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Background: Remnant cholesterol (RC) reportedly contributes to the development of diabetes mellitus. However, evidence on the relationship between maternal RC and the risk of developing gestational diabetes mellitus (GDM) during pregnancy is limited. This study aimed to assess the relationship between maternal RC and GDM risk during early pregnancy, and explore the potential pathways involved in the relationship between RC levels and GDM risk. Methods: From 2018 to 2021, a prospective birth cohort study was designed and carried out in China. The associations of maternal RC and other lipid parameters with GDM risk were estimated using logistic regression models and restricted cubic splines. Subgroup analyses were performed stratified by prepregnancy body mass index (pre-BMI), maternal age and gravidity. Mediation analyses were conducted to explore the mediating effect of some related factors on the relationship between RC levels and the risk of GDM. Results: A total of 33,018 pregnant women were included. The median RC level was 0.47 ± 0.20 mmol/L. The prevalence of GDM was 15.19%. As RC quartiles increased, the incidence of GDM increased substantially, reaching 19.24% for the highest quartile of RC (P < 0.001). Maternal RC in the first trimester was positively correlated with GDM risk (OR: 2.254, 95% CI: 1.943–2.615). Compared to the lowest RC quartile, higher RC quartiles were correlated with an increased risk of GDM, and the ORs (95% CIs) for Q3 and Q4 were 1.208 (1.101–1.325) and 1.489 (1.364–1.626), respectively. Moreover, a linear dose–response relationship was found for this association (P for all < 0.001, P for nonlinearity > 0.05) and was consistent across subgroups with different pre-BMIs, maternal ages and gravidities (all P values for interactions > 0.05). Furthermore, the correlation between RC level and GDM risk was partially mediated by pre-BMI (9.20%) and blood glucose level (-11.1%). Conclusions: Higher maternal RC levels in the early stage of pregnancy was positively associated with an increased risk of developing GDM. This association was partially mediated by pre- BMI and blood glucose levels. [ABSTRACT FROM AUTHOR]

Objective: To clarify the association between levothyroxine (LT4) treatment and various adverse pregnancy outcomes in pregnant women with thyrotropin (TSH) levels ranging between 2.5 and 10.0 mIU/L in the first trimester, stratified according to thyroid peroxidase antibody (TPOAb) positivity and TSH level. Methods: This retrospective analysis of retrospectively and prospectively collected cohort data included Chinese pregnant women with TSH levels of 2.5–10 mIU/L and normal free thyroxine levels (11.8–18.4 pmol/L) in the first trimester. All participants were followed up until the completion of pregnancy, and information on LT4 treatment, pregnancy complications, and pregnancy outcomes was recorded. A 1:1 nearest-neighbor propensity score matching (PSM) between the LT4-treated and - untreated groups with a caliper distance of 0.02 was performed using a multivariable logistic regression model. Multivariable-adjusted modified Poisson regression was used to estimate the relative risk (RR) and 95% confidence interval (CI) of LT4 treatment for adverse pregnancy outcomes. Subgroup analyses were also performed in four subgroups simultaneously stratified by TPOAb status (negative or positive) and TSH levels (2.5–4.0 mIU/L as high-normal group and 4.0–10.0 mIU/L as SCH group). The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100047394). Results: Among the 4,370 pregnant women in the study, 1,342 received LT4 treatment and 3,028 did not. The 1:1 PSM yielded 668 pairs of individuals and revealed that LT4 treatment was significantly associated with a decreased risk of pregnancy loss (RR = 0.528, 95% CI: 0.344–0.812) and an increased risk of small-for-gestational-age infants (RR = 1.595, 95% CI: 1.023–2.485). Subgroup analyses suggested that the above effects of LT4 treatment were mainly from TPOAb-negative participants. LT4 treatment was associated with an increased risk of preterm birth (RR = 2.214, 95% CI: 1.016–4.825) in TPOAb-positive pregnant women with high-normal TSH levels. Conclusion: LT4 treatment was significantly associated with a lower risk of pregnancy loss and a higher risk of small-for-gestational-age infants in pregnant women with TSH levels of 2.5–10 mIU/L. An increased risk of preterm birth was observed in the LT4-treated group among TPOAb-positive participants with TSH levels of 2.5–4.0 mIU/L. [ABSTRACT FROM AUTHOR]

