Determinants for Perinatal Mortality in South China: A Prospective Cohort Study.

Objective: To estimate the association of selected maternal and fetal characteristics with the risk of perinatal mortality in South China. Methods: A prospective cohort study was conducted from March 2013 to December 2019. The exposures of interest were maternal sociodemographic characteristics, lifestyle and habits during early pregnancy, and complications of pregnancy. Their effects on the development of perinatal death were analyzed in our study. Results: A total of 44,048 eligible pregnant women were included in the analysis. Of these, 596 fetuses were perinatal deaths (perinatal mortality was 13.5 per 1,000 births). After adjustment, maternal obesity, being employed, history of gestational hypertension, taking antidepressants during early pregnancy, history of gestational diabetes mellitus, gestational diabetes mellitus, infertility drug treatment and assisted reproductive techniques, history of neonatal death, preterm birth, and congenital malformations all significantly increased the risk of perinatal death. Ethnic minority, income > 5,000, multiparous women, and cesarean section associated with reduced risk of perinatal death. Conclusion: Some factors of maternal sociodemographic characteristics, abnormal pregnancy history, lifestyle and habits during early pregnancy, and complications of pregnancy were associated with the risk of perinatal death.

Association Between First-Trimester Maternal Cytomegalovirus Infection and Stillbirth: A Prospective Cohort Study.

Background: Given that the time lag between cytomegalovirus (CMV) screening and diagnosed testing, a better knowledge of the association between pregnant women with CMV screening test positive and stillbirth in an epidemiological perspective was required to assist people being counseled reframe their pregnancy and birth plans based on the magnitude of the risk. Methods: This study recruited 44048 eligible pregnant women from March 13, 2013 to December 31, 2019. Serological tests including CMV-specific IgM and IgG, and IgG avidity index were used to screen for maternal CMV infection and were measured by automated chemiluminescence immunoassay. The association was assessed using the inverse probability of group-weighted multivariate-adjusted log-binomial models. Results: A total of 540 infants ended with a stillbirth (12.3 per 1000 pregnancies), and 2472 pregnancies with maternal CMV infection were screened out (56.1 per 1000 pregnancies) among all eligible pregnancies. In the comparison analysis, 326 infants ended with a stillbirth (86.6 per 1000 pregnancies) in the maternal CMV infection group compared with 214 infants (7.8 per 1000 pregnancies) in the group where mothers were not infected with CMV (RR 12.17; 95% CI 9.43-15.71). After excluding the pregnancies of stillbirth with birth defects, a strong association between the two groups was still observed (RR 9.38; 95% CI 6.92-12.70). Conclusion: Our findings quantified the risk of a woman having a baby with stillbirth if she had a positive serologic CMV screening test in her first trimester, and supported the value of using CMV serologic tests as part of regular testing in pregnant women. Trial registration: Registered in Chinese Clinical Trial Registry Center; registration number, ChiCTR1800016635; registration date, 06/14/2018 (Retrospectively registered); URL of trial registry record, https://www.chictr.org.cn/showproj.aspx?proj=28300.

Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.

BACKGROUND: MTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations. METHODS: A case-control study of 464 mothers of CHD infants and 504 mothers of health controls was performed. The exposures of interest were maternal tobacco exposure, single nucleotide polymorphisms (SNPs) of maternal MTHFD1 gene. The logistic regression model was used for accessing the strength of association. RESULTS: Mothers exposed to secondhand smoke during 3 months before pregnancy (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI]: 1.13-2.15) and in the first trimester of pregnancy (aOR = 2.24; 95%CI: 1.57-3.20) were observed an increased risk of CHD. Our study also found that polymorphisms of maternal MTHFD1 gene at rs1950902 (AA vs. GG: aOR = 1.73, 95% CI: 1.01-2.97), rs2236222 (GG vs. AA: aOR = 2.38, 95% CI: 1.38-4.12), rs1256142 (GA vs.GG: aOR = 1.57, 95% CI: 1.01-2.45) and rs11849530 (GG vs. AA: aOR = 1.68, 95% CI: 1.02-2.77) were significantly associated with higher risk of CHD. However, we did not observe a significant association between maternal MTHFD1 rs2236225 and offspring CHD risk. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD1 gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure. CONCLUSIONS: Maternal polymorphisms of MTHFD1 gene, maternal tobacco exposure and their interactions are significantly associated with the risk of CHD in offspring in Han Chinese populations. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings. TRIAL REGISTRATION: Registration number: ChiCTR1800016635 .

Maternal Viral Infection in Early Pregnancy and Risk of Congenital Heart Disease in Offspring: A Prospective Cohort Study in Central China.

