Joint association of overweight/obesity, high electronic screen time, and low physical activity time with early pubertal development in girls: a case-control study.

To examine the joint association of electronic screen time (EST), moderate-to-vigorous physical activity time (MVPA) and overweight/obesity with early pubertal development (EPD) in girls. A case-control study of 177 EPD girls and 354 girls with normal pubertal development was conducted between October 2019 and August 2022. Overweight/obesity was defined as body mass index ≥ 85th percentiles for age and sex. We found a non-significant increase of EPD risk among girls with high EST alone [OR: 2.75 (0.65-11.58)] or low MVPA alone [OR: 2.54 (0.74-8.69)], but a significant increase of EPD risk among girls with overweight/obesity alone [OR: 4.91 (1.01-23.92)], compared to girls without any of the three risk factors (low MVPA, high EST and overweight/obesity). Girls with any two of the three risk factors faced increased risk of EPD, and girls with all three risk factors faced the highest risk of EPD [OR and 95% CI: 26.10 (6.40-106.45)]. Being overweight/obesity might be more important than having low MVPA or high EST as a correlate of EPD compared to girls without any of the three risk factors, but the co-presence of low MVPA, high EST and overweight/obesity would largely increase the risk of EPD in girls.

Interactive effects of gestational diabetes and high pre-pregnancy body mass index on adverse growth patterns of offspring.

AIMS: To examine the independent and interactive effects of maternal gestational diabetes mellitus (GDM) and high pre-pregnancy body mass index (BMI) on the risk of offspring adverse growth patterns. MATERIALS AND METHODS: One thousand six hundred and eighty one mother-child pairs were followed for 8 years in Tianjin, China. Group-based trajectory modelling was used to identify offspring growth patterns. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of GDM and high pre-pregnancy BMI for offspring adverse growth patterns. Restricted cubic spline was used to identify cut-off points. Additive interactions and multiplicative interactions were used to test interactive effects between GDM and high pre-pregnancy BMI for adverse growth patterns. RESULTS: Four distinct growth patterns were identified in offspring, including normal growth pattern, persistent lean growth pattern, late obesity growth pattern (LOGP), and persistent obesity growth pattern (POGP). Maternal high pre-pregnancy BMI was associated with LOGP and POGP (adjusted OR, 95% CI: 2.38, 1.74-3.25 & 4.92, 2.26-10.73). GDM greatly enhanced the adjusted OR of high pre-pregnancy BMI for LOGP up to 3.48 (95% CI: 2.25-5.38). Additive interactions and multiplicative interactions between both risk factors were significant for LOGP but not for POGP. CONCLUSIONS: Maternal high pre-pregnancy BMI was associated with increased risk of LOGP and POGP, whereas GDM greatly enhanced the risk of high pre-pregnancy BMI for LOGP.

Maternal gestational diabetes and childhood adiposity risk from 6 to 8 years of age.

BACKGROUND/OBJECTIVE: Previous studies found conflicting results on the association between maternal gestational diabetes mellitus (GDM) and childhood overweight/obesity. This study was to assess the association between maternal GDM and offspring's adiposity risk from 6 to 8 years of age. METHODS: The present study longitudinally followed 1156 mother-child pairs (578 GDM and 578 non-GDM) at 5.9 ± 1.2 years postpartum and retained 912 mother-child pairs (486 GDM and 426 non-GDM) at 8.3 ± 1.6 years postpartum. Childhood body mass index (BMI), waist circumference, body fat and skinfold were measured using standardized methods. RESULTS: Compared with the counterparts born to mothers with normal glucose during pregnancy, children born to mothers with GDM during pregnancy had higher mean values of adiposity indicators (waist circumference, body fat, subscapular skinfold and suprailiac skinfold) at 5.9 and 8.3 years of age. There was a positive association of maternal GDM with changes of childhood adiposity indicators from the 5.9-year to 8.3-year visit, and ß values were significantly larger than zero: +0.10 (95% CI: 0.02-0.18) for z score of BMI for age, +1.46 (95% CI: 0.70-2.22) cm for waist circumference, +1.78% (95% CI: 1.16%-2.40%) for body fat, +2.40 (95% CI: 1.78-3.01) mm for triceps skinfold, +1.59 (95% CI: 1.10-2.09) mm for subscapular skinfold, and +2.03 (95% CI: 1.35-2.71) mm for suprailiac skinfold, respectively. Maternal GDM was associated with higher risks of childhood overweight/obesity, central obesity, and high body fat (Odd ratios 1.41-1.57 at 5.9 years of age and 1.73-2.03 at 8.3 years of age) compared with the children of mothers without GDM. CONCLUSIONS: Maternal GDM was a risk factor of childhood overweight/obesity at both 5.9 and 8.3 years of age, which was independent from several important confounders including maternal pre-pregnancy BMI, gestational weight gain, children's birth weight and lifestyle factors. This significant and positive association became stronger with age.

