The roles of newborn anthropometrics in the association between maternal weight gain and childhood cardiovascular risks.

OBJECTIVE: The aim was to study the association between newborn anthropometrics and childhood cardiovascular risks and whether newborn anthropometrics mediate the effect of maternal gestational weight gain (GWG) on childhood risks. METHODS: Data of 926 mother-child dyads from the Hyperglycemia and Adverse Pregnancy Outcomes study were analyzed. Newborn anthropometrics were treated as predictors and mediators by using a regression model and causal mediation model, respectively. RESULTS: Newborn sum of skinfolds (SSF) was associated with childhood diastolic blood pressure (DBP) and pulse wave velocity (coefficients [95% CI]: 0.13 [0.06 to 0.20]; 0.08 [0.004 to 0.15]), whereas newborn ponderal index (PI) was inversely associated with childhood systolic blood pressure (SBP), DBP, and pulse wave velocity (-0.08 [-0.15 to -0.01]; -0.08 [-0.14 to -0.008]; -0.09 [-0.16 to -0.03]). Newborn SSF mediated the effects of maternal excessive GWG on childhood SSF and DBP (proportion of total effect 9% and 8%, respectively). In contrast, a significant negative mediation through newborn PI was found for the effect of maternal excessive GWG on childhood DBP (-8%) and its effect on childhood SBP through birth weight (-27%). CONCLUSIONS: Childhood cardiovascular risks are positively associated with newborn SSF but inversely associated with newborn PI. Newborn SSF mediates the impact of excessive maternal GWG on childhood BP, but birth weight and newborn PI negatively mediate it.

Comparing IADPSG and NICE Diagnostic Criteria for GDM in Predicting Adverse Pregnancy Outcomes.

OBJECTIVE: To compare the performance of diagnostic criteria for gestational diabetes mellitus (GDM) proposed by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) with those endorsed by the National Institute for Health and Care Excellence (NICE) in predicting adverse pregnancy outcomes. RESEARCH DESIGN AND METHODS: We performed a secondary data analysis of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study participants in five study centers. Logistic regression analyses were performed, and Akaike information criterion were applied for the comparison of different statistical prediction models. We further analyzed the performance by four racial/ethnic subgroups, namely, Whites, Hispanics, Asians, and Blacks. RESULTS: Among all, IADPSG criteria diagnosed 267 (4.1%) more women with GDM, but predicted primary caesarean section (CS) and large for gestational age (LGA) and neonatal adiposity better than did NICE criteria after adjustment for potential confounders. Among Whites, IADPSG criteria diagnosed 65 (2.5%) more subjects with GDM and predicted LGA and neonatal adiposity better, but predicted hypertensive disorders, primary CS and clinical neonatal hypoglycemia worse. Among Hispanics, the IADPSG criteria diagnosed 203 (12.1%) more with GDM but performed better in predicting hypertensive disorders, LGA, neonatal adiposity, and hyperinsulinemia. Among Asians, the IADPSG criteria diagnosed 34 (2.0%) fewer subjects with GDM but predicted hypertensive disorders better in the unadjusted model. In Blacks, IADPSG criteria diagnosed 34 (10.5%) more women with GDM. CONCLUSIONS: IADPSG criteria appear to be more favorable than NICE for identification of adverse pregnancy outcomes among Hispanic and Asian women, while they are comparable to NICE among White women.

Maternal Lipid Metabolism Is Associated With Neonatal Adiposity: A Longitudinal Study.

