Associations of Ambient Particulate Matter with Maternal Thyroid Autoimmunity and Thyroid Function in Early Pregnancy.

This prospective birth cohort study evaluated the association of exposure to PM2.5 (diameter ≤2.5 µm), PM1-2.5 (1-2.5 µm), and PM1 (≤1 µm) with maternal thyroid autoimmunity and function during early pregnancy. A total of 15,664 pregnant women were included at 6 to 13+6 gestation weeks in China from 2018 to 2020. Single-pollutant models using generalized linear models (GLMs) showed that each 10 µg/m3 increase in PM2.5 and PM1-2.5 was related with 6% (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.01, 1.12) and 15% (OR = 1.15, 95% CI: 1.08, 1.22) increases in the risk of thyroid autoimmunity, respectively. The odds of thyroid autoimmunity significantly increased with each interquartile range increase in PM2.5 and PM1-2.5 exposure (P for trend <0.001). PM1 exposure was not significantly associated with thyroid autoimmunity. GLM with natural cubic splines demonstrated that increases in PM2.5 and PM1-2.5 exposure were associated with lower maternal FT4 levels, while a negative association between PM1 and FT4 levels was found when exposure exceeded 32.13 µg/m3. Only PM2.5 exposure was positively associated with thyrotropin (TSH) levels. Our findings suggest that high PM exposure is associated with maternal thyroid disruption during the early pregnancy.

Levothyroxine treatment in pregnant women with thyroid stimulating hormone levels ranging between 2.5 and 10 mIU/L: A propensity score matched analysis.

OBJECTIVE: To clarify the association between levothyroxine (LT-4) treatment and various adverse pregnancy outcomes in pregnant women with thyroid stimulating hormone (TSH) levels ranging between 2.5 to 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 LT-4 treatment, pregnancy complications, and pregnancy outcomes was recorded. A 1:1 nearest-neighbor propensity score matching (PSM) between the LT-4-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 LT-4 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 LT-4 treatment, and 3,028 did not. The 1:1 PSM yielded 668 pairs of individuals and revealed that LT-4 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 LT-4 treatment were mainly from TPOAb-negative participants. LT-4 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: LT-4 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 LT-4-treated group among TPOAb-positive participants with TSH levels of 2.5-4.0 mIU/L.

The association between dyslipidaemia in the first trimester and adverse pregnancy outcomes in pregnant women with subclinical hypothyroidism: a cohort study.

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.

Association Between Maternal Thyroid Function in Early Pregnancy and Gestational Diabetes: A Prospective Cohort Study.

CONTEXT: Previous studies on the relationship between thyroid gland function and the development of gestational diabetes mellitus (GDM) have reported different results, leading to the need for a cohort study design with a large sample size. OBJECTIVE: We aimed to investigate the relationship between thyroid function in early pregnancy and GDM. METHODS: This was a prospective cohort study based on the China Birth Cohort Study (CBCS), from February 2018 to December 2020. The study took place at a tertiary maternal and child health hospital. A total of 36 256 pregnant women were successfully recruited based on the CBCS. The main outcome measure was GDM. RESULTS: This study consisted of 26 742 pregnant women who met the inclusion criteria, of whom 3985 (14.90%) were diagnosed with GDM, and the women with GDM were older than their healthy counterparts (33.26 ± 4.01 vs 31.51 ± 3.76 years, P < .001). After removing potential influencing variables, we found that increased thyroid-stimulating hormone (TSH) (adjusted odds ratio [aOR] 1.030, 95% CI 1.007, 1.054, P = .012) and subclinical hypothyroidism (aOR 1.211, 95% CI 1.010, 1.451, P = .039), but not free thyroxine or thyroid peroxidase antibody, were associated with the occurrence of GDM. Further analysis indicated a nonlinear relationship between TSH and GDM (P < .05): when TSH ≤ 1.24 mIU/L, the occurrence of GDM was elevated with increasing TSH, but when TSH > 1.24 mIU/L, this trend was not obvious. CONCLUSION: High TSH might be associated with increased risk of GDM.