Seasonal variation and its interaction with pre-pregnancy BMI for GDM: a large population-based study in Tianjin, China.

To evaluate the independent association of seasonal variation with GDM incidence in Tianjin, China, and to test whether there is an additive interaction between seasonal variation and pre-pregnancy body mass index (BMI) on GDM incidence. A population-based observational cohort study was conducted using the healthcare records data from Tianjin, China. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction between pre-pregnancy BMI groups and seasons was estimated by using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). Among the 112,639 pregnant women, 20.8% developed GDM at 24-28 weeks of gestation. The multivariable adjusted ORs and 95% CIs were 1.00, 1.00 (0.96-1.05), 1.15 (1.09-1.20) and 1.22 (1.16-1.29) respectively based on seasons (spring, summer, autumn and winter). Compared with the spring/summer and pre-pregnant BMI < 24 kg/m2 group, co-presence of autumn/winter and pre-pregnancy BMI ≥ 24 kg/m2 increased the OR from 1.00 to 2.70 (95% CI 2.28-3.20), with a significant additive interaction: RERI (0.32, 95% CI 0.19-0.45), S (1.21, 95% CI 1.12-1.31) and AP (0.11, 95% CI 0.07-0.16). Autumn/winter is an independent risk factor for GDM incidence, and can significantly amplify the obesity-associated risk for GDM incidence. The underlying mechanism warrants further investigations. We suggest that seasonality is an additional factor when interpreting OGTT results for the diagnosis of GDM.

Maternal insulin resistance and maternal ß-cell function during pregnancy for offspring overweight before 2 years of age among women with gestational diabetes.

OBJECTIVE: To explore associations of maternal insulin resistance and ß-cell dysfunction with offspring overweight before 24 months of age among children of Chinese women with gestational diabetes mellitus (GDM). METHODS: Offspring of women with GDM (n = 901) who were enrolled in a lifestyle trial during pregnancy were followed up to 24 months of age in Tianjin, China. Restricted cubic spline analysis was performed to examine full-range associations of maternal homeostatic model assessment of insulin resistance (HOMA-IR) and ß-cell function (HOMA-%ß) with childhood overweight. Logistic regression was performed to obtain the odds ratios (ORs) and 95% confidence interval (CI) of maternal high HOMA-IR and low HOMA-%ß at diagnosis of GDM for offspring overweight within 12 months of age and at 13-24 months of age. RESULTS: Maternal high HOMA-IR was associated with an increased risk of offspring being overweight within 12 months of age and at 13-24 months of age (OR: 1.71, 95%CI: 1.12-2.62 & 1.89, 1.13-3.17, respectively). Maternal low HOMA-%ß was associated with an increased risk of offspring being overweight at 13-24 months of age (1.64, 1.05-2.55). CONCLUSIONS: Both maternal increased insulin resistance and decreased ß-cell function at diagnosis of GDM were associated with elevated risk of offspring overweight in early childhood among Chinese women with GDM.

The association between breastfeeding and childhood obesity/underweight: a population-based birth cohort study with repeated measured data.

