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Blood lipid management is a key approach in the prevention of chronic kidney disease (CKD). Remnant cholesterol (RC) plays an important role in the development of multiple diseases via chronic inflammation. The aim of our study was to determine the relationship between RC and CKD and explore the role of inflammation in this relationship. The 7696 subjects from the Chinese Health and Nutrition Survey were divided into four subgroups according to the quartile of RC. The estimated glomerular filtration rate was calculated using the CKD Epidemiology Collaboration equation. Fasting RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Logistic regression analysis was employed to evaluate the relationships between RC and CKD. Mediation analysis was undertaken to identify potential mediators of high-sensitivity C-reactive protein (hs-CRP) and white blood cells (WBCs). Of all participants, the mean age was 51 years, and the male accounted for 47.8%. The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 1.40 (1.10–1.78, p for trend = 0.006) for CKD. RC and preinflammatory markers have combined effect on CKD. The preinflammatory state, presented by increased hs-CRP or WBCs, partially mediated the association between RC and CKD with proportion of 10.14% (p = 0.002) and 11.65% (p = 0.012), respectively. In conclusion, this study suggested a positive relationship between RC and CKD, which was partially mediated by preinflammatory state. These findings highlight the importance of RC and inflammation in renal dysfunction.IMPACT STATEMENTWhat is already known on this subject?: Dyslipidemia plays an important role in the development of chronic kidney disease (CKD). Remnant cholesterol (RC), as a triglyceride-rich particle, can contribute to target organ damage, primarily through inflammatory pathways. However, the relationship between RC and CKD in the community-dwelling population, particularly the role of inflammation, is not yet fully understood.What do the results of this study add?: This study shows that RC was significantly associated with CKD. RC and preinflammatory status exhibit a combined effect on CKD. Preinflammatory state, presented by increased high-sensitivity C-reactive protein or white blood cells, partially mediated the association between RC and CKD.What are the implications of these findings for clinical practice and/or further research?: The study provides us with a better understanding of the role of RC and inflammation in kidney dysfunction and raises the awareness of RC in the management of CKD.

Objectives: Sarcopenic obesity (SO) has been found to increase the risk of metabolic disorders, however, its relationship with cardiometabolic multimorbidity (CMM) remains unexplored. This study aims to investigate the potential association between SO and CMM in the middle-aged and older population. Methods: Our study subjects were from CHARLS. SO was defined as the combination of impaired grip strength (grip strength

Abstract Background Left atrial myxoma during pregnancy is rare. We present three cases in order to aid in the management. Case Presentation Three cases of left atrial myxoma during pregnancy were presented in this article. Three patients all received multidisciplinary team work and acquired good outcomes. The case 1 had no symptoms and delivered before traditional cardiac surgery. The case 2 and case 3 undergone totally endoscopic minimally invasive cardiac surgery during pregnancy. The case 3 maintained pregnancy to term and gave birth to a healthy baby via vaginal delivery. No relapse of the tumor was observed. Conclusions The management of left atrial myxoma during pregnancy ought to be individualized and combined with the gestational age. If the diagnosis was made in the first two trimesters of pregnancy, totally endoscopic minimally invasive cardiac surgery during pregnancy would be an optimal choice. The patients can benefit from the multidisciplinary team work.