PURPOSE: To examine the associations of maternal virus infection in early pregnancy with risk of offspring congenital heart disease (CHD) and its seven common subtypes including atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, Tetralogy of Tallot, pulmonary stenosis, and transposition of the great arteries. PATIENTS AND METHODS: A prospective cohort study was conducted in Central China. A total of 44,048 pregnant women with singleton pregnancies at 8-14 gestational weeks were finally included and followed to 3 months postpartum. Serum was tested for virus infection including hepatitis B virus (HBV), coxsackievirus-B, human cytomegalovirus (HCMV), herpes simplex virus (HSV), and rubella virus. Multivariable modified Poisson regression models were used to estimate the relative risks (RRs) of all CHDs as well as seven common subtypes of CHD in offspring of pregnant women with different types of virus infection in early pregnancy, adjusting for confounders identified by directed acyclic graphs. RESULTS: At the end of follow-up, 564 births were diagnosed with CHD. Multivariable analyses showed that the presence of maternal viral infection in early pregnancy was independently associated with increased risks of CHD in offspring, with an adjusted relative risk of 2.21 (95% CI: 1.66-2.95) for HBV infection, 2.21 (95% CI: 1.63-3.00) for coxsackievirus-B infection, 3.12 (95% CI: 2.44-3.98) for HCMV infection, and 2.62 (95% CI: 1.95-3.51) for rubella virus infection. More specifically, the offspring of pregnant women with HCMV infection had the highest increased risk of patent ductus arteriosus (RR=10.50, 95% CI: 6.24-17.66). These findings persisted in analyses that were further adjusted for the other virus of interest in this study. CONCLUSION: Our study proposed evidence that maternal virus infection in early pregnancy, including HBV, coxsackievirus-B, HCMV, and rubella virus, was implicated in CHD, although more studies remain needed to verify the results, especially associations in specific CHD phenotypes.

Effect of maternal alcohol consumption during the pre-pregnancy/early-pregnancy period on congenital heart disease: A prospective cohort study in Central China.

Evidence of associations between maternal alcohol consumption and congenital heart disease (CHD) are mixed. Previous studies have been potentially biased due to recall bias or unmeasured confounding. This study aimed to examine the association of maternal alcohol consumption in 3 months before pregnancy and in early pregnancy with risks of offspring congenital heart disease (CHD) and its seven common subtypes. A prospective cohort study was conducted in Central China. From 03/13/2013 to 12/31/2019, a total of 44,048 pregnant women with singleton pregnancies at 8-14 gestational weeks were included and followed to 3 months postpartum. 564 births were diagnosed with CHD at the end of follow-up. Multivariable modified Poisson regression models were used to estimate the relative risks (RRs) of CHD in offspring exposed to maternal alcohol consumption during the pre-pregnancy and early-pregnancy period, adjusting for confounders identified by directed acyclic graphs. In the multivariable analyses, increased risks of CHDs were found in offspring exposed to maternal alcohol consumption both in 3 months before pregnancy (adjusted-RR:3.14; 95% confidence intervals[CIs]:2.30-4.28) and in early pregnancy (adjusted-RR:1.86; 95%CIs:1.13-3.05). More specifically, the offspring exposed to maternal alcohol consumption in 3 months before pregnancy had the highest increased risk of Tetralogy of Fallot (adjusted-RR:8.62; 95%CIs:3.61-20.61). These findings persisted in analyses that were further adjusted for the other behavior variables other than the characteristic being assessed, and were also confirmed by sensitivity analyses. Our study supports the need for continued efforts for public health messages surrounding the potential risks of alcohol consumption prior to or during pregnancy.

CircZFR promotes hepatocellular carcinoma progression through regulating miR-3619-5p/CTNNB1 axis and activating Wnt/ß-catenin pathway.

Circular RNAs (circRNAs) have been discovered to exert essential roles in human cancers, including hepatocellular carcinoma. Although circZFR has been reported to facilitate the growth of papillary thyroid cancer, the role of circZFR in hepatocellular carcinoma (HCC) are largely unknown. In this study, bioinformatics analysis showed that circZFR was closely related with hepatocellular carcinoma. We then detect the expression of circZFR in HCC tissues using qRT-PCR. Furthermore, Kaplan-Meier method and log rank test revealed that high expression of circZFR was associated with the poor prognosis of patients with HCC. Subsequently, loss-of-function assay indicated that circZFR knockdown significantly suppressed cell proliferation and epithelial-mesenchymal transition (EMT) in HCC. In addition, microarray analysis was utilized to identify the differentially expressed mRNAs in response to circZFR knockdown. Moreover, Gene Ontology (GO) analysis further showed that circZFR might regulate Wnt/ß-catenin signaling pathway. The results were further confirmed by luciferase reporter assay and western blot assays. Then bioinformatics tools predicted that cicrZFR enhanced the CTNNB1 expression via sponging miR-3619-5p. In summary, our findings indicated that circZFR may exert carcinogenic role in HCC through regulating miR-3619-5p/CTNNB1 axis and activating Wnt/ß-catenin pathway. These findings may provide a novel perspective for the treatment of hepatocellular carcinoma.

Prevalence of depression or depressive symptoms among people living with HIV/AIDS in China: a systematic review and meta-analysis.