BACKGROUND: The impact of breastfeeding on childhood obesity has long been under debate, with most research showing significant association, and others showing weak or no association between breastfeeding and childhood obesity. What's more, almost all of the previous studies focused on the association between breastfeeding and childhood obesity, and no studies have assessed the association between breastfeeding and childhood underweight. This study aimed to examine the association between breastfeeding and childhood obesity as well as childhood underweight from 1 to 6 years old. METHODS: A retrospective population-based cohort study of 59,564 children born between May 2009 and April 2013 in China was conducted using the healthcare records data from the Tianjin Maternal and Child Healthcare System. Information on infant breastfeeding (exclusive breastfeeding, mixed feeding, and exclusive formula feeding) within 6 months old and childhood growth (6 times of repeated measured weight and height from 1 to 6 years old) was collected. Multinomial logistic regression was used to test the potential associations between infant feeding modalities and childhood growth (underweight, normal weight and obesity). RESULTS: Compared with exclusive formula feeding, breastfeeding was inversely associatied with childhood obesity from 2 to 6 years old, and there was a trend from mixed feeding to exclusive breastfeeding (Ptrend < 0.05). The largest association with obesity was displayed at 3 years old, with the multivariable adjusted odds ratios (ORs) for exclusive formula feeding, mixed feeding and exclusive breastfeeding of 1.00, 0.62 (95% CI 0.49, 0.80) and 0.57 (95% CI 0.44, 0.74) (Ptrend = 0.001), respectively. Compared with exclusive breastfeeding, exclusive formula feeding may increase the risk of childhood underweight at 3 and 5 years old. CONCLUSIONS: Breastfeeding was inversely associated with the risk of childhood obesity from 2 to 6 years old, and there was a trend from mixed feeding to exclusive breastfeeding. Infant exclusive formula feeding might be a risk factor for childhood underweight at preschool time.

Effects of a Lifestyle Intervention in Young Women with GDM and Subsequent Diabetes.

The purpose of this study was to examine whether a 9-month intensive lifestyle intervention could lead to weight loss and improve cardiovascular risk factors among young women with both gestational diabetes mellitus (GDM) and newly diagnosed diabetes. A total of 83 young women, who had GDM and were subsequently diagnosed as type 2 diabetes at an average of 2.6 years after delivery, participated in a 9-month intensive lifestyle intervention and a follow-up survey at 6-9 years postintervention. After the 9-month intervention, these women had a weight loss of 2.90 kg (-4.02% of initial weight), decreased waist circumference (-3.12 cm), body fat (-1.75%), diastolic blood pressure (-3.49 mmHg), fasting glucose (-0.98 mmol/L) and HbA1c (-0.72%). During the 6-9 years postintervention period, they still had lower weight (-3.71 kg; -4.62% of initial weight), decreased waist circumference (-4.56 cm) and body fat (-2.10%), but showed a slight increase in HbA1c (0.22%). The prevalence of using glucose-lowering agents increased from 2.4% at baseline to 34.6% after the 9-month lifestyle intervention, and to 48.4% at 6-9 years postintervention. A 9-month intensive lifestyle intervention can produce beneficial effects on body weight, HbA1c and other cardiovascular risk factors among young women with previous GDM who subsequently developed new diabetes.

Increased Gestational Weight Gain is Associated with a Higher Risk of Offspring Adiposity Before Five Years of Age: A Population-Based Cohort Study.

Objective: We aim to investigate the influence of weight gain during pregnancy on the risk of offspring adiposity before five years old. Methods: We retrospectively collected health information from the Tianjin mother-child cohort. Offspring outcome was BMI Z-score and prevalence of childhood adiposity from 0.5-5 years old. Gestational weight gain was analyzed using continuous and categorical variables evaluated by the IOM guidelines. Multivariate analysis adjusted maternal age, prepregnancy BMI, maternal height, smoking, cesarean section, gestational age at birth, birth weight, birth length, and mode of infant feeding during 0-6 months. Results: Gestational weight gain contributed to offspring's BMI Z-score from 1-5 years old, and the effect was most obvious in the first half of pregnancy (multivariate analysis, at 1, 2, 2.5, 3, 4, and 5 years of age: ß 0.011, 95% CI 0.008-0.014; ß 0.017, 95% CI 0.015-0.020; ß 0.005, 95%CI 0.002-0.008; ß 0.018, 95% CI 0.015-0.021; ß 0.014, 95% CI 0.009-0.020; ß 0.013, 95% CI 0.005-0.021). Excessive weight gain was associated with a higher prevalence of offspring adiposity before five years, even if prepregnancy BMI is normal. Multivariate regression analysis further confirmed that excessive weight gain during the first half of pregnancy significantly increased the risk of childhood obesity at aged one and three (AOR 1.083, 95% CI 1.003-1.169; AOR 1.158, 95% CI 1.036-1.293). Conclusion: Offspring have a higher risk of preschool adiposity when gestational weight gain was excessive during the first half of pregnancy.

