Objective: This study aimed to examine the associations of maternal early-pregnancy glucose and insulin concentrations with offspring cardiometabolic risk factors and fat distribution. Methods: In a population-based prospective cohort study among 3,737 mothers and their children, random maternal glucose and insulin concentrations were measured at a median gestational age of 13.2 (95% range 10.5-17.1) weeks. Childhood fat, blood pressure, and blood concentrations of lipids, glucose, and insulin at the age of 10 years were measured. Results: Higher maternal early-pregnancy glucose and insulin concentrations were associated with a higher risk of childhood overweight, and higher maternal early-pregnancy insulin concentrations were associated with an increased childhood risk of clustering of cardiometabolic risk factors (all P < 0.05). These associations were explained by maternal prepregnancy BMI. Independent of maternal prepregnancy BMI, one SD score (SDS) higher maternal early-pregnancy glucose and insulin concentrations were associated with higher childhood glucose (0.08 SDS, 95% CI: 0.04-0.11) and insulin concentrations (0.07 SDS, 95% CI: 0.03-0.10), but not with childhood blood pressure, lipids, and fat measures. Conclusions: These results suggest that maternal early-pregnancy random glucose and insulin concentrations are associated with childhood glucose and insulin concentrations but not with other childhood cardiometabolic risk factors.Obesity (2020) 28, 985-993.

Context Maternal prepregnancy BMI has a strong influence on gestational metabolism, but detailed metabolic alterations are unknown. Objective First, to examine the associations of maternal prepregnancy BMI with maternal early-pregnancy metabolite alterations. Second, to identify an early-pregnancy metabolite profile associated with birthweight in women with a higher prepregnancy BMI that improved prediction of birthweight compared to glucose and lipid concentrations. Design, setting and participants Prepregnancy BMI was obtained in a subgroup of 682 Dutch pregnant women from the Generation R prospective cohort study. Main outcome measures Maternal non-fasting targeted amino acid, non-esterified fatty acid, phospholipid and carnitine concentrations measured in blood serum at mean gestational age of 12.8 weeks. Birthweight, obtained from medical records. Results A higher prepregnancy BMI was associated with 72 altered amino acid, non-esterified fatty acid, phospholipid and carnitine concentrations and 6 metabolite ratios reflecting Krebs cycle, inflammatory, oxidative stress and lipid metabolic processes (p-values&lt;0.05). Using penalized regression models, a metabolite profile was selected including 15 metabolites and 4 metabolite ratios, based on its association with birthweight in addition to prepregnancy BMI. The adjusted R 2 of birthweight was 6.1% for prepregnancy BMI alone, 6.2% after addition of glucose and lipid concentrations and 12.9% after addition of the metabolite profile. Conclusions A higher maternal prepregnancy BMI was associated with altered maternal early-pregnancy amino acids, non-esterified fatty acids, phospholipids and carnitines. Using these metabolites, we identified a maternal metabolite profile which improved prediction of birthweight in women with a higher prepregnancy BMI compared to glucose and lipid concentrations.

Purpose Maternal hyperglycemia is associated with adverse birth outcomes. Maternal dietary glycemic index and load influence postprandial glucose concentrations. We examined the associations of maternal early pregnancy dietary glycemic index and load with fetal growth and risks of adverse birth outcomes. Methods In a population-based cohort study of 3471 pregnant Dutch women, we assessed dietary glycemic index and load using a food frequency questionnaire at median 13.4 (95% range 10.6; 21.2) weeks gestation. We measured fetal growth in mid-and late-pregnancy by ultrasound and obtained birth outcomes from medical records. Results Mean maternal early pregnancy dietary glycemic index and load were 57.7 (SD 3.3, 95% range 52.8; 63.5) and 155 (SD 47, 95% range 87; 243), respectively. Maternal early pregnancy dietary glycemic index was not associated with fetal growth parameters. A higher maternal early pregnancy dietary glycemic load was associated with a higher fetal abdominal circumference and estimated fetal weight in late-pregnancy (p values < 0.05), but not with mid-pregnancy or birth growth characteristics. A higher maternal early pregnancy dietary glycemic index was associated with a lower risk of a large-forgestational-age infant (p value < 0.05). Maternal early pregnancy glycemic index and load were not associated with other adverse birth outcomes. Conclusion Among pregnant women without an impaired glucose metabolism, a higher early pregnancy dietary glycemic load was associated with higher late-pregnancy fetal abdominal circumference and estimated fetal weight. No consistent associations of maternal dietary glycemic index and load with growth parameters in mid-pregnancy and at birth were present. A higher glycemic index was associated with a lower risk of a large-for-gestational-age infant.

