Serum CD44 levels in early pregnancy and its genetic variants for increased risk of gestational diabetes mellitus in Chinese pregnant women.

This study aimed to explore associations of serum cluster of differentiation 44 (CD44) level 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 10th gestational weeks). Binary conditional logistic regressions were performed to examine associations of serum CD44 level and its genetic variants with increased risk of GDM. In this study, we found that serum CD44 level in early pregnancy was associated with GDM risk in a U-shaped manner. High serum CD44 level 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 level, 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 level 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 function plays a causal role in occurrence of GDM. Specifically, it remains unknown whether CD44 in early pregnancy can predict the later occurrence of GDM. In this study, we found that high serum CD44 and its genetic variants in early pregnancy 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 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.

Amygdala and cognitive impairment in cerebral small vessel disease: structural, functional, and metabolic changes.

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.

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.

Long-term risk of overweight in offspring of Chinese women with gestational diabetes defined by IADPSG's but not by WHO's criteria.

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.

Adverse birth outcomes and childhood overweight at age of 3-8 years in a prospective cohort study in Tianjin, China.

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.

Low C0 and normal C16 and C18:1 masking the diagnosis of carnitine palmitoyltransferase II deficiency including a novel CPT2 variant: A case report.

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.

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.

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.

High-frequency ultrasound imaging to assess fetal pancreas: a promising application.

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 (R2＝0.87, 0.94, 0.92, 0.92,0.96, and 0.92) and AC (R2＝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.

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.

Serum mannan-binding lectin-associated serine proteases in early pregnancy for gestational diabetes in Chinese pregnant women.

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.

Serum Sulfur-Containing Amino Acids and Risk of Maternal Gestational Diabetes and Adverse Growth Patterns in Offspring.

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.

Identifying optimal ranges of weight gain at the end of the second trimester result from a population-based cohort study.

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.

Circulating hyaluronidase in early pregnancy and increased risk of gestational diabetes in Chinese pregnant women: A nested case control study.

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 10th 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.

Cleft palate in fetuses: feasibility of early diagnosis by Crystal and Realistic Vue rendering 3D ultrasound technology in the first trimester.

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.

Maternal weight and its association with risk of overweight in offspring: a trajectory analysis from a birth cohort in China.

BACKGROUND: Most studies on the association of maternal pregnancy weight with offspring weight trajectory have a short follow-up time. This study aimed to explore the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) with childhood weight trajectories in a 7-year birth cohort. METHODS: A total of 946 mother-child pairs (467 boys and 479 girls) from a longitudinal birth cohort in Tianjin City, China, were included in this study, ranging from pregnancy to offspring at 7 years. The outcome variable was defined as overweight or not overweight in offspring at the last round. A group-based trajectory model was applied to identify childhood BMI trajectory groups. RESULTS: Five discrete BMI trajectory groups were identified and characterized as constant underweight (25.2%), constant normal weight (42.8%), and high or increasing trajectory [at risk of overweight (16.9%), progressive overweight (11.0%) and progressive obesity (4.1%)]. Maternal prepregnancy overweight was associated with 1.72 (95% CI 1.14-2.60, P = 0.01) to 4.02 (95% CI 1.94-8.36, P < 0.001) times the risk of all high or increasing trajectory groups, and excessive GWG was related to groups at risk of overweight [relative risk ratio (RRR) 2.09, 95% CI 1.27-3.46, P = 0.004] and progressive obesity (RRR 3.33, 95% CI 1.13-9.79, P = 0.029). Children in all high or increasing trajectory groups were associated with greater overweight risk at the last round [risk ratios (RRs) ranged from 3.54 (95% CI 2.53-4.95, P < 0.001) to 6.18 (95% CI 4.05-9.42, P < 0.001)]. CONCLUSION: Maternal prepregnancy overweight and excessive gestational weight gain were associated with increasing or high-level childhood body mass index trajectories as well as a greater risk of overweight at 7 years.

Aromatic Amino Acids and Their Interactions with Gut Microbiota-Related Metabolites for Risk of Gestational Diabetes: A Prospective Nested Case-Control Study in a Chinese Cohort.

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.

Early prenatal exposure to air pollutants and congenital heart disease: a nested case-control study.

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/m3 increase of gestational exposure to PM2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1st-2nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O3 exposure during the 1st week and SO2 exposure during 6th-7th weeks in the first trimester, while no significant findings for other air pollutants. CONCLUSIONS: This study highlighted that gestational exposure to PM2.5, O3, and SO2 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.