Longitudinal plasma magnesium status during pregnancy and the risk of gestational diabetes mellitus: a prospective cohort study.

Emerging evidence has shown that magnesium (Mg) was associated with type 2 diabetes while few focused on abnormal glucose metabolism during pregnancy. The study is aimed at investigating the association between longitudinal changes in plasma Mg during pregnancy and subsequent risk of gestational diabetes (GDM) and exploring the possible influence of iron supplementation on the changes of plasma Mg levels. One thousand seven hundred fifty-six pregnant women from Tongji Maternal and Child Health Cohort (TMCHC) were involved. Blood samples were collected at gestational weeks 17.0 ± 0.9 and later 26.2 ± 1.4. Plasma Mg was measured by inductively coupled plasma mass spectrometry (ICP-MS) with decline rates calculated. Information on general characteristics and iron supplementation was collected by questionnaires. Oral glucose tolerance test (OGTT) was conducted at 24-28 gestational weeks to diagnose GDM. Poisson regression with robust error variance was used to estimate relative risks (RR) of GDM. Median concentrations of plasma Mg were 0.69 mmol/L and 0.63 mmol/L respectively at two collections. The prevalence of hypomagnesemia at the first collection was 73% and associated with a 1.59 (95%CI: 1.07, 2.37) fold risk of GDM. Adjusted RRs were 1.74 (95%CI: 1.06, 2.83) and 2.44 (95%CI: 1.54, 3.85) for women with hypomagnesemia and followed more tertile (T2 and T3 vs. T1) of Mg decrement. Iron supplementation above 30 mg/day was found associated with more Mg decrement (25.5% and 27.5% in T2 and T3 vs. 19.5% in T1). In conclusion, hypomagnesemia during pregnancy is prevalent and associated with increased GDM risk, especially in women followed by more plasma Mg decrement during pregnancy. High-dose iron supplementation may involve more plasma Mg decrement.

Fluoride-Induced Cortical Toxicity in Rats: the Role of Excessive Endoplasmic Reticulum Stress and Its Mediated Defective Autophagy.

The cerebral cortex is closely associated with learning and memory, and fluoride is capable of inducing cortical toxicity, but its mechanism is unclear. This study aimed to investigate the role of endoplasmic reticulum stress and autophagy in fluoride-induced cortical toxicity. Rats exposed to sodium fluoride (NaF) were used as an in vivo model. The results showed that NaF exposure impaired the learning and memory capacities and increased urinary fluoride levels in rats. In addition, NaF exposure induced excessive endoplasmic reticulum stress and associated apoptosis, as evidenced by elevated IRE1α, GRP78, cleaved caspase-12, and cleaved caspase-3, as well as defective autophagy, as evidenced by increased expression of Beclin1, LC3-II, and p62 in cortical areas. Importantly, the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated endoplasmic reticulum stress as well as defective autophagy, thus confirming the critical role of endoplasmic reticulum stress and autophagy in fluoride-induced cortical toxicity. Taken together, these results suggest that excessive endoplasmic reticulum stress and its mediated defective autophagy lead to fluoride-induced cortical toxicity. This provides new insights into the mechanisms of fluoride-induced neurotoxicity and a new theoretical basis for the prevention and treatment of fluoride-induced neurotoxicity.

Excessive Lysosomal Stress Response and Consequently Impaired Autophagy Contribute to Fluoride-Induced Developmental Neurotoxicity.

