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This study aimed to explore associations of serum cluster of differentiation 44 (CD44) levels and its genetic variants in early pregnancy with gestational diabetes mellitus (GDM). We conducted a 1:1 case-control study (n = 414) nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10 th gestational week). Binary conditional logistic regressions were performed to examine associations of serum CD44 levels and its genetic variants with increased risk of GDM. In this study, we found that serum CD44 levels in early pregnancy was associated with GDM risk in a U-shaped manner. High serum CD44 levels and its genetic risk score in early pregnancy were associated with markedly increased risk of GDM after adjustment for traditional confounders (OR: 1.95, 95%CI: 1.12-3.40 & 1.95, 1.05-3.61). Furthermore, after adjustment for serum CD44 levels, the OR of CD44 genetic risk score for GDM was slightly attenuated but not significant (1.84, 0.98-3.48). In conclusion, serum CD44 levels and its genetic variants in early pregnancy were associated with GDM risk in Chinese pregnant women, with the effect of CD44 genetic variants being accounted for by serum CD44. SIGNIFICANCE: Recent studies suggested that pregnant women with GDM may have abnormal levels of CD44 and abnormal expression of CD44 gene, but it is uncertain whether abnormal CD44 plays a causal role in occurrence of GDM. Specifically, it remains unknown whether serum CD44 levels in early pregnancy and its genetic variants can predict the later occurrence of GDM. In this study, we found that high serum CD44 levels in early pregnancy and its genetic variants were associated with markedly increased risk of GDM in Chinese pregnant women, with the effect of CD44 genetic variants being largely accounted for by serum CD44 levels. Our study is the first reporting that serum CD44 levels and its genetic variants were associated with markedly increased risk of GDM. These multi-omics risk markers may be useful for identification of women at high risk of GDM in early pregnancy. Our findings also provide new insights into the disease mechanisms., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: To examine long-term risk of overweight in offspring of women with gestational diabetes mellitus (GDM) defined by the International Association of Diabetes and Pregnancy Study Group (IADPSG)'s criteria but not by the 1999 World Health Organization (WHO)'s criteria., Methods: We followed up 1681 mother-child pairs for 8 years in Tianjin, China. Overweight in children aged 1-5 and 6-8 were respectively defined as body mass index-for-age and -sex above the 2 z-score and 1 z-score curves of the WHO's child growth standards. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of hyperglycemia indices at oral glucose tolerance test and GDMs defined by different criteria for offspring overweight at different ages., Results: Offspring of women with fasting plasma glucose ≥5.1 mmol/L were at increased risk of overweight at 6-8 years old (OR:1.45, 95% CI: 1.09-1.93). GDM defined by the IADPSG's criteria only was associated with increased risk of childhood overweight at 6-8 years old (1.65, 1.13-2.40), as compared with non-GDM by either of the two sets of criteria., Conclusions: Newly defined GDM by the IADPSG's criteria increased the risk of offspring overweight aged 6-8 years., Competing Interests: Declaration of Competing Interest The authors declared no conflict of interest., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Cerebral small vessel disease (CSVD) is a prevalent vascular disorder that has been consistently associated with vascular cognitive impairment (VCI). The diagnosis of CSVD continues to rely on magnetic resonance imaging (MRI). Epidemiological data indicate that the characteristic MRI features of CSVD, including white matter hyperintensity (WMH) and lacunar infarction, are very common among individuals over 40 years of age in community studies. This prevalence poses a significant burden on many low- and middle-income families. The amygdala plays a crucial role in integrating sensory and associative information to regulate emotional cognition. Although many previous studies have linked alterations in the amygdala to various diseases, such as depression, there has been little research on CSVD-associated alterations in the amygdala due to the complexity of CSVD. In this paper, we summarize the various imaging features of CSVD and discuss the correlation between amygdala changes and VCI. We also explore how new neuroimaging methods can assess amygdala changes early, laying a foundation for future comprehensive exploration of the pathogenesis of CSVD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cheng, Nie, Yang, Leng, Wang, Li and Guo.)

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., (© 2024. The Author(s).)

Objectives: To explore associations between adverse birth outcomes and childhood overweight at 3-8 years of age., Design: A prospective cohort study., Setting: Six central urban districts of Tianjin, China., Participants: 1681 woman-child pairs., Methods: 1681 woman-child pairs were followed up for 8 years in Tianjin, China. Demographic and clinical information including birth outcomes was collected longitudinally, commencing from first antenatal care visit till postpartum period. Offspring height and weight were measured at 3-8 years of age. High and low weight/length ratios (WLR) at birth were, respectively, defined as ≥90th and ≤10th gestational week and sex-specific percentiles. Overweight for children at 3-5 and 6-8 years of age were, respectively, defined as body mass index (BMI)-for-age and -sex above the 2 z-score and 1 z-score curves of the WHO's child growth standards. Binary logistic regression analysis was used to obtain ORs and 95% CI with a stepwise backward selection method to select independent predictors., Primary Outcomes Measures: Childhood overweight., Results: Of 1681 children, 10.7% (n=179) and 27.8% (n=468) developed overweight at 3-5 and 6-8 years of age, respectively. Large for gestational age (LGA) was associated with increased risk of overweight at 3-5 years of age (aOR: 1.86, 95% CI: 1.27 to 2.72) while high WLR at birth was associated with increased risk of overweight at 6-8 years of age (1.82, 1.41 to 2.34). Low WLR at birth was associated with decreased risk of overweight at 6-8 years of age (0.52, 0.30 to 0.90)., Conclusions: LGA and high WLR at birth predicted childhood overweight at 3-5 and 6-8 years of age, respectively. Low WLR at birth was associated with decreased risk of childhood overweight at 6-8 years of age., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023 John Wiley & Sons Ltd.)

