Background: Fasting glucose is higher in pregnancies with obesity (OB); less is known about postprandial (PP) and nocturnal patterns when the diet is eucaloric and fixed or about the continuous-glucose-monitor (CGM) metrics that predict neonatal adiposity (NB%fat). We hypothesized that continuous glucose monitors (CGMs) would reveal higher glycemia in OB vs. normal weight (NW) during Early (14–16 weeks) and Later (26–28 weeks) gestation despite macronutrient-controlled eucaloric diets and elucidate unique predictors of NB%fat. Methods: In a prospective, parallel-group comparative study, a eucaloric diet (NW: 25 kcal/kg; OB: 30 kcal/kg) was provided (50% carbohydrate [20% simple/30% complex; of total calories], 35% fat, 15% protein) to Early and Later gestation groups wearing a blinded CGM for three days. CGM metrics (mean fasting; 1 h and 2 h PP; daytime and nocturnal glucose; percent time-in-range (%TIR: 63–140 mg/dL); PP excursions; and area-under-the-curve [AUC]) were interrogated between groups and as predictors of NB%fat by dual X-ray absorptiometry(DXA). Results: Fifty-four women with NW (BMI: 23 kg/m2; n = 27) and OB (BMI: 32; n = 27) provided their informed consent to participate. Early, the daytime glucose was higher in OB vs. NW (mean ± SEM) (91 ± 2 vs. 85 ± 2 mg/dL, p = 0.017), driven by 2 h PP glucose (95 ± 2 vs. 88 ± 2, p = 0.004). Later, those with OB exhibited higher nocturnal (89 ± 2 vs. 81 ± 2), daytime (95 ± 2 vs. 87 ± 2), 1 h (109 ± 3 vs. 98 ± 2), and 2 h PP (101 ± 3 vs. 92 ± 2) glucose (all p < 0.05) but no difference in %TIR (95–99%). Postprandial peak excursions for all meals were markedly blunted in both the Early (9–19 mg/dL) and Later (15–26 mg/dL). In OB, the Later group’s 24 h AUC was correlated with NB%fat (r = 0.534, p = 0.02). Despite similar weight gain, infants of OB had higher birthweight (3528 ± 107 vs. 3258 ± 74 g, p = 0.037); differences in NB%fat did not reach statistical significance (11.0 vs. 8.9%; p > 0.05). Conclusions: Despite macronutrient-controlled eucaloric diets, pregnancies with OB had higher glycemia Early and Later in gestation; the Later 24 h glucose AUC correlated with NB%fat. However, glycemic patterns were strikingly lower than current management targets.

Objective Maternal obesity (OB) accounts for the majority of large‐for‐gestational‐age infants, and newborn percent fat (NB%fat) correlates strongest with childhood OB. In addition to maternal glucose, fasting triglycerides (TGs) may contribute, but postprandial triglycerides (PPTGs) are unstudied. It was hypothesized that fasting TGs and PPTGs are higher in women with OB compared with women with normal weight (NW) throughout pregnancy, correlate more strongly with NB%fat than glucose, and may relate to dietary chylomicron TGs. Methods Fasting TGs and PPTGs, free fatty acids, glucose, and insulin were prospectively measured 10 times over 4 hours after a controlled liquid breakfast early (14‐16 weeks) and later (26‐28 weeks) in pregnancy in 27 mothers with NW and 27 with OB. NB%fat was measured by dual x‐ray absorptometry. Results Fasting TGs and PPTGs were already ≥ 30% higher in mothers with OB at 14 to 16 weeks ( P < 0.001) versus mothers with NW. In mothers with OB, a simple 1‐hour ( r = 0.71; P < 0.01) or 2‐hour ( r = 0.69; P < 0.01) PPTG at 14 to 16 weeks correlated strongest with NB%fat. In mothers with NW, the increase in TGs from early to later pregnancy correlated strongest with NB%fat ( r = 0.57; P < 0.01). Maternal glucose did not statistically add to prediction models. Conclusions These novel data suggest that 1‐ or 2‐hour PPTGs might be a new target for early intervention in pregnancies with OB to prevent excess newborn adiposity and attenuate child OB risk.

OBJECTIVES:Neonatal adiposity is associated with chronic metabolic sequelae such as diabetes and obesity. Identifying fetuses at risk for excess neonatal body fat may lead to research aimed at limiting nutritional excess in the prenatal period. We sought to determine whether fetal arm and leg soft tissue measurements at 28 weeks' gestation were predictive of neonatal percent body fat METHODS : In this prospective observational cohort study of singleton term pregnancies, we performed sonography at 28 and 36 weeks' gestation, including soft tissue measurements of the fetal arm and thigh (fractional limb volume and cross-sectional area). We estimated the neonatal body composition (percent body fat) using anthropometric measurements and air displacement plethysmography. We estimated Spearman correlations between sonographic findings and percent body fat and performed modeling to predict neonatal percent body fat using maternal characteristics and sonographic findings. RESULTS:Our analysis of 44 women yielded a mean maternal age of 30 years, body mass index of 26 kg/m(2), and birth weight of 3382 g. Mean neonatal percent body fat was 8.1% by skin folds at birth and 12.2% by air displacement plethysmography 2 weeks after birth. Fractional thigh volume measurements at 28 weeks yielded the most accurate model for predicting neonatal percent body fat (R(2) = 0.697; P = .001), outperforming models that used abdominal circumference (R(2)= 0.516) and estimated fetal weight (R(2)= 0.489). CONCLUSIONS:Soft tissue measurements of the fetal thigh at 28 weeks correlated better with neonatal percent body fat than currently used sonographic measurements. After validation in a larger cohort, our models may be useful for prenatal intervention strategies aimed at the prevention of excess fetal fat accretion and, potentially, optimization of long-term metabolic health.

