Type 2 diabetes, glycaemic traits, structural brain capacity and cognitive function: A Mendelian randomization analysis.

AIM: To estimate the causal associations of type 2 diabetes and glycaemic traits with cognitive function, and to determine the potential mediating role of various brain imaging-derived phenotypes (IDPs) using Mendelian randomization (MR) analysis. METHODS: Using publicly available summary data, we performed a series of univariable and multivariable MR analysis to infer causality. Two-step MR analysis was then conducted in turn to evaluate the potential mediating role of each brain IDP. RESULTS: There was no evidence of causal associations between type 2 diabetes and cognitive function outcomes. Each 1-SD unit higher genetically predicted fasting proinsulin was associated with worse cognitive performance, as evidenced by both univariable (beta: -0.022; 95% confidence interval [CI] -0.038, -0.007) and multivariable MR analysis (beta: -0.027; 95% CI -0.048, -0.005). In addition, the univariable MR analysis identified several causal associations between fasting proinsulin and brain IDPs, and between brain IDPs and cognitive performance. The inverse association of genetically predicted fasting proinsulin with cognitive performance did not attenuate after adjusting for each of the brain IDPs in multivariable MR analysis. CONCLUSIONS: The present MR study provided credible evidence for the causal association between genetically predicted fasting proinsulin and cognitive function, informing a potential diagnosis and intervention target for patients with cognitive impairment. No significant brain IDP included in this study was identified as lying on the causal pathway from fasting proinsulin to cognitive performance. Future research involving more specific and granular brain IDP or other brain process is warranted to explore the potential biological mechanism underlying the association.

Associations between maternal syphilis infection during pregnancy and low birth weight and preterm birth: a prospective cohort study.

BACKGROUND: In recent years, syphilis is still the most common sexually transmitted disease worldwide. Pregnant women infected with syphilis can transmit it to the fetus in utero through mother-to-child transmission, which can directly lead to adverse pregnancy outcomes. The aim of this study was to investigate the associations between maternal syphilis infection and low birth weight and preterm birth in offspring. METHODS: Multinomial logistic regression model was used to analyze the associations between maternal syphilis infection and low birth weight and preterm birth, and to explore its stability through subgroup analysis. RESULTS: A total of 34,074 subjects were included in the study. After adjusting for potential confounders, maternal syphilis infection during pregnancy was associated with a 2.60-fold (95% CI 1.83-3.69) increased risk of low birth weight and a 1.91-fold (95% CI 1.35-2.69) increased risk of preterm birth. Subgroup analysis showed that the association was stable. CONCLUSION: We found that maternal syphilis infection during pregnancy was significantly associated with an increased risk of low birth weight and preterm birth. The implementation of reasonable syphilis screening and standardized treatment and follow-up of pregnant syphilis may have important practical significance in reducing the low birth weight and preterm birth rate in offspring.

The risk of attention-deficit hyperactivity disorder among children with congenital heart disease: A systematic review and meta-analysis.

BACKGROUND: Although current treatments are effective in dealing with congenital heart disease (CHD), non-cardiac comorbidities such as attention-deficit hyperactivity disorder (ADHD) have received widespread attention. The purpose of this systematic review and meta-analysis is to assess the risk of ADHD associated with CHD. METHODS: The literature search was carried out systematically through eight different databases by the end of September 2022. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. The heterogeneity of the studies was assessed by the Cochran Q test and the I2 statistic. Subgroup and sensitivity analyses were used to explore the potential sources of heterogeneity. RESULTS: Eleven studies were included in this study, which involved a total of 296 741 participants. Our study showed that the children with CHD were at a significantly increased risk of ADHD compared with the reference group (OR = 2.98, 95% CI: 2.18-4.08). The results were moderately heterogeneous. These factors including study design, geographic region and study quality were identified as the first three of the most relevant heterogeneity moderators by subgroup analyses. Sensitivity analysis yielded consistent results. There was no evidence of publication bias. CONCLUSIONS: The present study suggests that CHD children have a significantly higher risk of ADHD when compared with those without CHD. Early identification and intervention of ADHD is important to reduce its symptoms and adverse effects; therefore, clinicians should increase screening for ADHD in children with CHD and intervene promptly to reduce its effects whenever possible.

