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Key findings of the work: Maternal frequent intake of a sufficient amount (>3 times per week, or >50 g day−1) of yogurt in late pregnancy may benefit offspring by decreasing the risk of infantile eczema.

Background: To explore the correlations of cofilin1 (CFL1) and phosphorylation level of locus serine residue at position 3 (Ser3) with the sensitivity of elderly patients with non-small cell lung cancer (NSCLC) to radiotherapy. Methods: A total of 102 eligible patients treated from June 2013 to April 2015 were selected. The cases of complete remission and partial remission were included into radiotherapy-sensitive group (n=55), while those of stable disease and progressive disease were enrolled into radiotherapy-resistant group (n=47). Before treatment, tissues were collected to detect the expressions of CFL1 and CFL1 (phospho S3) by immunohistochemistry. The survival time and rate were recorded during follow-up. Results: Compared with the radiotherapy-sensitive group, the radiotherapy-resistant group had advanced tumor-node-metastasis (TNM) stage and higher lymph node metastasis rate (P=0.000, 0.000). Compared with the tissues with negative CFL1 expression, the tissues with positive CFL1 expression had advanced TNM stage and higher lymph node metastasis rate (P=0.013, 0.000). The positive expression rate of CFL1 in the radiotherapy-resistant group was higher than that of the radiotherapy-sensitive group, whereas the positive expression rate of CFL1 (phospho S3) in the former was lower (P=0.000, 0.000). Lymph node metastasis, high CFL1 expression, and low CFL1 (phospho S3) expression were independent predictors for resistance to radiotherapy (P=0.001, 0.006, 0.003). In the radiotherapy-sensitive group, the patients with negative CFL1 expression and positive CFL1 (phospho S3) expression had long progression-free survival and high 5-year survival rate (P=0.000, 0.000). Conclusion: The sensitivity to radiotherapy of elderly NSCLC patients is correlated negatively with CFL1 and positively with phosphorylation at locus Ser3. CFL1 and phosphorylation at locus Ser3 are independent predictors for sensitivity to radiotherapy.

Maternal gestational weight gain (GWG) is an important determinant of infant birth weight, and having adequate total GWG has been widely recommended. However, the association of timing of GWG with birth weight remains controversial. We aimed to evaluate this association, especially among women with adequate total GWG. In a prospective cohort study, pregnant women’s weight was routinely measured during pregnancy, and their GWG was calculated for the ten intervals: the first 13, 14–18, 19–23, 24–28, 29–30, 31–32, 33–34, 35–36, 37–38 and 39–40 weeks. Birth weight was measured, and small-for-gestational-age (SGA) and large-for-gestational-age were assessed. Generalized linear and Poisson models were used to evaluate the associations of GWG with birth weight and its outcomes after multivariate adjustment, respectively. Of the 5049 women, increased GWG in the first 30 weeks was associated with increased birth weight for male infants, and increased GWG in the first 28 weeks was associated with increased birth weight for females. Among 1713 women with adequate total GWG, increased GWG percent between 14 and 23 weeks was associated with increased birth weight. Moreover, inadequate GWG between 14 and 23 weeks, compared with the adequate GWG, was associated with an increased risk of SGA (43 (13·7 %) v. 42 (7·2 %); relative risk 1·83, 95 % CI 1·21, 2·76). Timing of GWG may influence infant birth weight differentially, and women with inadequate GWG between 14 and 23 weeks may be at higher risk of delivering SGA infants, despite having adequate total GWG.

Objective To investigate the association of the maternal serum albumin (MAlb) level with fetal growth and fetal growth restriction (FGR) risk in term-born singletons. Design Prospective cohort study. Setting Four hospital maternity units of the Tongji Maternal and Child Health Cohort study initiated from September 2013 to April 2016 at Wuhan City, in central China. Patient(s) A total of 3,065 mother–offspring pairs. Intervention(s) None. Main Outcome Measure(s) Fetal growth was evaluated by birth weight (BW) and birth length. Fetal growth restriction was defined as BW below the 10th percentile. Result(s) All MAlb levels were within the upper limit of normal. After adjustment for liver function parameters, inflammatory indicators, and others, a reverse U-shaped relationship between MAlb and fetal growth was observed. Specifically, BW increased significantly with an increasing MAlb level when the MAlb level was 36.1 g/L (per g/L: β = −15.1; 95% CI, −21.2, −8.9). There was a similar association between MAlb and birth length. Furthermore, the adjusted odd ratios of FGR across increasing tertiles of the MAlb levels were 1.0 (reference), 1.1 (0.7, 1.8), and 1.7 (1.0, 2.6). Conclusion(s) There was a reverse U-shaped association between MAlb and fetal growth. A higher MAlb level was associated with an increased risk of FGR. Clinical Trial Registration Number NCT03099837.

Manganese (Mn) intake has been found to be linked with risk of type 2 diabetes. However, the role of Mn in the development of gestational diabetes mellitus (GDM) remains to be investigated. This prospective study included pregnant women from the Tongji Maternal and Child Health Cohort. A total of 2327 participants with plasma specimens before 20 weeks were included. Among the pregnant women, 9.7% (225/2327) were diagnosed with GDM. After adjustment, pregnant women with the third and highest quartile of plasma Mn levels had 1.31-fold (RR, 2.31 [1.48, 3.61]) and 2.35-fold (RR, 3.35 [2.17, 5.17]) increased risk of GDM compared with those with the lowest quartile. A 1 standard deviation increment of ln-transformed plasma Mn levels (0.53 μg/L) was related to elevated risks of GDM with RRs of 1.28 [1.17, 1.40]. The positive associations between Mn and GDM remained consistent in all the subgroups. The weighted quantile sum index was significantly related to GDM (RR, 1.60 [1.37, 1.86]). The contribution of Mn (58.69%) to the metal mixture index was the highest related to GDM. Higher plasma Mn levels were found to be linked with elevated fasting and 2 h post-load blood glucose. This study revealed relationships of higher plasma Mn levels in early pregnancy and increased risk of GDM, suggesting that though essential, excess Mn in the body might be a potential important risk factor for GDM.

We prospectively evaluated the association between low-carbohydrate-diet (LCD) score during pregnancy and the risk of allergic diseases in infants up to 2 years.Participants were from a prospective mother-offspring cohort study in Wuhan, China. LCD score was calculated according to the percentage of dietary energy intake from carbohydrate, protein, and fat assessed in late pregnancy using validated food frequency questionnaires. Allergic diseases, including immunoglobulin E (IgE)-mediated allergic diseases, allergic contact dermatitis, and food allergy, were recorded at 3, 6, 12, and 24 months postpartum follow-up. Poisson regression models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs).Among 1636 mother-infant pairs included in the present analysis, 230 infants (14.1%) with IgE-mediated allergic diseases, 77 (4.7%) with allergic contact dermatitis, and 488 (29.8%) with food allergy were, respectively, reported. Independent of total energy intake and other potential confounders, both the lowest quintile (RR, 1.77; 95% CI, 1.13-2.77) and the highest quintile (RR, 1.72; 95% CI, 1.22-2.63), were associated with the risk of IgE-mediated allergic diseases compared with the middle quintile. Among high-carbohydrate-diet pregnant women, substituting 5% of energy from either protein or fat for carbohydrate was associated with a lower risk of IgE-mediated allergic diseases. While among low-carbohydrate-diet pregnant women, substituting 5% of energy from carbohydrate, especially high-quality carbohydrate, for fat was associated with a lower risk of IgE-mediated allergic diseases.Maternal low carbohydrate-high protein and fat, and high carbohydrate-low protein and fat diet were both associated with an increased risk of allergic diseases in the infants up to 2 years. This study may provide an intervention strategy for allergy prevention in early childhood.