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 β 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., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The cases were a pair of siblings with a carnitine palmitoyltransferase (CPT2) deficiency detected by tandem mass spectrometry. Their C16 and C18:1 levels were both within the normal range, while C0 was low, and the (C16+C18:1)/C2 ratio was high. Following genetic testing, a novel CPT2 gene mutation was identified in both patients. The male patient had a normal growth rate during 5 years of follow-up after treatment. By contrast, the female patient did not take l-carnitine supplements and died after an infectious disease-associated illness when she was 1 year old. These data emphasize the need to raise awareness about CPT2 deficiency so as to correctly diagnose and accurately manage the disease., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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/m 2 group, co-presence of autumn/winter and pre-pregnancy BMI ≥ 24 kg/m 2 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., (© 2023. The Author(s).)

Objectives: The purpose of this study is to establish a comprehensive reference range of quantitative characteristics of the fetal pancreas using a high-frequency transducer, and assess the growth and development of the fetal pancreas. Methods: Pregnant women referred to a tertiary center were recruited to undergo a detailed fetal scan from 16 to 37 weeks. We evaluated the visualization rate of the fetal pancreas with high-frequency and low-frequency transducers and measured the head, neck, body, tail, circumference, area, and abdominal circumference(AC) of the fetal pancreas at different gestational ages(GA) with the high-frequency transducer. Regression analysis was used to analyze the relationship between biological parameters and GA and AC. Results: During the time periods of 16 +1 ∼21 +6  weeks and 22 +1 ∼27 +6  weeks, the visualization rate of high-frequency transducers was higher compared to low-frequency transducers (83.33% vs 45% and 95.65% vs 70%, respectively). However, in the third trimester of pregnancy, the performance of the two transducers was similar (70.37% vs 74.07% for 28 +1 ∼33 +6  weeks and 41.67% vs 53.85% for 34 +1 ∼37 +6  weeks). The head, neck, body, and tail as well as the circumference and area of the pancreas were significantly positively correlated with GA (R 2 ＝0.87, 0.94, 0.92, 0.92,0.96, and 0.92) and AC (R 2 ＝0.87, 0.93, 0.91, 0.93,0.96, and 0.92). Conclusions: The high-frequency transducer was utilized to establish the normal reference, which can be used to evaluate normal pancreatic development and may help in the accurate diagnosis of fetal pancreatic abnormalities.

Aims: This study aimed to explore associations of mannan-binding lectin-associated serine protease (MASP) levels in early pregnancy with gestational diabetes mellitus (GDM). We also examined interactions of MASPs and deoxycholic acid (DCA)/glycoursodeoxycholic acid (GUDCA) for the GDM risk and whether the interactive effects if any on the GDM risk were mediated via lysophosphatidylcholine (LPC) 18:0., Materials and Methods: A 1:1 case-control study (n = 414) nested in a prospective cohort of pregnant women was conducted in Tianjin, China. Binary conditional logistic regressions were performed to examine associations of MASPs with the GDM risk. Additive interaction measures were used to examine interactions between MASPs and DCA/GUDCA for the GDM risk. Mediation analyses and Sobel tests were used to examine mediation effects of LPC18:0 between the copresence of MASPs and DCA/GUDCA on the GDM risk., Results: High MASP-2 was independently associated with GDM [odds ratio (OR): 2.62, 95% confidence interval (CI): 1.44-4.77], while the effect of high MASP-1 on GDM was attributable to high MASP-2 ( P for Sobel test: 0.003). Low DCA markedly increased the OR of high MASP-2 alone from 2.53 (1.10-5.85) up to 10.6 (4.22-26.4), with a significant additive interaction. In addition, high LPC18:0 played a significant mediating role in the links from low DCA to GDM and from the copresence of high MASP-2 and low DCA to GDM ( P for Sobel test <0.001) but not in the link from high MASP-2 to GDM., Conclusions: High MASP-1 and MASP-2 in early pregnancy were associated with GDM in Chinese pregnant women. MASP-2 amplifies the risk of low DCA for GDM, which is mediated via LPC18:0., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, Li, Zhang, Li, Li, Zhang, Wang, Wang, Fang, Yu, Hu, Leng and Yang.)

Objective: To identify the optimal weight gain at the end of the second trimester., Design: This was a population-based cohort study from the antenatal care system in Tianjin, China. We calculated gestational weight gain (GWG) based on the weight measured in the first trimester and the end of the second trimester. Restricted cubic spline analysis was performed to model the possible non-linear relationships between GWG and adverse outcomes. The optimal GWG was defined as the value of the lowest risk. Non-inferiority margins and the shape of the spline curves identified the recommended ranges in Chinese-specific BMI categories., Setting: Tianjin Maternal and Child Health Cohort., Participants: Singleton pregnant women aged 18-45 years., Results: In total, 69 859 pregnant women were included. Adverse outcome (including stillbirth, preterm birth, hypertensive disorders of pregnancy, gestational diabetes mellitus, small and large for gestational age) was significantly associated with GWG at the end of the second trimester. The risk score was non-linearly correlated with GWG in the underweight, normal weight and overweight groups. GWG at the end of the second trimester should not be < 7 kg in underweight group. For most normal-weight women, a GWG of about 8 kg is optimal. Pregnant women who are overweight should not have a GWG of more than 9 kg. We advised women with overweight and obesity to keep positive growth of GWG (> 0 kg) in the first and second trimesters., Conclusions: According to the comprehensive adverse maternal and infant outcomes, we recommend the optimal GWG at the end of the second trimester. This study may provide a considerable reference for weight management.

