Maternal prepregnancy BMI and GWG, including period-specific GWG, were positively and independently associated with neonatal adiposity. Associations of early and midpregnancy weight gain with neonatal adiposity support the hypothesis that greater maternal weight gain during pregnancy, regardless of prepregnancy BMI, is directly related to offspring adiposity at birth. The Healthy Start study was registered as an observational study at clinicaltrials.gov as NCT02273297.

Background and Objective Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass, %FM) at birth by increasing the fat mass (FM) component of neonatal body composition. Methods Our analysis was conducted using a pre-birth observational cohort of 1,079 mother-offspring pairs. Pregnancy diet was assessed via repeated Automated Self-Administered 24-hour dietary recalls, from which Healthy Eating Index-2010 (HEI-2010) scores were calculated for each mother. HEI-2010 was dichotomized into scores ≤ 57 and scores > 57, with low scores representing poorer diet quality. Neonatal %FM was assessed within 72 hours after birth with air displacement plethysmography. Using univariate and multivariate linear models, we analyzed the relationship between maternal diet quality and neonatal %FM, FM, and fat-free mass (FFM) while adjusting for pre-pregnancy body mass index (BMI), physical activity, maternal age, smoking, energy intake, preeclampsia, hypertension, infant sex, and gestational age. Results Total HEI-2010 score ranged between 18.2 and 89.5 (mean: 54.2, SD: 13.6). An HEI-2010 score ≤ 57 was significantly associated with higher neonatal %FM (β = 0.58, 95% CI 0.07, 1.1, p<0.05) and FM (β=20.74; 95% CI 1.49, 40.0; p<0.05) but no difference in FFM. Conclusions Poor diet quality during pregnancy increases neonatal adiposity independent of maternal pre-pregnancy BMI and total caloric intake. This further implicates maternal diet as a potentially important exposure for fetal adiposity.

Maternal obesity increases the risk for pediatric obesity; however, the molecular mechanisms in human infants remain poorly understood. We hypothesized that mesenchymal stem cells (MSCs) from infants born to obese mothers would demonstrate greater potential for adipogenesis and less potential for myogenesis, driven by differences in β-catenin, a regulator of MSC commitment. MSCs were cultured from the umbilical cords of infants born to normal-weight (prepregnancy [pp] BMI 21.1 ± 0.3 kg/m2; n = 15; NW-MSCs) and obese mothers (ppBMI 34.6 ± 1.0 kg/m2; n = 14; Ob-MSCs). Upon differentiation, Ob-MSCs exhibit evidence of greater adipogenesis (+30% Oil Red O stain [ORO], +50% peroxisome proliferator–activated receptor (PPAR)-γ protein; P < 0.05) compared with NW-MSCs. In undifferentiated cells, total β-catenin protein content was 10% lower and phosphorylated Thr41Ser45/total β-catenin was 25% higher (P < 0.05) in Ob-MSCs versus NW-MSCs (P < 0.05). Coupled with 25% lower inhibitory phosphorylation of GSK-3β in Ob-MSCs (P < 0.05), these data suggest greater β-catenin degradation in Ob-MSCs. Lithium chloride inhibition of GSK-3β increased nuclear β-catenin content and normalized nuclear PPAR-γ in Ob-MSCs. Last, ORO in adipogenic differentiating cells was positively correlated with the percent fat mass in infants (r = 0.475; P < 0.05). These results suggest that altered GSK-3β/β-catenin signaling in MSCs of infants exposed to maternal obesity may have important consequences for MSC lineage commitment, fetal fat accrual, and offspring obesity risk.

Maternal insulin resistance in the first half of pregnancy is highly predictive of neonatal FM%, whereas maternal glycemia, even within the normal range, is an important driver of neonatal adiposity in later pregnancy, independent of prepregnancy BMI. Our data provide additional insights on potential maternal factors responsible for fetal fat accretion and early development of adiposity.