Summary Background & aims Emerging evidence has shown the inverse association between dietary polyphenols intake and type 2 diabetes mellitus risk, however, few studies focus on the prospective effects of polyphenols on gestational diabetes mellitus (GDM). Thus, the aim was to evaluate whether higher polyphenols intake and the intake from fruits and vegetables was correlated to a lower risk of GDM. Methods Dietary intake of polyphenols of women with a singleton pregnancy and without any history of diabetes were obtained by a validated food frequency questionnaire from Tongji Maternal and Child Health Cohort study. Oral glucose tolerance tests were conducted at 24–28 weeks to screen for GDM. Logistic regression models were used to evaluate the association between dietary intake of polyphenols, and the results were presented as odds ratios (ORs) with 95% confidence interval (CIs). Generalized linear models were adopted to determine the association of polyphenols intake with blood glucose concentrations, and the results were presented as coefficients (β) with 95% CIs. Results 185 (8.3%) of 2231 pregnant women were diagnosed with GDM. The intake of total polyphenols was 319.9 (217.8–427.0) mg/d, and the intake from fruits and vegetables was 201.6 (115.3–281.8) mg/d and 63.2 (41.1–92.7) mg/d, respectively. Compared with the lowest quartile, the adjusted ORs (95% CIs) of GDM risk for women with the highest quartile of total polyphenols and flavonoids intake was 0.55 (0.30, 0.99), and 0.57 (0.32, 0.99). The adjusted ORs (95% CIs) of GDM risk was 0.55 0.51 (0.30, 0.87) (P for trend = 0.017) for polyphenols from fruits, 0.58 (0.34, 0.99) (P for trend = 0.038) for flavonoids from fruits, and 0.62 (0.38, 1.00) (P for trend = 0.065) for anthocyanidins from fruits comparing the highest versus lowest quartile. In addition, each 100 mg increase of total polyphenols and polyphenols from fruits was associated with 0.054 (0.008, 0.096) (P = 0.021) and 0.061 (0.012, 0.109) (P = 0.015) decrease in 2-h post-load blood glucose. No significant association was found between total polyphenols from vegetables intake and the risk of GDM. Conclusions Higher dietary intake of total polyphenols and flavonoids and the intake from fruits was associated with lower GDM risk. This study was registered at clinicaltrials.gov as NCT03099837.

Purpose: To evaluate the clinical implication of metabolic score for insulin resistance (METS-IR) during early midpregnancy on subsequent risk of gestational diabetes mellitus (GDM) in Chinese women.Methods: A total of 1747 pregnant women without pre-existing diabetes from the Tongji Maternal and Child Health Cohort (TMCHC) were included in this analysis. Blood glucose and lipid profiles (triglyceride [TG], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were measured during 15-19 weeks and 75-g 2-h oral glucose tolerance test was conducted during 24-28 weeks to diagnose GDM. METS-IR was calculated by a modified formula which originally as follows: Ln(2×FPG[mg/dl]+TG[mg/dl])×BMI[kg/m2] /Ln(HDL-C[mg/dl]).Results: The median (interquartile range) of age was 28 (26-30) years, and 19.7% of them were underweight and 11.7% were overweight/obese before pregnancy. The overall incidence of GDM was 9.4% and median (interquartile range) of METS-IR was 27.36 (24.57-31.07). The median METS-IR was significantly increased with the increasing pre-pregnancy BMI categories (22.92 vs 27.72 vs 35.55, P＜0.001). Based on quartiles of METS-IR in women with normal pre-pregnancy BMI, participants were classified into 4 groups. Compared with women in the lowest quartile of METS-IR (＜25.52) , the adjusted RRs (95% CIs) of GDM were 2.15 (1.23-3.74), 1.34 (0.72-2.49), and 3.63 (2.22-5.95) for women in quartile 2 (25.52-27.71), quartile 3 (27.72-30.39) and quartile 4 (≥30.40) after adjusting potential confounds. In addition, a significant increase risk of GDM (adjusted RR [95% CI]: 2.55 [1.83-3.55]) was found in women within the highest quartile of METS-IR (≥30.40) compared to the other 3 lower quartiles (＜30.40).Conclusions: Women with METS-IR (≥30.40) during early midpregnancy were more likely to develop GDM, thus the index might be a reliable early indicator for identifying women at high risk of GDM.

Background The evidence on the relationship between diet diversity in early life and allergic outcomes was few and inconsistent. We sought to determine the association of food diversity in the first year of life with allergic outcomes in the second year. Methods 2251 mother-infant pairs from Tongji Maternal and Child Health Cohort (TMCHC) were involved in the study. Information on complementary foods introduction was obtained by telephone interview at 6- and 12-months postpartum follow-up. Doctor-diagnosed any allergic diseases in the second year were recorded at 2 years postpartum follow-up. Food allergies in infancy were assessed and self-reported by mothers at each postpartum follow-up. Multivariable logistic regression was used to examine the effect of food diversity at 6 and 12 months of age on later allergic diseases and food allergy. Results 135(6.0%) infants reported allergic diseases at between 1 and 2 years of age. Independent of food allergy history of infants and other potential confounders, less food diversity at 6 months of age was associated with increased risk of later allergic diseases (OR 2.17, 95%CI 1.04-4.50 for 0 vs. 3-6 food groups). By 12 months of age, significant inverse associations with later allergic diseases (OR 2.35, 95%CI 1.03-5.32 for 1-5 vs. 8-11 food groups, and OR 1.98, 95%CI 1.16-3.37 for 6-7 vs. 8-11 food groups) and food allergy (OR 2.10, 95%CI 1.29-3.42 for 1-5 vs. 8-11 food groups) were observed. Children with higher food diversity in both periods had the lowest risk of allergic diseases during the second year of life. Conclusions A more diverse diet within the first year of life was associated with reduced risk of allergic diseases at 1-2 years of age. Introducing higher diversity of foods from 6 to 12 months of age might be an effective strategy to improve the allergy outcomes of infants in later life.

The associations among maternal diet, birth weight, and gestational weight gain are still inconclusive. This study aimed to investigate the associations between maternal dietary patterns and birth weight, and further explore whether GWG mediates these associations. A total of 3,334 pregnant women who completed a validated semi-quantitative food frequency questionnaire from the Tongji Maternal and Child Health Cohort were included. Dietary patterns were extracted by using principal component analysis. Regression models and mediation analyses were performed to explore the associations between dietary patterns and birth weight and the effects of GWG on these associations. Five dietary patterns were identified: “Beans-vegetables,” “Fish-meat-eggs,” “Nuts-whole grains,” “Organ-poultry-seafood” and “Rice-wheat-fruits.” Only women following the “Beans-vegetables” pattern had heavier newborns (β = 47.39; 95% CI: 12.25, 82.54). Women following the “Beans-vegetables” pattern had significantly lower GWG (β = −0.7; 95% CI: −1.15, −0.25) and had a 16% lower risk of excessive GWG and 11% higher odd of adequate GWG. The association between the “Beans-vegetables” pattern and birth weight was negatively mediated by GWG. A dietary pattern enriched in beans and vegetables is beneficial for effectively controlling GWG and increasing birth weight. GWG serves.Clinical Trial Registry: This trial was registered at ClinicalTrials.gov (NCT03099837).

