Background: Previous research suggested an association between maternal exposure to ambient air pollutants and the risk of congenital heart disease (CHD). However, the effect of individual prenatal exposure to indoor air pollutants on CHD occurrence was not reported. Methods: We performed a hospital-based case–control study to investigate the association between personal air pollution exposure during pregnancy and the risk of CHD in offspring. A total of 44 cases and 75 controls were included from two hospitals in East China. We investigated maternal and residential environmental characteristics using a questionnaire and obtained personal indoor air samples to assess particulate matter (PM) and volatile organic compounds (VOCs) from 22–30 gestational weeks. Formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOCs), PM_2.5, and PM₁₀ were assessed. Logistic regression was performed to assess associations and interactions between individual indoor air pollutants and CHD after adjusting for confounders. The potential residential environmental factors affecting the risks of indoor air pollutants on CHD were also assessed. Results: Median TVOC (0.400 vs. 0.005 mg/m³, P < 0.001) exposure levels in cases were significantly higher than controls. A logistic regression model adjusted for confounders revealed that exposure to high levels of indoor TVOCs (AOR 7.09, 95% CI 2.10–23.88) during pregnancy was associated with risks for CHD and the occurrence of some major CHD subtype in offspring. These risk effects were enhanced in pregnant women living in a newly renovated house but were mitigated by household use of smoke ventilators when cooking. We observed a positive interaction of maternal exposure to TVOCs and PM_2.5 and the risk for CHD. Conclusions: Maternal exposure to indoor VOCs and PMs may increase the risk of giving birth to foetuses with CHD.

Background: Maternal gestational weight gain (GWG) may be associated with cardiovascular diseases in the offspring from childhood to adulthood. We aimed to investigate the association between maternal GWG and the left ventricle (LV) geometry and function in the offspring, and explore the influence of the intrauterine environment on early childhood cardiac change.Methods: Data of 981 mother-offspring pairs from the Shanghai Birth Cohort was used. Maternal pre-pregnancy weight and height, weight in the first trimester (≤ 12 weeks), and before delivery were measured. The echocardiography, blood pressure, and anthropometry assessment were evaluated in the offspring at 4 years of age.Results: Interventricular septal thickness during diastole had a significantly positive correlation with total GWG [β = 0.009, (0.001, 0.017)]. In the second and third trimesters, LV mass index [β = 0.149, (0.015,0.282)], interventricular septal thickness in systole [β = 0.027, (0.011,0.043)], and in diastole [β = 0.014, (0.005,0.023)] were positively associated with GWG. The risks of eccentric [OR = 1.115, (1.232, 1.010)] and concentric hypertrophy [OR = 1.133, (1.259,1.018)] increased with the elevation of maternal GWG.Conclusions: This study suggested that the excessive maternal GWG was associated with the thickening of the interventricular septum in the offspring, especially during the second and third trimesters. Excessive GWG in the second and third trimesters was a risk factor for LV eccentric and concentric hypertrophy in the offspring.

This study utilized large-scale population data from the National Health and Nutrition Examination Survey (NHANES) to elucidate the relationship between the Klotho protein and metabolic syndrome along with its components. We further investigated the possible mediating effect of inflammation on these relationships. Our objective was to identify biomarkers for risk stratification and potential therapeutic targets for metabolic syndrome. This study enrolled 13,119 participants aged 40–79 years, spanning five NHANES cycles from 2007 to 2016, with complete information on metabolic syndrome and the Klotho protein. The definition of metabolic syndrome followed the criteria of the National Cholesterol Education Program-Adult Treatment Panel III. Survey-weighted logistic regression and subgroup analysis were used to explore the associations between serum Klotho protein levels and metabolic syndrome, along with its components. Mediation analysis was performed to investigate the mediating effects of inflammation-related markers, including white blood cells, neutrophils, lymphocytes, monocytes, the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII) and the monocyte-to-HDL ratio (MHR), with the aim of elucidating how the Klotho protein influences the onset and progression of metabolic syndrome. The study participants had an average age of 56.06 years (95% CI: 55.76–56.37), with a Klotho protein concentration of 798.10 pg/ml (95% CI: 656.50–980.50) and a 43.77% prevalence of metabolic syndrome (n = 5742). In the crude model, Klotho was negatively correlated with metabolic syndrome and its components, including central obesity, hypertension, and hypertriglyceridemia. After adjusting for all confounding factors, Klotho was demonstrated to be negatively associated only with metabolic syndrome (OR: 0.82, 95% CI: 0.70–0.97), hypertension (OR: 0.83, 95% CI: 0.70–0.98), and hypertriglyceridemia (OR: 0.78, 95% CI: 0.67–0.91). Subgroup and interaction analyses revealed significant interactions between age, sex, race/ethnicity, body mass index, and Klotho. Additionally, mediation analysis demonstrated that leukocytes, neutrophils and monocytes accounted for 34.78%, 31.91% and 7.13%, respectively, of the associations between Klotho and metabolic syndrome. The serum concentration of Klotho protein was negatively associated with metabolic syndrome, with the relationship being partly mediated by systemic immune inflammation. The findings of this research revealed that the Klotho protein may be a valuable biomarker for risk stratification and a potential therapeutic target for metabolic syndrome.

