Postoperative leukocyte counts as a surrogate for surgical stress response in matched robot- and video-assisted thoracoscopic surgery cohorts of patients: A preliminary report.

The objective is to preliminary evaluated postoperative leukocyte counts as a surrogate for the surgical stress response in NSCLC patients who underwent RATS or VATS for further prospective analyses with proper assessment of surgical stress response and tissue trauma. We retrospectively analyzed patients with stageI-IIIA NSCLC who underwent RATS or VATS at a hospital between 8 May 2020 and 31 December 2021. Analysis of leukocytes (including neutrophils and lymphocytes) and albumin on postoperative days (PODs) 1 and 3 in patients with NSCLC treated with RATS or VATS after propensity score matching (PSM). In total, 1824 patients (565 RATS and 1259 VATS) were investigated. The two MIS groups differed significantly with regard to operative time (p < 0.001), chronic lung disease (p < 0.001), the type of pulmonary resection (p < 0.001), the excision site of lobectomy (p = 0.004), and histology of the tumor (p = 0.028). After PSM, leukocyte and neutrophil levels in the RATS group were lower than those in the VATS group on PODs 1 and 3, with those on POD 3 (p < 0.001) being particularly notable. While lymphocyte levels in the RATS group were significantly lower than those in the VATS group only at POD 1 (p = 0.016). There was no difference in albumin levels between the RATS and VATS groups on PODs 1 and 3. The surgical stress response and tissue trauma was less severe in NSCLC patients who underwent RATS than in those who underwent VATS, especially reflected in the neutrophils of leukocytes.

Predictive model for identifying mild cognitive impairment in patients with type 2 diabetes mellitus: A CHAID decision tree analysis.

BACKGROUND: As the population ages, mild cognitive impairment (MCI) and type 2 diabetes mellitus (T2DM) become common conditions that often coexist. Evidence has shown that MCI could lead to reduced treatment compliance, medication management, and self-care ability in T2DM patients. Therefore, early identification of those with increased risk of MCI is crucial from a preventive perspective. Given the growing utilization of decision trees in prediction of health-related outcomes, this study aimed to identify MCI in T2DM patients using the decision tree approach. METHODS: This hospital-based case-control study was performed in the Endocrinology Department of Xiangya Hospital affiliated to Central South University between March 2021 and December 2022. MCI was defined based on the Petersen criteria. Demographic characteristics, lifestyle factors, and T2DM-related information were collected. The study sample was randomly divided into the training and validation sets in a 7:3 ratio. Univariate and multivariate analyses were performed, and a decision tree model was established using the chi-square automatic interaction detection (CHAID) algorithm to identify key predictor variables associated with MCI. The area under the curve (AUC) value was used to evaluate the performance of the established decision tree model, and the performance of multivariate regression model was also evaluated for comparison. RESULTS: A total of 1001 participants (705 in the training set and 296 in the validation set) were included in this study. The mean age of participants in the training and validation sets was 60.2  ±  10.3 and 60.4  ±  9.5 years, respectively. There were no significant differences in the characteristics between the training and validation sets (p > .05). The CHAID decision tree analysis identified six key predictor variables associated with MCI, including age, educational level, household income, regular physical activity, diabetic nephropathy, and diabetic retinopathy. The established decision tree model had 15 nodes composed of 4 layers, and age is the most significant predictor variable. It performed well (AUC = .75 [95% confidence interval (CI): .71-.78] and .67 [95% CI: .61-.74] in the training and validation sets, respectively), was internally validated, and had comparable predictive value compared to the multivariate logistic regression model (AUC = .76 [95% CI: .72-.80] and .69 [95% CI: .62-.75] in the training and validation sets, respectively). CONCLUSION: The established decision tree model based on age, educational level, household income, regular physical activity, diabetic nephropathy, and diabetic retinopathy performed well with comparable predictive value compared to the multivariate logistic regression model and was internally validated. Due to its superior classification accuracy and simple presentation as well as interpretation of collected data, the decision tree model is more recommended for the prediction of MCI in T2DM patients in clinical practice.