Neonatal adiposity is associated with obesity later in life. Identifying fetuses with early signs of increased adiposity may allow for future research aimed at reducing excess fat accretion in utero, with the goal of limiting long-term metabolic sequelae associated with prenatal nutritional excess. Our objective was to determine whether soft tissue measurements of the fetal arm and leg by ultrasound (U/S) at 28 weeks (w) are predictive of neonatal body fat. In this prospective observational cohort study of healthy singleton pregnancies, we performed U/S at 28w with standard biometry and soft tissue measurements of the fetal upper arm and thigh (fractional limb volume, mid-limb cross-sectional area). We assessed neonatal body composition using skin folds and air displacement plethysmography (PEAPOD), and adjusted neonatal % body fat (%BF) to 40w0d by ±0.1%/day. We determined Spearman correlations between U/S findings and %BF, and performed modeling to predict neonatal adiposity using maternal characteristics and U/S findings. Our analysis included 32 women with mean maternal age of 30y and neonatal birth weight 3382g. Mean neonatal %BF was 8.1% by skin folds (2d of life) and 12.2% by PEA POD (15d). Correlations between U/S and %BF were generally stronger with PEA POD than with skin fold measurements. Fractional leg volume (FLV) provided the highest correlation with neonatal body fat (r=0.71; 95% confidence interval 0.37, 0.88), better than all other ultrasound measurements including the abdominal circumference (r=0.5; 0.13, 0.74) and estimated fetal weight (r=0.49; 0.14, 0.74). Our best model to predict neonatal body fat included only the FLV (R2=0.697, p<0.001). Soft tissue measurements of the fetal thigh at 28w correlated well with neonatal body fat. After validation in a larger cohort, fractional limb volume may be explored as a marker of abnormal fetal adiposity that could be targeted in prenatal interventional strategies for the prevention of excess fat at birth.

OBJECTIVE Diet therapy in gestational diabetes mellitus (GDM) has focused on carbohydrate restriction but is poorly substantiated. In this pilot randomized clinical trial, we challenged the conventional low-carbohydrate/higher-fat (LC/CONV) diet, hypothesizing that a higher–complex carbohydrate/lower-fat (CHOICE) diet would improve maternal insulin resistance (IR), adipose tissue (AT) lipolysis, and infant adiposity. RESEARCH DESIGN AND METHODS At 31 weeks, 12 diet-controlled overweight/obese women with GDM were randomized to an isocaloric LC/CONV (40% carbohydrate/45% fat/15% protein; n = 6) or CHOICE (60%/25%/15%; n = 6) diet. All meals were provided. AT was biopsied at 37 weeks. RESULTS After ∼7 weeks, fasting glucose (P = 0.03) and free fatty acids (P = 0.06) decreased on CHOICE, whereas fasting glucose increased on LC/CONV (P = 0.03). Insulin suppression of AT lipolysis was improved on CHOICE versus LC/CONV (56 vs. 31%, P = 0.005), consistent with improved IR. AT expression of multiple proinflammatory genes was lower on CHOICE (P < 0.01). Infant adiposity trended lower with CHOICE (10.1 ± 1.4 vs. 12.6 ± 2%, respectively). CONCLUSIONS A CHOICE diet may improve maternal IR and infant adiposity, challenging recommendations for a LC/CONV diet.

BackgroundInfant adiposity better predicts childhood obesity/metabolic risk than weight, but technical challenges fuel controversy over the accuracy of adiposity estimates.ObjectiveWe prospectively measured adiposity (%fat) in term newborns (NB) at 2 weeks (n=41) and 1 year (n=30).Methods%fat was measured by dual X-ray absorptiometry (DXA), PEAPOD and skin-folds (SF). DXAs were analyzed using Hologic Apex software 3.2(DXAv1) and a new version 5.5.2(DXAv2).ResultsNB %fat by DXAv2 was 55% higher than DXAv1 (14.2% vs. 9.1%), 45% higher than SF (9.8%), and 36% higher than PEAPOD (10.4%). Among NB, Pearson correlations were 0.73-0.89, but agreement (intra-class correlations) poor between DXAv2 and DXAv1 (0.527), SF (0.354) and PEAPOD (0.618). At 1 year, %fat by DXAv2 was 51% higher than DXAv1 (33.6% vs. 22.4%), and twice as high compared with SF (14.6%). Agreement was poor between DXAv2 and DXAv1 (0.204), and SF (0.038). The absolute increase in %fat from 2 weeks to 1 year was 19.7% (DXAv2), 13.6% (DXAv1) and only 4.8% by SF.ConclusionAnalysis of the same DXA scans using new software yielded considerably higher adiposity estimates at birth and 1 year compared with the previous version. Using different modalities to assess body composition longitudinally is problematic. Standardization is gravely needed to determine how early life exposures affect childhood obesity/metabolic risk.