Abstract Background Cardiovascular disease (CVD) caused by air pollution poses a considerable burden on public health. We aim to examine whether lifestyle factors mediate the associations of air pollutant exposure with the risk of CVD and the extent of the interaction between lifestyles and air pollutant exposure regarding CVD outcomes. Methods We included 7000 participants in 2011–2012 and followed up until 2018. The lifestyle evaluation consists of six factors as proxies, including blood pressure, blood glucose, blood lipids, body mass index, tobacco exposure, and physical activity, and the participants were categorized into three lifestyle groups according to the number of ideal factors (unfavorable, 0–1; intermediate, 2–4; and favorable, 5–6). Satellite-based spatiotemporal models were used to estimate exposure to ambient air pollutants (including particles with diameters ≤ 1.0 μm [PM1], ≤ 2.5 μm [PM2.5], ≤ 10 μm [PM10], nitrogen dioxide [NO2], and ozone [O3]). Cox regression models were used to examine the associations between air pollutant exposure, lifestyles and the risk of CVD. The mediation and modification effects of lifestyle categories on the association between air pollutant exposure and CVD were analyzed. Results After adjusting for covariates, per 10 μg/m3 increase in exposure to PM1 (HR: 1.09, 95% CI: 1.05–1.14), PM2.5 (HR: 1.04, 95% CI: 1.00–1.08), PM10 (HR: 1.05, 95% CI: 1.03–1.08), and NO2 (HR: 1.11, 95% CI: 1.05–1.18) was associated with an increased risk of CVD. Adherence to a healthy lifestyle was associated with a reduced risk of CVD compared to an unfavorable lifestyle (HR: 0.65, 95% CI: 0.56–0.76 for intermediate lifestyle and HR: 0.41, 95% CI: 0.32–0.53 for favorable lifestyle). Lifestyle played a significant partial mediating role in the contribution of air pollutant exposure to CVD, with the mediation proportion ranging from 7.4% for PM10 to 14.3% for PM2.5. Compared to an unfavorable lifestyle, the relative excess risk due to interaction for a healthier lifestyle to reduce the effect on CVD risk was − 0.98 (− 1.52 to − 0.44) for PM1, − 0.60 (− 1.05 to − 0.14) for PM2.5, − 1.84 (− 2.59 to − 1.09) for PM10, − 1.44 (− 2.10 to − 0.79) for NO2, and − 0.60 (− 1.08, − 0.12) for O3. Conclusions Lifestyle partially mediated the association of air pollution with CVD, and adherence to a healthy lifestyle could protect middle-aged and elderly people from the adverse effects of air pollution regarding CVD.

Abstract Background Remnant cholesterol (RC) is recognized as a risk factor for diabetes mellitus (DM). Although iron status has been shown to be associated with cholesterol metabolism and DM, the association between RC, iron status, and DM remains unclear. We examined the relationship between RC and iron status and investigated the role of iron status in the association between RC and DM. Methods A total of 7308 patients were enrolled from the China Health and Nutrition Survey. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Iron status was assessed as serum ferritin (SF) and total body iron (TBI). DM was ascertained by self-reported physician diagnosis and/or antidiabetic drug use and/or fasting plasma glucose ≥ 126 mg/dL and/or glycated haemoglobin ≥ 6.5%. General linear models were used to evaluate the relationships between RC and iron status. Restricted cubic splines were used to assess the association between RC and DM. Mediation analysis was used to clarified the mediating role of iron status in the association between the RC and DM. Results The average age of the participants was 50.6 (standard deviation = 15.1) years. Higher RC was significantly associated with increased SF (β = 73.14, SE = 3.75, 95% confidence interval [CI] 65.79–80.49) and TBI (β = 1.61, SE = 0.08, 95% CI 1.44–1.78). J-shape relationships were found in the association between RC levels with DM, as well as iron status with DM. Significant indirect effects of SF and TBI in the association between RC and DM were found, with the index mediated at 9.58% and 6.37%, respectively. Conclusions RC has a dose–response relationship with iron status. The association between RC and DM was mediated in part by iron status. Future studies are needed to confirm these findings and further clarify the underlying mechanism.

Abstract The authors aimed to investigate the association between outdoor light at night (LAN) intensity and blood pressure. The study included 13 507 participants aged 45 and above from the 2011–2012 China Health and Retirement Longitudinal Study baseline survey. Blood pressure measurements were obtained by averaging the last two readings recorded (three measurements with an interval of 45–60 s between each measurement) during the survey. Outdoor LAN intensity was assessed using Defense Meteorological Satellite Program data. The study categorized participants based on quartiles of outdoor LAN intensity and employed statistical methods like linear regression, restricted cubic splines, and logistic models to analyze the connections. After adjusting for potential confounding factors, higher levels of outdoor LAN intensity were associated with increase in systolic blood pressure (0.592 mmHg/interquartile range [IQR], 95% confidence interval [CI]: 0.027,1.157), diastolic blood pressure (0.853 mmHg/IQR, 95% CI: 0.525,1.180) and mean arterial pressure (0.766 mmHg/IQR, 95% CI: 0.385,1.147). Interestingly, the relationship between LAN intensity and odds of hypertension followed a non‐linear pattern, resembling a reverse “L” shape on cubic splines. Participants with the highest quartile of outdoor LAN intensity had 1.31‐fold increased odds of hypertension (95% CI: 1.08–1.58) compared to the lowest quartile. Additionally, there was an observable trend of rising odds for high‐normal blood pressure with higher levels of LAN intensity in the crude model, but no statistically significant differences were observed after adjusting for confounding factors. In conclusion, this study underscores a significant connection between outdoor LAN intensity and the prevalence of hypertension.