Background: Living in higher greenness level community has many benefits for pregnancy outcomes, however, few research have explored the relationship between greenness and spontaneous abortion (SAB). We aimed to analyze relationships between SAB and community greenness in Chinese pregnant women, and further assessed the modifying effects from air pollutants. Methods: We studied 90 890 pregnant women from the China Birth Cohort Study from February 2018 to December 2021. We diagnosed SAB by certified obstetricians and gynecologists. The level of exposure to greenness during the first trimester was measured using the normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI). Particulate matter ≤ 2.5 μm (PM2.5), nitrogen dioxide (NO2) and ozone (O3) were used as proxies of ambient air pollution. Time-dependent multivariable adjusted Cox proportional hazards models, with gestational weeks as the time scale, were used to analyze the association between SAB and greenness. We additionally performed subgroup analyses stratified by age, urbanicity, research location, season of birth, temperature, humidity and air pollution levels. Results: Lower SAB prevalence was related to living in greener places. A 0.1 unit increase in NDVI500m and EVI500m was significantly associated with a 12.3% (95% CI 9.9%, 15.5%) and 16.2% (95% CI 11.4%, 20.6%) lower risks of SAB, respectively. In sensitivity analysis, these relationships remained consistent. The associations were stronger among older, participants lived in the north of China and lived in places with higher PM2.5 and lower NO2 levels. Conclusions: Our findings indicate significantly inverse associations between community greenness and SAB in Chinese pregnant women, especially for older and participants who live in the north of China, the PM2.5 and NO2 may modify the effects of greenness on SAB. [ABSTRACT FROM AUTHOR]

Background: Subclinical hypothyroidism (SCH) is linked to dyslipidaemia and adverse pregnancy outcomes. However, the impact of dyslipidaemia on the outcome of pregnancy in SCH is unclear. Methods: We enrolled 36,256 pregnant women and evaluated their pregnancy outcomes. The following data was gathered during the first trimester (≤ 13+ 6 weeks of gestation): total cholesterol (TC), low-density lipoprotein (LDL-C), triglyceride (TG), high-density lipoprotein (HDL-C), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations. The reference ranges for lipids were estimated to range from the 5th to the 95th percentile. Logistic regression assessed the relationships between dyslipidaemia and adverse pregnancy outcomes, including abortion, preeclampsia/eclampsia, low birth weight, foetal growth restriction, premature rupture of foetal membranes, gestational hypertension, preterm birth, macrosomia and gestational diabetes mellitus (GDM). Additionally, the best thresholds for predicting adverse pregnancy outcomes based on TSH, FT4, and lipid levels were determined using receiver operating characteristic curves. Results: In the first trimester, LDL-C > 3.24 mmol/L, TG > 1.92 mmol/L, HDL-C < 1.06 mmol/L, and TC > 5.39 mmol/L were used to define dyslipidaemia. In this cohort, 952 (3.56%) patients were diagnosed with SCH, and those who had dyslipidaemia in the first trimester had higher incidences of gestational hypertension (6.59% vs. 3.25%), preeclampsia/eclampsia (7.14% vs. 3.12%), GDM (22.53% vs. 13.77%), and low birth weight (4.95% vs. 2.08%) than did those without dyslipidaemia. However, after adjusting for prepregnancy body mass index (pre-BMI), dyslipidaemia was no longer related to these risks. Furthermore, elevated TG dyslipidaemia in SCH patients was connected to an enhanced potential of gestational hypertension (odds ratio [OR]: 2.687, 95% confidence interval [CI]: 1.074 ~ 6.722), and elevated LDL-C dyslipidaemia correlated with increased preeclampsia/eclampsia risk (OR: 3.172, 95% CI: 1.204 ~ 8.355) after accounting for age, smoking status, alcohol use, pre-BMI, and levothyroxine use. Additionally, the combination of TC, TG, LDL-C, pre-BMI, and TSH exhibited enhanced predictive capabilities for gestational hypertension, preeclampsia/eclampsia, and GDM. Values of 0.767, 0.704, and 0.706 were obtained from the area under the curve. Conclusions: Among pregnant women with SCH, dyslipidaemia in early pregnancy was related to elevated risks of adverse pregnancy consequences. The combined consideration of age, pre-BMI, TSH, and lipid levels in the first trimester could be beneficial for monitoring patients and implementing interventions to reduce adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