Conventional diet therapy in women with gestational diabetes (GDM) has focused on restriction of carbohydrate (CHO), which typically results in greater fat intake. Diets higher in fat are known to promote insulin resistance and thus may increase fetal adiposity.

The historic practice of advising a low-carbohydrate and higher fat diet in the management of gestational diabetes mellitus has not been sufficiently tested. In addition to glucose, high maternal triglycerides and free fatty acids are independent risk factors for fetal macrosomia and excess neonatal adiposity. We tested the hypothesis that a higher complex carbohydrate/lower fat diet would result in higher postprandial glucose excursions but an overall 24-hour glucose area-under-the-curve resulted that is no different or lower than that of a low-carbohydrate/higher fat diet.

OBJECTIVE We sought to define 24-h glycemia in normal-weight and obese pregnant women using continuous glucose monitoring (CGM) while they consumed a habitual and controlled diet both early and late in pregnancy. RESEARCH DESIGN AND METHODS Glycemia was prospectively measured in early (15.7 ± 2.0 weeks’ gestation) and late (27.7 ± 1.7 weeks’ gestation) pregnancy in normal-weight (n = 22) and obese (n = 16) pregnant women on an ad libitum and controlled diet. Fasting glucose, triglycerides (early pregnancy only), nonesterified fatty acids (FFAs), and insulin also were measured. RESULTS The 24-h glucose area under the curve was higher in obese women than in normal-weight women both early and late in pregnancy despite controlled diets. Nearly all fasting and postprandial glycemic parameters were higher in the obese women later in pregnancy, as were fasting insulin, triglycerides, and FFAs. Infants born to obese mothers had greater adiposity. Maternal BMI (r = 0.54, P = 0.01), late average daytime glucose (r = 0.48, P < 0.05), and late fasting insulin (r = 0.49, P < 0.05) correlated with infant percentage body fat. However, early fasting triglycerides (r = 0.67, P < 0.001) and late fasting FFAs (r = 0.54, P < 0.01) were even stronger correlates. CONCLUSIONS This is the first study to demonstrate that obese women without diabetes have higher daytime and nocturnal glucose profiles than normal-weight women despite a controlled diet both early and late in gestation. Body fat in infants, not birth weight, was related to maternal BMI, glucose, insulin, and FFAs, but triglycerides were the strongest predictor. These metabolic findings may explain higher rates of infant macrosomia in obese women, which might be targeted in trials to prevent excess fetal growth.

Data suggest that the in-utero environment affects neonatal body composition which is predictive of childhood obesity and metabolic syndrome. Percent fat at birth correlates poorly with birthweight (BW) and is more predictive than BW of offspring metabolic complications in later life. There are few data on the use of ultrasound (US) to predict neonatal adiposity yet US remains the basis for predicting abnormal growth and is necessary for any future fetal-based strategy. This study was undertaken to evaluate US measures of fetal adiposity and to correlate them with neonatal body composition. Obese and normal weight women carrying normal singleton pregnancies were prospectively enrolled at 14 weeks. Multiple US measures of fetal size and fat accretion (subcutaneous tissue area) were performed at 28 and 36 wks. These were compared with BW and with neonatal body composition as measured by dual x-ray absorptiometry (DXA). Among 9 women enrolled in the study, neonatal body composition ranged from 6-19% fat and correlated poorly with birth weight (R2=0.085, NS). However, body composition correlated well with mid-femur (R2=0.74, p=0.003) and mid-humerus (R2=0.59, p=0.015) cross-sectional area of subcutaneous (adipose) tissue at 36 weeks, and with femur length (R2=0.45, P = 0.047) at 28 weeks. The AC at 36 weeks was not predictive of % fat at birth (R2=0.16). Liver length at 36 weeks was most predictive of neonatal adiposity with an R2 of 0.95, p=0.008 (Figure). This is the first study to demonstrate that fetal liver length and subcutaneous tissue (mid-femur & mid-humerus) correlate with neonatal % body fat. As previously published, BW and neonatal body composition did not correlate. These observations hold practical implications for antenatal estimation of fetal fat accretion and may be clinically useful in the development of a fetal-based strategy directed toward the prevention of neonatal adiposity and later childhood obesity.

Sit of 22 mothers with gestational diabetes mellitus had infants with macrosomia, cord blood hyperinsulinemia, and increased amounts of a key mitogenic intermediate, farnesylated p21-Ras. The ability of fetal hyperinsulinemia to increase the availability of farnesylated p21-Ras may represent one mechanism of the growth-promoting action of insulin during fetal development.