Abstract Background Epidemiological study of sex differences in incidence and risk factors of heart failure (HF), and subsequent mortality attributed to HF in the Chinese general population is lacking. This study aims to assess the sex differences in the incidence and risk factors of hospitalization for HF and evaluate the sex differences in population attributable fractions (PAFs) for the subsequent mortality among the general population. Methods Data were from a sub-cohort of the Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project in China. Fine and Gray models were conducted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) accounting for the competing risk of all-cause mortality. Propensity score matching analysis and subgroup analyses were used to verify the robustness of the results. Adjusted PAFs of HF for all-cause and cardiovascular mortality were evaluated by sex. Results Of the 102,278 participants, 60.5% were women, and the mean age was 54.3 years. After a median follow-up of 3.52 years, 1588 cases of hospitalization for HF were identified. After adjusting for the covariates, women had 31% (95% CI: 0.61–0.79) lower risk for HF than men. The results were consistent in the propensity score matching cohort and across all subgroup analyses (all P sex-subgroups interaction > 0.05). Although women were associated with a lower risk of HF, they had a higher PAF (24.2%, 95% CI: 16.0-31.6) for subsequent cardiovascular mortality than men (16.5%, 95% CI: 11.3–21.5). Several significant differences in risk factors for HF were noted between sexes. Conclusion In the southern Chinese population, women had a lower risk of HF but had a higher cardiovascular mortality fraction attributed to HF than men. Sex-specific preventative strategies and management for HF should be warranted.

Abstract The association of blood pressure (BP) classification defined by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline with cardiometabolic multimorbidity (CMM) remains unclear. The present study aimed to investigate this research gap in the Chinese adults. Cross‐sectional data were collected from a population‐based cohort conducted in Southern China. Participants were categorized as having normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension according to the 2017 ACC/AHA guideline. CMM was defined as having two or more of the following diseases: coronary heart disease, stroke, and diabetes. The relationship between the BP classifications and CMM was examined by multivariate logistic regression. A total of 95 649 participants (mean age: 54.3 ± 10.2 years, 60.7% were women) were enrolled in this study. Multivariable‐adjusted logistic regression models revealed that stage 1 hypertension (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.03–1.78) and stage 2 hypertension (OR, 3.53; 95% CI, 2.82–4.47) were significantly associated with a higher prevalence of CMM compared with normal BP. The association between stage 1 hypertension and CMM were profound in women (OR, 1.76; 95% CI, 1.17–2.67) and in the middle‐aged group (OR, 1.53; 95% CI, 1.02–2.35) compared with men and older individuals, respectively. Our study showed that among Chinese adults, stage 1 hypertension defined by the 2017 ACC/AHA guideline was already associated with higher odds of CMM compared with normal BP, particularly in women and middle‐aged participants. Managing stage 1 hypertension may be an important measure to prevent CMM in Chinese adults.

Background Evidence regarding sex differences in the associations of traditional risk factors with incident heart failure (HF) hospitalization among Chinese general adults is insufficient. This study aimed to evaluate the potential sex differences in the associations of traditional risk factors with HF among Chinese general adults. Methods and Results Data were from a subcohort of the China PEACE (Patient‐Centered Evaluative Assessment of Cardiac Events) Million Persons Project. The traditional risk factors were collected at baseline, and the study outcome was HF‐related hospitalization identified from the Inpatients Registry. A total of 102 278 participants (mean age, 54.3 years; 39.5% men) without prevalent HF were recruited. A total of 1588 cases of HF‐related hospitalization were captured after a median follow‐up of 3.52 years. The incidence rates were significantly higher in men (2.1%) than in women (1.2%). However, the observed lower risk of HF in women was significantly attenuated or even vanished when several traditional risk factors were poorly controlled (P for sex‐by‐risk factors