Causal relationship between air pollution and chronic obstructive pulmonary disease in European and East Asian populations: a Mendelian randomization study.

Epidemiologic studies have suggested a possible association between air pollution and chronic obstructive pulmonary disease (COPD), but it is controversial and difficult to draw causal inferences. Five methods were adopted to evaluate the causal relationship between air pollution and COPD in European and East Asian populations by using MR Analysis. A statistically significant causal relationship between PM2.5 and COPD was observed in the European population (OR: 2.34; 95% CI: 1.06-5.05; p = 0.033). Statistical significance remained after adjustment for confounding factors (adjusted OR: 2.28; 95% CI: 1.01-5.20; p = 0.048). In East Asian populations, PM2.5 absorbance, a proxy for black carbon, was statistically associated with COPD (OR: 1.41; 95% CI: 1.09-1.81; p = 0.007). We did not adjust for confounders in East Asian populations, as the association was independent of known confounders (e.g. smoking, respiratory tract infections, etc.). In conclusion, increased concentrations of PM2.5 and PM2.5 absorbance were associated with an increased risk of COPD.

[A case-control study on the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with risk of congenital heart disease in offspring]. / çˆ¶æ¯å›´å­•æœŸå¸çƒŸå’Œé¥®é ’åŠå ¶äº¤äº’ä½œç”¨ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— å ³è”çš„ç— ä¾‹å¯¹ç §ç ”ç©¶.

OBJECTIVES: To explore the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with risk of congenital heart disease (CHD) in offspring. METHODS: The parents of children with simple CHD aged 0 to 1 year (n=683) were recruited as the case group, while the parents of healthy children aged 0 to 1 year (n=740) served as the control group. A case-control study was conducted, and a questionnaire was used to collect information on perinatal exposures. After controlling for relevant confounding factors using multivariate logistic regression analysis and propensity score matching, the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with CHD were examined, as well as the cumulative effects of smoking and drinking on CHD risk. RESULTS: Maternal active smoking (OR=2.91, 95%CI: 1.60-5.30), passive smoking (OR=1.94, 95%CI: 1.56-2.42), and alcohol consumption (OR=2.59, 95%CI: 1.89-3.54), as well as paternal smoking (OR=1.52; 95%CI: 1.22-1.90) and drinking (OR=1.48, 95%CI: 1.19-1.84), were associated with an increased risk of CHD in offspring. There was no interaction between parental smoking and drinking behaviors during the periconceptional period concerning the risk of CHD in offspring (P>0.05). The more parents' smoking and drinking behaviors during the perinatal pregnancy, the higher the risk of CHD in their offspring (OR=1.50, 95%CI: 1.36-1.65). CONCLUSIONS: Parental smoking and alcohol consumption during the periconceptional period are associated with the occurrence of CHD in offspring, and there is a cumulative effect on CHD risk, suggesting that reducing tobacco and alcohol exposure during the periconceptional period may lower the incidence of CHD.

[Maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation in relation to offspring ventricular septal defects]. / 母亲MTRåŸºå› å¤šæ€æ€§åŠå ¶ä¸Žå›´å­•æœŸå¶é ¸è¡¥å çš„äº¤äº’ä½œç”¨ä¸Žå­ä»£å®¤é—´éš”ç¼ºæŸçš„å ³è”ç ”ç©¶.