CONTEXT: Pregnancy is characterized by progressive decreases in glucose insulin sensitivity. Low insulin sensitivity resulting in hyperglycemia is associated with higher neonatal adiposity. However, less is known regarding lipid metabolism, particularly lipid insulin sensitivity in pregnancy and neonatal adiposity. OBJECTIVE: Because higher maternal prepregnancy body mass index is strongly associated with both hyperlipidemia and neonatal adiposity, we aimed to examine the longitudinal changes in basal and clamp maternal lipid metabolism as contributors to neonatal adiposity. METHODS: Twelve women planning a pregnancy were evaluated before pregnancy, in early (12-14 weeks), and late (34-36 weeks) gestation. Body composition was estimated using hydrodensitometry. Basal and hyperinsulinemic-euglycemic clamp glucose and glycerol turnover (GLYTO) were measured using 2H2-glucose and 2H5-glycerol and substrate oxidative/nonoxidative metabolism with indirect calorimetry. Total body electrical conductivity was used to estimate neonatal body composition. RESULTS: Basal free-fatty acids decreased with advancing gestation (P = 0.0210); however, basal GLYTO and nonoxidative lipid metabolism increased over time (P = 0.0046 and P = 0.0052, respectively). Further, clamp GLYTO and lipid oxidation increased longitudinally over time (P = 0.0004 and P = 0.0238, respectively). There was a median 50% increase and significant positive correlation during both basal and clamp GLYTO from prepregnancy through late gestation. Neonatal adiposity correlated with late pregnancy basal and clamp GLYTO (r = 0.6515, P = 0.0217; and r = 0.6051, P = 0.0371). CONCLUSIONS: Maternal prepregnancy and late pregnancy measures of basal and clamp lipid metabolism are highly correlated. Late pregnancy basal and clamp GLYTO are significantly associated with neonatal adiposity and account for ~40% of the variance in neonatal adiposity. These data emphasize the importance of maternal lipid metabolism relating to fetal fat accrual.

Oral Glucose Tolerance Test-based Measures of Insulin Secretory Response in Pregnancy.

BACKGROUND: Oral glucose tolerance test (OGTT)-based measures of insulin secretory response have not been validated in pregnancy. METHODS: In a secondary analysis of a longitudinal study, participants were studied prepregnancy (n = 40), in early pregnancy (n = 36; 12-14 weeks' gestation), and in late pregnancy (n = 36; 34-36 weeks' gestation). Participants underwent an OGTT, an intravenous glucose tolerance test (IVGTT), and a hyperinsulinemic-euglycemic clamp at each timepoint. We calculated homeostatic model assessment of beta-cell function (HOMA-2B), insulinogenic index (IGI), corrected insulin response (CIR), ratio of the area under the insulin curve and the area under the glucose curve (AUCins/AUCglu), and Stumvoll first-phase estimate (Stumvoll) from OGTT insulin and glucose levels. We used Pearson correlation to compare measures from OGTT and IVGTT. We used mixed effects models to examine longitudinal changes in insulin secretory response. RESULTS: Stumvoll was the only OGTT-based measure that was significantly correlated with first-phase insulin response prior to and across gestation (prepregnancy: r = 0.44, P = 0.01; early pregnancy: r = 0.67, P = 0.0001; late pregnancy: r = 0.67, P = 0.0001). In early and late pregnancy, AUCins/AUCglu had the strongest correlation with first-phase insulin response (early pregnancy: r = 0.79, P < 0.0001; late pregnancy: r = 0.69, P < 0.0001) but was not significantly correlated prepregnancy. IGI and CIR were significantly correlated with first-phase insulin response prepregnancy (IGI: r = 0.50, P = 0.005; CIR r = 0.47, P = 0.008) and in late pregnancy (IGI: r = 0.68, P = 0.0001; CIR r = 0.57, P = 0.002) but not in early pregnancy. HOMA-2B was the weakest correlate of first-phase insulin response. Stumvoll and AUCins/AUCglu recapitulated the longitudinal changes in insulin secretory response observed by IVGTT. CONCLUSIONS: Stumvoll and AUCins/AUCglu are valid OGTT-based insulin secretory response measures for pregnancy studies.

Optimal gestational weight gain for Chinese women - analysis from a longitudinal cohort with childhood follow-up.