Sleep quality and its associated factors among patients with type 2 diabetes mellitus in Hunan, China: a cross-sectional study.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a serious public health issue. Compared with the general population, patients with T2DM have a higher risk of poor sleep quality, which could ultimately result in poor prognosis. Therefore, this study aimed to evaluate sleep quality and its associated factors among patients with T2DM in Hunan, China. DESIGN: This was a cross-sectional study. SETTING: A tertiary hospital in Hunan, China. PARTICIPANTS: Patients with T2DM hospitalised at the Endocrinology Department were consecutively enrolled between March 2021 and December 2022. Sociodemographic characteristics, lifestyle factors and T2DM-related information were collected retrospectively. PRIMARY AND SECONDARY OUTCOME MEASURES: Sleep quality was evaluated using the Pittsburgh Sleep Quality Index, with a cut-off value of >7 suggesting poor sleep quality. Multivariate logistic regression analysis was used to determine factors associated with poor sleep quality. RESULTS: Of the 1039 participants included, 1001 provided complete data. The mean age of the study sample was 60.24±10.09 years, and 40.5% (95% CI 37.5% to 43.5%) of patients had poor sleep quality. Multivariate logistic regression analysis showed that female sex (adjusted OR (aOR) 1.70, 95% CI 1.25 to 2.29), unmarried status (aOR 1.72, 95% CI 1.05 to 2.83), diabetic retinopathy (aOR 1.38, 95% CI 1.04 to 1.83), diabetic foot (aOR 1.80, 95% CI 1.11 to 2.93) and a per capita monthly household income of >5000 RMB (aOR 0.66, 95% CI 0.47 to 0.93) were associated with poor sleep quality. CONCLUSIONS: Nearly two-fifths of patients with T2DM reported poor sleep quality in Hunan, China. Sex, marital status, diabetic retinopathy, diabetic foot and household income were independently associated with sleep quality among patients with T2DM in Hunan, China.

Relationships between Maternal Folic Acid Supplementation and GATA4 Gene Polymorphisms in Patients with Non-Chromosomal Congenital Heart Disease: A Hospital-Based Case-Control Study in China.

This study aimed to investigate the relationships between maternal FA supplementation and nine single-nucleotide variants of the GATA4 gene in non-chromosomal CHD and further explore the gene-environment interactions associated with CHD. A total of 585 CHD patients and 600 controls were recruited in the case-control study. Maternal FA (FA-containing multivitamin) supplementation information and nine polymorphisms of the GATA4 gene were collected in this study. Adjusted ORs (aOR) and their 95% confidence intervals (CIs) were calculated using proper statistical methods to analyze the relationships between the two main exposures of interest with respect to CHD. After adjusting the suspicious confounding factors, a significantly increased risk for CHD in offspring was found with non-FA supplementation before/during the pregnancy to CHD in offspring (aOR = 1.58, 95% CI: 1.01-2.48). We suggested taking FA supplementation before/during the pregnancy to prevent CHD in offspring, especially in the preconception period (aOR = 0.53, 95% CI: 0.32-0.90). The genetic results showed that the polymorphisms of rs4841588, rs12458, and rs904018 under specific genotypes and genetic models were significantly related to CHD. The gene-environment interaction between rs10108052 and FA supplementation before/during pregnancy could increase the risk of CHD (aOR = 5.38, 95% CI: 1.67-17.09, Pinteraction = 0.004). Relationships between maternal FA supplementation and specific polymorphisms of the GATA4 gene, as well as the gene-environment interaction, were significantly associated with CHD in offspring.

Prevalence of Anxiety and Associated Factors Among Inpatients with Type 2 Diabetes Mellitus in China: A Cross-Sectional Study.

This study aimed to investigate the prevalence of anxiety and its associated factors among inpatients with type 2 diabetes mellitus (T2DM) in China. This study was a cross-sectional study. Inpatients with T2DM admitted to the Endocrinology Department of Xiangya Hospital, Central South University in Hunan Province of China from March 2021 to December 2021 were consecutively included in this study. Participants were interviewed to obtain the data on socio-demographic characteristics, lifestyle characteristics, T2DM-related information, and social support. Anxiety was measured using the Hospital Anxiety and Depression Scale-anxiety subscale by experienced physicians. Multivariable logistic regression analysis was used to estimate the independent contribution of each independent variable to anxiety. A total of 496 inpatients with T2DM were included in this study. The prevalence of anxiety was 21.8% (95% confidence interval [CI]: 18.1%-25.4%). The results of multivariable logistic regression analysis indicated that age of at least 60 (adjusted odd ratio [aOR] = 1.79, 95% CI: 1.04-3.08), and having diabetes specific complications (aOR = 4.78, 95% CI: 1.02-22.44) were risk factors for anxiety, and an educational level of high school or above (aOR = 0.55, 95% CI: 0.31-0.99), regular physical activity (aOR = 0.36, 95% CI: 0.22-0.58), and high social support (aOR = 0.30, 95% CI: 0.17-0.53) were protective factors for anxiety. A predictive model based on these five variables showed good performance (area under the curve = 0.80). Almost one in five inpatients with T2DM suffered from anxiety in China. Age, educational level, regular physical activity, diabetes specific complications, and social support were independently associated with anxiety.