OBJECTIVES: To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects (VSD) in offspring. METHODS: A case-control study was conducted, recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants. A questionnaire survey collected data on maternal exposures, and blood samples were analyzed for genetic polymorphisms. Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD. Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake. RESULTS: The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD (P<0.05). The GC and CC genotypes at rs3768139, AG and GG at rs1050993, AT and TT at rs4659743, GG at rs3768142, and GT and TT at rs3820571 were associated with a decreased risk of VSD (P<0.05). The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD (P<0.05). CONCLUSIONS: Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring. Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period, suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

Association between gut microbiome and intracerebral hemorrhage based on genome-wide association study data. / 基于GWASæ•°æ®åˆ†æžè‚ é“èŒç¾¤ä¸Žè„‘å‡ºè¡€çš„å ³ç³».

OBJECTIVES: Intracerebral hemorrhage (ICH) has the highest mortality and disability rates among various subtypes of stroke. Previous studies have shown that the gut microbiome (GM) is closely related to the risk factors and pathological basis of ICH. This study aims to explore the causal effect of GM on ICH and the potential mechanisms. METHODS: Genome wide association study (GWAS) data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium. Based on the GWAS data, we first performed Mendelian randomization (MR) analysis to evaluate the causal association between GM and ICH. Then, a conditional false discovery rate (cFDR) method was conducted to identify the pleiotropic variants. RESULTS: MR analysis showed that Pasteurellales, Pasteurellaceae, and Haemophilus were negatively correlated with the risk of ICH, whileVerrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae, Akkermansia, Holdemanella, and LachnospiraceaeUCG010 were positively correlated with ICH. By applying the cFDR method, 3 pleiotropic loci (rs331083, rs4315115, and rs12553325) were found to be associated with both GM and ICH. CONCLUSIONS: There is a causal association and pleiotropic variants between GM and ICH.

Prevalence of Malnutrition in Children with Congenital Heart Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the global prevalence of malnutrition in children with congenital heart disease (CHD). STUDY DESIGN: A systematic review and meta-analysis were performed. Web of Science, PubMed, Embase, Wanfang Database, China National Knowledge Infrastructure, and China Biology Medicine disc databases were searched for studies published through April 2021. Random-effect model meta-analyses were performed to derive the pooled the prevalence of preoperative underweight, stunting, and wasting in children with CHD. Time-trend analyses of postoperative malnutrition prevalence were undertaken. Subgroup and sensitivity analyses were conducted to explore sources of heterogeneity. Egger test and funnel plots were used to explore public bias. RESULTS: A total of 39 studies were included in this meta-analysis. The pooled estimates of preoperative malnutrition in children with CHD were 27.4% (95% CI, 21.7-34.0) for underweight, 24.4% (95% CI, 19.5-30.0) for stunting, and 24.8% (95% CI, 19.3-31.3) for wasting. Catch-up growth was found in the postoperative period among some children. Different continents were identified as heterogeneity moderators by subgroup analyses. CONCLUSIONS: Children with CHD have a high prevalence of preoperative malnutrition and some show catch-up growth postoperatively. These data can be used as benchmarks in efforts to improve the nutritional status of children with CHD.

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.

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 .

Association of periconceptional folate supplements and FOLR1 and FOLR2 gene polymorphisms with risk of congenital heart disease in offspring: A hospital-based case-control study. / æ¯äº²å›´å­•æœŸæœç”¨å¶é ¸åŠFOLR1和FOLR2åŸºå› å¤šæ€æ€§ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— å ³è”çš„ç— ä¾‹å¯¹ç §ç ”ç©¶.