BACKGROUND: Maternal gestational weight gain (GWG) influences not only on pregnancy outcome but also impacts on mothers' and children's long-term health. However, there is no consensus on recommendations of optimal GWG in Asians or the Chinese population. METHODS: We performed a secondary analysis of the birth outcome of Chinese women who had joined the "Hyperglycemia and Adverse Pregnancy Outcome" study in Hong Kong and their children's cardiometabolic risk at 7-year of age. Optimal ranges of GWG were derived from models based on the probabilities of small for gestational age and large for gestational age (model 1), lean and fat infants (model 2) and the integration of model 1 and 2 (model 3), and were compared with that recommended by the Institute of Medicine (IOM) on children's cardiometabolic risk. FINDINGS: GWG range derived from model 2 is associated with 8 cardiometabolic risk factors, while that from models 1 and 3 are associated with 1 and 7 of them respectively. Mothers whose GWG lie within the recommended range increases from 40.8% according to the IOM recommendation to 50.2% according to that derived from model 2. INTERPRETATION: Optimal GWG derived from model 2 (i.e. 14.0-18.5 kg, 9.0-16.5 kg and 5.0-11.0 kg for underweight, normal weight and overweight Chinese women, respectively) appeared to be associated with the lowest cardiometabolic risk in the offspring. FUNDING: General Research Fund of the Research Grants Council of the Hong Kong SAR, China (grants CUHK 473408 and, in part, CUHK 471713).

Prediction of large-for-gestational age infants in relation to hyperglycemia in pregnancy - A comparison of statistical models.

AIMS: Using data from a large multi-centre cohort, we aimed to create a risk prediction model for large-for-gestational age (LGA) infants, using both logistic regression and naïve Bayes approaches, and compare the utility of these two approaches. METHODS: We have compared the two techniques underpinning machine learning: logistic regression (LR) and naïve Bayes (NB) in terms of their ability to predict large-for-gestational age (LGA) infants. Using data from five centres involved in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, we developed LR and NB models and compared the predictive ability and stability between the models. Models were developed combining the risks of hyperglycaemia (assessed in three forms: IADPSG GDM yes/no, GDM subtype, OGTT z-score quintiles), demographic and clinical variables as potential predictors. RESULTS: The two approaches resulted in similar estimates of LGA risk (intraclass correlation coefficient 0.955, 95% CI 0.952, 0.958) however the AUROC for the LR model was significantly higher (0.698 vs 0.682; p < 0.001). When comparing the three LR models, use of individual OGTT z-score quintiles resulted in statistically higher AUROCs than the other two models. CONCLUSIONS: Logistic regression can be used with confidence to assess the relationship between clinical and biochemical variables and outcome.

Association of weight status and carbohydrate intake with gestational weight gain.

Test the hypothesis that women with obesity have greater gestation weight gain (GWG) with a moderately higher, vs lower, carbohydrate (CHO) diet, independent of energy intake, whereas GWG for women of normal weight would not differ by CHO group. This was a secondary analysis of data collected from glucose tolerant women with normal weight (NW) or obesity in pregnancy. Women completed a three-day food diary 16 to 20 weeks. A median split for percent kilocalories from CHO (median = 49.6%) categorized women into moderately highCHO vs lowCHO groups (n = 13-15/group). GWG was calculated between consent and the last prenatal care visit. A two-way ANOVA was used to examine whether there was an interaction between weight status and CHO group on GWG, independent of energy intake, time between consent and last prenatal visit, and age. Women in both highCHO groups consumed more sugars and starches compared to women in the lowCHO groups (P < .05). A significant interaction between weight status and CHO content of the diet was found (P < .05), such that, for women with obesity, those consuming a lowCHO diet had less GWG than those consuming a highCHO diet, whereas the pattern was opposite for women with NW. Results suggest that intake of a moderately lower CHO diet may help limit GWG among glucose tolerant women with obesity. Given that women in this study were eligible only if they had normal fasting glucose concentrations in early pregnancy, it is not clear if these results would generalize to all women with obesity during pregnancy.