Background: To estimate associations of sulfur-containing amino acids (SAAs) in the early trimester of pregnancy and gestational diabetes mellitus (GDM) and estimate associations of maternal SAAs with adverse growth patterns in offspring., Methods: We established a 1:1 matched case-control study (n = 486) from our cohort of pregnant women, and 401 children were followed up at ages 1 to 8 years. We conducted binary conditional logistic regression to estimate the risk associations of serum SAAs with GDM. Multinomial logistic regression was implemented to explore associations of maternal SAAs with adverse growth patterns in the offspring., Results: High serum methionine and cystine were independently associated with increased GDM risk (OR: 1.92, 95%CI: 1.18-3.13 and 2.69, 1.59-4.53). Conversely, a low level of serum taurine was independently associated with increased GDM risk (2.61, 1.64-4.16). Maternal high cystine and low taurine were also associated with an increased risk of persistent obesity growth pattern (POGP) in offspring (OR: 2.79, 95%CI: 1.09-7.17 and 3.92, 1.11-13.89) and the effect was largely independent of GDM., Conclusions: High serum methionine, cystine and low serum taurine in the early trimester of pregnancy were associated with a greatly increased risk of GDM. Maternal high cystine and low taurine were associated with elevated risk of offspring POGP, largely independent of GDM.

Background and Aims: To explore association of serum hyaluronidase 1 (HYAL1) level in early pregnancy with gestational diabetes mellitus (GDM), and to examine interactive effects of HYAL1 with ceramides species on GDM risk., Materials and Methods: We conducted a 1:1 matched case-control study (n = 414) of pregnant women from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10 th gestational weeks). Binary conditional logistic regression and restricted cubic spline (RCS) analysis were used to examine full-range risk association between HYAL1 and GDM. Additive interactions and multiplicative interactions were employed to test interactive effects of HYAL1 with ceramides species on GDM risk., Results: Ln HYAL1 was linearly associated with GDM risk and the adjusted OR of HYAL1 ≥ vs. < its median for GDM was significant (1.65, 95%CI: 1.08-2.52). High HYAL1 markedly enhanced the ORs of high ceramide 18:0 for GDM from 2.31 (1.06-5.01) to 6.74 (2.85-16.0), and low ceramide 24:0 from 3.08 (1.33-7.11) to 8.15 (3.03-21.9), with significant additive interactions., Conclusions: High HYAL1 in early pregnancy may increase the risk of GDM in Chinese women, possibly via enhancing the effects of high ceramide 18:0 and low ceramide 24:0 on GDM risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to evaluate the feasibility of direct visualization of a normal fetal palate and detect cleft palate in the first trimester with a novel three-dimensional ultrasound (3D US) technique, Crystal and Realistic Vue (CRV) rendering technology., Methods: Two-dimensional (2D) images and 3D volumes of healthy and cleft palate fetuses at 11-13 +6 weeks were obtained prospectively. 2D ultrasound views included the coronal view of the retronasal triangle and the midsagittal view of the face. 3D-CRV views were analyzed by multiplanar mode display. The pregnancy outcomes of all fetuses were determined during the follow-up period., Results: In our study, 124 fetuses were recruited, including 100 healthy fetuses and 24 cleft palate fetuses. The cleft palate with lip was observed in 23 fetuses (bilateral in 15, unilateral in 6, median in 2), and one cleft palate was only found in the abnormal group. The bilateral ( n  = 12) and median ( n  = 2) cleft palates with lips and the cleft palate alone ( n  = 1) were associated with other anatomical or chromosomal abnormalities, and one unilateral cleft palate with cleft lip had concomitant NT thickening. In the cleft palate fetus group, 16 fetuses suffered intrauterine death, which was associated with other structural or chromosomal abnormalities in 14 fetuses, seven cases were terminated after consultation, and one was delivered at term. The coronal view of the retronasal triangle and the midsagittal view was easily obtained in all fetuses. 3D-CRV images of palatal parts were clearly obtained in all cases. Unilateral, bilateral, and median cleft palates with cleft lips were visually demonstrated and classified by the 3D-CRV technique., Conclusion: It is feasible to identify the palate by 3D-CRV in the first trimester in both healthy and cleft palate fetuses. Together with 2D ultrasonography as a complementary diagnostic tool, 3D-CRV is helpful in classifying the cleft palate with a reasonable degree of certainty., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Shi, Wen, Leng, Wang, Wang, Luo, Chen, Qin, Liang, Tan and Li.)

Objective: To explore associations of maternal insulin resistance and β-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 β-cell function (HOMA-%β) 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-%β 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-%β 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 β-cell function at diagnosis of GDM were associated with elevated risk of offspring overweight in early childhood among Chinese women with GDM., (© 2022 World Obesity Federation.)