OBJECTIVES: Maternal periconceptional folic acid supplement is by far the most effective primary prevention strategy to reduce the incidence of congenital heart disease (CHD) in offspring. It was revealed that the underlying mechanisms are complex, including a combination of genetic and environmental factors. The purpose of this study is to investigate the association between periconceptional folic acid supplement, the genetic polymorphisms of maternal folic acid receptor 1 gene (FOLR1) and folic acid receptor 2 gene (FOLR2) and the impact of their interaction on the risk of CHD in offspring, and to provide epidemiological evidence for individualized folic acid dosing in hygienic counseling. METHODS: A case-control study on 569 mothers of CHD infants and 652 mothers of health controls was performed. The interesting points were periconceptional folate supplements, single nucleotide polymorphisms (SNPs) of maternal FOLR1 gene and FOLR2 gene. RESULTS: Mothers who took folate in the periconceptional period were observed a decreased risk of CHD [adjusted odds ratio (aOR)=0.58, 95% CI 0.35 to 0.95]. Our study also found that polymorphisms of maternal FOLR1 gene at rs2071010 (G/A vs G/G: aOR=0.67, 95% CI 0.47 to 0.96) and FOLR2 gene at rs514933 (T/C vs T/T: aOR=0.60, 95% CI 0.43 to 0.84; C/C vs T/T: aOR=0.55, 95% CI 0.33 to 0.90; the dominant model: T/C+ C/C vs T/T: aOR=0.59, 95% CI 0.43 to 0.81; and the addictive model: C/C vs T/C vs T/T: aOR=0.70, 95% CI 0.56 to 0.88) were significantly associated with lower risk of CHD [all P<0.05, false discovery rate P value (FDR_P)<0.1]. Besides, significant interaction between periconceptional folate supplements and rs2071010 G→A (aOR=0.59, 95% CI 0.41-0.86) and rs514933 T→C (aOR=0.52, 95% CI 0.37 to 0.74) on CHD risk were observed (all P<0.05, FDR_P<0.1). CONCLUSIONS: Periconceptional folate supplements, polymorphisms of FOLR1 gene and FOLR2 gene and their interactions are significantly associated with risk of CHD. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.

[Association of maternal MTHFD1 and MTHFD2 gene polymorphisms with congenital heart disease in offspring]. / 母亲MTHFD1及MTHFD2åŸºå› å¤šæ€æ€§ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— çš„å ³è”.

OBJECTIVES: To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) gene polymorphisms with congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD. RESULTS: The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR=1.49; GG vs AA: OR=2.04) andat rs1256142 (GA vs GG: OR=2.34; AA vs GG: OR=3.25) significantly increased the risk of CHD in offspring (P<0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR=0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR=0.68) significantly reduced the risk of CHD in offspring (P<0.05). The haplotypes of G-G-G (OR=1.86) and G-A-G (OR=1.35) in mothers significantly increased the risk of CHD in offspring (P<0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD (P<0.05). CONCLUSIONS: Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.

Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring.

BACKGROUND: Although many studies showed that the risk of congenital heart disease (CHD) was closely related to genetic factors, the exact pathogenesis is still unknown. Our study aimed to comprehensively assess the association of single nucleotide polymorphisms (SNPs) of maternal MTHFR gene with risk of CHD and its three subtypes in offspring. METHODS: A case-control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed. RESULTS: Our study showed that genetic polymorphisms of maternal MTHFR gene at rs4846052 and rs1801131 were significantly associated with risk of CHD in the homozygote comparisons (TT vs. CC at rs4846052: OR = 7.62 [95%CI 2.95-19.65]; GG vs. TT at rs1801131: OR = 5.18 [95%CI 2.77-9.71]). And six haplotypes of G-C (involving rs4846048 and rs2274976), A-C (involving rs1801133 and rs4846052), G-T (involving rs1801133 and rs4846052), G-T-G (involving rs2066470, rs3737964 and rs535107), A-C-G (involving rs2066470, rs3737964 and rs535107) and G-C-G (involving rs2066470, rs3737964 and rs535107) were identified to be significantly associated with risk of CHD. Additionally, we observed that a two-locus model involving rs2066470 and rs1801131 as well as a three-locus model involving rs227497, rs1801133 and rs1801131 were significantly associated with risk of CHD in the gene-gene interaction analyses. For three subtypes including atrial septal defect, ventricular septal defect and patent ductus arteriosus, similar results were observed. CONCLUSIONS: Our study indicated genetic polymorphisms of maternal MTHFR gene were significantly associated with risk of fetal CHD in the Chinese population. Additionally, there were significantly interactions among different SNPs on risk of CHD. However, how these SNPs affect the development of fetal heart remains unknown, and more studies in different ethnic populations and with a larger sample are required to confirm these findings.