Objective Fresh fruit intake has been found to be associated with risk of gestational diabetes mellitus (GDM); however, the evidence is limited and the findings are inconsistent. We aimed to assess the association of fresh fruit intake by fruit subgroups based on their glycemic index (GI) and glycemic load (GL) values and GDM incidence in Chinese pregnant women. Methods We included 3300 eligible women from the Tongji Maternal and Child Health Cohort. Dietary intakes were assessed by using a validated semiquantitative food frequency questionnaire. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test. In the adjusted logistic regression model, odds ratios and 95% confidence intervals for GDM were computed for the highest compared with lowest quintiles of fruit intake. Results GDM occurred in 378 (11.5%) of 3300 pregnant women. The average fresh fruit consumption was 381.7 g/d. The adjusted odds ratios (95% confidence intervals) for GDM from the lowest to highest quintile of whole fruit consumption were 1.00 (referent), 0.80 (0.56, 1.12), 0.74 (0.52, 1.05), 0.63 (0.44, 0.92), and 0.41 (0.27, 0.62), respectively; Ptrend Conclusions Our findings suggested an inverse association of fresh fruit intake with the risk of GDM in Chinese pregnant women. In women with GDM risk, low GI and GL fresh fruit consumption should be privileged versus those with high GI and GL.

Background Maternal iodine status has been suggested to affect birth outcomes. Few studies have focused on its effects on fetal growth during pregnancy. Objective This study aimed to assess maternal iodine status during early pregnancy and further examine the relation between maternal iodine status and fetal growth. Methods A total of 2087 singleton-pregnant women participating in the Tongji Maternal and Child Health Cohort study were involved. Urinary iodine concentration (UIC) and creatinine concentration were measured in spot urine samples collected in early pregnancy (

Background: Compliance with dietary guidelines among pregnant women can positively influence not only their own health but also the health of their babies. Measuring the compliance requires professional skills in nutrition and dietary counseling. In China, few simple and effective techniques assess dietary quality among pregnant women, especially in rural areas. We aimed to establish a new simple and effective assessment technique, the “Chinese Dietary Guidelines Compliance Index for Pregnant Women (CDGCI-PW)” and assess the association between maternal dietary compliance and risks of pregnancy complications. Methods: The CDGCI-PW consists of 13 main components which were based on the 2016 edition of the Chinese dietary guidelines for pregnant women. Each component was assigned a different score range, and the overall score ranged from 0 to 100 points. The Tongji Maternal and Child Health Cohort study (from September 2013 to May 2016) was a prospective cohort study designed to examine maternal dietary and lifestyle effects on the health of pregnant women and their offspring. The maternal diet during the second trimester was compared with the corresponding recommended intake of the Chinese balanced dietary pagoda for pregnant women to verify their compliance with dietary guidelines. The association between maternal dietary quality and risks of pregnancy complications was estimated by regression analysis. Receiver operating characteristic (ROC) curves were constructed to identify the optimal cut-off values of CDGCI-PW for gestational hypertension and gestational diabetes mellitus (GDM). Results: Among the 2708 pregnant women, 1489 were eventually followed up. The mean CDGCI-PW score was 74.1 (standard deviation (SD) 7.5) in the second trimester. The majority of foods showed the following trend: the higher the CDGCI-PW score, the higher the proportion of pregnant women who reported food intake within the recommended range. Moreover, a higher maternal CDGCI-PW score was significantly associated with lower risks of gestational hypertension [odds ratio (OR) (95% confidence interval [(CI): 0.30 (0.20, 0.37)] and GDM [OR (95% CI): 0.38 (0.31, 0.48)]. The optimal CDGCI-PW cut-off value for gestational hypertension was ≥68.5 (sensitivity 82%, specificity: 61%, area under the ROC curve, AUC = 0.743), and the optimal CDGCI-PW cut-off score for GDM was ≥75.5 (sensitivity 43%, specificity: 81%, area under the ROC curve, AUC = 0.714). Conclusions: The CDGCI-PW is a simple and useful technique that assesses maternal diet quality during pregnancy, while adherence to the CDGCI-PW is associated with a lower risk of gestational hypertension and GDM.

The high overall plant-based diet index (PDI) is considered to protect against type 2 diabetes in the general population. However, whether the PDI affects gestational diabetes mellitus (GDM) risk among pregnant women is still unclear. We evaluated the association between PDI and GDM risk based on a Chinese large prospective cohort – the Tongji Maternal and Child Health Cohort. Dietary data were collected at 13–28 weeks of pregnancy by a validated semi-quantitative FFQ. The PDI was obtained by assigning plant food groups positive scores while assigning animal food groups reverse scores. GDM was diagnosed by a 75 g 2-h oral glucose tolerance test at 24–28 weeks of gestation. Logistic regression models were fitted to estimate OR of GDM, with associated 95 % CI, comparing women in different PDI quartiles. Among the total 2099 participants, 169 (8·1 %) were diagnosed with GDM. The PDI ranged from 21·0 to 52·0 with a median of 36·0 (interquartile range (IQR) 33·0–39·0). After adjusting for social-demographic characteristics and lifestyle factors etc., the participants with the highest quartile of PDI were associated with 57 % reduced odds of GDM compared with women in the lowest quartile of PDI (adjusted OR 0·43; 95 % CI 0·24, 0·77; Pfor trend = 0·005). An IQR increment in PDI was associated with 29 % decreased odds of GDM (adjusted OR 0·71; 95 % CI 0·56, 0·90). Findings suggest that adopting a plant-based diet during pregnancy could reduce GDM risk among Chinese women, which may be valuable for dietary counselling during pregnancy.

Background The association between iron supplementation and gestational diabetes mellitus (GDM) is still inconclusive, and this association has not been extensively studied in relation to plasma ferritin in the early second trimester. Objectives We aimed to prospectively examine the independent and combined associations of plasma ferritin concentrations and iron supplement use with GDM. Methods We studied 2117 women from the Tongji Maternal and Child Health Cohort in Wuhan, China. Plasma ferritin around 16 weeks' gestation was measured by ELISA kits and information on iron supplement use was collected by questionnaires. GDM was diagnosed by a 75-g oral-glucose-tolerance test (OGTT) at 24-28 weeks' gestation. A log-Poisson regression model was used to estimate the RR of GDM associated with plasma ferritin and iron supplementation. Results The median and IQR of plasma ferritin was 52.1 (29.6-89.9) ng/mL, and 863 (40.8%) participants reported use of iron supplements during the second trimester. A total of 219 (10.3%) participants developed GDM. Adjusted RRs (95% CIs) for GDM across increasing quartiles of plasma ferritin were 1.00 (reference), 2.14 (1.37, 3.34), 2.03 (1.30, 3.19), and 2.72 (1.76, 4.21), respectively. After adjustment, supplemental iron ≥60 mg/d during the second trimester was associated with an increased risk of GDM compared with nonusers (RR: 1.37; 95% CI: 1.02, 1.84). Conclusions Both elevated plasma ferritin concentrations in the early second trimester and use of ≥60 mg/d of supplemental iron during pregnancy are independently associated with increased risk of GDM. Further clinical trials with precision nutrition approaches considering both baseline iron status and supplement use are needed to evaluate the benefits and risks of iron supplementation during pregnancy.

Associations between environmental tobacco smoke (ETS) and the risk of adverse birth outcomes may be confounded. We aimed to clarify the associations of ETS before and during pregnancy with the risk of adverse birth outcomes and determine whether the associations were modified by key potential confounders. A total of 7147 non-smoking mothers from the Tongji Maternal and Child Health Cohort (TMCHC) in Wuhan, China, were included in the final analyses. ETS status was self-reported by pregnant women at their first antenatal care visit before 16 gestational weeks. Information on birth outcomes was extracted from delivery records. Poisson regression was used to identify the association between ETS before and during pregnancy and the risk of adverse birth outcomes. Exposures to ETS before and during pregnancy were reported by 645 (9.0%) and 464 (6.5%) mothers, respectively. Compared with no ETS, continued ETS during pregnancy was associated with an increased risk of preterm birth (PTB) (RR: 1.55, 95% CI: 1.07, 2.25) after adjustment for potential confounders. The association remained consistent in medically indicated PTB and late PTB. The risk of PTB associated with continued ETS during pregnancy was significantly increased in mothers more educated (P for interaction < 0.05). However, the increased risk of low birth weight (LBW) or small for gestational age (SGA) births by ETS during pregnancy was not observed. Exposure to ETS during pregnancy was associated with a higher risk of PTB, but not LBW or SGA births in a Chinese birth cohort.