Fluoride can cause developmental neurotoxicity; however, the precise mechanism has yet to be determined. We aimed to explore the possible role and mechanism of fluoride-induced developmental neurotoxicity, specifically the significance of the lysosomal stress response. As an in vivo model, Sprague Dawley rats were exposed to sodium fluoride (NaF) from embryo to 2 months of age. We found that NaF caused autophagic flux blockage and apoptosis in the rat hippocampus. These results were validated in human neuroblastoma (SH-SY5Y) cells in vitro. In addition, in SH-SY5Y cells, NaF hindered autophagosome-lysosome fusion, decreased lysosomal degradation, and elevated lysosomal pH, which is the most prominent hallmark of a lysosomal stress response. Interestingly, rapamycin promoted autophagosome-lysosome fusion, effectively restoring autophagic flux and reducing apoptosis. Notably, bafilomycin A1, a lysosomal lumen alkalizer, unsurprisingly exacerbated the NaF-induced increase in lysosomal pH and decreased lysosomal degradability, as well as enhanced apoptosis of SH-SY5Y cells. In conclusion, our results suggest that NaF exposure initiates excessive lysosomal stress response, resulting in elevated lysosomal pH, decreased lysosomal degradation, and blocked autophagic flux, which leads to neuronal apoptosis. Thus, the lysosomal stress response may be a promising target for the prevention and treatment of fluoride-induced developmental neurotoxicity.

Plasma Manganese Levels and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study.

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.

The association of maternal vaginal bleeding and progesterone supplementation in early pregnancy with offspring outcomes: a prospective cohort study.

BACKGROUND: Progesterone is widely used to improve the adverse pregnancy outcomes related to vaginal bleeding during early pregnancy. However, the evidence of its effectiveness is equivocal. METHODS: Six thousand six hundred fifteen mother-infant pairs from Tongji Maternal and Child Health Cohort (TMCHC) were involved in the study. Information on vaginal bleeding, progesterone administration in early pregnancy were obtained at enrolment. Birth outcomes were obtained from the hospital notes. Body weight of the infants at 12 months of age was collected by telephone interview. Multivariable logistic regression was conducted to estimate the effect of vaginal bleeding and progesterone administration in early pregnancy on birth outcomes and weight status of infants at 12 months of age. RESULTS: 21.4% (1418/6615) participants experienced bleeding in early pregnancy, and 47.5% (674/1418) of them were treated with progesterone. There were no significant associations between progesterone supplementation in early pregnancy and offspring outcomes. Compared to women without bleeding or any therapy, women with bleeding and progesterone therapy experienced increased risk of preterm (OR 1.74, 95% CI 1.21-2.52), and delivering a small-for-gestational-age (SGA) (OR 1.46, 95% CI 1.07-1.98) or low birth weight (LBW) (OR 2.10, 95% CI 1.25-3.51) neonate, and offspring of them had an increased risk of weight for age z-score (WAZ) < -1 at 12 months of age (OR 1.79, 95%CI 1.01-3.19). CONCLUSIONS: Offspring of mothers with bleeding and progesterone therapy were more likely to be a premature, SGA or LBW neonate, and had lower weight at 12 months of age. Progesterone supplementation may have no beneficial effect on improving adverse offspring outcomes related to early vaginal bleeding. TRIAL REGISTRATION: TMCHC was registered at clinicaltrials.gov as NCT03099837 on 4 April 2017.

Impaired V-ATPase leads to increased lysosomal pH, results in disrupted lysosomal degradation and autophagic flux blockage, contributes to fluoride-induced developmental neurotoxicity.

Fluoride is capable of inducing developmental neurotoxicity, yet its mechanisms remain elusive. We aimed to explore the possible role and mechanism of autophagic flux blockage caused by abnormal lysosomal pH in fluoride-induced developmental neurotoxicity, focusing on the role of V-ATPase in regulating the neuronal lysosomal pH. Using Sprague-Dawley rats exposed to sodium fluoride (NaF) from gestation through delivery until the neonatal offspring reached six months of age as an in vivo model. The results showed that NaF impaired the cognitive abilities of the offspring rats. In addition, NaF reduced V-ATPase expression, diminished lysosomal degradation capacity and blocked autophagic flux, and increased apoptosis in the hippocampus of offspring. Consistently, these results were validated in SH-SY5Y cells incubated with NaF. Moreover, NaF increased the SH-SY5Y lysosomal pH. Mechanistically, V-ATPase B2 overexpression and ATP effectively restored V-ATPase expression, reducing NaF-induced lysosomal alkalinization while increasing lysosomal degradation capacity. Notably, those above pharmacological and molecular interventions diminished NaF-induced apoptosis by restoring autophagic flux. Collectively, the present findings suggested that NaF impairs the lysosomal pH raised by V-ATPase. This leads to reduced lysosomal degradation capacity and triggers autophagic flux blockage and apoptosis, thus contributing to neuronal death. Therefore, V-ATPase might be a promising indicator of developmental fluoride neurotoxicity.