Association of maternal folate use and reduced folate carrier gene polymorphisms with the risk of congenital heart disease in offspring.

Although it is generally recognized that genetic and environmental factors are associated with the risk of congenital heart disease (CHD), the mechanism remains largely uncertain. This study aimed to investigate the association of maternal folate use, the time when folate use was started, and polymorphisms of the reduced folate carrier (RFC1) gene with the risk of CHD in offspring of Chinese descent, which can help provide new insight into the etiology of folate-related birth defects. A case-control study of 683 mothers of CHD patients and 740 mothers of healthy children was performed. The present study showed that mothers who did not use folate were at a significantly increased risk of CHD (OR=2.04; 95% CI: 1.42-2.93). When compared with those who started using folate prior to conception, mothers who started using folate from the first trimester of pregnancy (OR=1.90; 95% CI: 1.43-2.54) or from the second trimester of pregnancy (OR=8.92; 95% CI: 4.20-18.97) had a significantly higher risk of CHD. Maternal RFC1 gene polymorphisms at rs2236484 (AG vs AA: OR=1.79 [95% CI: 1.33-2.39]; GG vs AA: OR=1.64 [95% CI: 1.15-2.35]) and rs2330183 (CT vs CC: OR=1.54 [95% CI: 1.14-2.09]) were also significantly associated with CHD risk. Additionally, the risk of CHD was significantly decreased among mothers who had variant genotypes but used folate when compared with those who had variant genotypes and did not use folate.Conclusion: In those of Chinese descent, maternal folate use and the time when use started are significantly associated with the risk of CHD in offspring. Furthermore, maternal folate supplementation may help to offset some of the risks of CHD in offspring due to maternal RFC1 genetic variants. What is Known: • Folate use could help prevent CHD, but the relationship between the time when folate use is started and CHD has not received sufficient attention. • Studies have assessed the associations of folate metabolism-related genes with CHD, but genes involved in cellular transportation of folate, such as the RFC1 gene, have not garnered enough attention. What is New: • In those of Chinese descents, the time when folate use is started is significantly associated with the risk of CHD in offspring. • Maternal RFC1 polymorphisms were significantly associated with the risk of CHD. • Folate supplementation may help to offset some risks of CHD due to RFC1 genetic variants.

Heterotopic Cesarean Scar Pregnancy: An Analysis of 20 Cases Following in vitro Fertilization-Embryo Transfer.

We report a series of 20 cases of heterotopic cesarean scar pregnancy in this study. The results show that transvaginal sonography offers highly accurate diagnoses of heterotopic cesarean scar pregnancy during the first trimester. Careful exclusion of cesarean scar pregnancy is of great clinical importance for patients with a history of cesarean section after in vitro fertilization-embryo transfer, even when an intrauterine pregnancy has been detected. We recommend single embryo transfer for patients with a history of cesarean section. Expectant management may provide the opportunity for a live cesarean scar pregnancy to develop, albeit at high risks of placenta accreta and hemorrhage, and this needs further verification in the future.

Epidemiological characteristics and spatial epidemiology of hand-foot-mouth disease in Hunan Province, China, from 2008 to 2019. / 2008~2019å¹´æ¹–å—çœæ‰‹è¶³å£ç— æµè¡Œç‰¹å¾åŠç©ºé—´æµè¡Œç— å­¦åˆ†æž.