Current results regarding the effect of folic acid (FA) supplement use on gestational hypertension (GH) and preeclampsia are limited and inconsistent. We aimed to investigate whether FA supplement use was associated with GH and preeclampsia. Participants from the Tongji Maternal and Child Health Cohort with information on periconceptional FA supplement use and diagnosis of GH/preeclampsia were included (n=4853). Robust Poisson regression was used to assess the association of FA supplement use and GH and preeclampsia. Among the 4853 participants in this study, 1161 (23.9%) and 161 (3.3%) women were diagnosed with GH and preeclampsia, respectively. The risk ratio of developing GH was higher in women who used ≥800 µg/d FA supplement from prepregnancy through midpregnancy than nonusers (risk ratio, 1.33 [1.08–1.65]). After adjusting for social-demographic, reproductive, lifestyle factors, family history of hypertension, other supplement use, and gestational weight gain, the adverse association remained significant (risk ratio, 1.32 [1.06–1.64]). Restricting the analysis among women with normal weight, without family history of hypertension, and without gestational diabetes mellitus, the positive FA-GH association still existed. We did not find any significant association between FA supplement use and preeclampsia regardless of adjustment. High-dose (≥800 µg/d) FA supplement use from prepregnancy through midpregnancy was associated with increased risk of GH. Attention should be given to avoid the potential risk of GH due to inappropriate FA supplement use in women who are planning or capable of pregnancy.

Background: A growing number of epidemiologic studies have estimated associations between type 2 diabetes mellitus and exposure to metals. However, studies on the associations of internal assessments of metal exposure and gestational diabetes mellitus (GDM) are limited in scope and have inconsistent outcomes. Objectives: This investigation aimed to explore the associations between urinary nickel (Ni), arsenic (As), cadmium (Cd), antimony (Sb), cobalt (Co), or vanadium (V) in early pregnancy and the subsequent risk of GDM in Chinese pregnant women. Methods: The study population included 2090 women with singleton pregnancy from the Tongji Maternal and Child Health Cohort (TMCHC). Urine samples were collected before 20 gestational weeks, and an oral glucose tolerance test (OGTT) was conducted at 24–28 gestational weeks to diagnose GDM. The concentrations of urinary metals were measured using inductively coupled plasma mass spectrometry (ICP-MS) and were corrected for urinary creatinine. The associations between the risk of GDM and urinary metals were assessed using Poisson regression with a robust error variance with generalized estimating equations (GEE) models and Bayesian kernel machine regression (BKMR). Results: A total of 241 participants (11.53%) were diagnosed with GDM. Five metals (Ni, As, Sb, Co, and V) were found significantly and positively associated with GDM based on single-metal models. In multiple-metal models, for each unit increase of ln-transformed urinary Ni or Sb, the risk of GDM increased 18% [relative risk (RR):1.18, 95%confidence interval (CI): 1.00, 1.38 or RR: 1.18, 95%CI: 1.00, 1.39, respectively]. The BKMR analysis revealed a statistically significant and positive joint effect of the six metals on the risk of GDM, when the urinary levels of the six metals were all above the 55th percentile, compared to the median levels. The effect of metal Ni was significant when the concentrations of the other metals were all fixed at their 25th percentile, and metal Sb displayed a significant and positive effect when all the other metals were fixed at 25th, 50th, and 75th percentiles. Conclusions: To the best of our knowledge, this study is the first to demonstrate that increased concentrations of urinary Ni in early pregnancy are associated with an elevated risk of GDM, either evaluated individually or as a metal mixture. All six metals mixed exposure was positively associated with the risk of GDM, while Sb and Ni were demonstrated more important effects than the other four metals in the mixture. Keywords: GDM, Urinary metals, Single-metal models, Multiple-metal models, BKMR models

To assess the longitudinal associations between maternal total bile acid (TBA) levels during early mid-pregnancy and the subsequent risk of gestational diabetes mellitus (GDM). In a prospective cohort study, pregnant women who were enrolled prior to gestational week 16 were followed until delivery. TBA levels were tested during weeks 14–18 of gestation. Using logistic regression, we analyzed the associations between quartiles of TBA and GDM based on a 75-g oral glucose tolerance test (OGTT) at 24–28 gestational weeks. The GDM rate was 7.9% (114/1441). The mean TBA level was higher in women with GDM than in those without GDM (2.1 ± 2.0 vs 1.5 ± 1.0 µmol/L, P = 0.000). The highest TBA level quartile (2.1–10.7 µmol/L) had a 1.78-fold (95% CI 1.01, 3.14) increased risk of GDM compared with that of the lowest quartile (0.0–0.8 µmol/L) after adjusting for pre-pregnancy body mass index (BMI), gestational, age at TBA test and other confounders. High TBA levels were involved in the fasting glucose level rather than that at 1 h and 2 h after OGTT in all participants. Pregnant women with higher serum TBA levels during early mid-pregnancy have a higher risk of developing GDM. TBA may be a new risk factor for GDM.

Objective Information is limited regarding the possible relationship between diet-related inflammation and the risk of gestational diabetes mellitus (GDM). This study investigated the association between the inflammatory potential of the diet, measured by the dietary inflammatory index (DII), and GDM risk in pregnant Chinese women. Methods This study included 2639 eligible women from the Tongji Maternal and Child Health Cohort. Dietary intake was assessed by a validated semiquantitative food frequency questionnaire and was used to calculate the DII score. The DII was then validated using C-reactive protein measurements in a subsample of 133 pregnant women. GDM diagnoses were collected from medical records based on the results of a 75 g oral glucose tolerance test at 24 to 28 wk gestation. Multivariable-adjusted logistic regression models were performed to estimate the odds ratios (ORs) for GDM risk by DII score, modeled continuously and in tertiles. Results Of the 2639 participants, 13.1% were diagnosed with GDM. DII scores ranged from –4.45 to 3.15 and were positively associated with C-reactive protein (adjusted β : 1.28, 95% confidence interval [CI]: 0.16, 2.40; P trend = 0.023) when comparing DII tertile 3 (most pro-inflammatory) to tertile 1 (most anti-inflammatory). A significant and positive association was observed between DII scores and GDM risk (adjusted OR: 1.43; 95% CI: 1.05, 1.95; P trend = 0.022) comparing the highest versus lowest tertiles. The stratified analysis showed that this association was stronger in pregnant women who were overweight or obese before pregnancy (adjusted OR: 2.20; 95% CI: 1.03, 4.69). Conclusions These findings suggest that a higher DII score, corresponding to a more proinflammatory diet, is associated with a higher risk of GDM, particularly in pregnant women who were overweight or obese before pregnancy.