ObjectiveInfants born to mothers with obesity have greater adiposity, ectopic fat storage, and are at increased risk for childhood obesity and metabolic disease compared with infants of normal weight mothers, though the cellular mechanisms mediating these effects are unclear.MethodsWe tested the hypothesis that human, umbilical cord-derived mesenchymal stem cells (MSCs) from infants born to obese (Ob-MSC) versus normal weight (NW-MSC) mothers demonstrate altered fatty acid metabolism consistent with adult obesity. In infant MSCs undergoing myogenesis in vitro, we measured cellular lipid metabolism and AMPK activity, AMPK activation in response to cellular nutrient stress, and MSC DNA methylation and mRNA content of genes related to oxidative metabolism.ResultsWe found that Ob-MSCs exhibit greater lipid accumulation, lower fatty acid oxidation (FAO), and dysregulation of AMPK activity when undergoing myogenesis in vitro. Further experiments revealed a clear phenotype distinction within the Ob-MSC group where more severe MSC metabolic perturbation corresponded to greater neonatal adiposity and umbilical cord blood insulin levels. Targeted analysis of DNA methylation array revealed Ob-MSC hypermethylation in genes regulating FAO (PRKAG2, ACC2, CPT1A, SDHC) and corresponding lower mRNA content of these genes. Moreover, MSC methylation was positively correlated with infant adiposity.ConclusionsThese data suggest that greater infant adiposity is associated with suppressed AMPK activity and reduced lipid oxidation in MSCs from infants born to mothers with obesity and may be an important, early marker of underlying obesity risk.

Background Consistent evidence of an influence of maternal dietary intake during pregnancy on infant body size and composition in human populations is lacking, despite robust evidence in animal models. Objective To evaluate the influence of maternal macronutrient intake and balance during pregnancy on neonatal body size and composition, including fat mass and fat free mass. Study Design The analysis was conducted among 1040 mother-offspring pairs enrolled in the prospective pre-birth observational cohort: The Healthy Start Study. Diet during pregnancy was collected using repeated 24 hour dietary recalls (up to 8). Direct measures of body composition were obtained using air displacement plethysmography. The National Cancer Institute measurement error model was used to estimate usual dietary intake during pregnancy. Multivariable partition (non-isocaloric) and nutrient density (isocaloric) linear regression models were used to test the associations between maternal dietary intake and neonatal body composition. Results The median macronutrient composition during pregnancy was 32.2% from fat, 15.0% from protein and 47.8% from carbohydrates. In the partition multivariate regression model, individual macronutrient intake values were not associated with birth weight or fat free mass, but were associated with fat mass. Respectively, 100 kilocalorie increases in total fat, saturated fat, unsaturated fat and total carbohydrates were associated with 4.2 gram (p=0.03), 11.1 gram (p=0.003), 5.9 gram (p=0.04) and 2.9 gram (p=0.02) increases in neonatal fat mass, independent of pre-pregnancy BMI. In the nutrient density multivariate regression model, macronutrient balance was not associated with fat mass, fat free mass or birth weight after adjustment for pre-pregnancy BMI. Conclusions Neonatal adiposity, but not birth weight, is independently associated with increased maternal intake of total fat, saturated fat, unsaturated fat, and total carbohydrates, but not protein, suggesting that most forms of increased caloric intake contribute to fetal fat accretion.

Aims/hypothesis In women who are overweight or obese before or during pregnancy there is an associated risk of increased fetal growth and higher birthweight. The metabolic phenotype of the overweight/obese pregnant woman, characterised by higher than normal insulin resistance (IR) and increased circulating fuels, suggests a mechanism resulting in fetal overnutrition and subsequent increased adiposity. We tested the fuel-mediated hypothesis in an observational pre-birth cohort of 951 mother–offspring pairs, the Healthy Start study. Methods We conducted a path analysis to estimate the simultaneous effects of maternal IR and maternal fuels (fasting glucose, triacylglycerol [TG] and NEFA levels) in late pregnancy in mediating the relationship between maternal pre-pregnancy BMI and neonatal adiposity (per cent fat mass [%FM]). Results The total effect of maternal BMI on neonatal %FM was significant (total effect 0.16, 95% CI 0.08, 0.22, p < 0.001). The mediated path including maternal IR and glucose levels together accounted for 21% (p < 0.01) of the total effect of maternal BMI on neonatal %FM while the mediating effects of all other fuels were non-significant. Conclusions/interpretation Using a novel application of path analysis our data implicate maternal IR and glucose levels as important mediators of the association between maternal and infant adiposity.

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