Methylmalonic acidaemia (MMA) has been reported to be associated with cardiovascular involvement, especially for the combined type with homocystinuria. We have screened 80 control subjects and 99 MMA patients (23 isolated type and 76 combined type) using electrocardiograph and echocardiography. 32 cases (34%) of ECG changes were found including sinus tachycardia (n = 11), prolonged QTc interval (n = 1), I-degree atrioventricular block (n = 1), left axis deviation (n = 5) and T wave change (n = 14). By echocardiography, 8 cases of congenital heart disease were found in 4 combined MMA patients (5.3%) including ventricular septal defect (n = 2), atrial septal defect (n = 3), patent ductus arteriosus (n = 1) and coronary artery-pulmonary artery fistula (n =2). Pulmonary hypertension (n = 2) and hypertrophic cardiomyopathy (n = 1) in combined subtype were also noted. Moreover, echocardiographic parameters were analyzed by multiple regression to clarify the influence of different subtypes on cardiac function. It was found that the left ventricular mass index (LVMI) was significantly reduced only in combined subtype [R = −3.0, 95%CI (−5.4, −0.5), P = 0.017]. For left ventricle, the mitral E' velocity was significantly reduced [isolated type: R = −1.8, 95%CI (−3.3, −0.4), P = 0.016; combined type: R = −2.5, 95%CI (−3.5, −1.5), P < 0.001], the global longitudinal strain (GLS) was the same [isolated type: R = −1.4, 95%CI (−2.3, −0.4), P = 0.007; Combined type: R = −1.1, 95%CI (−1.8, −0.4), P = 0.001], suggesting weakened left ventricular diastolic and systolic functions in both subtypes. For right ventricle, only in combined subtype, the tricuspid E' velocity was significantly reduced [R = −1.4, 95%CI (−2.6, −0.2), P = 0.021], and the tricuspid annular plane systolic excursion (TAPSE) was the same [R = −1.3, 95%CI (−2.3, −0.3), P=0.013], suggesting impaired right ventricular systolic and diastolic function. In conclusion, isolated and combined types showed different pattern of cardiac dysfunction, specifically the former only affected the left ventricle while the latter affected both ventricles. And it is necessary to perform echocardiographic screening and follow up in both MMA subtypes.

Holt–Oram syndrome (HOS) is an autosomal dominant disorder, which is characterized by deformities of upper limbs and congenital heart defects. Alterations of TBX5 gene have been identified to be the leading cause of HOS, while some cases could not be explained by TBX5 mutations. In our study, we preliminarily diagnosed a newborn baby, who had Tetralogy of Fallot, thumb agenesis, facial dysplasia, and right ear canal malformation, as HOS. Chromosome microarray analyses showed no pathological deletions or replications of chromosome segments; whole exome sequencing screened out six candidate genes that were involved in cardiac diseases or syndromes among which SALL4 has been reported as HOS related gene. We evaluated the pathogenicity of SALL4 mutant sites by series of software. The results indicated that SALL4-M143V may be a polymorphism site, and SALL4-R418C could cause disease. HOPE and SWISS PDB viewer showed that SALL4-R418C leads to changes in amino acid properties, loss of protein hydrogen bond, and functional impact of SALL4 zinc finger domain. These results further confirmed the pathogenic significance of SALL4-R418C mutant. When genetic analyses coupled with bioinformatic analyses, we identified a SALL4 gene rare mutation which might contribute to a newborn with HOS. Although some doubts need to be further discussed and explored, our study deepened the understanding of phenotype difference among syndromes and role of SALL4 mutations in disease occurrence.