Aims Iron supplementation has been recommended for healthy pregnancy, but concerns have been raised regarding the potential adverse effects. We sought to examine the impact of periconceptional iron supplement use on subsequent gestational diabetes mellitus (GDM) risk. Methods Participants (N = 5101) with information on periconceptional micronutrient supplementation and diagnosis of GDM were involved. Information on iron supplementation and general characteristics were collected at enrollment and follow-up visits. GDM was diagnosed by oral glucose tolerance tests (OGTT) conducted at 24–28 weeks of gestation. Robust Poisson regression model was used to estimate the relative risks (RRs) and 95% confidence intervals (CI) for the effect of iron supplement use on GDM. Results 10.5% of the participants were diagnosed with GDM and the incidence was significantly higher in users with iron >30 mg/d for more than 3 months (Iron >30-L) than in nonusers. Adjusted RRs (95% CI) were 1.53 (1.21, 1.93) in Iron >30-L group, 1.14 (0.80, 1.61) in users with iron >30 mg/d for 30-S) and 1.15 (0.86, 1.54) in users with iron ≤30 mg/d for any duration (Iron ≤30) respectively, compared to nonusers. This link in Iron >30-L group was even stronger (adjusted RR: 1.70, 95% CI: 1.25, 2.31) when restricting the analysis among primiparous and iron-replete participants without family history of diabetes. There were no significant differences in birth outcomes among groups. Conclusions Periconceptional iron supplementation >30 mg/d for long-term was associated with increased GDM risk. The need and safety of prophylactic iron supplement in iron-replete pregnant women should be reconsidered.

OBJECTIVES: Concerns relative to excessive iron intake are raised when high iron status exposure has been linked in observational studies to a greater risk of gestational diabetes mellitus (GDM). We aimed to examine the association between iron intake during pregnancy and GDM risk in Chinese women. METHODS: The study included 2174 pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC), a prospective cohort in Wuhan, China. Iron intakes from food and supplementation prior to GDM diagnosis were assessed using a validated food frequency questionnaire (FFQ) and a detailed supplement questionnaire collected at 13–28 weeks of gestation. GDM was ascertained by an oral glucose tolerance test at 24–28 weeks of gestation. Odd ratios (ORs) of GDM in relation to categories of iron intake (i.e., quartiles of total and food iron intake, categories of supplemental iron intake [0, 0–30, >30 mg/day]) were estimated using logistic regression models, with adjustment for demographic, dietary and lifestyle factors. RESULTS: A total of 242 (11.1%) women were diagnosed with GDM. The adjusted ORs (95% CIs) for the risk of GDM associated with the higher quartiles compared with the lowest quartile of total iron intake were 1.44 (0.89, 2.33), 2.03 (1.27, 3.25), and 2.86 (1.84, 4.43), respectively (P for trend 30 mg/day during pregnancy had an OR for GDM of 2.32 (95% CI: 1.60, 3.36). Moreover, the significant positive effect of supplemental iron was mainly attributed to iron supplementation during mid-pregnancy (≥60 vs. 0 mg/day, OR: 1.46, 95% CI: 1.00, 2.13), while no effect of iron supplementation during early pregnancy was observed. No significant association was found between food iron intake and GDM. CONCLUSIONS: Higher supplemental iron intake during pregnancy was significantly associated with elevated GDM risk. Adverse effect of indiscriminate iron supplementation, especially inappropriate supplementation during mid-pregnancy, would likely outweigh benefits for maternal health. FUNDING SOURCES: Funding was received from the National Natural Science Foundation of China (NSFC81673159), National Program on Basic Research Project of China (NO.2013FY114200) and the Fundamental Research Funds for the Central Universities (HUST 2019kfyXMPY008) (Nianhong.Yang.).

Objectives To examine the relationship between prenatal nitrogen dioxide (NO 2 ) exposure and foetal growth in a prospective cohort of 1001 Chinese women. Methods The maternal NO 2 exposure levels were estimated using land-use regression models based on home address. The biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL) and estimated foetal weight (EFW) were evaluated via ultrasonography. The multiple linear regression model was used to adjust for confounders, and the mixed-effect model was used to assess longitudinal effect. Results With a 10 μg/m 3 increase in NO 2 exposure, the BPD, HC, AC, FL and EFW in the second trimester decreased by 0.40 mm (95% CI −0.56 to −0.24), 1.07 mm (95% CI −1.60 to −0.54), 1.02 mm (95% CI −1.57 to −0.48), 0.24 mm (95% CI −0.37 to −0.12) and 7.84 g (95% CI −11.59 to −4.08), respectively; the BPD and HC in the third trimester decreased by 0.26 mm (95% CI −0.50 to −0.02) and 0.71 mm (95% CI −1.37 to −0.06), respectively. The longitudinal analyses showed inverse associations of NO 2 exposure with BPD, HC, AC and FL (all p 2 on the HC, FL and EFW in the second trimester were stronger among female babies and that the effect of NO 2 on EFW in the third trimester was stronger among smoking mothers (all p Conclusions In this prospective study of Chinese women, maternal NO 2 exposure was inversely associated with foetal growth, and the association was stronger among female babies and smoking mothers.

Bilirubin concentrations have been recently reported to be negatively associated with type 2 diabetes mellitus. We examined the association between bilirubin concentrations and gestational diabetes mellitus. In a prospective cohort study, 2969 pregnant women were recruited prior to 16 weeks of gestation and were followed up until delivery. The value of bilirubin was tested and oral glucose tolerance test was conducted to screen gestational diabetes mellitus. The relationship between serum bilirubin concentration and gestational weeks was studied by two-piecewise linear regression. A subsample of 1135 participants with serum bilirubin test during 16-18 weeks gestation was conducted to research the association between serum bilirubin levels and risk of gestational diabetes mellitus by logistic regression. Gestational diabetes mellitus developed in 8.5 % of the participants (223 of 2969). Two-piecewise linear regression analyses demonstrated that the levels of bilirubin decreased with gestational week up to the turning point 23 and after that point, levels of bilirubin were increased slightly. In multiple logistic regression analysis, the relative risk of developing gestational diabetes mellitus was lower in the highest tertile of direct bilirubin than that in the lowest tertile (RR 0.60; 95 % CI, 0.35-0.89). The results suggested that women with higher serum direct bilirubin levels during the second trimester of pregnancy have lower risk for development of gestational diabetes mellitus.

We aimed to assess protein nutrition status during pregnancy by maternal plasma total protein (MTP) levels in urban pregnant women and to explore the association between the trimester‐specific MTP levels and risk of preterm birth (PTB). A prospective design was conducted in 3,382 mother‐newborn pairs with the second‐trimester maternal MTP information and in 3,478 mother‐newborn pairs with the third‐trimester MTP information. Multiple Cox proportional hazard regression and multiple linear regression were used to analyse the associations between MTP levels and PTB risk as well as gestational duration, respectively. Nearly all the second‐trimester MTP levels were within the clinical reference range, but more than 40% of the third‐trimester MTP levels were less than the lower limit of normal. No significant association was found between the second‐trimester MTP level and PTB risk. However, the adjusted hazard ratios (HRs) of PTB across increasing quartiles of the third‐trimester MTP levels were 1.00 (reference), 0.59 (0.36, 0.95), 0.35 (0.20, 0.60), and 0.32 (0.19, 0.53) (p for trend < 0.001), respectively. Each standard deviations increment of the third‐trimester MTP was associated with increase of 0.13 weeks in gestational duration. Moreover, stratified analyses showed that the effects of third‐trimester MTP on PTB risk and gestational duration were stronger in pregnant women carrying female offspring than those carrying male offspring (p for interaction < 0.05). The third‐trimester MTP level was inversely associated with PTB risk and was positively associated with gestational duration. Improving third‐trimester MTP level may be helpful for preventing PTB.