Relationship between gestational body mass index change and the risk of gestational diabetes mellitus: a community-based retrospective study of 41,845 pregnant women.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse health consequences for women and their offspring. It is associated with maternal body mass index (BMI) and may be associated with gestational weight gain (GWG). But due to the heterogeneity of diagnosis and treatment and the potential effect of GDM treatment on GWG, the association between the two has not been thoroughly clarified. Compared to body weight, BMI has the advantage that it considers height during the whole course of pregnancy. Understanding BMI changes during pregnancy may provide new evidence for the prevention of GDM. METHODS: This study investigated the BMI change of pregnant women based on a retrospective study covering all communities in Tianjin, China. According to the results of GDM screening at 24-28 weeks of gestation, pregnancies were divided into the GDM group and the non-GDM group. We compared gestational BMI change and GWG in the two groups from early pregnancy to GDM screening. GWG was evaluated according to the IOM guidelines. Logistic regression was applied to determine the significance of variables with GDM. RESULTS: A total of 41,845 pregnant women were included in the final analysis (GDM group, n = 4257 vs. non-GDM group, n = 37,588). BMI gain has no significant differences between the GDM and non-GDM groups at any early pregnancy BMI categories (each of 2 kg/m2), as well as weight gain (P > 0.05). Early pregnancy BMI was a risk factor for GDM (OR 1.131, 95% CI 1.122-1.139). And BMI gain was associated with a decreased risk of GDM in unadjusted univariate analysis (OR 0.895, 95% CI 0.869-0.922). After adjusting on early pregnancy BMI and other confounding factors, the effect of BMI gain was no longer significant (AOR 1.029, 95% CI 0.999-1.061), as well as weight gain (AOR 1.006, 95% CI 0.995-1.018) and GWG categories (insufficient: AOR 1.016, 95% CI 0.911-1.133; excessive: AOR 1.044, 95% CI 0.957-1.138). CONCLUSIONS: BMI in early pregnancy was a risk factor for GDM, while BMI gain before GDM screening was not associated with the risk of GDM. Therefore, the optimal BMI in early pregnancy is the key to preventing GDM.

Adverse pregnancy outcomes are associated with an increased risk of postpartum prediabetes and diabetes in Chinese women with gestational diabetes.

AIMS: To explore associations between adverse pregnancy outcomes and risk of postpartum diabetes and prediabetes among Chinese women with gestational diabetes mellitus (GDM). METHODS: A total of 507 women with GDM who participated in a randomized controlled trial were successfully followed up at a median of 9.1  (interquartile range: 7.7-11.3) weeks after delivery and underwent a 75 g 2-h oral glucose tolerance test. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Group's criteria. Postpartum diabetes and prediabetes were defined by the World Health Organization's. Generalized logit model was used to obtain odds ratios (OR) and 95% confidence interval (CI) of adverse pregnancy outcomes for postpartum diabetes, prediabetes and abnormal glucose regulation (AGR). RESULTS: Of 507 women with GDM, 3.7% (19) women developed postpartum diabetes, 35.1% (178) women developed postpartum prediabetes. Preterm birth was associated with increased risk of postpartum prediabetes and AGR (adjusted OR: 3.24, 95%CI: 1.48-7.07 & 3.16, 1.46-6.85). Low birth weight was associated with the risk of postpartum prediabetes, diabetes and AGR (adjusted OR: 2.78, 95%CI: 1.13-6.86; 5.21, 1.13-24.02 & 2.99, 1.24-7.21). CONCLUSIONS: Preterm birth and low birth weight were predictive of postpartum prediabetes, diabetes or AGR in Chinese women with GDM.

Association of leukocyte counts in the first trimester with glucose intolerance during pregnancy.