Newborn Adiposity and Cord Blood C-Peptide as Mediators of the Maternal Metabolic Environment and Childhood Adiposity.

OBJECTIVE: Excessive childhood adiposity is a risk factor for adverse metabolic health. The objective was to investigate associations of newborn body composition and cord C-peptide with childhood anthropometrics and explore whether these newborn measures mediate associations of maternal midpregnancy glucose and BMI with childhood adiposity. RESEARCH DESIGN AND METHODS: Data on mother/offspring pairs (N = 4,832) from the epidemiological Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and HAPO Follow-up Study (HAPO FUS) were analyzed. Linear regression was used to study associations between newborn and childhood anthropometrics. Structural equation modeling was used to explore newborn anthropometric measures as potential mediators of the associations of maternal BMI and glucose during pregnancy with childhood anthropometric outcomes. RESULTS: In models including maternal glucose and BMI adjustments, newborn adiposity as measured by the sum of skinfolds was associated with child outcomes (adjusted mean difference, 95% CI, P value) BMI (0.26, 0.12-0.39, <0.001), BMI z-score (0.072, 0.033-0.11, <0.001), fat mass (kg) (0.51, 0.26-0.76, <0.001), percentage of body fat (0.61, 0.27-0.95, <0.001), and sum of skinfolds (mm) (1.14, 0.43-1.86, 0.0017). Structural equation models demonstrated significant mediation by newborn sum of skinfolds and cord C-peptide of maternal BMI effects on childhood BMI (proportion of total effect 2.5% and 1%, respectively), fat mass (3.1%, 1.2%), percentage of body fat (3.6%, 1.8%), and sum of skinfolds (2.9%, 1.8%), and significant mediation by newborn sum of skinfolds and cord C-peptide of maternal glucose effects on child fat mass (proportion of total association 22.0% and 21.0%, respectively), percentage of body fat (15.0%, 18.0%), and sum of skinfolds (15.0%, 20.0%). CONCLUSIONS: Newborn adiposity is independently associated with childhood adiposity and, along with fetal hyperinsulinemia, mediates, in part, associations of maternal glucose and BMI with childhood adiposity.

Effect of Omega-3 Supplementation in Pregnant Women with Obesity on Newborn Body Composition, Growth and Length of Gestation: A Randomized Controlled Pilot Study.

Maternal obesity, a state of chronic low-grade metabolic inflammation, is a growing health burden associated with offspring adiposity, abnormal fetal growth and prematurity, which are all linked to adverse offspring cardiometabolic health. Higher intake of anti-inflammatory omega-3 (n-3) polyunsaturated fatty acids (PUFA) in pregnancy has been associated with lower adiposity, higher birthweight and longer gestation. However, the effects of n-3 supplementation specifically in pregnant women with overweight and obesity (OWOB) have not been explored. We conducted a pilot double-blind randomized controlled trial of 72 pregnant women with first trimester body mass index (BMI) ≥ 25 kg/m2 to explore preliminary efficacy of n-3 supplementation. Participants were randomized to daily DHA plus EPA (2 g/d) or placebo (wheat germ oil) from 10-16 weeks gestation to delivery. Neonatal body composition, fetal growth and length of gestation were assessed. For the 48 dyads with outcome data, median (IQR) maternal BMI was 30.2 (28.2, 35.4) kg/m2. In sex-adjusted analyses, n-3 supplementation was associated with higher neonatal fat-free mass (ß: 218 g; 95% CI 49, 387) but not with % body fat or fat mass. Birthweight for gestational age z-score (-0.17 ± 0.67 vs. -0.61 ± 0.61 SD unit, p = 0.02) was higher, and gestation longer (40 (38.5, 40.1) vs. 39 (38, 39.4) weeks, p = 0.02), in the treatment vs. placebo group. Supplementation with n-3 PUFA in women with OWOB led to higher lean mass accrual at birth as well as improved fetal growth and longer gestation. Larger well-powered trials of n-3 PUFA supplementation specifically in pregnant women with OWOB should be conducted to confirm these findings and explore the long-term impact on offspring obesity and cardiometabolic health.

