Objective:To assess the association between maternal smoking, passive exposure to smoking, or paternal smoking in the first trimester and the risk of congenital heart disease (CHD) in offspring.Methods:A meta-analysis was performed on selected case-control studies on parents in the first trimester and CHD involving CHD patients regardless of age or ethnicity, after searching PubMed, Web of Science, Cochrane Library, CNKI, WanFang Data, and China Biology Medicine up to April 2021. The main outcome was CHD confirmed by cardiac ultrasound or cardiac surgery and the quality of included studies was assessed using the Newcastle-Ottawa Scale (≥4 scores). Statistical analysis was carried out using RevMan5.4 software and heterogeneity was determined by Q test combined with I 2 test. In accordance with the heterogeneity test results, the appropriate model (random or fixed) was selected. Subgroup analysis was performed according to the subtype of CHD. Potential publication bias was assessed by funnel plots. Results:A total of 35 studies involving 38 125 subjects were included. The pooled results showed that the risk of CHD in offspring born to mothers who were active or passive smokers in the first trimester was 1.20 ( OR=1.20, 95% CI:1.15-1.26, Z=8.15, P<0.001, I 2=35%) and 1.95 times ( OR=1.95, 95% CI:1.70-2.24, Z=9.52, P<0.001, I 2= 69%) that of non-smoking mothers. The risk of CHD in offspring of fathers who smoked in the first trimester was 1.88 times higher than that of non-smoking parents ( OR=1.88, 95% CI:1.49-2.36, Z=5.39, P<0.001, I 2= 69%). Subgroup analysis indicated an association between active maternal smoking in the first trimester and an increased risk of atrial septal defect ( OR=1.41, 95% CI:1.03-1.92, P=0.030, I 2= 71%) as well as between maternal passive smoking and increased risk of atrioventricular septal defect ( OR=1.76, 95% CI:1.37-2.26, P<0.001, I 2= 11%). Conclusion:Maternal and paternal smoking in the first trimester may both increase the risk of CHD in offspring.

Objective    To explore the prognostic value of serum cystatin C (Cys C) in patients with congenital heart disease-associated pulmonary arterial hypertension (PAH-CHD). Methods    A retrospective cohort study was conducted on adult PAH-CHD patients who were hospitalized for the first time in the First Affiliated Hospital of Xinjiang Medical University from January 2010 to January 2020. The serum Cys C and other related data of patients were collected. The median follow-up time was 57 months. The main end event was all-cause death. According to the prognosis, the patients were divided into a survival group and a death group. Cox regression was used to analyze the risk factors for all-cause death in patients with PAH-CHD. Results    A total of 456 patients were enrolled, including 160 males and 296 females, aged 38.99±14.72 years. The baseline data showed that there were statistical differences in resting heart rate, serum Cys C, creatinine, NT-proB-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), high-sensitivity C reactive protein (hs-CRP), New York Heart Association (NYHA) cardiac function classification and serum potassium between the survival group and the death group. Univariate Cox regression analysis showed that serum  Cys C, NT-proBNP, hs-cTnT, creatinine and NYHA cardiac function classification were related risk factors for all-cause death in patients with PAH-CHD. Multivariate Cox regression analysis showed that serum Cys C (HR=3.820, 95%CI 2.053-7.108, P<0.001), NYHA grade Ⅲ (HR=2.234, 95%CI 1.316-3.521, P=0.010), NYHA grade Ⅳ (HR=4.037, 95%CI 1.899-7.810, P=0.002) and NT-proBNP (HR=1.026, 95%CI 1.013-1.039, P<0.001) were independent risk factors for all-cause death in patients with PAH-CHD and had a good predictive value. Conclusion    As a new cardiac marker, serum Cys C can predict all-cause death in patients with PAH-CHD and is an independent risk factor.