Aims: To examine the associations of parental obesity prior to pregnancy with offspring overweight before two years of age among children of Chinese women with gestational diabetes mellitus (GDM)., Methods: Offspring of women with GDM (n = 774) who were diagnosed in 2010-2012 were followed up to two years of age in Tianjin, China. Multinomial logistic regression was used to obtain odds ratios (ORs) and 95% confidence interval (CI) of maternal and paternal prepregnancy obesity with offspring overweight at < 1, 1-1.5, and 1.5-2 years of age., Results: Among 774 offspring of women with GDM, 457 (59.0%) of the offspring developed overweight before two years of age. Maternal prepregnancy obesity was associated with increased risk of offspring overweight at 1-1.5 years of age and 1.5-2 years of age (ORs: 1.98, 95%CI: 1.09-3.59 & 2.14, 1.10-4.15, respectively). Paternal prepregnancy obesity was only associated with elevated risk of offspring overweight at 1.5-2 years of age (1.82, 1.08-3.06). Furthermore, copresence of both maternal and paternal obesity prior to pregnancy had an additive effect on the risk of offspring overweight at 1.5-2 years of age (3.73, 1.50-9.27)., Conclusions: Parental prepregnancy obesity predicted offspring overweight before two years of age among children of Chinese women with GDM., Competing Interests: Declaration of Competing Interest All authors declared no conflict of interest., (Copyright © 2022 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study was to explore associations of aromatic amino acids (AAA) in early pregnancy with gestational diabetes mellitus (GDM), and whether high AAA and gut microbiota-related metabolites had interactive effects on GDM risk., Methods: We conducted a 1:1 case-control study (n = 486) nested in a prospective cohort of pregnant women from 2010 to 2012. According to the International Association of Diabetes and Pregnancy Study Group's criteria, 243 women were diagnosed with GDM. Binary conditional logistic regression was performed to examine associations of AAA with GDM risk. Interactions between AAA and gut microbiota-related metabolites for GDM were examined using additive interaction measures., Results: High phenylalanine and tryptophan were associated with increased GDM risk (OR: 1.72, 95% CI: 1.07-2.78 and 1.66, 1.02-2.71). The presence of high trimethylamine (TMA) markedly increased the OR of high phenylalanine alone up to 7.95 (2.79-22.71), while the presence of low glycoursodeoxycholic acid (GUDCA) markedly increased the OR of high tryptophan alone up to 22.88 (5.28-99.26), both with significant additive interactions. Furthermore, high lysophosphatidylcholines (LPC18:0) mediated both interactive effects., Conclusions: High phenylalanine may have an additive interaction with high TMA, while high tryptophan may have an additive interaction with low GUDCA toward increased risk of GDM, both being mediated via LPC18:0., (© 2023 S. Karger AG, Basel.)

Background: Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease., Methods: The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease., Results: A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m 3 increase of gestational exposure to PM 2.5 , the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1 st -2 nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O 3 exposure during the 1 st week and SO 2 exposure during 6 th -7 th weeks in the first trimester, while no significant findings for other air pollutants., Conclusions: This study highlighted that gestational exposure to PM 2.5 , O 3 , and SO 2 had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.

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.

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 (P trend  < 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) (P trend  = 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., (© 2022. The Author(s).)

Background: Interactions between genetic, metabolic, and environmental factors lead to gestational diabetes mellitus (GDM). We aimed to examine interactive effects of cyclin-dependent kinase 5 regulatory subunit-associated protein1-like 1(CDKAL1) rs7747752 polymorphism with low serum levels of L-carnitine, choline, and betaine for GDM., Methods: A nested case-control study of 207 GDM women and their one-to-one, age-matched controls was organized from a prospective cohort of pregnant women in Tianjin, China. Conditional logistic regressions were used to test associations between CDKAL1 rs7747752 and serum levels of L-carnitine, choline, and betaine, and the risk of GDM. Additive interactions were performed to examine interactive effects of rs7747752 and low serum levels of L-carnitine, choline, and betaine on the risk of GDM., Results: The CDKAL1 rs7747752 G > C was associated with GDM in additive, dominant, and recessive model (P <0.05). The rs7747752 CC genotype enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 6.14 (2.61-14.4) to 19.6 (5.65-68.1) and the OR of choline ≤ vs. > 110 nmol/mL from 2.37 (1.07-5.28) to 12.1 (3.22-45.6), with significant additive interactions. Similarly, CG genotype also enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 4.70 (2.01-11.0) to 11.4 (3.98-32.9), with a significant additive interaction. However, the additive interaction between rs7747752 and betaine ≤ 200 nmol/mL on the risk of GDM was not significant., Conclusions: The CC or CG genotype carriers in rs7747752 of CDKAL1 who have a low serum level of L-carnitine or choline are at a particular high risk of GDM. Randomized controlled trials are warranted to test the effect of supplement of L-carnitine or choline on the risk of GDM in the high-risk group., (© 2022. The Author(s).)

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: β 0.011, 95% CI 0.008-0.014; β 0.017, 95% CI 0.015-0.020; β 0.005, 95%CI 0.002-0.008; β 0.018, 95% CI 0.015-0.021; β 0.014, 95% CI 0.009-0.020; β 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., Competing Interests: The authors declared no conflicts of interest in this work., (© 2022 Zhang et al.)