The heterogeneity of oral glucose tolerance test (OGTT) patterns during pregnancy remains unclear. This study aims to identify latent OGTT patterns in pregnant women and investigate the high-risk population for late-onset gestational diabetes mellitus (GDM). This study including 17,723 participants was conducted from 2018 to 2021. Latent mixture modeling was used to identify subgroups. Modified Poisson regression was performed to explore the relationship between OGTT patterns and late-onset GDM or adverse perinatal outcomes. Three distinct glucose patterns, high, medium, and low glucose levels (HG, MG, and LG patterns) were identified. The HG pattern represented 28.5% of the participants and 5.5% of them developed late-onset GDM. A five-fold higher risk of late-onset GDM was found in HG pattern than in LG pattern (relative risk [RR]: 5.17, 95% confidence interval [CI]: 3.38-7.92) after adjustment. Participants in HG pattern were more likely to have macrosomia, large for gestational age, preterm birth, and cesarean deliveries, with RRs of 1.59 (1.31-1.93), 1.55 (1.33-1.82), 1.30 (1.02-1.64) and 1.15 (1.08-1.23), respectively. Three distinct OGTT patterns presented different risks of late-onset GDM and adverse perinatal outcomes, indicating that timely monitoring of glucose levels after OGTT should be performed in pregnant women with HG pattern. [ABSTRACT FROM AUTHOR]

To quantitatively synthesize evidence from prospective observational studies regarding the mean levels of circulating adiponectin in patients with gestational diabetes mellitus (GDM) and the association between adiponectin levels and GDM risk. PubMed, EMBASE and Web of Science were searched from their inception until November 8th, 2022, for nested case-control studies and cohort studies. Random-effect models were applied to the synthesized effect sizes. The difference in circulating adiponectin levels between the GDM and control groups was measured using the pooled standardized mean difference (SMD) and 95% confidence interval (CI). The relationship between circulating adiponectin levels and GDM risk was examined using the combined odds ratio (OR) and 95% CI. Subgroup analyses were performed according to the study continent, GDM risk in the study population, study design, gestational weeks of circulating adiponectin detection, GDM diagnostic criteria, and study quality. Sensitivity and cumulative analyses were performed to evaluate the stability of the meta-analysis. Publication bias was assessed by funnel plots and Egger's test. The 28 studies included 13 cohort studies and 15 nested case-control studies, containing 12,256 pregnant women in total. The mean adiponectin level in GDM patients was significantly lower than in controls (SMD = −1.514, 95% CI = −2.400 to −0.628, p =.001, I2 = 99%). The risk of GDM was significantly decreased among pregnant women with increasing levels of circulating adiponectin (OR = 0.368, 95% CI = 0.271–0.500, p <.001, I2=83%). There were no significant differences between the subgroups. Our findings indicate that increasing circulating adiponectin levels were inversely associated with the risk of GDM. Given the inherent heterogeneity and publication bias of the included studies, further well-designed large-scale prospective cohort or intervention studies are needed to confirm our finding. Increasing circulating adiponectin levels in the first to the second trimester could decrease the risk of incident GDM. [ABSTRACT FROM AUTHOR]