Association of Maternal Longitudinal Hemoglobin with Small for Gestational Age during Pregnancy: A Prospective Cohort Study.

Background: Few studies have investigated the association of maternal longitudinal hemoglobin (Hb) with small for gestational age during pregnancy. The current study examined the associations of maternal Hb concentrations and Hb changes throughout the middle and late stages of pregnancy with small for gestational age (SGA) in a large prospective cohort study. Methods: This was a prospective cohort study, which enrolled pregnant women at 8−16 weeks of gestation and followed up regularly. Maternal Hb concentrations were measured at the middle (14−27 weeks) and late (28−42 weeks) stages of pregnancy, and the Hb change from the middle to late stage of pregnancy was assessed. The Log-Poisson regression model was used to identify the association of maternal Hb with SGA, including the implications of Hb during specific pregnancy periods and Hb change across the middle to late stages of pregnancy. Of the total 3233 singleton live births, 208 (6.4%) were SGA. After adjusting for potential confounders, compared with Hb 110−119 g/L, Hb ≥ 130 g/L at late pregnancy was significantly associated with a higher risk of SGA (adjusted RR: 2.16; 95% CI: 1.49, 3.13). When Hb changes from the middle to late stages of pregnancy were classified by tertiles, the greatest change in the Hb group (<−6.0 g/L) was significantly associated with a lower risk of SGA (adjusted RR: 0.56; 95% CI: 0.37, 0.85) compared with the intermediate group (−6.0~1.9 g/L). In conclusion, for women at low risk of iron deficiency, both higher Hb concentrations in late pregnancy and less Hb reduction during pregnancy were associated with an increased risk of SGA.

Profiling pharmacokinetics of double-negative T cells and cytokines via a single intravenous administration in NSG mice.

This study was intended to delineate the profile of double-negative T cells (DNTs) in NOD.Cg-Prkdcscid Il2rgtm1wj /SzJ mice and cytokines released from DNTs in vivo and in vitro. Total 4 × 107 cells of RC1012 injection per mice were intravenously infused. IFN-γ, TNF-α, IL-1ß, IL-2, IL-4, IL-6, IL-10 were measured in vivo and in vitro. A quantitative polymerase chain reaction (PCR) was employed to determine the gene copies of Notch2-NLA per DNT cell from collected organs. Cytokines were significantly increased in vitro (4 h) and in vivo (3 h). DNT cells were distributed into the lung, liver, heart, and kidney earlier, and redistributed to lymphocyte homing spleen and bone marrow, which seemed to frame a two-compartment pharmacokinetics (PK) model but more data are needed to confirm this, and the clearance of DNT cells fell into first-order kinetics.

Periconceptional iron supplementation and risk of gestational diabetes mellitus: A prospective cohort study.

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<3 months (Iron > 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.

Association between maternal plasma ferritin concentration, iron supplement use, and the risk of gestational diabetes: a prospective cohort study.

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.

Association between Chinese Dietary Guidelines Compliance Index for Pregnant Women and Risks of Pregnancy Complications in the Tongji Maternal and Child Health Cohort.

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.

Folic Acid Supplement Use and Increased Risk of Gestational Hypertension.

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.

The Associations of Ambient Fine Particulate Matter Exposure During Pregnancy With Blood Glucose Levels and Gestational Diabetes Mellitus Risk: A Prospective Cohort Study in Wuhan, China.

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.

Exposure to multiple metals in early pregnancy and gestational diabetes mellitus: A prospective cohort study.

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.

Delayed Lactogenesis Is Associated with Suboptimal Breastfeeding Practices: A Prospective Cohort Study.