Objective: We aimed to explore associations of branched-chain amino acids (BCAA) in early pregnancy with gestational diabetes mellitus (GDM), and whether high BCAAs and lipidomics markers had interactive effects on the risk of GDM., Methods: We conducted a 1:1 case-control study (n = 486) nested in a prospective cohort of pregnant women in Tianjin, China. Blood samples were collected at their first antenatal care visit (median 10 gestational weeks). Serum BCAAs, saturated fatty acids (SFA) and lysophosphatidylcholines (LPC) were measured by liquid chromatography-tandem mass spectrometry analysis. Conditional logistic regression was performed to examine associations of BCAAs with the risk of GDM. Interactions between high BCAAs and high SFA16:0 for GDM were examined using additive interaction measures., Results: High serum valine, leucine, isoleucine, and total BCAAs were associated with markedly increased risk of GDM (OR of top vs bottom tertiles: 1.91 [95% CI, 1.22-3.01]; 1.87 [1.20-2.91]; 2.23 [1.41-3.52]; 1.93 [1.23-3.02], respectively). The presence of high SFA16:0 defined as ≥ 17.1 nmol/mL (ie, median) markedly increased the ORs of high leucine alone and high isoleucine alone up to 4.56 (2.37-8.75) and 4.41 (2.30-8.43) for the risk of GDM, with significant additive interaction. After adjustment for LPCs, the ORs were greatly elevated (6.33, 2.25-17.80 and 6.53, 2.39-17.86) and the additive interactions became more significant., Conclusion: BCAAs in early pregnancy were positively associated with the risk of GDM, and high levels of leucine and isoleucine enhanced the risk association of high SFA16:0 with GDM, independent of LPCs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Inappropriate weight gain may increase the risk of gestational diabetes mellitus (GDM). However, the relationship between pre-pregnancy body mass index (BMI), weight gain, and GDM has not been precisely quantified. This study aimed to explore whether gestational weight gain played a mediating role between pre-pregnancy BMI and GDM and whether the mediating effect was sex specific., Methods: This study established a population-based observational cohort to assess weight gain in pregnant women. Mediation analyses were performed to quantify whether weight gain mediated the association between pre-pregnancy BMI and GDM., Results: A total of 67,777 pregnant women were included in the final analysis, among whom 6751 (10.0%) were diagnosed with GDM. We verified that both pre-pregnancy BMI and weight gain were associated with GDM, and that BMI negatively contributed to weight gain. We also found that weight gain had a significant mediating effect on the relationship between pre-pregnancy BMI and GDM (Z a  × Z b confidence intervals [CIs] 0.00234-0.00618). Furthermore, the effect was sex-specific, in that it was only significant in overweight women carrying female fetuses (Z a  × Z b CIs 0.00422-0.01977), but not male fetuses (Z a  × Z b CIs -0.00085 to 0.01236)., Conclusions: Weight gain during pregnancy had a fetal sex-specific mediating effect between pre-pregnancy BMI and GDM., (© 2022. The Author(s).)

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/m 2 ), 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., (© 2022. The Author(s).)

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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Circumstantial evidence links one-carbon metabolism (OCM) related nutrients, such as folate and vitamin B 12 , with gestational diabetes mellitus (GDM). However, few studies have evaluated the combined effects of these nutrients with OCM related gene polymorphisms on GDM. This study investigated whether OCM related genetic variants modified the associations of folate and B 12 with GDM. Logistic regression was used to estimate odds ratios (ORs) for OCM related nutrients and single nucleotide polymorphisms (SNPs) in genes encoding main OCM related enzymes ( MTHFR , MTR , and MTRR ) on GDM. Higher folate concentrations were associated with increased GDM risk (OR: 1.59; 95% CI: 1.22, 2.13). However, higher B 12 concentrations were associated with reduced GDM risk (OR: 0.76; 95% CI: 0.65, 0.92). Pregnancies with MTHFR rs1801131 G alleles had a significantly lower risk of GDM than pregnancies with T alleles (OR: 0.65; 95% CI: 0.47, 0.91) under the dominant model. The genotype-stratified analysis revealed the association between folate and GDM (OR: 1.66, 95% CI: 1.20, 2.30) or B 12 and GDM (OR: 0.80, 95% CI: 0.65, 0.98) was more evident in pregnancies with TT genotype. Higher folate and lower B 12 are associated with GDM. Pregnancies with MTHFR rs1801131 TT genotype are more susceptible to OCM nutrient-related GDM.

Aims: The study aimed to explore additive interactions of CDKAL1 rs7747752 and GUDCA/DCA for GDM risk and whether the interactive effects on the risk of GDM was mediated via increasing lysophosphatidylcholines (LPC) 18:0 and/or saturated fatty acid (SFA) 16:0., Methods: A 1:1 age-matched study nested in a prospective cohort of pregnant women (207 pairs) was organized in Tianjin, China. Additive interactions were used to test interaction effects while mediation analyses and Sobel tests were used to test mediation effects of LPC18:0 and SFA16:0 between copresence of rs7747752 and low GUDCA/DCA, and GDM risk., Results: The CDKAL1 rs7747752 was associated with GDM (P<0.05). The rs7747752 C polymorphism markedly enhanced ORs of low GUDCA from 4.04 (0.72-22.8) to 9.02 (1.63-49.7) and low DCA from 1.67 (0.68-4.11) to 4.24 (1.84-9.76), both with significant additive interactions. Further adjustment for LPC18:0 attenuated the interactive effects of rs7747752 and low DCA, with a significant mediation effect (P=0.003). High SFA16:0 did not mediate the interactive effects of rs7747752 and low DCA/GUDCA on GDM risk., Conclusions: The CDKAL1 rs7747752 C carrier status and low GUDCA/DCA had significant additive interactions on the risk of GDM with the effect from interaction with DCA being partially mediated via increasing LPC18:0., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Li, Leng, Li, Liu, Yan, Yu, Hu, Ma, Fang, Wang and Yang.)

