid (DHA) per standard deviation (SD) increase at GW 23–31 in association with birthweight z-score, neonatal length, and neonatal fat mass were 0.25 (95% CI: 0.08–0.41), 0.57 (0.11–1.03) cm, and 54.99 (23.57–86.42) g, respectively; all false discovery rates (FDRs) < 0.05. Estimated Δ5-desaturase activity per SD increase at GW 33–39 but not at other time points was positively associated with birthweight z-score: 0.29 (95% CI: 0.08–0.33); neonatal length: 0.61 (0.29–0.94) cm; and neonatal fat mass: 32.59 (8.21–56.96) g; all FDRs < 0.05. Longitudinal analysis showed consistent results. Our findings suggest that mid-to-late pregnancy presented as critical windows for primarily diet-derived DHA and Δ5-desaturase activity in relation to neonatal anthropometric measures.

Foetal hyperinsulinaemia and increased fat mass correlate negatively with circulating fatty acid concentrations in neonates of gestational diabetic mothers with dietary-controlled glycaemia.

Higher accretion of prenatal fat is associated with a higher proportion of obesity in children. However, most of the data on regulatory factors involved in fetal adipogenesis come from animal studies; in humans there is no evidence on how fetal insulin affects fatty acid concentrations and fetal adiposity. We evaluate the relationship between fetal adipose tissue accretion with insulin and fetal consumption of circulating fatty acid (FA). In fasting maternal blood at term and cord samples, from 41 gestational diabetes mellitus women (GDM) and 68 non-diabetic controls, serum compounds were determined. Individual FA were analyzed and expressed as concentrations of FA (mmol/L). Both groups had similar maternal serum glucose, insulin, triacylglycerol (TAG), non-esterified FA (NEFA), glycerol and leptin concentrations, but most individual maternal serum FA were lower in GDM than controls. Neonatal fat mass (FM) was higher in the GDM group even though neonatal birth weights were similar. In GDM cord serum glucose, insulin, NEFA and leptin were higher than controls, but glycerol and all individual FA were lower. In GDM neonates only, a negative correlation was found between each FA and FM, and there was a strong negative correlation between the concentrations of umbilical blood insulin and five major FA. Our results show for the first time that hyperinsulinemia in fetuses of GDM women increases FA utilization, which may contribute to to their increased adiposity.

Accelerated developmental adipogenesis programs adipose tissue dysfunction and cardiometabolic risk in offspring born to dams with metabolic dysfunction.

This study determined if a perturbation in in utero adipogenesis leading to later life adipose tissue (AT) dysfunction underlies programming of cardiometabolic risk in offspring born to dams with metabolic dysfunction. Female mice heterozygous for the leptin receptor deficiency (Hetdb) had 2.4-fold higher prepregnancy fat mass and in late gestation had higher plasma insulin and triglycerides compared with wild-type (Wt) females (P < 0.05). To isolate the role of the intrauterine milieu, wild-type (Wt) offspring from each pregnancy were studied. Differentiation potential in isolated progenitors and cell size distribution analysis revealed accelerated adipogenesis in Wt pups born to Hetdb dams, accompanied by a higher accumulation of neonatal fat mass. In adulthood, whole body fat mass by NMR was higher in male (69%) and female (20%) Wt offspring born to Hetdb versus Wt pregnancies, along with adipocyte hypertrophy and hyperlipidemia (all P < 0.05). Lipidomic analyses by gas chromatography revealed an increased lipogenic index (16:0/18:2n6) after high-fat/fructose diet (HFFD). Postprandial insulin, ADIPO-IR, and ex vivo AT lipolytic responses to isoproterenol were all higher in Wt offspring born to Hetdb dams (P < 0.05). Intrauterine metabolic stimuli may direct a greater proportion of progenitors toward terminal differentiation, thereby predisposing to hypertrophy-induced adipocyte dysfunction.NEW & NOTEWORTHY This study reveals that accelerated adipogenesis during the perinatal window of adipose tissue development predisposes to later life hypertrophic adipocyte dysfunction, thereby compromising the buffering function of the subcutaneous depot.