To examine optimal gestational weight gain(GWG) for Chinese pregnant women.A total of 6998 women with singleton and term pregnancy recruited to the Tongji Maternal and Child Health Cohort during January 2013 to May 2016 in Wuhan, Hubei were included. Information on sociodemographic, medical and family history of disease was obtained by questionnaire, body weight and height were measured at the first antenatal care during 8-16 weeks of gestation. Prenatal weight of mothers were measured, and gestational week, mode of delivery, pregnancy complications, gender of newborn, birth weight and length were collected from medical records after delivery. Restricted cubic spline was used to model nonlinear relationships between GWG and the occurrence of small for gestational age(SGA), large for gestational age(LGA), low birth weight(LBW), macrosomia, cesarean, gestational hypertension(GH)and gestational diabetes mellitus(GDM), respectively. The GWG of the lowest risks for adverse pregnant outcomes was regarded as optimal GWG recommended by Tongji(TJ) for pregnant women. The P25-P75 of GWG was defined as the optimal GWG recommended by percentile method. Logistic regression was used to analyze the effect of excessive or insufficient GWG on adverse pregnancy outcomes, while the recommendations of TJ and percentile method were used as references, respectively.(1) The GWG with lower risk of adverse pregnant outcomes based on pre-gravid body mass index(BMI) are 12. 0-17. 0 kg for underweight, 9. 0-14. 0 kg for normal weight and 7. 0-11. 0 kg for overweight, respectively, which are defined as TJ recommendations. The recommended GWG by percentile method are 14. 0-19. 0 kg for underweight, 13. 0-19. 0 kg for normal weight, 10. 8-18. 0 kg for overweight and 9. 0-15. 8 kg for obesity, respectively. (2) Compared to women gain within the TJ recommendations, OR of LGA is 2. 94(95%CI 2. 31-3. 73), macrosomia is 3. 13(95%CI 2. 38-4. 13), cesarean is 1. 53(95%CI 1. 38-1. 71) and GH is 2. 18(95%CI 1. 50-3. 17) for those with excessive GWG, OR of SGA is 1. 82(95%CI 1. 32-2. 53) for those who gain less. The corresponding ORs according to percentile method are 2. 11(95%CI 1. 76-2. 54) for LGA, 2. 16(95%CI 1. 76-2. 65) for macrosomia, 1. 53(95%CI 1. 36-1. 72) for cesarean, 1. 39(95%CI 1. 02-1. 90) for GH and 1. 60(95%CI 1. 29-1. 99) for SGA, respectively.The optimal GWG of Chinese pregnant women recommended by the study are 12. 0-17. 0 kg for pre-gravid underweight women, 9. 0-14. 0 kg for normal weight women and 7. 0-11. 0 kg for overweight, respectively.

Investigators in previous studies have drawn inconsistent conclusions regarding the relationship between relatively low exposure to fine particulate matter (particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5)) and risk of gestational diabetes mellitus (GDM), while the association between high PM2.5 exposure and GDM risk has not been well studied. We investigated the association of high PM2.5 exposure during pregnancy with blood glucose levels and GDM risk in Chinese women. The present study was conducted from August 2013 to May 2016 among 3,967 pregnant women in the Tongji Maternal and Child Health Cohort in Wuhan, China. PM2.5 exposure during pregnancy for each participant was estimated by means of land-use regression models. An interquartile-range increase in PM2.5 exposure (33.84 μg/m3 for trimester 1 and 33.23 μg/m3 for trimester 2) was associated with 36% (95% confidence interval (CI): 1.15, 1.61) and 23% (95% CI: 1.01, 1.50) increased odds of GDM during trimester 1 and trimester 2, respectively. An interquartile-range increment of PM2.5 exposure during trimester 1 increased 1-hour and 2-hour blood glucose levels by 1.40% (95% CI: 0.42, 2.37) and 1.82% (95% CI: 0.98, 2.66), respectively. The same increment of PM2.5 exposure during trimester 2 increased fasting glucose level by 0.85% (95% CI: 0.41, 1.29). Our findings suggest that high PM2.5 exposure during pregnancy increases blood glucose levels and GDM risk in Chinese women.

This study aimed to determine whether increased carotenoids intake was associated with reduced risk of gestational diabetes mellitus (GDM). We performed a cross-sectional analysis using data from Tongji Maternal and Child Health Cohort study. The dietary carotenoids intake of 1978 pregnant women was assessed using a researcher-administered FFQ before undertaking an oral glucose tolerance test at 24–28 weeks. Multivariate logistic and linear regression analyses were used to obtain the effect estimates. Participants in the highest quartile of lycopene intake showed a lower risk of GDM (OR 0·50; 95 % CI 0·29, 0·86;Pfor trend= 0·007) compared with those in the lowest quartile; each 1 mg increase in lycopene consumption was associated with a 5 % (95 % CI 0·91, 0·99;Pfor trend= 0·020) decrease in GDM risk. No significant association was found between α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin intake and GDM risk. Multiple linear regression analysis suggested an inverse association between lycopene intake and fasting blood glucose (FBG) (Pfor trend< 0·001); each 1 mg increase in lycopene intake was associated with 0·005 (95 % CI 0·002, 0·007;Pfor trend< 0·001) mmol/l decrease in FBG. Interaction analysis indicated consistent effect on each age or pre-BMI subgroup; however, a stronger protective effect of lycopene intake against GDM was observed among primigravid women (OR 0·20; 95 % CI 0·07, 0·55 in the highestv. the lowest quartile of intake;Pfor interaction= 0·036). In conclusion, dietary lycopene intake was mainly assumed via reducing FBG to decrease GDM risk, and the protection was relatively increased among primigravid women.

Periconceptional folic acid (FA) supplementation is widely recommended for substantial benefits on preventing neural tube defects (1), but concerns regarding the potential side effects on both mothers and their infants have been raised recently (2,3). Higher plasma folate was found to be associated with higher risk of gestational diabetes mellitus (GDM) (4). A Chinese cohort had reported association between FA supplement use in early pregnancy and increased GDM risk (5). However, no details on FA doses and durations had been addressed. To further understand the safe dose and duration of FA supplement use regarding GDM risk, for the first time, we evaluated the impact of FA supplement use on GDM with consideration of both doses and durations. Participants came from the Tongji Maternal and Child Health Cohort (TMCHC), a cohort investigating the role of maternal nutritional, environmental, and lifestyle influences on the outcomes of pregnant women and their offspring. Information on social-demographic status, reproductive factors, lifestyle factors, illnesses, and medical records was collected via questionnaire-based interviews at enrollment (

Emerging clinical evidence has implied that alkaline phosphatase (ALP) may contribute to gestational diabetes mellitus (GDM). However, there were no studies to reveal the independent and prospective associations between ALP and GDM. Our aim was to explore the independent and prospective associations between early maternal ALP level and GDM risk and glucose regulation. In a prospective cohort study with 2073 singleton mothers at four maternity units in China, maternal serum ALP levels were measured before 20 gestational weeks. Using logistic regression, we analyzed the relationship between maternal ALP level and risk of GDM. We further explored the relationships of ALP level to fasting blood glucose (FBG), 1-h and 2-h post-load blood glucose (1-h, 2-h PBG) with multiple linear regression. Finally, we analyzed the association between maternal ALP level and isolated impaired fasting glucose (i-IFG) and isolated impaired glucose tolerance (i-IGT) risk. The maximum value of maternal ALP level was 90 U/L, within the normal range. After adjustment for confounding factors, the odds ratio (ORs) of GDM increased linearly with ALP level (p for overall association = 0.002, p for nonlinear association = 0.799), with the OR comparing the highest versus lowest quartile of 2.47 (95% CI 1.47, 4.15). Moreover, each additional of 10 U/L ALP level was associated with a 2% higher FBG (p = 0.043) and a 12% higher 1-h PBG (p = 0.004). Higher ALP level also increased the risk of i-IFG (OR 3.73, 95% CI 1.17–11.86) and i-IGT (OR 2.03, 95% CI 1.07–3.84). Even within the upper limit of normal, higher early maternal ALP level could increase the risk of GDM. Moreover, both FBG and PBG were increased with early maternal ALP.