AIMS/INTRODUCTION: We investigated the association between leukocyte counts and glucose challenge test (GCT) level during pregnancy. MATERIALS AND METHODS: We collected prenatal information of women who had their first clinic visit in early pregnancy. Women underwent GCT at 24-28 gestational weeks, and a result of ≥7.8 mmol/L was considered positive. Participants were divided into quartiles of leukocyte counts, and association with GCT results and positive rate were analyzed by logistic regression. RESULTS: Among 20,707 pregnant women, the median of leukocyte counts was higher in the positive group than the normal group (8.5 × 109 /L vs 8.2 × 109 /L, P < 0.01). There was a linear trend in GCT results and positive rate with increasing leukocyte quartiles. Compared with the lowest quartile, the highest leukocyte quartile (>9.70 × 109 /L) was significantly associated with positive GCT results (adjusted odds ratio 1.378, 95% confidence interval 1.246-1.524), and the linear relationship between increased risk of positive result and increasing leukocyte quartiles persisted (P for linear trend <0.01). In multivariable analysis, the risk of a positive result increased by 2.2% with each 1-unit increase in leukocyte counts (adjusted odds ratio 1.022, 95% confidence interval 1.011-1.033). CONCLUSIONS: Elevated leukocyte counts in early pregnancy were independently and linearly associated with the risk of positive GCT levels, indicating that inflammation might play an important role in the development of gestational diabetes mellitus.

Novel epigenetic link between gestational diabetes mellitus and macrosomia.

Background & objectives: Examine maternal gestational diabetes mellitus (GDM), macrosomia and DNA methylation in candidate genes IGF1, IGF2, H19, ARHGRF11, MEST, NR3C1, ADIPOQ and RETN. Materials & methods: A total of 1145 children (572 GDM cases and 573 controls) from the Tianjin GDM study, including 177 with macrosomia, had blood DNA collection at median age 5.9 (range: 3.1-10.0). We used logistic regression to screen for associations with GDM and model macrosomia on 37 CpGs, and performed mediation analysis. Results: One CpG was associated with macrosomia at false discovery rate (FDR) <0.05 (cg14428359 in MEST); two (cg19466922 in MEST and cg26263166 in IGF2) were associated at p < 0.05 but mediated 26 and 13%, respectively. Conclusion:MEST and IGF2 were previously identified for potential involvement in fetal growth and development (Trial Registration number: NCT01554358 [ClinicalTrials.gov]).

Lay abstract Many women who get gestational diabetes during pregnancy go on to give birth to larger (macrosomic) babies. These babies then grow up to have greater risk of being overweight or obese, and all the health concerns this entails. We sought to examine whether epigenetic factors could help explain this link, by examining the blood of some children whose mothers were enrolled in a gestational diabetes study in China. We identified three sites on two different genes as being associated with both gestational diabetes and macrosomia. The way these genes work suggest a mechanism for how they contribute to macrosomia, providing a promising new avenue for future research, early detection and precision prevention (Trial Registration number: NCT01554358 [ClinicalTrials.gov]).

The association between overweight and obesity on bone mineral density in 12 to 15 years old adolescents in China.

ABSTRACT: Overweight/obesity can influence bone mineral accretion, but the conclusions are not consistent. We aimed to examine the association between bone mineral density (BMD) levels and body mass index (BMI) in 12 to 15 years old adolescents.We performed a cross-sectional study including 8365 adolescents. BMD was evaluated using a quantitative ultrasound device. Z scores for BMI were evaluated using World Health Organization references. Logistic regression models were performed to evaluate the association between BMD levels and BMI.Totally 1866 (22.3%) adolescents had low /reduced BMD, and boys had a higher rate than girls (72.6% vs 27.4%, P < .001). The rates of thinness, normal weight, overweight, and obesity were 2.8%, 57.1%, 22.3%, and 17.8%, respectively. The multivariable-adjusted (age, sex, systolic blood pressure, and height Z score) ORs (95% CIs) of low/reduced BMD associated with BMI groups (thinness, normal [reference], overweight, and obesity) were 0.59 (0.39-0.89), 1.00, 1.61 (1.41-1.84), and 1.98 (1.69-2.30), respectively (Ptrend < .001). This positive association existed in boys and girls though the differences were not significant between normal weight and thin girls. The multivariable-adjusted ORs for each 1-unit increase in BMI Z score were 1.36 (1.24-1.49) for girls, and 1.23 (1.16-1.30) for boys, and 1.26 (1.20-1.32) for all participants.We observed a positive association between BMI and low/reduced BMD in 12 to 15 years old adolescents. More attention should be paid on overweight and obese adolescents to reduce the risk of low BMD. Further studies are needed to explore the mechanisms of this association.

Physical activity and sleep duration during pregnancy have interactive effects on caesarean delivery: a population-based cohort study in Tianjin, China.