Longitudinal Assessment of Relationships Between Health Behaviors and IL-6 in Overweight and Obese Pregnancy.

BACKGROUND: Inflammation is a common factor in adverse pregnancy outcomes (APOs). Behavioral factors influence inflammatory markers and APOs but rarely have been investigated simultaneously in pregnancy. Our purpose was to determine how diet, physical activity, and obesity are associated with interleukin (IL)-6 in early and late pregnancy. METHODS: We conducted a secondary analysis of 49 overweight/obese pregnant women. Health behavior data, including diet quality using the Dietary Inflammatory Index (DII®); physical activity (Leisure Time Physical Activity scale); body mass index (BMI); and plasma IL-6 concentrations were collected at 13-16 weeks (early pregnancy) and 34-36 weeks (late pregnancy) gestation. Multiple linear regression analyses were used to determine the amount of variance explained in early and late pregnancy IL-6 concentrations by early and late pregnancy diet, physical activity, and BMI. RESULTS: Early diet and early BMI were the strongest predictors of early IL-6 concentrations (R2 = 0.43; p < .001) and late IL-6 concentrations (R2 = 0.30; p < .001). Late BMI predicted late IL-6 (R2 = .11; p = .02). Change in diet over pregnancy predicted late IL-6 (R2 = 0.17; p = .03). CONCLUSION: These findings suggest that maternal diet and BMI in early pregnancy, which likely reflects prepregnancy status, may have a greater impact on inflammatory processes than factors later in pregnancy. Future work should assess if behavioral factors before pregnancy produce similar relationships to those reported here, which may clarify the timing and type of lifestyle interventions to effectively reduce APOs.

Reliability of routine anthropometric measurements to estimate body composition in term infants.

BACKGROUND: Birth weight percentiles provide limited information on qualitative infant growth. Body composition provides estimates of fat mass, fat-free mass, and body fat percentage (adiposity). We sought to implement assessment of body composition at birth into clinical practice using a validated anthropometric equation and to evaluate measurement reliability. METHODS: Body composition was incorporated into newborn nursery admission procedure. Body fat percentage derived from skinfold measurements performed by clinical nurses were compared to a historical database of similar measurements performed on newborns by experienced research staff. Body Mass Index (BMI) and Ponderal Index (PI) were used as surrogates for adiposity. Comparison of correlations between groups assessed measurement reliability. P < 0.05 was considered significant. RESULTS: Nine hundred and ninety-one infants had body composition evaluated. Correlations were similar between BMI and %BF for measurements performed by research and clinical nurses (r2 = 0.82 versus r2 = 0.80; P = 0.142 for the difference between correlation coefficients) demonstrating good reliability. Similar results were found using PI (r2 = 0.58 versus r2 0.53; P = 0.105). CONCLUSIONS: Body composition can be assessed at birth using a validated anthropometric equation. Measurements performed by clinical RNs were found to be reliable, allowing for a qualitative measure of growth beyond birth weight. IMPACT: Assessment of neonatal body composition at birth can be implemented into routine clinical practice using an anthropometric equation to estimate fat free-mass, fat mass, and percentage body fat. It provides a detailed, reproducible protocol to incorporate into routine practice. Assessment of fat mass, fat-free mass, and adiposity at birth allows for a qualitative measure of intrauterine growth beyond birth weight. Routine assessment of body composition provides a foundation for longitudinal follow-up of metabolic health in infancy and childhood.

Do variations in insulin sensitivity and insulin secretion in pregnancy predict differences in obstetric and neonatal outcomes?