Association of maternal methionine synthase reductase gene polymorphisms with the risk of congenital heart disease in offspring: a hospital-based case-control study.

BACKGROUND: Evidence suggests that periconceptional folic acid supplementation may prevent congenital heart disease (CHD). Methionine synthase reductase (MTRR) is one of the key regulatory enzymes in the folate metabolic pathway. This study aimed to comprehensively evaluate the association of single nucleotide polymorphisms (SNPs) in the maternal MTRR gene with CHD risk in offspring. METHODS: A hospital-based case-control study involving 740 mothers of CHD cases and 683 health controls was conducted. RESULTS: The study showed that maternal MTRR gene polymorphisms at rs1532268 (C/T vs. C/C: aOR = 1.524; T/T vs. C/C: aOR = 3.178), rs1802059 (G/A vs. G/G: aOR = 1.410; A/A vs. G/G: aOR = 3.953), rs2287779 (G/A vs. G/G: aOR = 0.540), rs16879334 (C/G vs. C/C: aOR = 0.454), and rs2303080 (T/A vs. T/T: aOR = 0.546) were associated with the risk of CHD. And seven haplotypes were observed to be associated with the risk of CHD, T-G-A haplotype (OR = 1.298), C-A-C-C (OR = 4.824) and A-G haplotype (OR = 1.751) were associated with increased risk of CHD in offspring; A-A-A (OR = 0.773), T-A-A (OR = 0.557), G-A-C-C (OR = 0.598) and G-C (OR = 0.740) were associated with decreased risk of CHD in offspring. CONCLUSIONS: Maternal MTRR gene polymorphisms were associated with CHD in offspring, and its haplotypes have affected the occurrence of CHD. Furthermore, given the complexity and heterogeneity of CHD, the mechanisms by which these factors influence offspring cardiac development remain unknown, and studies in larger samples in an ethnically diverse population are needed.

The use of nomogram for detecting mild cognitive impairment in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is highly prevalent worldwide and may lead to a higher rate of cognitive dysfunction. This study aimed to develop and validate a nomogram-based model to detect mild cognitive impairment (MCI) in T2DM patients. METHODS: Inpatients with T2DM in the endocrinology department of Xiangya Hospital were consecutively enrolled between March and December 2021. Well-qualified investigators conducted face-to-face interviews with participants to retrospectively collect sociodemographic characteristics, lifestyle factors, T2DM-related information, and history of depression and anxiety. Cognitive function was assessed using the Mini-Mental State Examination scale. A nomogram was developed to detect MCI based on the results of the multivariable logistic regression analysis. Calibration, discrimination, and clinical utility of the nomogram were subsequently evaluated by calibration plot, receiver operating characteristic curve, and decision curve analysis, respectively. RESULTS: A total of 496 patients were included in this study. The prevalence of MCI in T2DM patients was 34.1% (95% confidence interval [CI]: 29.9%-38.3%). Age, marital status, household income, diabetes duration, diabetic retinopathy, anxiety, and depression were independently associated with MCI. Nomogram based on these factors had an area under the curve of 0.849 (95% CI: 0.815-0.883), and the threshold probability ranged from 35.0% to 85.0%. CONCLUSIONS: Almost one in three T2DM patients suffered from MCI. The nomogram, based on age, marital status, household income, duration of diabetes, diabetic retinopathy, anxiety, and depression, achieved an optimal diagnosis of MCI. Therefore, it could provide a clinical basis for detecting MCI in T2DM patients.

Prevalence of comorbid depression and associated factors among hospitalized patients with type 2 diabetes mellitus in Hunan, China.