OBJECTIVES: To investigate the epidemic situation of hand-foot-mouth disease (HFMD) in Hunan Province, China, from 2008 to 2019, as well as its spatial autocorrelation characteristics and spatial-temporal clustering, and to provide a reference for the prevention and control of HFMD in Hunan Province. METHODS: Spatial autocorrelation and spatial-temporal clustering analyses were used to analyze the monitoring data of HFMD in Hunan Province from 2008 to 2019. RESULTS: The epidemic situation of HFMD in Hunan Province from 2008 to 2019 showed obvious seasonal distribution, with a low incidence rate in January to March and a high incidence rate in April to July. As for population distribution, children aged 0-5 years had the highest number of HFMD cases and accounted for 95.89% (1 460 391/1 522 910) of all cases, with a mean annual incidence rate of 2 197.784/100 000, and scattered children had the highest number of cases and accounted for 82.59% (1 257 739/1 522 910) of all cases. The global spatial autocorrelation analysis showed that the onset of HFMD in Hunan Province showed a significant clustering distribution, and the local spatial autocorrelation analysis showed that the high clustering areas of HFMD were mainly the districts and counties of Changsha, Zhuzhou, and Yueyang cities. Time-space scanning showed that clustering time was mainly April to July; the cases were clustered in the northeast of Hunan Province from 2008 to 2010 and in the central part of Hunan Province from 2011 to 2019. CONCLUSIONS: The high incidence rate of HFMD is observed in April to July in Hunan Province. Children under 5 years of age are at a high risk of this disease. Spatial-temporal clustering is observed for the epidemic of HFMD, mainly clustered in the northeastern and central areas of Hunan Province. It is suggested that the results may be used as guidance to determine the key areas for HFMD prevention and control in Hunan Province and optimize the allocation of health resources.

Risk factors for preterm birth: a prospective cohort study. / æ—©äº§å±é™©å› ç´ çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To investigate the incidence of preterm birth and risk factors for preterm birth. METHODS: A prospective cohort study was performed for the pregnant women in early pregnancy and their spouses, who underwent prenatal examination for the first time in Hunan Provincial Maternal and Child Health Care Hospital from May 2014 to December 2016 and decided to be hospitalized for delivery. A questionnaire survey was performed to collect exposure information possibly related to preterm birth. The hospital's medical record system was used for information verification and to record the pregnancy outcome. A multivariate logistic regression analysis was used to investigate the risk factors for preterm birth. RESULTS: A total of 6 764 pregnant women with complete data were included, and the incidence rate of preterm birth was 17.09%. The multivariate logistic regression analysis showed that a history of adverse pregnancy outcomes, eating areca nut before pregnancy, a history of pregnancy complications, a history of hepatitis, no folate supplementation during pregnancy, medication during pregnancy, active smoking and passive smoking during pregnancy, drinking during pregnancy, unbalanced diet during pregnancy, high-intensity physical activity during pregnancy, and natural conception after treatment of infertility or assisted conception as the way of conception were risk factors for preterm birth (P<0.05). Additionally, the pregnant women whose spouses were older, had a higher body mass index or smoked had an increased risk for preterm birth (P<0.05). A higher level of education of pregnant women or their spouses and lower gravidity were protective factors against preterm birth (P<0.05). CONCLUSIONS: There are many risk factors for preterm birth. Special attention should be paid to the life behaviors of pregnant women during pregnancy, and health education should be strengthened for pregnant women and their spouses to develop good living habits and reduce the incidence of preterm births.

[Association between maternal reduced folate carrier gene polymorphisms and congenital heart disease in offspring: a case-control study].

OBJECTIVE: To study the association between maternal reduced folate carrier (RFC) gene polymorphisms and congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of RFC gene polymorphisms and their haplotypes with CHD. A generalized multifactor dimensionality reduction method was used to analyze gene-gene interactions. RESULTS: After control for confounding factors, the multivariate logistic regression analysis showed that maternal RFC gene polymorphisms at rs2236484 (AG vs AA:OR=1.91, 95%CI:1.45-2.51; GG vs AA: OR=1.96, 95%CI:1.40-2.75) and rs2330183 (CT vs CC:OR=1.39, 95%CI:1.06-1.83) were significantly associated with the risk of CHD in offspring. The haplotypes of G-G (OR=1.21, 95%CI:1.03-1.41) and T-G (OR=1.25, 95%CI:1.07-1.46) in mothers significantly increased the risk of CHD in offspring. The interaction analysis showed significant gene-gene interactions between different SNPs of the RFC gene in CHD (P < 0.05). CONCLUSIONS: Maternal RFC gene polymorphisms and interactions between different SNPs are significantly associated with the risk of CHD in offspring.