Although previous meta-analyses have shown that prenatal PFASs exposure is associated with reduction in birth weight, effects of prenatal PFASs exposure on birth outcomes have not been fully explored. We conducted a meta-analysis of 23 eligible studies searched from Embase, PubMed, and Web of Science before March 21, 2021 to analyze the association between prenatal PFASs exposure and birth outcomes, including premature birth (PTB), low birth weight (LBW), small for gestational age (SGA) and miscarriage. Odds ratio (OR) and corresponding confidence intervals were extracted for analysis. According to the heterogeneity of the included studies, fixed-effects (I 2  ≤ 50%) and random-effects (I 2  > 50%) models were applied respectively. The significant associations between PFOS and PTB (pooled OR = 1.54, 95% CI: 1.20-1.98), PFOA and miscarriage (pooled OR = 1.40, 95% CI: 1.15-1.70), and PFOS and LBW (pooled OR = 1.52, 95% CI: 1.19-1.94) were obtained. There were differences between included studies with different study regions, sampling time, and samples type used for PFASs assessment. These findings may provide insight in risk assessment and decision-making in producing products that contain PFASs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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 × 10 9 /L vs 8.2 × 10 9 /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 × 10 9 /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., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims: To investigate the associations and predictive values of serum metabolites in early pregnancy for later development of gestational diabetes mellitus (GDM), and further explore their metabolic pathways to GDM., Methods: We conducted a 1:1 nested case-control study including 486 pregnant women from Tianjin, China, and collected blood samples at their first registration (median at 10th gestational week). Liquid chromatography-tandem mass spectrometry was used to measure serum metabolites. Orthogonal partial least squares discriminant analysis was used to select specific metabolites associated with GDM, and pathway analysis was used to identify the metabolic pathways related to GDM., Results: A total of 64 serum metabolites were included in this analysis, 17 of which were identified as specific metabolites associated with GDM. Ten metabolites increased and seven metabolites decreased GDM risk. Inclusion of these specific metabolites to the model of traditional risk factors greatly increased the predictive value from 0.69 (95% confidence interval: 0.64-0.74) to 0.92 (0.90-0.95). In addition, we found that glycerophospholipid metabolism, sphingolipid metabolism and primary bile acid biosynthesis were main metabolic pathways related to GDM., Conclusion: We identified a set of serum metabolites and their metabolic pathways in early pregnancy associated with GDM, which provided a theoretical basis for further research on the molecular pathways to GDM and early identification of GDM., (Copyright © 2021. Published by Elsevier Inc.)

Background: Interactions between genetic and nutritional factors can contribute to the risk of gestational diabetes mellitus (GDM)., Objectives: We aimed to explore the associations of cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (CDKAL1) single-nucleotide polymorphism (SNP) rs7747752 and serum concentrations of SFAs with the risk of GDM in Chinese women., Methods: We conducted a 1:1 case-control study in a prospective cohort of pregnant women in Tianjin, China. Serum SFA data were collected from a total of 243 women with GDM and their controls matched by maternal age (±1 y). Among them, 207 case-control pairs had high-quality sequencing data. P/L and S/P ratios were defined as palmitic acid (16:0)/lauric acid (12:0) and stearic acid (18:0)/palmitic acid, respectively. Conditional logistic regression analysis was performed to estimate associations of CDKAL1 SNP rs7747752 and serum concentrations of SFAs with the risk of GDM. An additive interaction between rs7747752 and palmitic acid was analyzed to test the contribution of their interaction to the risk of GDM., Results: Among the 5 tested SFAs, palmitic acid was positively whereas lauric acid was negatively associated with the risk of GDM. A P/L ratio ≥12.2 and an S/P ratio ≤0.71 were independently and synergistically associated with an increased risk of GDM. The CDKAL1 rs7747752 G > C variant was significantly associated with an increased risk of GDM (P < 0.05). Furthermore, the presence of the rs7747752 G > C variant increased the OR (95% CI) of high palmitic acid concentration from 1.55 (0.61, 3.97) to 4.34 (2.04, 9.23), with a significant additive interaction., Conclusions: The interaction between high serum palmitic acid concentration and the CDKAL1 rs7747752 G > C variant played a critical role in GDM. Given that a hypocaloric low-carbohydrate diet can lower palmitic acid concentrations, it is worthwhile to test whether such a diet is effective in reducing the risk of GDM, especially among women who have both risk factors., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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., (© 2021 John Wiley & Sons Ltd.)

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., (© 2021 Diabetes UK.)