BACKGROUND: Depression and diabetes are major health challenges, with heavy economic social burden, and comorbid depression in diabetes could lead to a wide range of poor health outcomes. Although many descriptive studies have highlighted the prevalence of comorbid depression and its associated factors, the situation in Hunan, China, remains unclear. Therefore, this study aimed to identify the prevalence of comorbid depression and associated factors among hospitalized type 2 diabetes mellitus (T2DM) patients in Hunan, China. METHODS: This cross-sectional study involved 496 patients with T2DM who were referred to the endocrinology inpatient department of Xiangya Hospital affiliated to Central South University, Hunan. Participants' data on socio-demographic status, lifestyle factors, T2DM-related characteristics, and social support were collected. Depression was evaluated using the Hospital Anxiety and Depression Scale-depression subscale. All statistical analyses were conducted using the R software version 4.2.1. RESULTS: The prevalence of comorbid depression among hospitalized T2DM patients in Hunan was 27.22% (95% Confidence Interval [CI]: 23.3-31.1%). Individuals with depression differed significantly from those without depression in age, educational level, per capita monthly household income, current work status, current smoking status, current drinking status, regular physical activity, duration of diabetes, hypertension, chronic kidney disease, stroke, fatty liver, diabetic nephropathy, diabetic retinopathy, insulin use, HbA1c, and social support. A multivariable logistic regression model showed that insulin users (adjusted OR = 1.86, 95% CI: 1.02-3.42) had a higher risk of depression, while those with regular physical activity (adjusted OR = 0.48, 95% CI: 0.30-0.77) or greater social support (adjusted OR = 0.20, 95% CI: 0.11-0.34) had a lower risk of depression. The area under the curve of the receiver operator characteristic based on this model was 0.741 with a sensitivity of 0.785 and specificity of 0.615. CONCLUSIONS: Depression was moderately prevalent among hospitalized T2DM patients in Hunan, China. Insulin treatment strategies, regular physical activity, and social support were significantly independently associated with depression, and the multivariable model based on these three factors demonstrated good predictivity, which could be applied in clinical practice.

Association between paternal pre-pregnancy body mass index with preterm birth and low birth weight.

Background: With the current global epidemic of obesity, especially among men, there is a need to understand its impact on adverse pregnancy outcomes. This study aimed to assess whether paternal pre-pregnancy body mass index (BMI) was associated with preterm birth and low birth weight in offspring. Methods: Multinomial logistic regression model was used to analyze associations between paternal BMI and preterm birth and low birth weight in different subgroups, the final model was adjusted for confounding factors of mothers and fathers. Further subgroup analysis was conducted to explore the stability of the risk associations. Results: A total of 34,104 participants were included in this study, including 1,442 (4.2%) underweight, 13,930 (40.9%) overweight and 5,008 (14.7%) obese according to paternal BMI. The total incidence of preterm birth was 11.85% (4041/34104), and the incidence of low birth weight was 8.86% (3020/34104). In the total study population, compared with normal weight men, paternal pre-pregnancy overweight or obese was associated with a significantly increased risk of preterm birth [aOR; 95% CI respectively (1.34; 1.25-1.45 vs. 1.26; 1.14-1.40)] and low birth weight [aOR; 95% CI respectively (1.60; 1.46-1.74 vs. 1.40; 1.25-1.58)] in offspring. The results of subgroup analysis showed that the direction of the risk association was consistent, indicating good stability. Conclusion: Paternal pre-pregnancy overweight and obesity were associated with an increased risk of preterm birth and low birth weight in their offspring.

Association of methylenetetrahydrofolate reductase gene polymorphisms and maternal folic acid use with the risk of congenital heart disease.

Background: To systematically evaluate the association of MTHFR genetic polymorphisms, maternal folic acid intake, and the time when folic acid intake was started with the risk of congenital heart disease (CHD) and investigated the role of their interaction on infant CHD risk in Chinese populations. Methods: A case-control study involving 592 CHD cases, 617 health controls, and their mothers was performed. The exposures of interest were single nucleotide polymorphisms (SNPs) of the MTHFR gene, maternal folic acid use, and the time when folic acid use was started. We applied the logistic regression model to explore the strength of association. Results: Our findings showed that mothers lacking folic acid intake had a significantly higher risk of CHD in offspring (aOR = 2.00; 95%CI: 1.34-2.98). Mothers who started to use folic acid from the first trimester of the fetation (aOR = 1.65; 95% CI: 1.22-2.23) or from the second trimester of the fetation (aOR = 7.77; 95% CI: 2.52-23.96), compared with those starting to use folic acid from 3 months previous to the conception, were at a significantly higher risk of CHD in offspring. Genetic variants at rs2066470 (AA vs. GG: aOR = 5.09, 95%CI: 1.99-13.03), rs1801133 (AA vs. GG: aOR = 2.49, 95%CI: 1.58-3.93), and rs1801131 (TG vs. TT: aOR = 1.84, 95%CI: 1.36-2.50; GG vs. TT: aOR = 3.58, 95%CI: 1.68-7.63) were significantly associated with the risk of CHD based on the multivariate analysis. Additionally, statistically significant interactions between maternal folic acid intake and genetic variants of the MTHFR gene at rs1801133 and rs1801131 were observed. Conclusion: An association of maternal folic acid intake and the time when intake was started with the risk of CHD in offspring was found. What's more, maternal folic acid fortification may help counteract partial of the risks of CHD in offspring attributable to MTHFR genetic mutations. Registration number: http://www.chictr.org.cn/edit.aspx?pid=28300&htm=4, identifier: ChiCTR1800016635.