Perfluorooctane sulfonate (PFOS), an endocrine-disrupting chemical pollutant, affects embryonic heart development; however, the mechanisms underlying its toxicity have not been fully elucidated. Here, Single-cell RNA sequencing (scRNA-seq) was used to investigate the overall effects of PFOS on myocardial differentiation from human embryonic stem cells (hESCs). Additionally, apoptosis, mitochondrial membrane potential, and ATP assays were performed. Downregulated cardiogenesis-related genes and inhibited cardiac differentiation were observed after PFOS exposure in vitro. The percentages of cardiomyocyte and cardiac progenitor cell clusters decreased significantly following exposure to PFOS, while the proportion of primitive endoderm cell was increased in PFOS group. Moreover, PFOS inhibited myocardial differentiation and blocked cellular development at the early- and middle-stage. A Gene Ontology analysis and pseudo-time trajectory illustrated that PFOS disturbed multiple processes related to cardiogenesis and oxidative phosphorylation in the mitochondria. Furthermore, PFOS decreased mitochondrial membrane potential and induced apoptosis. These results offer meaningful insights into the cardiogenic toxicity of PFOS exposure during heart formation as well as the adverse effects of PFOS on mitochondria.

Accumulating evidence strongly suggests that exposure to ambient air pollution is linked with increased frailty. However, little is known about the effect of improved air quality on frailty progression. We aimed to investigate whether improvements in air quality (PM1, PM2.5, PM10, NO2, and O3) can alleviate frailty progression, particularly in the aftermath of implementation of the “Clean Air Action” policy in China. The study involved 12,891 participants with geocoded environmental data from the nationwide China Health and Retirement Longitudinal Study (CHARLS) during the period from May 2011 to August 2015. Multivariate logistic regression models were used to analyze the association of air pollution improvements and frailty progression. The protective effects were noted for PM1, PM2.5, PM10, and NO2 indices, with an aOR (adjusted odds ratio) ranging from 0.72 to 0.79. Air quality improvement in PM1, PM2.5, PM10, and NO2 could alleviate the progression of frailty. The study is the first to examine the association between the improvement of air quality and the progression of frailty, setting a precedent for the importance of a nationwide clean air policy and its impact on healthy ageing.

Abstract Background: We aimed to evaluate the burden of cardiovascular (CV) risk factors in the community populations of Guangdong Province and its association with sociodemographic status (SDS). Method: The data were from the community populations of Guangdong Province who have participated in the China PEACE Million Persons Project between 2016 and 2020 (n = 102,358, women 60.5% and mean age 54.3 years). The prevalence of CV risk factors (smoking, drinking, overweight/obesity, hypertension, dyslipidemia and diabetes mellitus) and its association with SDS (age, sex and socioeconomic status [SES]) was evaluated cross-sectionally. Results: The prevalence of overweight/obesity was 48.9%, hypertension 39.9%, dyslipidemia 18.6%, smoking 17.2%, diabetes mellitus 16.1% and drinking 5.3%. Even in young adults (aged 35–44), nearly 60% had at least 1 CV risk factor. Overweight/obesity often coexisted with other risk factors, including smoking, hypertension, dyslipidemia and diabetes mellitus. The proportion of people with no risk factor decreased with increasing age. Women were more likely than men to have no CV risk factor (29.4% vs. 12.7%). People with ≥ high school degree were more likely than those with

Abstract Aims/Introduction Abdominal obesity is a risk factor for developing diabetes mellitus, but trajectories of abdominal obesity over time and incident diabetes mellitus have not been considered. We derived trajectories of abdominal volume index (AVI) over 16 years of follow up, and examined the associations between AVI trajectories and risk of diabetes mellitus. Materials and Methods Data were used from the China Health and Nutrition Survey, and 5,267 participants were enrolled to fit the trajectory of AVI by using latent class growth models. Multivariate logistic regression models explored the relationship between different AVI trajectories and risk of diabetes mellitus. In addition, we examined the slope of the AVI trajectories in relation to age to identify appropriate life course intervention opportunities for the prevention of diabetes mellitus. Results Three trajectories were derived reflecting graded categories in the speed and slope of increase in AVI over time: slow, intermediate and fast increase group, respectively. After multivariate adjustment, the odds ratios for diabetes mellitus among those in the intermediate and fast increase groups were 1.81 (95% confidence interval 1.37–2.38, P