Maternal dietary patterns and macronutrients intake have been shown to affect the development of gestational diabetes mellitus (GDM), but the findings are inconsistent. We aimed to identify maternal dietary patterns and examine their associations with GDM risk, and to evaluate the contributions of macronutrients intake to these associations. We included 2755 Chinese pregnant women from the Tongji Maternal and Child Health Cohort. Dietary intakes were assessed using a validated semi-quantitative FFQ 2 weeks before the diagnosis of GDM. GDM (n 248) was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24–28 weeks gestation. We derived five different dietary patterns from a principal component analysis. The results showed that high fish–meat–eggs scores, which were positively related to protein intake and inversely related to carbohydrate intake, were associated with a higher risk of GDM (adjusted OR for quartile 4 v. quartile 1: 1·83; 95 % CI 1·21, 2·79; Ptrend=0·007) and higher plasma glucose levels. In contrast, high rice–wheat–fruits scores, which were positively related to carbohydrate intake and inversely related to protein intake, were associated with lower risk of GDM (adjusted OR for quartile 3 v. quartile 1: 0·54; 95 % CI 0·36, 0·83; Ptrend=0·010) and lower plasma glucose levels. In addition, dietary protein and carbohydrate intake significantly contributed to the associations between dietary patterns and GDM risk or glucose levels. These findings suggest that a dietary pattern characterised by high protein and low carbohydrate intake in pregnancy was associated with a higher risk of GDM, which may provide important clues for dietary guidance during pregnancy to prevent GDM.

OBJECTIVES: The overall plant-based diet index (PDI) has been demonstrated to be protective against type 2 diabetes (T2D) in the general population. Whether the PDI was linked to gestational diabetes mellitus (GDM) is unclear. We aimed to assess the association of the PDI with GDM incidence in Chinese pregnant women. METHODS: A total of 2099 pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) were included in the present study. Dietary data were collected at 13–28 wks of pregnancy by using a validated semi-quantitative food frequency questionnaire (FFQ). Food groups including cereals, fruits, vegetables, nuts, beans, vegetable oil, dairy, eggs, meat, and fish, were ranked into quintiles and given positive (1–5 for plant food groups) or reverse (5–1 for animal food groups) scores. The PDI was obtained by summing the 10 food group scores, with a theoretical range of 10 to 50. GDM was diagnosed by the 75-g 2-h oral glucose tolerance test at 24–28 wks. Cubic-restricted spline function and logistic regression analyses were used to examine the association between the PDI during pregnancy and GDM. RESULTS: GDM was reported by 8.1% of the 2099 pregnancies. The PDI score ranged from 17 to 43 (theoretical range: 10–50), the mean (SD) was 30.2 (4.4). After adjusting for maternal age, ethnicity, education, income, parity, gravidity, family history of diabetes, total energy intake per day, and other pre-pregnancy information such as body mass index (BMI), smoking status, drinking status, exercise, and sleep quality, a linear association between the PDI and GDM risk was demonstrated by the restricted cubic splines (P for overall association = 0.024, P for nonlinearity = 0.370). Compared to the lowest quartile 1 of PDI, ORs (95% CI) were 0.91 (0.59, 1.42) for quartile 2, 0.91 (0.58, 1.41) for quartile 3, and 0.52 (0.30, 0.89) for quartiles 4 (P for trend = 0.040) in the adjusted model. CONCLUSIONS: Our study suggests that higher PDI is associated with a substantially lower risk of developing GDM, which indicates that adopt plant-based diets during pregnancy could be an easy avenue to reduce GDM risk. FUNDING SOURCES: Funding was received from the National Program on Basic Research Project of China (NO.2013FY114200) and the Fundamental Research Funds for the Central Universities (HUST2016YXZD040) for Nianhong Yang.

Background: Antimony (Sb) has been associated with type 2 diabetes in previous studies. However, the role of Sb in the incidence of Gestational diabetes mellitus (GDM) remains unclear. Objectives: We investigated the association between Sb exposure during early pregnancy and the risk of GDM. Methods: We performed a prospective study of 2093 pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC). Sb concentrations were measured in urine samples during early pregnancy by ICP-MS. The association between urinary Sb concentration and GDM incidence was assessed using robust Poisson regression model after adjustment for confounders. Results: The 95th percentile value of creatinine-corrected Sb (CC-Sb) concentration in the urine of all pregnant women was 1.33 μg/g. The CC-Sb concentrations were significantly higher in women with GDM than those without GDM (median value: 0.49 μg/g vs. 0.38 μg/g, p = 0.001). After adjustment for potential confounders, for each one natural logarithmic unit increase in Sb concentration, there was 29% [adjusted relative risk (RR) = 1.29; 95% confidence interval (CI): 1.06, 1.57] increase in the risk of GDM. Women in the highest tertile for CC-Sb had a 1.92-fold (95% CI: 1.42, 2.60) higher risk of GDM compared with women in the lowest tertile (p-value for trend

Summary Background & aims Oxidative stress has been implicated in the pathogenesis of gestational diabetes mellitus (GDM). Vitamin C as natural antioxidant may help to increase the body's antioxidant capacity. The study is aimed to determine whether vitamin C intake during pregnancy is associated with lower risk of GDM. Methods Women with singleton pregnancy and without any history of diabetes were drawn from the ongoing Tongji Maternal and Child Health Cohort (TMCHC). Oral glucose tolerance tests (OGTT) were conducted during weeks 24–28 of gestation to screen for GDM. A validated food frequency questionnaire (FFQ) was used to assess dietary intake during mid pregnancy. Use of multivitamins and specific supplements of vitamin C was assessed by questionnaires. Odds ratios (ORs) of GDM risk were calculated by logistic regression models, adjusted for potential confounders. Results 344 (11.4%) of the 3009 women were diagnosed with GDM. Dietary vitamin C intake was inversely associated with the risk of GDM. Women with above adequate dietary vitamin C intake (more than 200 mg/day) experienced lower odds of GDM (OR 0.68, 95% CI: 0.49–0.95) than those with adequate intake (115–200 mg/day). There was no association between the total consumption of vitamin C and the risk of GDM (OR 1.04, 95% CI: 0.71–1.53). Conclusion This data suggests that higher dietary consumption of vitamin C during pregnancy is independently associated with lower odds of GDM. Above 200 mg/day of dietary vitamin C intake may help reduce the odds of GDM. However, no such association between total vitamin C intake and the risk of GDM was found. Hence, sufficient vegetables and fruits rich in vitamin C should be recommended to protect pregnant women from developing gestational diabetes.

Summary Background & aims The Scientific Report of 2015 Dietary Guidelines Advisory Committee recommended the elimination of dietary cholesterol limits. However, cholesterol intake increases during pregnancy and studies regarding the association between dietary cholesterol and gestational diabetes mellitus (GDM) are limited. We evaluate the association of total dietary cholesterol and different sources of cholesterol intake during pregnancy, with GDM risk and blood glucose levels in a Chinese prospective cohort study. Methods A total of 2124 pregnant women from the Tongji Maternal and Child Health Cohort was included. A validated semi-quantitative food frequency questionnaire was used to assess dietary cholesterol intake prior to GDM diagnosis. GDM was diagnosed by the 75-g 2-h oral glucose tolerance test. Cubic-restricted spline function and logistic regression analyses were used to evaluate the association between dietary cholesterol intake during pregnancy and GDM. Generalized linear models were conducted to examine the associations of cholesterol intake with fasting blood glucose (FBG), 1-h post-load blood glucose (PBG) and 2-h PBG. Results The average dietary cholesterol intake was 379.1 mg/d, and cholesterol from eggs explained 64.2% of the variability. Total dietary cholesterol intake and cholesterol from eggs rather than other foods, were linearly associated with GDM risk, with adjusted OR for GDM of 2.10 (95%CI: 1.24, 3.58) for total cholesterol intake and 1.83 (95%CI: 1.08, 3.07) for cholesterol from eggs comparing the highest versus lowest quintile. A 100-mg/d increase in total cholesterol and cholesterol from eggs intake were associated with an increased GDM risk by 18% and 16%, respectively. Moreover, higher maternal dietary total cholesterol could increase FBG and 1-h PBG, while cholesterol from eggs increased FBG only. Conclusion Higher dietary cholesterol from eggs intake during pregnancy was associated with greater risk of GDM.