Gestational Diabetes Mellitus and High Triglyceride Levels Mediate the Association between Pre-Pregnancy Overweight/Obesity and Macrosomia: A Prospective Cohort Study in Central China.

The purpose of this study is to investigate whether the link between pre-pregnancy overweight/obesity and risk of macrosomia is mediated by both gestational diabetes mellitus (GDM) and high maternal triglyceride (mTG) levels. This prospective study finally included 29,415 singleton term pregnancies. The outcome of interest was macrosomia (≥4000 g). High mTG levels were denoted as values ≥90th percentile. GDM was diagnosed using a standard 75 g 2 h oral glucose tolerance test. The mediation analysis was conducted using log-binomial regression while controlling for maternal age, education, parity, gestational weight gain, gestational hypertension, smoking, drinking and infant sex. Overall, 15.9% of pregnant women were diagnosed with GDM, and 4.3% were macrosomia. Mediation analysis suggested that overweight had a total effect of 0.009 (95% CI, 0.006-0.013) on macrosomia, with a direct effect of 0.008 (95% CI, 0.004-0.012) and an indirect effect of 0.001 (95% CI, 0.001-0.002), with an estimated proportion of 11.1% mediated by GDM and high mTG levels together. Furthermore, we also discovered a total effect of obesity on macrosomia of 0.038 (95% CI, 0.030-0.047), consisting of a direct effect of 0.037 (95% CI, 0.028-0.045) and an indirect effect of 0.002 (95% CI, 0.001-0.002), with an estimated proportion of 5.3% mediated by GDM and high mTG levels combined. Both GDM and high mTG levels enhanced the risk of macrosomia independently and served as significant mediators in the relationship between pre-pregnancy overweight/obesity and macrosomia.

Effect of Maternal Antidepressant Use During the Pre-pregnancy/Early Pregnancy Period on Congenital Heart Disease: A Prospective Cohort Study in Central China.

Background: With the increase in maternal antidepressant prescribing before/during pregnancy, concerns about the safety of antidepressants have come into focus. The purpose of this study was to explore the association between maternal antidepressant use before pregnancy/in early pregnancy and the risk of congenital heart disease (CHD) in children, and to provide a scientific basis for clinical safety of antidepressant use. Methods: The prospective cohort study ultimately included 34,104 singleton pregnancies. Modified Poisson regression model with robust error variances was used to evaluate RRs and 95% confidence intervals (CIs) for the risk of CHD in offspring exposed to maternal antidepressant in the 3 months before pregnancy and early pregnancy. In addition, sensitivity analysis was further performed to explore the robustness of the results. Results: In this study, the maternal antidepressant exposure rate was 2.83% in the 3 months before pregnancy, 2.42% in early pregnancy, and the incidence of CHD was 8.973 per 1,000 live births. We found that maternal antidepressant use in the 3 months before pregnancy and early pregnancy were all associated with an increased risk of CHD, ~2.54 times and 2.87 times, respectively, of non-use of antidepressants after adjusting for potential confounders. This association was also found in CHD specific phenotypic analysis. Of these, offspring whose mothers were exposed to antidepressants in the 3 months before pregnancy had the highest risk of transposition of the great arteries (aOR = 5.50, 95% CI: 1.91-15.88). The offspring of mothers exposed to antidepressants in early pregnancy had the highest risk of developing ventricular septal defect (aOR = 4.80, 95% CI: 2.50-9.24). Sensitivity analysis verified the stability of the results. Conclusions: Maternal antidepressant use in the 3 months before pregnancy and early pregnancy were all associated with an increased risk of CHD in their offspring. In order to reduce the risk of teratogenesis, we recommend that pregnant women prepare for pregnancy after their condition improves or receive the minimum effective dose of medication.

High Maternal Triglyceride Levels Mediate the Association between Pre-Pregnancy Overweight/Obesity and Macrosomia among Singleton Term Non-Diabetic Pregnancies: A Prospective Cohort Study in Central China.