Aim: The rise of diabetes mellitus (DM) and impaired fasting glucose (IFG) in children has become a worldwide challenge, but population-based survey targeted on pre-school children is lacking. The aim of the study was to determine the prevalence of DM and IFG in pre-school children and their association with obesity and susceptible behaviours., Methods: A population-based survey was conducted and 21,571 Chinese children aged 5-6 years were recruited from 66 kindergartens in Tianjin, China during the year of 2016-2018. Fasting glucose was measured for all participants. Children with fasting glucose over 7.0 mmol/L was defined as DM, and 5.6-6.9 mmol/L was defined as IFG., Results: The prevalence of DM and IFG in the current study among Chinese children aged 5-6 years old was 0.05% and 1.18%, respectively, with significant gender and regional disparities (p < 0.001). The risk of abnormal fasting glucose increased with obesity (OR 1.44, 95% CI 1.00-2.06, p < 0.05), especially with moderate/severe obesity (OR 1.84, 95% CI 1.10-3.10, p < 0.05). Further analyses found that as compared to children who had at least 2 h/day physical activity, physical activity <1 h/day increased the risk of abnormal fasting glucose independently of BMI z-score (OR 1.79, 95% CI 1.10-2.91, p < 0.05)., Conclusions: The study was the first population-based large-scale survey of DM and IFG which targeted on pre-school children, and demonstrated that moderate/severe obesity and inadequate physical activity raised the risk of DM and IFG early from pre-school. The findings highlighted the necessity of early detection for abnormal glucose and control of obesity and susceptible behaviours., (© 2021 John Wiley & Sons Ltd.)

Introduction: To investigate associations between genetic variants related to beta-cell (BC) dysfunction or insulin resistance (IR) in type 2 diabetes (T2D) and bile acids (BAs), as well as the risk of gestational diabetes mellitus (GDM)., Research Design and Methods: We organized a case-control study of 230 women with GDM and 217 without GDM nested in a large prospective cohort of 22 302 Chinese women in Tianjin, China. Two weighted genetic risk scores (GRSs), namely BC-GRS and IR-GRS, were established by combining 39 and 23 single nucleotide polymorphisms known to be associated with BC dysfunction and IR, respectively. Regression and mediation analyses were performed to evaluate the relationship of GRSs with BAs and GDM., Results: We found that the BC-GRS was inversely associated with taurodeoxycholic acid (TDCA) after adjustment for confounders (Beta (SE)=-0.177 (0.048); p=2.66×10 -4 ). The BC-GRS was also associated with the risk of GDM (OR (95% CI): 1.40 (1.10 to 1.77); p = 0.005), but not mediated by TDCA. Compared with individuals in the low tertile of BC-GRS, the OR for GDM was 2.25 (95% CI 1.26 to 4.01) in the high tertile. An interaction effect of IR-GRS with taurochenodeoxycholic acid (TCDCA) on the risk of GDM was evidenced (p=0.005). Women with high IR-GRS and low concentration of TCDCA had a markedly higher OR of 14.39 (95% CI 1.59 to 130.16; p = 0.018), compared with those with low IR-GRS and high TCDCA., Conclusions: Genetic variants related to BC dysfunction and IR in T2D potentially influence BAs at early pregnancy and the development of GDM. The identification of both modifiable and non-modifiable risk factors may facilitate the identification of high-risk individuals to prevent GDM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

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]).

Aims: This study aimed to develop a machine learning-based prediction model for gestational diabetes mellitus (GDM) in early pregnancy in Chinese women., Materials and Methods: We used an established population-based prospective cohort of 19,331 pregnant women registered as pregnant before the 15th gestational week in Tianjin, China, from October 2010 to August 2012. The dataset was randomly divided into a training set (70%) and a test set (30%). Risk factors collected at registration were examined and used to construct the prediction model in the training dataset. Machine learning, that is, the extreme gradient boosting (XGBoost) method, was employed to develop the model, while a traditional logistic model was also developed for comparison purposes. In the test dataset, the performance of the developed prediction model was assessed by calibration plots for calibration and area under the receiver operating characteristic curve (AUR) for discrimination., Results: In total, 1484 (7.6%) women developed GDM. Pre-pregnancy body mass index, maternal age, fasting plasma glucose at registration, and alanine aminotransferase were selected as risk factors. The machine learning XGBoost model-predicted probability of GDM was similar to the observed probability in the test data set, while the logistic model tended to overestimate the risk at the highest risk level (Hosmer-Lemeshow test p value: 0.243 vs. 0.099). The XGBoost model achieved a higher AUR than the logistic model (0.742 vs. 0.663, p < 0.001). This XGBoost model was deployed through a free, publicly available software interface (https://liuhongwei.shinyapps.io/gdm&#95;risk&#95;calculator/)., Conclusion: The XGBoost model achieved better performance than the logistic model., (© 2020 John Wiley & Sons Ltd.)

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.

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.