Single-cell transcriptomics identify TNFRSF1B as a novel T-cell exhaustion marker for ovarian cancer.

BACKGROUND: Ovarian cancer (OC) patients routinely show poor immunotherapeutic response due to the complex tumour microenvironment (TME). It is urgent to explore new immunotherapeutic markers. METHODS: Through the single-cell RNA sequencing (scRNA-seq) analyses on high-grade serous OC (HGSOC), moderate severity borderline tumour and matched normal ovary, we identified a novel exhausted T cells subpopulation that related to poor prognosis in OC. Histological staining, multiple immunofluorescences, and flow cytometry were applied to validate some results from scRNA-seq. Furthermore, a tumour-bearing mice model was constructed to investigate the effects of TNFRSF1B treatment on tumour growth in vivo. RESULTS: Highly immunosuppressive TME in HGSOC is displayed compared to moderate severity borderline tumour and matched normal ovary. Subsequently, a novel exhausted subpopulation of CD8+ TNFRSF1B+ T cells is identified, which is associated with poor survival. In vitro experiments demonstrate that TNFRSF1B is specifically upregulated on activated CD8+ T cells and suppressed interferon-γ secretion. The expression of TNFRSF1B on CD8+ T cells is closely related to OC clinical malignancy and is a marker of poor prognosis through 140 OC patients' verification. In addition, the blockade of TNFRSF1B inhibits tumour growth via profoundly remodeling the immune microenvironment in the OC mouse model. CONCLUSIONS: Our transcriptomic results analyzed by scRNA-seq delineate a high-resolution snapshot of the entire tumour ecosystem of OC TME. The major applications of our findings were an exhausted subpopulation of CD8+ TNFRSF1B+ T cells for predicting OC patient prognosis and the potential therapeutic value of TNFRSF1B. These findings demonstrated the clinical value of TNFRSF1B as a potential immunotherapy target and extended our understanding of factors contributing to immunotherapy failure in OC.

Ambient cold exposure amplifies the effect of ambient PM1 on blood pressure and hypertensive disorders of pregnancy among Chinese pregnant women: A nationwide cohort study.

BACKGROUND: Little evidence exists regarding the combined effect between ambient temperature and air pollution exposure on maternal blood pressure (BP) and hypertensive disorders of pregnancy (HDP). OBJECTIVES: To assess effect modification by temperature exposure on the PM1-BP/HDP associations among Chinese pregnant women based on a nationwide study. METHODS: We conducted a cross-sectional country-based population study in China, enrolling 86,005 participants from November 2017 to December 2021. BP was measured with standardized sphygmomanometers. HDP was defined according to the American College of Obstetricians and Gynecologists' recommendations. Daily temperature data were obtained from the European Centre for Medium-Range Weather Forecasts. PM1 concentrations were evaluated using generalized additive model. Generalized linear mixed models were used to examine the health effects, controlling for multiple covariates. We also performed a series of stratified and sensitivity analyses. RESULTS: The pro-hypertensive effect of PM1 was observed in the first trimester. Cold exposure amplifies the first-trimester PM1-BP/HDP associations, with adjusted estimate (aß) for systolic blood pressure (SBP) of 3.038 (95 % CI: 2.320-3.755), aß for diastolic blood pressure (DBP) of 2.189 (95 % CI: 1.503-2.875), and aOR for HDP of 1.392 (95 % CI: 1.160-1.670). Pregnant women who were educated longer than 17 years or living in urban areas appeared to be more vulnerable to the modification in the first trimester. These findings remained robust after sensitivity analyses. CONCLUSIONS: First trimester maybe the critical exposure window for the PM1-BP/HDP associations among Chinese pregnant women. Cold exposure amplifies the associations, and those with higher education level or living in urban areas appeared to be more vulnerable.

Serum uric acid and the risk of gestational diabetes mellitus: a systematic review and meta-analysis.

AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The effect of circulating adiponectin levels on incident gestational diabetes mellitus: systematic review and meta­analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Association of ambient PM1 exposure with maternal blood pressure and hypertensive disorders of pregnancy in China.

Evidence concerning PM1 exposure, maternal blood pressure (BP), and hypertensive disorders of pregnancy (HDP) is sparse. We evaluated the associations using 105,063 participants from a nationwide cohort. PM1 concentrations were evaluated using generalized additive model. BP was measured according to the American Heart Association recommendations. Generalized linear mixed models were used to assess the PM1-BP/HDP associations. Each 10 µg/m3 higher first-trimester PM1 was significantly associated with 1.696 mmHg and 1.056 mmHg higher first-trimester SBP and DBP, and with 11.4% higher odds for HDP, respectively. The above associations were stronger among older participants (> 35 years) or those educated longer than 17 years or those with higher household annual income (> 400,000 CNY). To conclude, first-trimester PM1 were positively associated with BP/HDP, which may be modified by maternal age, education level, and household annual income. Further research is warranted to provide more information for both health management of HDP and environmental policies enactment.

Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13.

BACKGROUND: Metastasis, the leading cause of cancer-related death in patients diagnosed with ovarian cancer (OC), is a complex process that involves multiple biological effects. With the continuous development of sequencing technology, single-cell sequence has emerged as a promising strategy to understand the pathogenesis of ovarian cancer. METHODS: Through integrating 10 × single-cell data from 12 samples, we developed a single-cell map of primary and metastatic OC. By copy-number variations analysis, pseudotime analysis, enrichment analysis, and cell-cell communication analysis, we explored the heterogeneity among OC cells. We performed differential expression analysis and high dimensional weighted gene co-expression network analysis to identify the hub genes of C4. The effects of RAB13 on OC cell lines were validated in vitro. RESULTS: We discovered a cell subcluster, referred to as C4, that is closely associated with metastasis and poor prognosis in OC. This subcluster correlated with an epithelial-mesenchymal transition (EMT) and angiogenesis signature and RAB13 was identified as the key marker of it. Downregulation of RAB13 resulted in a reduction of OC cells migration and invasion. Additionally, we predicted several potential drugs that might inhibit RAB13. CONCLUSIONS: Our study has identified a cell subcluster that is closely linked to metastasis in OC, and we have also identified RAB13 as its hub gene that has great potential to become a new therapeutic target for OC.

Potential impact of ambient temperature on maternal blood pressure and hypertensive disorders of pregnancy: A nationwide multicenter study based on the China birth cohort.

Limited evidence exists regarding the association between ambient temperature and blood pressure (BP) level of pregnant women. To investigate the associations of ambient temperature with maternal BP and hypertensive disorders of pregnancy (HDP), we studied 105,063 participants in 38 centers of 17 provinces from November 2017 to December 2021. BP was measured with standardized automated digital sphygmomanometers. Ambient temperature was classified into five classes as very hot, moderate hot, mild, moderate cold, and very cold. Generalized linear mixed models were used to investigate the ambient temperature-BP/HDP associations, controlling for multiple covariates. No significant associations of first-trimester ambient temperature with maternal BP and HDP prevalence were observed. Compared with mild temperature, second-trimester very cold and second-trimester moderate cold were statistically associated with the increase of 1.239 mmHg (95% CI: 0.908, 1.569) and 0.428 mmHg (95% CI: 0.099, 0.757) for second-trimester systolic blood pressure (SBP), respectively. Similar trends were also observed in the association between second-trimester cold exposure and second-trimester diastolic blood pressure (DBP), in the association between second-trimester cold exposure and third-trimester SBP/DBP as well as in the association between third-trimester cold exposure and third-trimester SBP/DBP although some estimates were not statistically significant. Furthermore, in the second and third trimester, very cold [second trimester: adjusted odds ratio (aOR) = 1.298; third trimester: aOR = 1.236) and moderate cold (second trimester: aOR = 1.208; third trimester: aOR = 1.146) exposures also increased the odds of HDP, and these associations were stronger among participants aged ≥35 years or from North China. The second and third trimesters are the critical exposure windows for ambient temperature exposure-BP/HDP associations. During this period, exposure to cold ambient temperature was associated with elevated BP as well as increased HDP prevalence among most Chinese pregnant women, those aged ≥35 years or from North China being more vulnerable.