This study aimed at examining the risk of macrosomia, in relation to maternal pre-pregnancy overweight/obesity mediated via high maternal triglyceride (mTG) levels. In this prospective study, 24,730 singleton term non-diabetic pregnancies were finally included. Serum mTG levels were measured using fasting blood samples that were collected after 28 weeks of gestation. High mTG levels were defined as values ≥ the 90th percentile. The outcome of interest was macrosomia (≥4000 g). Log-binomial regression was used to assess the mediation path between overweight/obesity, high mTG levels, and macrosomia. The mediation analysis found a total effect of overweight on macrosomia of 0.006 (95% CI, 0.001-0.010), including a direct effect of 0.005 (95% CI, 0.001, 0.009) and indirect effect of 0.001 (95% CI, 0.000-0.001), with an estimated proportion of 11.1% mediated by high mTG levels. Additionally, we also found a total effect of obesity on macrosomia of 0.026 (95% CI, 0.018-0.036), including a direct effect of 0.025 (95% CI, 0.017-0.036) and indirect effect of 0.001 (95% CI, 0.000-0.001), with an estimated proportion of 3.8% mediated by high mTG levels. In conclusion, non-diabetic women with overweight or obesity had an increased risk of macrosomia, and this positive association was partly mediated by high mTG levels.

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.

Hypertensive Disorders in Pregnancy Are Associated With Congenital Heart Defects in Offspring: A Systematic Review and Meta-Analysis.

Background: Although research indicates an association between hypertensive disorders of pregnancy (HDP) and congenital heart defects (CHDs) in offspring, consistency is still lacking. Therefore, we aimed to synthesize the updated published epidemiologic evidence to estimate the association of maternal HDP with the risk of total CHDs and its phenotypes in offspring. Methods: A systematic search of Web of Science Database, PubMed, and Embase were searched from inception through April 30, 2021 based on a preprepared protocol, and the reference lists were also manually searched. The combined risk estimates were calculated using either the fixed-effect models or random-effect models. Possible heterogeneity moderators were detected by subgroup, sensitivity analyses, and Galbraith plot. Results: Twenty-four studies involving 477,839 CHDs cases among 40,394,699 participants were included in our meta-analysis. Mothers who had HDP exposure were significantly associated with an increased risk of total CHDs compared with non-exposure. When maternal HDP exposure was further subdivided into pre-eclampsia (OR = 1.79, 95% CI: 1.50-2.13), gestational hypertension (OR = 1.16, 95% CI: 1.02-1.31), and chronic hypertension (OR = 1.68, 95% CI: 1.49-1.89), a significantly increased risk of total CHDs were still presented. Furthermore, a statistically significant increased association was found between maternal HDP exposure and most CHD phenotypes. Besides, relevant heterogeneity moderators have been identified by subgroup and sensitivity analyses. Conclusion: Our study suggested that maternal HDP exposure may be associated with an increase in the risk of CHDs in offspring. These findings highlight the need for greater surveillance of pregnant women with HDP exposure to allow early prevention that may be good for reducing the risk of CHDs in offspring. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [CRD42021268093].

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.

Pre-Pregnancy Body Mass Index and Risk of Macrosomia and Large for Gestational Age Births with Gestational Diabetes Mellitus as a Mediator: A Prospective Cohort Study in Central China.

This study aimed to examine the risk of macrosomia and large for gestational age (LGA) births in relation to maternal pre-pregnancy body mass index (BMI) status mediated through gestational diabetes mellitus (GDM). This prospective study included 34,104 singleton pregnancies at 8-14 weeks of gestation. The interesting outcomes were macrosomia (≥4000 g) and LGA (≥90th percentile). Mediation analyses were conducted using log-binomial regression adjusted for age, education, parity, fetal sex, and gestational weight gain. The proportion mediated was estimated based on the risk difference scale, and the E-value was utilized to assess potential confounders. Overall, 15.9% of women had GDM, and there were 4.0% macrosomia and 9.9% LGA births. The proportion mediated by GDM on macrosomia was up to 40% among obese women, and the estimate of the total effect was 6.18 (95% CI: 5.26-7.26), of the natural direct effect was 4.10 (95% CI: 3.35-4.99), and of the natural indirect effect was 1.51 (95% CI: 1.31-1.76). Likewise, among overweight women, the proportion mediated by GDM on macrosomia was up to 40%. Furthermore, consistent findings were evident for the outcome of LGA births. Pre-pregnancy overweight/obesity increased the risk of macrosomia and LGA births independently and partly mediated by GDM.

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 .

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.