BACKGROUND: There were inconsistent findings in the literature regarding the associations of physical activity and sleep duration during pregnancy with caesarean delivery for different reasons. It was also unknown whether physical activity and sleep duration during pregnancy had interactive effects on the risks of different types of caesarean delivery. The study aimed to investigate the effects of physical activity, sleep duration and their interactions on the risk of caesarean delivery for medical reasons and non-medical reasons. METHODS: From October 2010 to August 2012, a prospective population-based cohort of 13,015 pregnant women was established in six central urban districts of Tianjin, China. Pregnancy outcomes were retrieved from an electronic database and caesarean delivery was divided into caesarean delivery for medical reasons and caesarean delivery for non-medical reasons. Physical activity and sleep status were collected at 24-28 weeks of gestation using self-reported questionnaires. Logistic regression and additive interaction were used to examine physical activity, sleep duration and their interactive effects on risk of caesarean delivery. RESULTS: In the cohort, 5692 (43.7%) and 2641 (20.3%) of women had caesarean delivery for medical reasons and non-medical reasons, respectively. Low physical activity increased the risk of caesarean delivery for medical reasons (adjusted OR: 1.13, 95%CI 1.04-1.23) but not caesarean delivery for non-medical reasons. Sleep duration < 7 h/day and poor sleep quality were not associated with caesarean delivery. Sleep duration ≥9 h/day increased the risk of caesarean delivery for medical reasons (1.12, 1.02-1.22) and caesarean delivery for non-medical reasons (1.16, 1.05-1.29). Co-presence of low physical activity and sleep duration ≥9 h/day increased risk of caesarean delivery (1.25, 1.12-1.41), and their additive interaction was statistically significant for caesarean delivery for medical reasons but not for caesarean delivery for non-medical reasons. CONCLUSIONS: Low physical activity and excessive sleep duration during pregnancy each increased the risk of caesarean delivery, and they had an interactive effect on the risk of caesarean delivery for medical reasons but not on the risk of caesarean delivery for non-medical reasons. Increasing physical activity and maintaining recommended sleep duration during pregnancy may have benefits for perinatal health.

Maternal gestational diabetes and childhood hyperlipidemia.

AIMS: Aim of this study is to assess dyslipidemia risk between children exposed to maternal gestational diabetes mellitus (GDM) and those not exposed. METHODS: We recruited 1144 mother-child pairs (572 GDM and 572 non-GDM women matched by their offspring's age and sex). The age of offspring ranged from 3 to 9 years old. We used general linear models to compare mean values of different lipid profiles among children born to mothers with and without GDM. Logistic regression models were used to assess associations of maternal GDM with abnormal lipid profiles in offspring. RESULTS: After adjustment for maternal and children's characteristics, children born to mothers with GDM had lower mean values of high-density-lipoprotein (HDL) cholesterol (1.40 ± 0.01 vs. 1.50 ± 0.01; p < 0.001) and higher mean levels of triglycerides/HDL cholesterol ratio (0.37 ± 0.01 vs. 0.35 ± 0.01; p < 0.05) in comparison with their counterparts born to mothers without GDM. Multivariate-adjusted odds ratios among children exposed to mothers with GDM compared with the counterparts were 2.11 (95% confidence interval [CI 1.15-3.88]) for low HDL cholesterol and 1.35 (95% CI 1.00-1.81) for high triglycerides/HDL cholesterol ratio, respectively. CONCLUSIONS: Maternal GDM was associated with an increased risk of hyperlipidemia in the offspring during early childhood aged from 3 to 9 years old.

Risks of Macrosomia Associated with Catechol-O-Methyltransferase Genotypes and Genetic-Epigenetic Interactions among Children with and without Gestational Diabetes Exposure.

Background: Gestational diabetes mellitus (GDM) is a major macrosomia risk factor. Variations in the catechol-O-methyltransferase (COMT; rs4680) genotypes are associated with heightened susceptibility to environmental exposures and nutritional conditions. However, macrosomia risks associated with COMT genetics, epigenetics, and the interaction between genetic and epigenetics among children with and without exposure to GDM are unknown. Methods: Data from women/children pairs (n = 1087) who participated in the Tianjin Gestational Diabetes Birth Cohort were used to examine the odds of being born with macrosomia associated with COMT-genotypes, 55 CpG sites located on the COMT gene, and genetic and epigenetic interactions. Odds of macrosomia associated with COMT genetic, epigenetic, genetic and epigenetic interactions, and moderations with GDM were tested using adjusted logistic regression models. Results: Overall, 16.1% (n = 175) of children were born with macrosomia. Models showed that children with at least one copy of the minor allele (A) had higher odds of macrosomia (odds ratio, 1.82; 95% confidence interval 1.25-2.64) compared with children with the GG-genotype. After false discovery rate corrections, none of the 55 CpG sites located on the COMT gene was associated with odds of macrosomia. The genetic and epigenetic associations were not modified by exposure to GDM. Conclusion: Findings suggest carriers of the COMT GG-genotype had lower odds of macrosomia, and this association was not modified by epigenetics or exposure to GDM.