Association between Maternal Blood Glucose Levels during Pregnancy and Birth Outcomes: A Birth Cohort Study.

OBJECTIVE: This study aimed to investigate the relationship between maternal blood glucose levels during pregnancy and neonatal birth outcomes in Northwest China. METHODS: This population-based cohort study included 10,010 first-trimester pregnant women who joined the birth cohort of the Northwest Women's and Children's Hospital from July 2018 to July 2020. Basic demographic characteristics, lifestyle and behavior patterns were collected. Oral glucose tolerance test (OGTT) results during the second trimester and pregnancy outcomes after childbirth were also collected. A generalized linear model was constructed to analyze the effects of blood glucose levels on neonatal birth outcomes. RESULTS: We found that every 1 mmol/L increase in fasting plasma glucose (FPG) was associated with an increase in birth weight (ß = 100.22 g, 95% confidence interval (95%CI): 81.91, 118.52), birth weight Z score (ß = 0.23, 95%CI: 0.19, 0.27) and birth weight Z centile (ß = 6.72%, 95%CI: 5.51, 7.94). Moreover, the risk of macrosomia, premature birth and being born large for gestational age (LGA) increased by 2.01 (95%CI: 1.67, 2.43), 1.35 (95%CI: 1.09, 1.66) and 1.80 (95%CI: 1.57, 2.07) times, respectively. Additionally, for every 1 mmol/L increase in FPG associated with a decrease in gestational age (ß = -0.12 weeks, 95%CI: -0.19, -0.06), the risk of SGA decreased by 0.70 (OR = 0.70, 95%CI: 0.55, 0.89) times. Every 1 mmol/L increase in 1/2-h PG had similar outcomes as FPG, besides premature birth and SGA. CONCLUSIONS: Higher blood glucose in pregnant women may increase neonatal birth weight, decrease gestational age and lead to a higher risk of macrosomia, premature birth and LGA. Mothers should actively prevent and control hyperglycemia to promote maternal and infant health.

NUF2 promotes tumorigenesis by interacting with HNRNPA2B1 via PI3K/AKT/mTOR pathway in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is one of the commonest and deadliest diseases that threaten the health of women worldwide. It is essential to find out its pathogenic mechanisms and therapeutic targets for OC patients. Although NUF2 (Ndc80 kinetochore complex component) has been suggested to play an important role in the development of many cancers, but little is known about its function and the roles of proteins that regulate NUF2 in OC. This study aimed to investigate the effect of NUF2 on the tumorigenicity of OC and the activities of proteins that interact with NUF2. METHODS: Oncomine database and immunohistochemical (IHC) staining were used to evaluate the expression of NUF2 in OC tissues and normal tissues respectively. Normal ovarian epithelial cell lines (HOSEpiC) and OC cell lines (OVCAR3、HEY、SKOV3) were cultured. Western blot was applied to analyze the expression of NUF2 in these cell lines. Small interfering RNA (siRNA) was used to silence the expression of NUF2 in OC cell lines, SKOV3 and HEY. Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), the CCK-8 method, colony formation assay and flow cytometry were conducted to analyze the biological functions of NUF2 in vitro. OC subcutaneous xenograft tumor models were used for in vivo tests. Immunoprecipitation and mass spectrometry (IP/MS) were performed to verify the molecular mechanisms of NUF2 in OC. IP, immunofluorescence, IHC staining, and Gene Expression Profiling Interactive Analysis platform (GEPIA) were used to analyze the relationship between HNRNPA2B1 and NUF2 in OC cells. SiRNA was used to silence the expression of HNRNPA2B1 in SKOV3 cells, reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay and western blot were used to detect the effect of HNRNPA2B1 on NUF2. GEPIA, The Cancer Genome Atlas (TCGA) database, GSEA and western blot were used to detect the potential signaling pathways related to the roles of HNRNPA2B1 and NUF2 in OC cells. RESULTS: Our results showed high NUF2 expression in OC tissues and OC cell lines, which was associated with shorter overall survival and progression-free survival in patients. NUF2 depletion by siRNA suppressed the proliferation abilities and induced cell apoptosis of OC cells in vitro, and impeded OC growth in vivo. Mechanistically, NUF2 interacted with HNRNPA2B1 and activated the PI3K/AKT/mTOR signaling pathway in OC cells. CONCLUSION: NUF2 could serve as a prognostic biomarker, and regulated the carcinogenesis and progression of OC. Moreover, NUF2 may interact with HNRNPA2B1 by activating the PI3K/AKT/mTOR signaling pathway to promote the development of OC cells. Our present study supported the key role of NUF2 in OC and suggested its potential as a novel therapeutic target.