Background: The associations between per- and polyfluoroalkyl substances (PFAS) and obesity in adolescent remained unclear when considering imaging based methods such as dual-energy X-ray absorptiometry (DXA) scanning. Methods: The 2011-2018 National Health and Nutrition Examination Survey (NHANES) was used in this study. There were four highly detected PFAS including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). We calculated total mass, fat mass and fat-free mass (i.e., lean mass including bone mineral content) indexes (mass/height2) of total body and three regions [head, trunk and subtotal (i.e., total minus head)]. We assessed the associations using weighted multivariable linear regression and weighted quantile sum (WQS) regression. Results: A total of 1067 participants aged 12-18 years were included in this study. When adjusting for potential covariates, PFHxS exposure was negatively associated with total fat mass index while positively associated with total fat-free mass index [β=-0.16, 95% confidence interval (CI): -0.27 to -0.04; β=0.16, 95%CI: 0.05 to 0.28]. When entering the PFAS mixture in the WQS model, we found similar associations of WQS index with total fat or fat-free mass index (β=-0.04, 95%CI: -0.08 to -0.00; β=0.04, 95%CI: 0.00 to 0.08). Within the PFAS mixture, PFOA exposure made major contributions to the overall effect (56.6% and 44.1% for total fat and fat-free mass index). We did not find any significant association with regard to PFAS exposure and total mass index. Conclusions: Among US adolescents, higher PFHxS exposure was associated with lower body fat mass and higher fat-free mass in single PFAS models. We observed similar associations of the PFAS mixture with fat and fat-free mass, and PFOA exposure made major contributions to the overall effect. Overall, PFAS exposure might disturb energy balance and body composition in adolescents, and more studies are needed to confirm our findings.

BackgroundA provincial program combining the effect of a government investment in prenatal screening and a specialized cardiac center was introduced in 2004, to improve prenatal diagnosis by echocardiography for congenital heart diseases (CHDs) in the Guangdong Registry of Congenital Heart Disease, China.ObjectivesTo evaluate the effects of this program on the prenatal diagnosis rate (PDR) by echocardiography and termination of pregnancy (TOP).MethodsA retrospective study from 2004-2015 included 9782 fetuses and infants diagnosed with CHDs. The PDR was calculated for major and minor CHDs during pre-, mid- and post-program time-intervals. Multivariable logistic regression was utilized to analyze the associations between program implementation and the timing of CHD diagnosis (prenatal vs. postnatal) by different hospital levels. The rate for TOP were also evaluated.ResultsThe PDR increased by 44% for major CHDs in the post-program interval relative to the pre-program interval. The three most frequently diagnosed subtypes prenatally were hypoplastic left heart syndrome (84%), double outlet right ventricle (83%) and severe pulmonary stenosis (82%). Participants with a high school education experienced a greater increase in PDR than those without a high school education. The odds for a prenatal vs. a postnatal diagnosis for major CHD were greater after introduction of the program than before (adjusted odd ratio= 20.95, 95% CI:2.47, 178.06 in secondary hospitals; and adjusted odd ratio=11.65, 95% CI:6.52, 20.81 in tertiary hospitals). The TOP rate decreased from 52.3% pre-program to 19.6% post-program among minor CHD fetuses with a prenatal diagnosis (P for trend =0.041). A lower proportion of TOP were attributed to minor CHDs after the program.ConclusionsThe program combining the advantages of government investment and a specialized cardiac center appeared to increase the PDR by echocardiography for CHDs in an unselected population. The TOP rate among minor cases with prenatal diagnosis declined significantly after implementation of the program.