BACKGROUND: Breastfeeding has many established health benefits to both babies and mothers. There is limited evidence on the association between delayed lactogenesis and breastfeeding practices. OBJECTIVE: We assessed the association between delayed lactogenesis and breastfeeding practices in women initiating breastfeeding. DESIGN: We used data from a prospective cohort study in Wuhan, China, which enrolled pregnant women at 8-16 weeks of gestation and followed up to postpartum. Women were included who had a singleton live birth, initiated breastfeeding, and provided information on infant feeding. Maternal lactogenesis status was assessed by face-to-face interview at day 4 postpartum. Breastfeeding practices (full breastfeeding and/or any breastfeeding) were queried by telephone interview at 3, 6, and 12 mo postpartum. Poisson regression and Cox regression were used to identify the association between delayed lactogenesis and breastfeeding practices. RESULTS: Delayed lactogenesis was reported by 17.9% of the 2877 participants. After adjusting for potential confounders, when compared with timely lactogenesis, delayed lactogenesis was significantly associated with higher risk of inability to sustain full breastfeeding at 3 mo postpartum (RR: 1.24, 95% CI: 1.10, 1.39) and 6 mo postpartum (RR: 1.14, 95% CI: 1.04, 1.24). Delayed lactogenesis was also significantly associated with early termination of any breastfeeding (HR: 1.15, 95% CI: 1.01, 1.30) in the adjusted model. In a combined analysis, women with higher gestational weight gain (GWG, ≥16 kg for underweight and normal weight, 15 kg for overweight/obesity) and who subsequently experienced delayed lactogenesis had the highest risk of ending any breastfeeding earlier (adjusted HR: 1.32, 95% CI: 1.11, 1.55) compared with those who gained less GWG and experienced timely lactogenesis. CONCLUSIONS: This study shows that delayed lactogenesis was associated with low rate of full breastfeeding and shorter duration of any breastfeeding. Greater efforts to promote breastfeeding should be targeted towards women with delayed lactogenesis.

[Optimal gestational weight gain for Chinese urban women].

OBJECTIVE: To examine optimal gestational weight gain(GWG) for Chinese pregnant women. METHODS: 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. RESULTS: (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. CONCLUSION: 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.

The Variable Regulatory Effect of Arsenic on Nrf2 Signaling Pathway in Mouse: a Systematic Review and Meta-analysis.

Arsenic is known to cause oxidative damage. Nuclear factor E2-relate factor-2 (Nrf2) can resist this toxicity. Scholars demonstrated that Nrf2 pathway was activated by arsenic. In contrast, other articles established arsenic-induced inhibition of Nrf2 pathway. To resolve the contradiction and elucidate the mechanism of Nrf2 induced by arsenic, 39 publications involving mouse models were identified through exhaustive database retrieval and were analyzed. The pooled results suggested that arsenic obviously elevated transcription and translation levels of Nrf2 and its downstream genes, NAD(P)H dehydrogenase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and GST-glutathione-S-transferase1/2 (GSTO1/2). Arsenic increased the level of reactive oxygen species (ROS), but reduced the level of glutathione (GSH). Subgroup analysis between arsenic and control groups showed that the levels of Nrf2 and its downstream genes are greater in high dose than that in the low dose, higher in short-term exposure than long term, female subjects tolerated better than males, higher in mice than the rats, and greater in other organs than the liver. However, the contents of genes of Nrf2 pathway between the arsenic and control groups were lower in rats than in mice and were less for long-term exposure than the short term (P < 0.05). Conclusively, a variable regulation of arsenic on Nrf2 pathway is noted. Higher dose and short-term exposure of female mice organs except for liver promoted Nrf2 pathway. On the other hand, arsenic inhibited Nrf2 pathway for long-term exposure on rats.

Antimony in urine during early pregnancy correlates with increased risk of gestational diabetes mellitus: A prospective cohort study.

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 <0.001). CONCLUSION: To our knowledge, this is the first research of an association between urinary Sb levels during pregnancy and GDM. Our study suggests that pregnant women with higher Sb exposure levels may have a higher risk of GDM and this association remains consistent even after stratification.