Elevated lipid oxidation is associated with exceeding gestational weight gain recommendations and increased neonatal anthropometrics: a cross-sectional analysis

BackgroundDeviations from gestational weight gain (GWG) recommendations are associated with unfavorable maternal and neonatal outcomes. There is a need to understand how maternal substrate metabolism, independent of weight status, may contribute to GWG and neonatal outcomes. The purpose of this study was to explore the potential link between maternal lipid oxidation rate, GWG, and neonatal anthropometric outcomes.MethodsWomen (N = 32) with a lean pre-pregnancy BMI were recruited during late pregnancy and substrate metabolism was assessed using indirect calorimetry, before and after consumption of a high-fat meal. GWG was categorized as follows: inadequate, adequate, or excess. Shortly after delivery (within 48 h), neonatal anthropometrics were obtained.ResultsUsing ANOVA, we found that fasting maternal lipid oxidation rate (grams/minute) was higher (p = 0.003) among women with excess GWG (0.1019 ± 0.0416) compared to women without excess GWG (inadequate = 0.0586 ± 0.0273, adequate = 0.0569 ± 0.0238). Findings were similar when lipid oxidation was assessed post-meal and also when expressed relative to kilograms of fat free mass. Absolute GWG was positively correlated to absolute lipid oxidation expressed in grams/minute at baseline (r = 0.507, p = 0.003), 2 h post-meal (r = 0.531, p = 0.002), and 4 h post-meal (r = 0.546, p = 0.001). Fasting and post-meal lipid oxidation (grams/minute) were positively correlated to neonatal birthweight (fasting r = 0.426, p = 0.015; 2-hour r = 0.393, p = 0.026; 4-hour r = 0.540, p = 0.001) and also to neonatal absolute fat mass (fasting r = 0.493, p = 0.004; 2-hour r = 0.450, p = 0.010; 4-hour r = 0.552, p = 0.001).ConclusionsA better understanding of the metabolic profile of women during pregnancy may be critical in truly understanding a woman’s risk of GWG outside the recommendations. GWG counseling during prenatal care may need to be tailored to women based not just on their weight status, but other metabolic characteristics.

Effect of type 2 diabetes mellitus on placental expression and activity of nutrient transporters and their association with birth weight and neonatal adiposity

AimsInfants born to women with Type 2 Diabetes Mellitus (T2DM) are at risk of being born large for gestational age due to excess fetal fat accretion. Placental nutrient transport determines fetal nutrient availability, impacting fetal growth. The aims of the study were to evaluate the effect of T2DM on placental insulin signaling, placental nutrient transporters and neonatal adiposity. MethodsPlacentas were collected from BMI-matched normoglycemic controls (NGT, n = 9) and T2DM (n = 9) women. Syncytiotrophoblast microvillous (MVM) and basal (BM) plasma membranes were isolated. Expression of glucose (GLUT1, -4), fatty acid (FATP2, -4, -6, FAT/CD36), amino acid (SNAT1, -2, -4, LAT1, -2) transporters, insulin signaling, and System A transporter activity was determined. Neonatal fat mass (%) was measured in a subset of neonates born to T2DM women. ResultsGLUT1 protein expression was increased (p = 0.001) and GLUT4 decreased (p = 0.006) in BM from T2DM. MVM FATP6 expression was increased (p = 0.02) and correlated with birth weight in both T2DM and NGT groups (r = 0.65, p = 0.02). BM FATP6 expression was increased (p = 0.01) in T2DM. In MVM of T2DM placentas, SNAT1 expression was increased (p = 0.05) and correlated with birth weight (r = 0.84, p = 0.004); SNAT2 was increased (p = 0.01), however System A transporter activity was not different between groups. MVM LAT1 expression was increased (p = 0.01) in T2DM and correlated with birth weight (r = 0.59, p = 0.04) and neonatal fat mass (r = 0.76, p = 0.06). ConclusionIn pregnancies complicated by T2DM placental protein expression of transporters for glucose, amino acids and fatty acids is increased, which may contribute to increased fetal growth and neonatal adiposity.

Mediators Linking Maternal Weight to Birthweight and Neonatal Fat Mass in Healthy Pregnancies.

ContextLifestyle interventions have not efficaciously reduced complications caused by maternal weight on fetal growth, requiring insight into explanatory mediators.ObjectiveWe hypothesized that maternal mediators, including adiponectin, leptin, insulin, and glucose, mediate effects of pregestational BMI (pBMI) and gestational weight gain (GWG) on birthweight and neonatal fat mass percentage (FM%) through placental weight and fetal mediators, including insulin levels (Ifv) and venous-arterial glucose difference (ΔGfva). Hypothesized confounders were maternal age, gestational age, and parity.MethodsA cross-sectional study of healthy mother-offspring-pairs (n = 165) applying the 4-vessel in vivo sampling method at Oslo University Hospital, Norway. We obtained pBMI, GWG, birthweight, and placental weight. FM% was available and calculated for a subcohort (n = 84). We measured circulating levels of adiponectin, leptin, glucose, and insulin and performed path analysis and traditional mediation analyses based on linear regression models.ResultsThe total effect of pBMI and GWG on newborn size was estimated to be 30 g (range, 16-45 g) birthweight and 0.17 FM% (range, 0.04-0.29 FM%) per kg∙m–2 pBMI and 31 g (range, 18-44 g) and 0.24 FM% (range, 0.10-0.37 FM%) per kg GWG. The placental weight was the main mediator, mediating 25-g birthweight and 0.11 FM% per kg∙m–2 pBMI and 25-g birthweight and 0.13 FM% per kg GWG. The maternal mediators mediated a smaller part of the effect of pBMI (3.8-g birthweight and 0.023 FM% per kg∙m–2 pBMI) but not GWG.ConclusionPlacental weight was the main mediator linking pBMI and GWG to birthweight and FM%. The effect of pBMI, but not GWG, on birthweight and FM%, was also mediated via the maternal and fetal mediators.