Serum uric acid (SUA) is considered as a risk factor for gestational diabetes mellitus (GDM). However, current studies showed inconsistent results. This study aimed to explore the relationship between SUA levels and GDM risk. Eligible studies were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and Wanfang databases up to November 1, 2022. The pooled standardized mean difference (SMD) and 95% confidence interval (CI) were used to represent the difference in SUA levels between GDM women and controls. The combined odds ratios (OR) and 95% CI were applied to assess association between SUA levels and GDM risk. Subgroup analyses were conducted on study continents, design, and quality, detection time of SUA, and GDM diagnostic criteria. Totally 11 studies including five case-control and six cohort studies, in which 80,387 pregnant women with 9815 GDM were included. The overall meta-analysis showed that the mean SUA level in GDM group was significantly higher than in controls (SMD = 0.423, 95%CI = 0.019–0.826, p =.040, I2 = 93%). Notably, pregnant women with elevated levels of SUA had a significantly increased risk of GDM (OR = 1.670, 95%CI = 1.184–2.356, p =.0035, I2 = 95%). Furthermore, subgroup analysis performed on the detection time of SUA showed a significant difference in the association between SUA and GDM risk within different trimesters (1st trimester: OR = 3.978, 95%CI = 2.177–7.268; 1st to 2nd trimester: OR = 1.340, 95%CI = 1.078–1.667; p between subgroups <.01). Elevated SUA was positively associated with GDM risk, particularly in the 1st trimester of pregnancy. Further studies with high quality are required to validate the findings of this study. [ABSTRACT FROM AUTHOR]

Background: There is no consensus reference range for serum lipid levels during pregnancy. The benefit of levothyroxine (L-T4) on serum lipid levels are unclear among pregnant women with subclinical hypothyroidism (SCH).Objective: To determine the recommended reference ranges for serum lipid concentrations during pregnancy and effects of L-T4 treatment on serum lipids in pregnant women with SCH.Design: Cohort study.Methods: A analysis of 20,365 women in the first trimester was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University during 2018-2020. After excluding women with adverse pregnancy outcomes, we determined the reference range of serum lipid in the first and third trimesters of pregnancy by using median and quartile to determine appropriate percentiles. Next, we divided into three groups as follows: SCH L-T4 treatment group (n = 319), SCH non-intervention group (n = 103) and the control group(n = 9598).Results: The recommended reference range for serum lipids in the first trimester of pregnancy should be: TC < 5.33 mmol/L, TG < 1.73 mmol/L, LDL-C < 3.12 mmol/L and HDL-C > 1.1 mmol/L, and in third trimester of pregnancy should be: TC < 8.47 mmol/L, TG < 4.86 mmol/L, LDL-C < 5.3 mmol/L and HDL-C > 1.34 mmol/L. There are significant differences in TC and LDL-C levels between SCH treatment group and SCH non-intervention Group (P = 0.043, P = 0.046; respectively).Conclusions: We determine the recommended reference ranges for serum lipid concentrations during pregnancy. TC and LDL-C levels in pregnant women with SCH could improve after L-T4 treatment. [ABSTRACT FROM AUTHOR]