Emerging per-/polyfluoroalkyl substances (PFASs), such as chlorinated polyfluorinated ether sulfonates (Cl-PFESAs), have been detected in human samples, yet investigation on their occurrence in pregnant women remains limited. Herein, ten legacy PFASs, branched perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA), two Cl-PFESAs, perfluoro-2-propoxypropanoic acid (HFPO-DA), and ammonium 4,8-dioxa-3H-perfluorononanoate (ADONA) were detected in serum samples from 480 pregnant women in Tianjin, China. The influencing effects of age, body mass index, gravidity, and parity were also evaluated. PFOS [geographic mean (GM): 7.05 ng/mL], 6:2Cl-PFESA (GM: 5.31 ng/mL), and PFOA (GM: 2.82 ng/mL) were the dominant PFASs in the serum of pregnant women, while neither HFPO-DA nor ADONA was detectable in any serum. The serum concentration of Cl-PFESAs and 6:2Cl-PFESA/PFOS ratio in the present study were 2-5 times higher than that in previous studies of pregnant women in China. Serum concentrations of Cl-PFESAs were significantly correlated with all detected PFAAs (Spearman's Rho: 0.15-0.69, p < 0.01) excepting perfluoropentanesulfonate (PFPeS), indicating common exposure sources for Cl-PFESAs and PFAAs and some particular exposure source for PFPeS. Younger age and multi-parity were associated with lower serum concentrations of PFOS and several perfluoroalkyl sulfonates but not associated with Cl-PFESAs or PFOA, suggesting an increasing exposure to Cl-PFESAs and PFOA which neutralized the impact of age and parity. Overall, this study indicated a relatively high exposure level and composition of 6:2Cl-PFESA in pregnant women in the north coast of China, which highlights the need to investigate the exposure sources in this area., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aims: To explore associations between ceramides in early pregnancy and gestational diabetes mellitus (GDM); and interactions between ceramides and trimethylamine N-oxide (TMAO) metabolites for GDM., Methods: We organized a 1:1 nested case-control study (n = 486) from a prospective cohort of pregnant women. Conditional logistic regression and additive interaction were performed to examine relationships between ceramides and TMAO metabolites for GDM. We defined trimethylamine (TMA) conversion ratio (TMA R ) as TMA/its precursors and TMAO conversion ratio (TMAO R ) as TMAO/TMA. Copresence of high TMA R and low TMAO R indicated TMA accumulation status., Results: High ceramides 18:0 (per SD), 18:1 (per SD) and low ceramide 24:0 (≤ 3.60 nmol/mL) were associated with increased GDM risk (OR: 1.69, 1.72 & 3.59, respectively). High TMA enhanced the OR of low ceramide 24:0 for GDM from 1.53 (95%CI: 0.88-2.66) to 10.3 (2.83-37.5), high TMA R enhanced it from 1.31 (0.67-2.56) to 24.3 (6.57-89.5) and TMA accumulation enhanced it from 1.42 (0.72-2.77) to 25.5 (6.80-95.7), with all additive interactions being significant. However, the interactions between high ceramide 18 and TMAO metabolites were not significant., Conclusions: High ceramides 18:0, 18:1 and low ceramide 24:0 in early pregnancy were associated with increased GDM risk. Notably, TMA accumulation greatly amplified the risk-promoting effect of low ceramide 24:0 for GDM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Previous analysis showed that passive smoking and overweight were associated with an increased risk of gestational diabetes mellitus (GDM) in a synergistic manner, while GDM increased the risk of macrosomia/large for gestational age (LGA). This study aimed to examine any interactive effects between passive smoking and overweight/obesity on risk of macrosomia/LGA., Methods: From 2010 to 2012, 22,302 pregnant women registered for pregnancy at a primary hospital in Tianjin, China. Data were collected longitudinally; that is, from their first antenatal care visit, at the glucose challenge test (GCT) time (24-28 weeks of gestation) and at delivery. Passive smoking was self-reported. Macrosomia was defined as birth weight ≥4,000 g. Binary logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction was used to test the synergistic effect., Results: Passive smokers accounted for 57.4% of women (n = 8,230). Using nonpassive smoking and prepregnancy body mass index (BMI) <24.0 kg/m2 as the reference, the adjusted ORs of overweight alone and passive smoking alone for macrosomia were 2.39 (95% CI: 2.11-2.71) and 1.17 (95% CI: 1.04-1.32). Copresence of passive smoking and prepregnancy BMI ≥24.0 kg/m2 increased the OR to 2.70 (95% CI: 2.28-3.20), with a significant additive interaction. After further adjustment for GDM or GCT, the OR of copresence of both risk factors was slightly attenuated to 2.52 (2.13-3.00) and 2.51 (2.11-2.98), with significant additive interaction. However, the additive interaction between prepregnancy overweight/obesity and passive smoking for LGA was nonsignificant., Conclusions: Prepregnancy overweight/obesity was associated with an increased risk of macrosomia in Chinese women synergistically with passive smoking during pregnancy, and most of the association was not modified by hyperglycemia during pregnancy., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Objective: The purpose of this study was to estimate the associations of genetically determined maternal blood glucose levels with obesity-related outcomes among children from pregnancies with and without gestational diabetes mellitus (GDM)., Methods: A total of 1,114 mothers with (N = 560) and without (N = 554) GDM and their children were included in the present study. A maternal genetic risk score (GRS) for blood glucose was constructed on the basis of 17 single-nucleotide polymorphisms identified from a recent genome-wide association study., Results: It was found that maternal GRS for blood glucose showed different associations with offspring risk of overweight and obesity, as well as adiposity measures (all P for interaction  < 0.05). Among mothers without GDM, genetically determined maternal blood glucose levels were associated with an 89% higher risk of overweight in their children (95% CI: 42%-152% per SD increase in GRS, P = 1.40 × 10 -5 ) and a 120% higher risk of obesity (44%-235%, P = 2.61 × 10 -4 ) after adjustment for covariates. In addition, higher maternal GRS for blood glucose was associated with children's increased obesity-related traits (all P < 0.05). However, no significant associations were observed among children of mothers with GDM., Conclusions: This study indicates that GDM status may modify the relation between genetically determined glucose levels and obesity risk among children., (© 2020 The Obesity Society.)