Coronavirus Disease 2019 Pandemic-Related Long-Term Chronic Impacts on Psychological Health of Perinatal Women in China.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has caused far-reaching changes in all areas of society. However, limited data have focused on the long-term impacts on perinatal psychological health. This study aims to evaluate long-term impacts of COVID-19 pandemic crisis on psychological health among perinatal women and investigate associated factors. STUDY DESIGN: A multicenter, cross-sectional study, the psychological subproject of China Birth Cohort Study (CBCS), was conducted in 2021. Demographic and obstetric characteristics, pregnancy outcomes, psychological status, and COVID-19-pandemic-related factors were obtained. The symptoms of depression, anxiety, and insomnia of participants were assessed by Patient Health Questionnaire, Edinburgh Postpartum Depression Scale, Generalized Anxiety Disorder Scale, and Insomnia Severity Index, respectively. Multivariate logistic regression was used to identify associated factors of adverse psychological symptoms. RESULTS: Totally, 1,246 perinatal women were enrolled, with the overall prevalence of depression, anxiety, and insomnia symptoms being 63.16, 41.89, and 44.38%, respectively. Perinatal women who needed psychological counseling and were very worried about the COVID-19 pandemic were 1.8 to 7.2 times more likely to report symptoms of depression, anxiety, and insomnia. Unemployment, flu-like symptoms, younger maternal age, and previous diseases before pregnancy were risk factors for depression, anxiety, or insomnia. CONCLUSION: Our study revealed that the prevalence of perinatal depression, anxiety, and insomnia symptoms was at a high level even 1 year after the pandemic outbreak, implying pandemic-associated long-term psychological impacts on perinatal women existed. Government should not only pay attention to the acute effects of psychological health but also to long-term psychological impacts on perinatal women after major social events. KEY POINTS: · The prevalence of perinatal psychological symptoms was at a high level after the COVID-19 outbreak.. · Perinatal women who were very worried about COVID-19 were more often to have psychological symptoms.. · Perinatal women with demands of mental counseling were more likely to report psychological symptoms..

Is the Tradeoff between Folic Acid or/and Multivitamin Supplementation against Birth Defects in Early Pregnancy Reconsidered? Evidence Based on a Chinese Birth Cohort Study.