Usefulness of cut-off points of International criteria for prediction of post-partum diabetes and prediabetes among Chinese women with gestational diabetes.

AIMS: This study tests whether cut-off points of the International Association of Diabetes and Pregnancy Study Group's (IADPSG) criteria had threshold effects on post-partum prediabetes and diabetes among Chinese pregnant women with gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A total of 507 out of 1000 women with GDM (948 of them enrolled in a lifestyle trial during pregnancy) turned up for the follow-up study and underwent a 75-g 2-h oral glucose tolerance test. GDM was diagnosed based on the IADPSG's criteria while post-partum diabetes and prediabetes were defined by the World Health Organization's. Generalized logit model was used to obtain odds ratios (OR) and 95% confidence interval (CI) of fasting, 1-h and 2-h plasma glucoses (PGs) for post-partum diabetes and prediabetes. Restricted cubic spline was used to identify any threshold effects. RESULTS: At a median of 9.1 weeks post-partum, 3.7% (n = 19) women developed post-partum diabetes and 35.1% (n = 178) developed post-partum prediabetes. Fasting PG ≥ 5.1 mmol/L was associated with markedly increased risk of post-partum diabetes without a discernible threshold (adjusted OR: 3.87, 95% CI: 1.03-14.52) while 2-h PG ≥ 8.5 and ≥ 9.0 mmol/L had threshold effects on post-partum prediabetes (2.10, 1.33-3.30) and diabetes (4.02, 1.04-15.56). The 1-h PG also had a threshold at ≥10.0 mmol/L for prediabetes (1.67, 1.06-2.64), but it was not significant for post-partum diabetes. CONCLUSIONS: Among Chinese women with GDM, fasting PG ≥ 5.1 mmol/L was associated with post-partum diabetes without any discernible threshold effects while 2-h PG ≥ 8.5 and ≥ 9.0 mmol/L respectively identified women at high risk of post-partum prediabetes and diabetes.

Prenatal gestational diabetes mellitus exposure and accelerated offspring DNA methylation age in early childhood.

Background: We investigated the association between prenatal GDM exposure and offspring DNA methylation (DNAm) age at 3-10 years of age in the Tianjin GDM Observational Study. Methods: This study included 578 GDM and 578 non-GDM mother-child pairs. Children underwent an exam with anthropometric measurements and blood draw for DNAm analysis (Illumina 850 K array) at a median age of 5.9 years (range 3.1-10.2). DNAm age was calculated using two epigenetic clock algorithms (Horvath and Hannum). The residual resulting from regressing DNAm age on chronological age was used as a metric for age acceleration. Results: Chronological age was positively correlated with Horvath DNAm age (r = 0.53, p < 0.0001) and Hannum DNAm age (r = 0.38, p < 0.0001). Offspring age acceleration was higher in the GDM group than non-GDM group after adjustment for potential confounders (Horvath: 4.96 months higher, adjusted for sex, pre-pregnancy BMI, cell-type proportions, and technical bias, p = 0.0002; Hannum: 11.2 months higher, adjusted for cell-type proportions and technical bias, p < 0.0001). Increased offspring DNAm age acceleration was associated with increased offspring weight-for-age Z-score, BMI-for-age-Z-score, waist circumference, body fat percentage, subscapular skinfold, suprailiac skinfold, upper-arm circumference, and blood pressure; findings were stronger in the GDM group. Conclusions: We found that offspring of women with GDM exhibit accelerated epigenetic age compared to control participants, independent of other maternal factors. Epigenetic age in offspring was associated with cardiometabolic risk factors, suggesting that GDM and GDM-associated factors may have long-term effects on offspring epigenetic age and contribute to health outcomes.