A. D. Zhao

Background: Evidences regarding the associations between maternal upper respiratory tract infection/influenza during pregnancy and the risk of congenital heart disease (CHD) is still controversial. This study was specifically designed to examine the associations by a case-control study and a meta-analysis of the published evidences and our finding.Methods: A hospital-based case-control study involving 262 children with simple CHD and 262 children with complex CHD, along with 262 control children, was conducted through June, 2016 to December, 2017. All children were aged 0–2 years old. Furthermore, a meta-analysis based on both previously published studies and our case-control study was performed.Results: In the case-control study, after adjusting for possible confounders, maternal upper respiratory tract infection/influenza during early pregnancy was found to be related to an increased risk of CHD (OR = 3.40 and 95% CI: 2.05–5.62 for simple CHD; OR = 2.39 and 95% CI: 1.47–3.88 for complex CHD). After a meta-analysis, the adverse impact was still kept significant (OR = 1.47 and 95% CI: 1.28–1.67 for simple CHD; OR = 1.44 and 95% CI: 1.14–1.75 for complex CHD). The very similar associations were also observed among single type of CHD, herein, ventricular septal defects (VSD) and tetralogy of fallot (TOF) in the case-control study. In the subsequent meta-analysis, however, the significant association only existed in VSD.Conclusions: Although there is still conflicting in TOF, the results are overall consistent, which provide new enforced evidence that maternal upper respiratory tract infection/influenza during early pregnancy, in general, play an important role in the occurrence of CHD.

Background: Previous studies suggested that maternal subjective feeling of stress seemed to be involved in the incidence of congenial heart disease in offspring. To better understand the findings, our study would discuss the relationships of maternal exposure to stressful life event and social support, which are more objective and comprehensive indicators of stress, around periconceptional period with the risk of ventricular septal defect (VSD), the most popular subtype of congenital heart disease. Methods: A hospital-based case-control study was conducted through June, 2016 to December, 2017. We collected maternal self-reports of 8 social support questions in 3 aspects and 8 stressful life events among mothers of 202 VSD cases and 262 controls. Social support was categorized into low, medium high, and high (higher is better), and stressful life event was indexed into low, medium low, and high (higher is worse). Logistic regression models were applied to estimate adjusted odds ratios and 95% confidence intervals (95% CI). Results: The adjusted odds ratio of high stressful life event was 2.342 (95% CI: 1.348, 4.819) compared with low stressful life event. After crossover analysis, compared with low event & high support, the adjusted odds ratio of low event & low support, high event & high support, and high event & low support were 2.059 (95% CI: 1.104, 3.841), 2.699 (95% CI: 1.042, 6.988) and 2.781 (95% CI: 1.033, 7.489), respectively. Conclusions: In summary, we observed an increased risk of VSD when pregnant women exposed to stressful life events, however, social support could, to some extent, reduce the risk of stressful life event.

To study DNA methylation patterns of non-syndromic cleft lip/palate(NSCL/P) using bioinformatic methods, including methylated positions and regions. Whole blood DNA methylation data of NSCL/P samples was download from Gene Expression Omnibus(GEO) database, including 67 NSCL/P cases and 59 controls without birth defects. Data analysis included ①data cleaning, such as probes filtering, quality control and normalization; ②differential methylation analysis, including methylated positions and regions; ③Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on differential methylated genes. R 3.4.3 software was used for data cleaning, differential methylated positions and regions analysis. DAVID6.8 tool was used for GO and KEGG analysis. 814 differential methylated positions were detected (adjusted P＜0.001，|Δβ|＞0.125）, of which 178 were hypermethylated in NSCL/P patients, and 636 were hypomethylated. In addition, 386 differential methylated regions were identified (P＜0.05), of which 204 were hypermethylation regions and 182 were hypomethylation regions. GO analysis showed that 38 differential methylated genes were involved in 7 kinds of biological processes, 163 differential methylated genes were involved in 3 kinds of molecular functions, and 114 differential methylated genes were involved in 3 kinds of cellular components (P＜0.01). KEGG analysis showed that 59 differential methylated genes were involved in 9 kinds of signal pathways. Abnormal DNA methylation patterns of NSCL/P might be an important epigenetic mechanism affecting the development of NSCL/P. This study might contribute to the identification of identification of biomarkers and targeted interventions of NSCL/P.