BACKGROUND: The number of people living with HIV/AIDS (PLHA) in China continues to increase. Depression, a common mental disorder in this population, may confer a higher likelihood of worse health outcomes. An estimate of the prevalence of this disorder among PLHA is required to guide public health policy, but the published results vary widely and lack accuracy in China. The goal of this study was to estimate the pooled prevalence of depression or depressive symptoms among PLHA in China. METHODS: A systematic literature search of several databases was conducted from inception to June 2017, focusing on studies reporting on depression or depressive symptoms among PLHA in China. The risk of bias of individual studies was assessed using a modified version of the Newcastle-Ottawa scale. The overall prevalence estimates were pooled using random-effects meta-analysis. Differences according to study-level characteristics were examined using stratified meta-analysis and meta-regression. RESULTS: Seventy-four observational studies including a total of 20,635 PLHA were included. The pooled prevalence of depression or depressive symptoms was 50.8% (95% CI: 46.0-55.5%) among general PLHA, 43.9% (95% CI: 36.2-51.9%) among HIV-positive men who have sex with men, 85.6% (95% CI: 64.1-95.2%) among HIV-positive former blood/plasma donors, and 51.6% (95% CI: 31.9-70.8%) among other HIV-positive populations. Significant heterogeneity was detected across studies regarding these prevalence estimates. Heterogeneity in the prevalence of depression among the general population of PLHA was partially explained by the geographic location and baseline survey year. CONCLUSIONS: Because of the significant heterogeneity detected across studies regarding these prevalence estimates of depression or depressive symptoms, the results must be interpreted with caution. Our findings suggest that the estimates of depression or depressive symptoms among PLHA in China are considerable, which highlights the need to integrate screening and providing treatment for mental disorders in the treatment package offered to PLHA, which would ultimately lead to better health outcomes in PLHA.

Gemcitabine and cisplatin regimen facilitates prognosis of advanced nasopharyngeal carcinoma.

This study was conducted to assess the efficacy and adverse effects of GP (gemcitabine + cisplatin) regimen and FP (fluouracil + cisplatin) regimen in treatment of advanced nasopharyngeal carcinoma. Systematic online searches were performed in PubMed, Web of Sciences, China Knowledge Infrastructure and Weipu from the inception to November 15, 2017. Potential studies were assessed using the Cochrane risk of bias scale. Statistical analyses were performed on Stata 14.0 and RevMan 5.3. Finally, twelve studies entered final qualitative synthesis and quantitative analysis. The GP regimen compared with the FP regimen had significantly higher 1-year survival rate (relative risk (RR) = 1.07, 95% confidence interval (CI): 1.01-1.13), significantly better performance in the fixed-effect model (RR = 1.16, 95%CI: 1.04-1.30) and significantly higher remission rate (RR = 1.17, 95%CI: 1.05-1.29). Significant differences between regimens were found in gastrointestinal effects (RR = 0.58, 95%CI: 0.45-0.74). No significant differences between regimens were found in reduced hemoglobin rate (RR = 0.55, 95%CI: 0.36-1.21), neutropenia (RR = 1.84, 95%CI: 0.93-5.02), or reduced platelet (RR = 1.25, 95%CI: 0.85-1.75) and mucosal inflammation (RR = 0.81, 95%CI: 0.57-1.16). Sensitivity analysis indicated the results remained stable. The funnel plot indicated some publication bias. In conclusion, the GP regimen outperforms the FP regimen in treatment of advanced nasopharyngeal carcinoma with no difference in adverse effects. We may consider the GP regimen a better choice, but this conclusion should be confirmed by high-quality trials.

Diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B: a meta-analysis of diagnostic test.

This study is aimed at evaluating the diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B through a meta-analysis of diagnostic test. We conducted a comprehensive search in the Pubmed, Embase, Web of Science, and Chinese National Knowledge Infrastructure before October 31, 2016. Stata 14.0 software was used for calculation and statistical analyses. We used the sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), diagnostic odds ratio (DOR) and 95% confidence intervals (CIs) to evaluate the diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B. Twenty-six studies were included in the final analyses, with a total of 8274 individuals. The pooled parameters are calculated from all studies: sensitivity of 0.69 (95%CI:0.63-0.75), specificity of 0.81 (95%CI: 0.73-0.87), PLR of 3.63 (95%CI:2.66-4.94), NLR of 0.38 (95%CI:0.32-0.44), DOR of 9.57 (95%CI: 6.67-13.74), and area under the curve (AUC) of 0.80 (95%CI: 0.76-0.83). We also conducted subgroup based on the range of cut-off values. Results from subgroup analysis showed that cut-off was the source of heterogeneity in the present study. The sensitivity and specificity of cut-off>2 were 0.69 and 0.95 with the AUC of 0.90 (95%CI: 0.87-0.92). The overall diagnostic value of FIB-4 is not very high for liver fibrosis in patients with hepatitis B. However, the diagnostic value is affected by the cut-off value. FIB-4 has relatively high diagnostic value for detecting liver fibrosis in patients with hepatitis B when the diagnostic threshold value is more than 2.0.