Body composition in term offspring after maternal gestational diabetes does not predict postnatal hypoglycemia

BackgroundOffspring of mothers with gestational diabetes mellitus (GDM) have an increased risk of neonatal complications like birth trauma due to macrosomia or postnatal hypoglycemia, as well as long-term metabolic sequelae. Neonatal body composition may be a sensitive marker of metabolic effects on the fetus caused by suboptimal glycemic control during pregnancy.ObjectiveTo determine body composition in offspring of mothers with GDM compared to a reference cohort of healthy term neonates and to assess whether increased body fat would be associated with postnatal hypoglycemia.MethodsThis prospective, observational, cross-sectional study included 311 full-term, singleton infants born between June 2014 and July 2015. Body composition was measured within 96 h of birth using air displacement plethysmography. Results are indicated as median (1st Quartile – 3rd Quartile).ResultsOf 311 infants, 40 (12.9%) were born to mothers with GDM. Birth weight standard deviation scores (SDS) (0.24 vs. − 0.07, p = 0.04), fat mass (370 g vs. 333 g, p = 0.02) as well as fat mass/total body mass (BF%; 11.4% vs. 10.8%, p = 0.03) were significantly higher in infants following maternal GDM than in controls. In GDM offspring, anthropometric parameters, fat mass or BF% did not differ between infants with or without postnatal hypoglycemia. In this cohort, SDS for birth weight, fat mass, fat free mass, BF% or postnatal hypoglycemia were not associated with maternal blood glucose levels measured at an oral glucose tolerance test.ConclusionsSDS for birth weight, neonatal fat mass, and BF% were significantly higher in newborns following maternal GDM. In these infants born to mothers with GDM, body composition did not differ between those with or without postnatal hypoglycemia.

53746 Body Composition and Metabolic Profiles in Infants of Diabetic Mothers (IDM) as Predictors of Hunger Signaling Gene Expression

ABSTRACT IMPACT: This study aims to advance the understanding of the biological mechanisms associated with feeding disturbances in infants born to diabetic mothers through non-invasive salivary gene expression analyses and body composition measurements at birth. OBJECTIVES/GOALS: To determine if non-invasive salivary gene expression analyses and body composition measurements at birth could elucidate biological mechanisms associated with aberrant feeding behaviors and disrupted metabolic profiles commonly seen in infants born to diabetic mothers. METHODS/STUDY POPULATION: This prospective cohort study enrolls subjects born at ≥35 weeks’ gestation without a history of intrauterine growth restriction or major congenital anomalies. The diabetic cohort is defined as infants born to mothers with gestational diabetes or type 2 diabetes. The primary outcome is salivary expression of the hunger signaling genes, AMPK and NPY2R. Secondary outcomes include infant body composition measurements, obtained by skinfold measurement and/or air displacement plethysmography, and salivary expression of the adipokines, leptin, ghrelin, and adiponectin. Multiple logistic regression will be used to determine which factors are associated with AMPK and NPY2R expression. RESULTS/ANTICIPATED RESULTS: We propose that poor oral intake seen in infants of diabetic mothers may be due to alterations in the expression of hunger signaling genes (decreased expression of AMPK; increased expression of NPY2R) resulting in a diminished feeding drive in these large for gestational age infants. In addition, infant adiposity and the expression of genes involved in the adipoinsular axis will be inversely proportional to feeding volume intake. Namely, increased neonatal fat mass will be associated with increased expression of leptin and decreased expression of ghrelin and adiponectin. DISCUSSION/SIGNIFICANCE OF FINDINGS: Infants of diabetic mothers are at higher risk of poor oral feeding in the newborn period. This study aims to elucidate the link between neonatal body composition, adipoinsular axis, and hunger signaling to explain this unique feeding phenotype.

Predictors of neonatal adiposity and associations by fetal sex in women with gestational diabetes mellitus and normal glucose-tolerant women.

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 ≥ 25kg/m2) normal glucose-tolerant women (NGT). 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 (13.9mm ± 2.9 vs 13.3mm ± 2.6, p = 0.067), neonatal fat mass (1333.0g ± 166.8 vs 1307.3g ± 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 (14.3mm ± 2.6 vs 13.2mm ± 2.6, p < 0.001), neonatal fat mass (1386.0g ± 168.6 vs 1307.3g ± 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.