Birth prevalence of congenital heart disease in China, 1980-2019: a systematic review and meta-analysis of 617 studies.

To assess the birth prevalence and spatial distribution of congenital heart disease (CHD) in China by conducting a complete overview and using spatial epidemiological methods. Unrestricted searches were conducted on seven electronic databases, with an end-date parameter of May 2019. Data on the birth prevalence of CHD and its subtypes were collected and combined using either the random-effect model or fixed-effect model. Subgroup sensitivity analyses were performed to explore potential heterogeneity moderators. The three-dimensional trend analysis and a visualization of CHD birth prevalence among different provinces were performed to describe the spatial distribution characteristics. Total 617 studies involving 76,961,354 births and 201,934 CHD individuals were included. Overall, total CHD birth prevalence increased continuously over time, from 0.201‰ in 1980-1984 to 4.905‰ in 2015-2019. The study on the high-income provinces, population-based monitoring model, male births, and urban regions reported a significantly higher prevalence of total CHD compared with upper-middle-income provinces, hospital-based monitoring model, female births, and rural regions, respectively. National CHD birth prevalence increased gradually from western region to eastern region, but decreased gradually from southern to northern region. Relevant heterogeneity moderators including gender, geographic region, income levels, and monitoring models have been identified by subgroup analyses. Sensitivity analysis yielded consistent results. Total CHD birth prevalence in China increases continuously in the past 40 years. Significant differences in gender, geographical regions, income levels, and monitoring models were found. In the future, population wide prospective birth defect registries covering the entire Chinese population need to determine the exact birth prevalence.

Reference intervals of gestational sac, yolk sac, embryonic length, embryonic heart rate at 6-10 weeks after in vitro fertilization-embryo transfer.

BACKGROUND: Accurately determining the normal range of early pregnancy markers can help to predict adverse pregnancy outcomes. The variance in ovulation days leads to uncertain accuracy of reference intervals for natural pregnancies. While the gestational age (GA) is accurate estimation during in vitro fertilization-embryo transfer (IVF-ET). Thus, the objective of this research is to construct reference intervals for gestational sac diameter (GSD), yolk sac diameter (YSD), embryonic length (or crown-rump length, CRL) and embryonic heart rate (HR) at 6-10 gestational weeks (GW) after IVF-ET. METHODS: From January 2010 to December 2016, 30,416 eligible singleton pregnancies were retrospectively recruited. All included participants had full records of early ultrasound measurements and phenotypically normal live neonates after 37 GW, with birth weights > the 5th percentile for gestational age. The curve-fitting method was used to screen the optimal models to predict GSD, CRL, YSD and HR based on gestational days (GD) and GW. Additionally, the percentile method was used to calculate the 5th, 50th, and 95th percentiles. RESULTS: There were significant associations among GSD, CRL, YSD, HR and GD and GW, the models were GSD = - 29.180 + 1.070 GD (coefficient of determination [R2] = 0.796), CRL = - 11.960 - 0.147 GD + 0.011 GD2 (R2 = 0.976), YSD = - 2.304 + 0.184 GD - 0.011 GD2 (R2 = 0.500), HR = - 350.410 + 15.398 GD - 0.112 GD2 (R2 = 0.911); and GSD = - 29.180 + 7.492 GW (R2 = 0.796), CRL = - 11.960 - 1.028 GW + 0.535 GW2 (R2 = 0.976), YSD = - 2.304 + 1.288 GW - 0.054 GW2 (R2 = 0.500), HR = - 350.410 + 107.788 GW - 5.488 GW2 (R2 = 0.911), (p < 0.001). CONCLUSIONS: Reference intervals for GSD, YSD, HR and CRL at 6-10 gestational weeks after IVF-ET were established.