BACKGROUND: Several studies have reported conflicting results on the association between maternal exposure to folic acid (FA) and/or multivitamin (MV) supplements and the risk of birth defects (BDs), especially for different subtypes of BDs. The present study aimed to identify the association between maternal exposure to FA or/and MV and BDs in offspring. METHODS: In the Chinese Birth Cohort Study initiated from 20 November 2017, 120,652 pregnant women completed follow-up until 20 August 2021. The participants were classified into four groups: without exposure to FA and MV, exposure to only FA, exposure to only MV, and exposure to FA and MV. Birth defects were coded by the International Classification of Diseases (ICD)-10. In order to explore the structural relationship between maternal FA or MV supplements and BDs, directed acyclic graphs were drawn. Then, an inverse probability treatment weighting was utilized to reduce the systematic differences in the baseline characteristics among the different groups. Lastly, a two-level mixed-effect log binomial regression analysis was used to estimate the relative risk (RR) value of the different subtypes of BDs under different exposures to FA and/or MV. RESULTS: Compared with the maternal group without exposure to FA and MV, the RR values of nervous system defects, face, ear, and neck defects, limb defects, and CHDs in the maternal group with only FA supplementation were less than 1.0, but they were not statistically significant. The RR values of genitourinary defects, abnormal chromosomes, and oral clefts were more than 1.0, and they were also not statistically significant. However, the risk of genitourinary defects (RR: 3.22, 95% CI: 1.42-7.29) and chromosomal abnormalities (RR: 2.57, 95% CI: 1.16-5.73) in the maternal group with only MV supplementation increased more than those in the maternal group without exposure to FA and MV. In addition, the RR values of all subtypes of BDs in the maternal group with exposure to FA and MV were closer to 1.0 than those in maternal group with exposure to only MV, but they were not statistically significant. CONCLUSIONS: It was indicated that the simultaneous supplementation of FA and MV in early pregnancy may have an interaction for the prevention of BDs and may have inconsistent effects for different subtypes of BDs. At the same time, excessive FA supplementation in pregnant women may increase the risk of BDs in their offspring. Although the mechanism is not clear, this evidence reminded us that more trade-offs are necessary for formulating strategies for the prevention of BDs with FA and/or MV supplementation in early pregnancy.

Prenatal exposure to silver is associated with an elevated risk for neural tube defects: a case-control study.

Exposure to copper, silver, and titanium has been reported to be associated with a variety of adverse effects on humans, but it is little focused on the fetus. We investigated the associations between prenatal exposure to the three metals (copper, silver, and titanium) and risk for fetal neural tube defects (NTDs). Placental samples from 408 women with pregnancies affected by NTDs and 593 women with normal pregnancies were collected from 2003 to 2016 in Pingding, Xiyang, Shouyang, Taigu, and Zezhou counties of China. Multilevel mixed-effects logistic regression and Bayesian kernel machine regression (BKMR) were used to evaluate the single and joint effects of the metals on NTDs. Silver was associated with an increased risk for NTDs in a dose-response fashion in single-metal logistic regression, with adjusted odds ratios (95% confidence intervals) of 1.78 (1.04-3.06) and 1.92 (1.11-3.32) in the second and third tertiles, respectively, compared to the lowest tertile. BKMR revealed toxic effects of silver on NTDs and the association appeared to be linear. No interaction of silver with any of the other two metals was observed. Besides, silver concentration was positively correlated with maternal certain dietary intakes. Placental high silver concentrations are associated with an elevated risk for NTDs. Maternal diet may be a source of silver exposure.

Identify gestational diabetes mellitus by deep learning model from cell-free DNA at the early gestation stage.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy, which has significant adverse effects on both the mother and fetus. The incidence of GDM is increasing globally, and early diagnosis is critical for timely treatment and reducing the risk of poor pregnancy outcomes. GDM is usually diagnosed and detected after 24 weeks of gestation, while complications due to GDM can occur much earlier. Copy number variations (CNVs) can be a possible biomarker for GDM diagnosis and screening in the early gestation stage. In this study, we proposed a machine-learning method to screen GDM in the early stage of gestation using cell-free DNA (cfDNA) sequencing data from maternal plasma. Five thousand and eighty-five patients from north regions of Mainland China, including 1942 GDM, were recruited. A non-overlapping sliding window method was applied for CNV coverage screening on low-coverage (~0.2×) sequencing data. The CNV coverage was fed to a convolutional neural network with attention architecture for the binary classification. The model achieved a classification accuracy of 88.14%, precision of 84.07%, recall of 93.04%, F1-score of 88.33% and AUC of 96.49%. The model identified 2190 genes associated with GDM, including DEFA1, DEFA3 and DEFB1. The enriched gene ontology (GO) terms and KEGG pathways showed that many identified genes are associated with diabetes-related pathways. Our study demonstrates the feasibility of using cfDNA sequencing data and machine-learning methods for early diagnosis of GDM, which may aid in early intervention and prevention of adverse pregnancy outcomes.