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is generally defined based on glycaemia during an OGTT, but aetiologically includes women with defects in insulin secretion, insulin sensitivity or a combination of both. In this observational study, we aimed to determine if underlying pathophysiological defects evaluated as continuous variables predict the risk of important obstetric and neonatal outcomes better than the previously used dichotomised or categorical approaches. METHODS: Using data from blinded OGTTs at mean gestational week 28 from five Hyperglycemia and Adverse Pregnancy Outcome study centres, we estimated insulin secretion (Stumvoll first phase) and sensitivity (Matsuda index) and their product (oral disposition index [DI]) in 6337 untreated women (1090 [17.2%] with GDM as defined by the International Association of Diabetes and Pregnancy Study Groups). Rather than dichotomising these variables (i.e. GDM yes/no) or subtyping by insulin impairment, we related insulin secretion and sensitivity as continuous variables, along with other maternal characteristics, to obstetric and neonatal outcomes using multiple regression and receiver operating characteristic curve analysis. RESULTS: Stratifying by GDM subtype offered superior prediction to GDM yes/no only for neonatal hyperinsulinaemia and pregnancy-related hypertension. Including the DI and the Matsuda score significantly increased the area under the receiver operating characteristic curve (AUROC) and improved prediction for multiple outcomes (large for gestational age [AUROC 0.632], neonatal adiposity [AUROC 0.630], pregnancy-related hypertension [AUROC 0.669] and neonatal hyperinsulinaemia [AUROC 0.688]). Neonatal hypoglycaemia was poorly predicted by all models. Combining the DI and the Matsuda score with maternal characteristics substantially improved the predictive power of the model for large for gestational age, neonatal adiposity and pregnancy-related hypertension. CONCLUSION/INTERPRETATION: Continuous measurement of insulin secretion and insulin sensitivity combined with basic clinical variables appeared to be superior to GDM (yes/no) or subtyping by insulin secretion and/or sensitivity impairment in predicting obstetric and neonatal outcomes in a multi-ethnic cohort. Graphical abstract.

Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study: newborn anthropometrics and childhood glucose metabolism.

AIMS/HYPOTHESIS: We aimed to examine associations of newborn anthropometric measures with childhood glucose metabolism with the hypothesis that greater newborn birthweight, adiposity and cord C-peptide are associated with higher childhood glucose levels and lower insulin sensitivity. METHODS: Data from the international, multi-ethnic, population-based Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and the HAPO Follow-Up Study were used. The analytic cohort included 4155 children (mean age [SD], 11.4 [1.2] years; 51.0% male). Multiple linear regression was used to examine associations of primary predictors, birthweight, newborn sum of skinfolds (SSF) and cord C-peptide, from HAPO with continuous child glucose outcomes from the HAPO Follow-Up Study. RESULTS: In an initial model that included family history of diabetes and maternal BMI during pregnancy, birthweight and SSF demonstrated a significant, inverse association with 30 min and 1 h plasma glucose levels. In the primary model, which included further adjustment for maternal sum of glucose z scores from an oral glucose tolerance test during pregnancy, the associations were strengthened, and birthweight and SSF were inversely associated with fasting, 30 min, 1 h and 2 h plasma glucose levels. Birthweight and SSF were also associated with higher insulin sensitivity (Matsuda index) (ß = 1.388; 95% CI 0.870, 1.906; p < 0.001; ß = 0.792; 95% CI 0.340, 1.244; p < 0.001, for birthweight and SSF higher by 1 SD, respectively) in the primary model, while SSF, but not birthweight, was positively associated with the disposition index, a measure of beta cell compensation for insulin resistance (ß = 0.034; 95% CI 0.012, 0.056; p = 0.002). Cord C-peptide levels were inversely associated with Matsuda index (ß = -0.746; 95% CI -1.188, -0.304; p < 0.001 for cord C-peptide higher by 1 SD) in the primary model. CONCLUSIONS/INTERPRETATION: This study demonstrates that higher birthweight and SSF are associated with greater childhood insulin sensitivity and lower glucose levels following a glucose load, associations that were further strengthened after adjustment for maternal glucose levels during pregnancy. Graphical abstract.