The China birth cohort study (CBCS) is a prospective longitudinal, mega-cohort study and the first national-based birth cohort study, aiming to establish a birth cohort covering representative geographical areas of the whole of China to investigate risk factors for birth defects and develop strategies for their reduction. Pregnant women who are of Chinese nationality, are 6–13+6 weeks of gestation, plan to attend the routine antenatal examination and deliver in the study site, and give their informed, written consent are eligible to participate in this study. All participants are followed-up through an in-person interview at 20–23+6 weeks and again at 28–33+6 weeks of gestation, and at delivery, respectively. CBCS has been divided into three phases from 20th November 2017 to 31st December 2021, and the first two phases have now been completed on 29th February 2020, enrolling 120 377 eligible pregnant women during this period. During the same period a total of 40 837 participants had been followed up to the end of pregnancy. Study recruitment will continue until December 2021 to achieve the target of 500 000 participants. Meanwhile, biological samples including peripheral blood, amniocytes, cord blood, placenta, or umbilical cord tissue have been collected from participants according to various conditions. The incidence of birth defects in this group is 2.5% and congenital heart disease is the most common type of birth defect seen so far. A website is in the advanced stages of planning, to allow seamless data transfer and facilitate collaboration with groups around the world. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess whether maternal first-trimester low body mass index (BMI) has a protective effect against macrosomia. Methods: This was a cross-sectional study from January 1, 2011, to June 30, 2021, and 84,900 participants were included. The predictive performance of maternal first-trimester and parental pre-pregnancy BMI for macrosomia was assessed using the area under the receiver-operating characteristics curve (AUC). Multivariate logistic regression analyses were performed to evaluate the independent effect of maternal first-trimester low BMI on macrosomia. Interactions were investigated to evaluate the potential variation of the effect of first-trimester low BMI across different groups. Furthermore, interactions were also examined across groups determined by multiple factors jointly: a) gestational diabetes mellitus (GDM)/GDM history status, parity, and maternal age; and b) GDM/GDM history status, fetal sex, and season of delivery. Results: The proportion of macrosomia was 6.14% (5,215 of 84,900). Maternal first-trimester BMI showed the best discrimination of macrosomia (all Delong tests: P < 0.001). The protective effect of maternal first-trimester low BMI against macrosomia remained significant after adjusting for all confounders of this study [adjusted odds ratios (aOR) = 0.37, 95% CI: 0.32–0.43]. Maternal first-trimester low BMI was inversely associated with macrosomia, irrespective of parity, fetal sex, season of delivery, maternal age, and GDM/GDM history status. The protective effect was most pronounced among pregnant women without GDM/GDM history aged 25 to 29 years old, irrespective of parity (multipara: aOR = 0.32, 95% CI: 0.22–0.47; nullipara: aOR = 0.32, 95% CI: 0.24–0.43). In multipara with GDM/GDM history, the protective effect of low BMI was only observed in the 30- to 34-year-old group (aOR = 0.12, 95% CI: 0.02–0.86). For pregnant women without GDM/GDM history, the protective effect of maternal first-trimester low BMI against macrosomia was the weakest in infants born in winter, irrespective of fetal sex (female: aOR = 0.45, 95% CI: 0.29–0.69; male: aOR = 0.39, 95% CI: 0.28–0.55). Conclusion: Maternal first-trimester low BMI was inversely associated with macrosomia, and the protective effect was most pronounced among 25- to 29-year-old pregnant women without GDM/GDM history and was only found among 30- to 34-year-old multipara with GDM/GDM history. The protective effect of maternal first-trimester low BMI against macrosomia was the weakest in winter among mothers without GDM/GDM history. [ABSTRACT FROM AUTHOR]

Evidence suggests that maternal exposure to heat might increase the risk of preterm birth (PTB), but no study has investigated the effect from urban heat island (UHI) at individual level. Our study aimed to investigate the association between individual UHI exposure and PTB. We utilized data from the ongoing China Birth Cohort Study (CBCS), encompassing 103,040 birth records up to December 2020. UHI exposure was estimated for each participant using a novel individual assessment method based on temperature data and satellite-derived land cover data. We used generalized linear mixed-effects models to estimate the association between UHI exposure and PTB, adjusting for potential confounders including maternal characteristics and environmental factors. Consistent and statistically significant associations between UHI exposure and PTB were observed up to 21 days before birth. A 5 °C increment in UHI exposure was associated with 27 % higher risk (OR = 1.27, 95 % confident interval: 1.20, 1.34) of preterm birth in lagged day 1. Stratified analysis indicated that the associations were more pronounced in participants who were older, had higher pre-pregnancy body mass index level, of higher socioeconomic status and living in greener areas. Maternal exposure to UHI was associated with increased risk of PTB. These findings have implications for developing targeted interventions for susceptible subgroups of pregnant women. More research is needed to validate our findings of increased risk of preterm birth due to UHI exposure among pregnant women. [ABSTRACT FROM AUTHOR]