Summary Background & aims Delayed onset of lactogenesis II (OL) negatively affects breastfeeding and consequently, the health of the newborn. Few studies have examined the association between gestational weight gain (GWG) throughout pregnancy and risk of delayed OL. Methods We used data from a prospective cohort study in Wuhan of China, which enrolled pregnant women at 8–16 weeks of gestation and followed-up regularly. GWG was assessed by the last available weight measurement (LAWM) during pregnancy and the self-reported pre-pregnancy weight at enrollment. The outcome was delayed OL self-reported after 4 days postpartum. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from multivariate logistic regression. Results Delayed OL was reported by 18.4% of the 3282 participants. After adjustment for the demographic, clinical and breastfeeding characteristics, compared to the lowest quartile 1 of GWG, ORs (95% CIs) were 1.20 (0.91, 1.57) for quartile 2, 1.47 (1.13, 1.92) for quartile 3, and 1.42 (1.08, 1.86) for quartile 4 (P for trend = 0.006). When GWG was classified by the 2009 Institute of Medicine (IOM) guidelines, compared with women with adequate GWG, the adjusted ORs (95% CIs) were 0.82 (0.61, 1.10) for inadequate GWG, and 1.13 (0.93, 1.38) for excessive GWG. Conclusions Women with higher GWG throughout pregnancy are more likely to suffer from delayed OL in Chinese population.

Background The microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) has been reported as a novel and independent risk factor for the development of cardiovascular and metabolic diseases, but the association with gestational diabetes mellitus (GDM) remains unclear. Objective The aim of this study was to investigate the association between plasma TMAO concentration and GDM in a 2-phase study. Design A 2-phase design was used in the current study. An initial phase included 866 participants (433 GDM cases and 433 matched controls) with fasting blood samples collected at the time of GDM screening (24-32 wk of gestation). An independent-phase study, with 276 GDM cases and 552 matched controls who provided fasting blood samples before 20 wk of gestation and who had GDM screened during 24-32 wk of gestation, was nested within a prospective cohort study. These 2 studies were both conducted in Wuhan, China, and the incidence of GDM in the cohort study was 10.8%. Plasma TMAO concentrations were determined by stable isotope dilution liquid chromatography-tandem mass spectrometry. GDM was diagnosed according to the American Diabetes Association criteria by using an oral-glucose-tolerance test. Results In the initial case-control study, the adjusted OR of GDM comparing the highest TMAO quartile with the lowest quartile was 1.94 (95% CI: 1.28, 2.93). Each SD increment of ln-transformed plasma TMAO was associated with 22% (95% CI: 5%, 41%) higher odds of GDM. In the nested case-control study, women in the highest quartile also had increased odds of GDM (adjusted OR: 2.06; 95% CI: 1.28, 3.31) compared with women in the lowest quartile, and the adjusted OR for GDM per SD increment of ln-transformed plasma TMAO was 1.26 (95% CI: 1.08, 1.47). Conclusions Consistent findings from this 2-phase study indicate a positive association between plasma TMAO concentrations and GDM. Future studies are warranted to elucidate the underlying mechanisms. This trial was registered at www.clinicaltrials.gov as NCT03415295.

Objectives To examine the relationship between poor sleep quality during pregnancy and the risk of gestational diabetes mellitus (GDM). Methods A total of 4066 singleton pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) without overt diabetes before pregnancy were analyzed. Sleep quality and duration during early pregnancy were self-reported by enrolled women at their first antenatal care visit before 16 weeks of gestation. Gestational diabetes mellitus (GDM) was assessed with a 75-g, 2-h oral glucose tolerance test at 24–28 weeks of gestation. Information about self-reported sleep quality and duration in mid-pregnancy were also collected at this time. Odds ratios (OR) and 95% CIs were calculated by multivariable logistic regression models, and adjusted for potential confounders to estimate the effect of poor sleep quality and the interaction between sleep quality and duration on the development of GDM. Stratified analyses were performed according to age, parity, family history of diabetes and napping. Results A total of 335 (8.2%) participants were diagnosed with GDM. Poor sleep quality was reported in 259 (6.4%) women during early pregnancy and 248 (6.1%) in mid-pregnancy. The risk of GDM was increased in women with poor sleep quality during early pregnancy (OR 1.77, 95% CI 1.20–2.61). No association was found between poor sleep quality during mid-pregnancy and the risk of GDM. The risk of GDM was highest in women with poor sleep and longer nighttime sleep duration during early pregnancy (OR 2.27, 95% CI 1.20–4.29) when compared with those who reported good sleep and 7.0–8.5 h of sleep duration per night. Stratified analysis found that the association between poor sleep quality in early pregnancy and the risk of GDM was stronger among women aged ≥30 years (OR 2.35, 95% CI 1.35–4.09) and those with a family history of diabetes (OR 4.02, 95% CI 1.54–10.48). Conclusions Poor sleep quality during early pregnancy was associated with an increased risk of GDM. Screening for and treating sleep problems in early pregnancy could potentially reduce the risk of GDM.

Summary Background & aims Gestational diabetes mellitus is associated with adverse short- and long-term consequences for both the mother and the offspring. To examine the relationship between the rates of gestational weight gain (RGWG) during early and mid-pregnancy and the risk of gestational diabetes mellitus (GDM). Methods 2090 singleton pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) without overt diabetes before pregnancy were analyzed in our study. Gestational weight were measured regularly in every antenatal visit. Gestational diabetes mellitus was assessed with the 75-g, 2-h oral glucose tolerance test at 24–28 weeks of gestation. Multivariable logistic regression was performed to estimate effect of RGWG on GDM. Results A total of 8.3% (n = 173) of pregnant women were diagnosed with GDM. Women with elevated rate of gestational weight gain prior to glucose screening test (RGWG-PG) increased the risk of GDM (adjusted p -trend = 0.004; odds ratios (OR) 1.64, 95% confidence intervals (CI) 1.01–2.68 and OR 2.30,95% CI 1.44–3.66 for 0.297–0.384 kg/wk and 0.385 kg/wk or more vs. 0.213 kg/wk or less, respectively). Women with greater rate of gestational weight gain in the first trimester (RGWG-F) increased the risk of GDM (adjusted p -trend = 0.048; OR 1.83, 95% CI 1.14–2.94 and OR 1.76, 95% CI 1.10–2.83 for 0.086–0.200 kg/wk and 0.201 kg/wk or more vs. −0.025 kg/wk or less, respectively). The rate of gestational weight gain in the second trimester (RGWG-S) was significantly associated with GDM only among women with RGWG-F more than 0.086 kg/wk (adjusted p -trend = 0.035; OR 2.04, 95% CI 1.16–3.59 for 0.658 kg/wk or more vs. 0.418 kg/wk or less). Conclusions Greater early pregnancy weight gain are associated with increased risk of GDM. Elevated weight gain in mid-pregnancy increased the risk of GDM only among pregnant women with greater weight gain in the first trimester.

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