Testing for gestational diabetes during the COVID-19 pandemic. An evaluation of proposed protocols for the United Kingdom, Canada and Australia.

AIMS: We assessed how altered diagnostic processes and criteria for gestational diabetes mellitus (GDM) recommended by the United Kingdom (UK), Canada and Australia for use during the COVID-19 pandemic would affect both GDM frequency and related adverse outcomes. METHODS: Secondary analysis of 5974 HAPO study women with singleton pregnancies who underwent 75 g OGTTs and HbA1c assays between 24 and 32 weeks' gestation and who received no treatment for GDM. RESULTS: All post COVID-19 modified pathways reduced GDM frequency - UK (81%), Canada (82%) and Australia (25%). Canadian women whose GDM would remain undetected post COVID-19 (missed GDMs) displayed similar rates of pregnancy complications to those with post COVID-19 GDM. Using UK modifications, the missed GDM group were at slightly lower risk whilst the women missed using the Australian modifications were at substantially lower risk. CONCLUSIONS: The modifications in GDM diagnosis proposed for the UK, Canada and Australia result in differing reductions of GDM frequency. Each has both potential benefits in terms of reduction in potential exposure to COVID-19 and costs in terms of missed opportunities to influence pregnancy and postpartum outcomes. These factors should be considered when deciding which protocol is most appropriate for a particular context.

The Joint Associations of Maternal BMI and Glycemia with Childhood Adiposity.

CONTEXT: An obesogenic perinatal environment contributes to adverse offspring metabolic health. Previous studies have been limited by lack of direct adiposity measurements and failure to account for potential confounders. OBJECTIVE: Examine the joint associations of maternal midpregnancy body mass index (BMI) and glycemia with direct adiposity measures in 10-14 year old offspring. DESIGN AND SETTING: International, epidemiological study: Hyperglycemia and Adverse Pregnancy Outcome (HAPO) and HAPO Follow-up Study, conducted between 2000-2006 and 2013-2016, respectively. PARTICIPANTS AND MAIN OUTCOME MEASURES: In 4832 children, adiposity measures for body mass index (BMI), body fat with air displacement plethysmography, skinfold thickness, and waist circumference were obtained at mean age 11.4 years. RESULTS: Maternal BMI and glucose, as continuous and categorical variables, were the primary predictors. In fully adjusted models controlling for child age, sex, field center, and maternal characteristics, maternal BMI had significant, positive associations with all childhood adiposity outcomes, while maternal glycemia had significant, positive associations with childhood adiposity outcomes except BMI. In joint analyses, and compared with a nonobese, nongestational diabetes mellitus (GDM) reference group, maternal obesity and GDM were associated with higher odds (maternal obesity odds ratio; OR [95% confidence interval; CI], GDM OR [95% CI]; combined OR [95% CI]) of childhood overweight/obese BMI (3.00 [2.42-3.74], 1.39 [1.14-1.71], 3.55 [2.49-5.05]), obese BMI (3.54 [2.70-4.64], 1.73 [1.29-2.30], 6.10 [4.14-8.99]), percent body fat >85th percentile (2.15 [1.68-2.75], 1.33 [1.03-1.72], 3.88 [2.72-5.55]), sum of skinfolds >85th percentile (2.35 [1.83-3.00], 1.75 [1.37-2.24], 3.66 [2.55-5.27]), and waist circumference >85th percentile (2.52 [1.99-3.21], 1.39 [1.07-1.80], 4.18 [2.93-5.96]). CONCLUSIONS: Midpregnancy maternal BMI and glycemia are independently and additively associated with direct adiposity measures in 10-14 year old children. The combination of maternal obesity and GDM is associated with the highest odds of childhood adiposity.