BACKGROUND AND OBJECTIVES: Celiac disease (CeD) is associated with psychopathology in children. It is unknown whether this association is present in children with celiac disease autoimmunity (CDA) identified by screening. We examined the associations between subclinical CDA and emotional and behavioral problems in children without previous CeD diagnosis. METHODS: In a population-based cohort study of 3715 children (median age: 6 years), blood titers of tissue transglutaminase autoantibodies were analyzed. CDA was defined as a measurement of tissue transglutaminase autoantibodies $7 U/mL (n = 51). Children with previous CeD diagnosis or children on a gluten-free diet, were excluded. The Child Behavior Checklist (CBCL) was filled in by parents and was used to assess behavioral and emotional problems of children at a median age of 5.9 years. Multiple linear regression models were applied to evaluate the cross-sectional associations between CDA and CBCL scores. Sensitivity analyses were done in a subgroup of children who were seropositive carrying the HLA antigen risk alleles for CeD. RESULTS: In basic models, CDA was not associated with emotional and behavioral problems on the CBCL scales. After adjustment for confounders, CDA was significantly associated with anxiety problems (b = .29; 95% confidence interval 0.02 to 0.55; P = .02). After exclusion of children who did not carry the HLA-DQ2 and/or HLA-DQ8 risk alleles (n = 4), CDA was additionally associated with oppositional defiant problems (b = .35; 95% confidence interval 0.02 to 0.69). Associations were not explained by gastrointestinal complaints. CONCLUSIONS: Our results reveal that CDA, especially combined with the HLA-DQ2 and HLA-DQ8 risk alleles, is associated with anxiety problems and oppositional defiant problems. Further research should be used to establish whether behavioral problems are a reflection of subclinical CeD. WHAT'S KNOWN ON THIS SUBJECT: Diagnosed celiac disease (CeD) has been linked with several emotional and behavioral problems in children, including anxiety, depression, and aggressive behavior. However, whether this association is already present in children with subclinical CeD identified by screening is unknown. WHAT THIS STUDY ADDS: Screening-based celiac disease autoimmunity is associated with anxiety and oppositional defiant problems in children with subclinical CeD identified by screening, independent of gastrointestinal complaints.

Gestational diabetes mellitus has been associated with offspring cardiac congenital malformations, ventricular hypertrophy, and diastolic dysfunction in large observational cohort studies and experimental animal models. We assessed the associations of maternal random glucose concentrations across the full range with childhood cardiac ventricular structure and function. RESEARCH DESIGN AND METHODSIn a population-based prospective cohort among 1,959 women and their offspring, maternal random glucose concentrations were measured at a median 13.1 weeks' gestation (95% range 10.5-16.8 weeks). We obtained offspring cardiac outcomes, relative to body size, through cardiac MRI at 10 years. RESULTSThe mean maternal random glucose concentration was 4.4 mmol/L (SD 0.8). The highest quintile of maternal glucose concentrations, compared with the lowest quintile, was associated with a lower childhood left ventricular mass (20.19 SD score [SDS]; 95% CI 20.31, 20.07) and left ventricular end-diastolic volume (20.17 SDS; 95% 20.28, 20.05). Also, higher maternal glucose concentrations across the full range per 1 mmol/L increase were associated with a lower childhood left ventricular mass and left ventricular end-diastolic volume (P values £0.05). Adjustment for maternal prepregnancy BMI, gestational age, and weight at birth or childhood BMI and blood pressure did not influence the effect estimates. Maternal glucose concentrations were not significantly associated with childhood right ventricular end-diastolic volume or left and right ventricular ejection fraction. CONCLUSIONSHigher maternal random glucose concentrations in the first half of pregnancy are associated with a lower childhood left ventricular mass and left ventricular enddiastolic volume, with the strongest associations for childhood left ventricular mass. These associations were not explained by maternal, birth, or childhood characteristics. Further studies are needed to replicate these findings using repeated maternal glucose measurements throughout pregnancy and offspring cardiac outcomes throughout childhood and adulthood.