Is glucose pattern of OGTT associated with late-onset gestational diabetes and adverse pregnant outcomes?

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Integrating single-cell RNA sequencing and prognostic model revealed the carcinogenicity and clinical significance of FAM83D in ovarian cancer.

Background: Ovarian cancer (OC) is a fatal gynecological tumor with high mortality and poor prognosis. Yet, its molecular mechanism is still not fully explored, and early prognostic markers are still missing. In this study, we assessed carcinogenicity and clinical significance of family with sequence similarity 83 member D (FAM83D) in ovarian cancer by integrating single-cell RNA sequencing (scRNA-seq) and a prognostic model. Methods: A 10x scRNA-seq analysis was performed on cells from normal ovary and high-grade serous ovarian cancer (HGSOC) tissue. The prognostic model was constructed by Lasso-Cox regression analysis. The biological function of FAM83D on cell growth, invasion, migration, and drug sensitivity was examined in vitro in OC cell lines. Luciferase reporter assay was performed for binding analysis between FAM83D and microRNA-138-5p (miR-138-5p). Results: Our integrative analysis identified a subset of malignant epithelial cells (C1) with epithelial-mesenchymal transition (EMT) and potential hyperproliferation gene signature. A FAM83D+ malignant epithelial subcluster (FAM83D+ MEC) was associated with cell cycle regulation, apoptosis, DNA repair, and EMT activation. FAM83D resulted as a viable prognostic marker in a prognostic model that efficiently predict the overall survival of OC patients. FAM83D downregulation in SKOV3 and A2780 cells increased cisplatin sensitivity, reducing OC cell proliferation, migration, and invasion. MiR-138-5p was identified to regulate FAM83D's carcinogenic effect in OC cells. Conclusions: Our findings highlight the importance of miR-138 -5p/FAM83D/EMT signaling and may provide new insights into therapeutic strategies for OC.

Psychological health status in postpartum women during COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis pooled the prevalence of psychological symptoms during the COVID-19 pandemic and examined the effects of the pandemic on psychological health in postpartum women. METHODS: A systematic literature search and identification were performed in PubMed, EMBASE, Web of Science, and PsycINFO databases until June 16th, 2021. The fixed or random effect models to estimate the pooled prevalence of postpartum psychological symptoms during the COVID-19 pandemic and the odds ratio (OR) of COVID-19 for psychological symptoms. RESULTS: A total of 29 articles including 20,225 postpartum women during the COVID-19 pandemic and 8312 before the COVID-19 pandemic were identified. During the COVID-19 pandemic, the prevalence of postpartum depressive, anxiety, stress, and post-traumatic stress disorder symptoms were 26.7 % (95 % CI: 22.0-31.9 %), 33.8 % (95 % CI: 21.1-49.4 %), 55.0 % (95%CI: 27.9-79.5 %), and 33.7 % (95%CI: 19.6-51.5 %), respectively. The ORs of COVID-19 pandemic for postpartum depressive and anxiety symptoms were 1.54 (95 % CI: 1.00-2.36) and 2.56 (95%CI: 1.62-4.04). Subgroup analyses revealed that women with >6 weeks after delivery, younger than 35 years old, low income, less education and without breastfeeding experienced a higher risk of depressive or anxiety symptoms after delivery. LIMITATIONS: Only a few of prospective studies were included, and significant but inevitable heterogeneities were found in some analyses. CONCLUSION: A significantly higher proportion of postpartum women were suffered from psychological symptoms during COVID-19 pandemic, particularly in those with >6 weeks after delivery, younger than 35 years old, low income, less education and formula feeding.