The lack of accessible noninvasive tools to examine the molecular alterations limits our understanding of the causes of total anomalous pulmonary venous connection (TAPVC), as well as the identification of effective operational strategies. Here, we consecutively enrolled peripheral leukocyte transcripts of 26 preoperative obstructive and 22 non-obstructive patients with TAPVC. Two-hundred and fifty six differentially expressed mRNA and 27 differentially expressed long noncoding RNA transcripts were dysregulated. The up-regulated mRNA was enriched in the hydrogen peroxide catabolic process, response to mechanical stimulus, neutrophil degranulation, hemostasis, response to bacterium, and the NABA CORE MATRISOME pathway, all of which are associated with the development of fibrosis. Furthermore, we constructed predictive models using multiple machine-learning algorithms and tested the performance in the validation set. The mRNA NR3C2 and lncRNA MEG3 were screened based on multiple iterations. The random forest prediction model can predict preoperative obstruction patients in the validation set with high accuracy (area under curve = 1; sensitivity = 1). These data highlight the potential of peripheral leukocyte transcripts to evaluate obstructive-related pathophysiological alterations, leading to precision healthcare solutions that could improve patient survival after surgery. It also provides a novel direction for the study of preoperative obstructive TAPVC.

Objective: Congenital heart diseases (CHDs) are associated with an extremely heavy global disease burden as the most common category of birth defects. Genetic and environmental factors have been identified as risk factors of CHDs previously. However, high volume clinical indicators have never been considered when predicting CHDs. This study aimed to predict the occurrence of CHDs by considering thousands of variables from self-reported questionnaires and routinely collected clinical laboratory data using machine learning algorithms.Methods: We conducted a birth cohort study at one of the largest cardiac centers in China from 2011 to 2017. All fetuses were screened for CHDs using ultrasound and cases were confirmed by at least two pediatric cardiologists using echocardiogram. A total of 1,127 potential predictors were included to predict CHDs. We used the Explainable Boosting Machine (EBM) for prediction and evaluated the model performance using area under the Receive Operating Characteristics (ROC) curves (AUC). The top predictors were selected according to their contributions and predictive values. Thresholds were calculated for the most significant predictors.Results: Overall, 5,390 mother-child pairs were recruited. Our prediction model achieved an AUC of 76% (69-83%) from out-of-sample predictions. Among the top 35 predictors of CHDs we identified, 34 were from clinical laboratory tests and only one was from the questionnaire (abortion history). Total accuracy, sensitivity, and specificity were 0.65, 0.74, and 0.65, respectively. Maternal serum uric acid (UA), glucose, and coagulation levels were the most consistent and significant predictors of CHDs. According to the thresholds of the predictors identified in our study, which did not reach the current clinical diagnosis criteria, elevated UA (>4.38 mg/dl), shortened activated partial thromboplastin time (

Background: Accumulating evidence suggests that environmental pollutants may contribute to the occurrence of congenital heart defects (CHDs). However, no previous studies have evaluated the impact of perfluoroalkyl substances (PFAS), persistent environmental pollutants, on CHDs. This exploratory study aimed to generate testable hypotheses of the association between gestational PFAS and the risk of CHDs. Methods: A nested case-control study was conducted in a cohort of 11,578 newborns. Exposure odds ratios were compared between 158 CHD cases and 158 non-malformed controls delivered at the same hospital, individually matched by maternal age (±5 years) and parity. Concentrations of 27 PFAS, including linear and branched isomers, were determined in maternal peripheral blood and cord blood plasma collected before and during delivery using a ultra-performance liquid chromatography coupled to mass spectrometry. Conditional logistic regression was utilized to evaluate associations between individual PFAS and the risk of CHDs, adjusted for confounding variables. Results: Maternal gestational exposure to the highly branched perfluorooctanesulfonate (PFOS) isomer potassium 6-trifluoromethyperfluoroheptanesulfonate [6 m-PFOS, adjusted odds ratio (aOR) (95% CI) = 2.47(1.05,5.83)] and perfluorodecanoic acid [PFDA, aOR (95% CI) = 2.33(1.00,5.45)] were associated with increased odds of septal defects with statistical significance, while linear PFOS [aOR (95% CI) = 3.65(1.09,12.16)] and perfluoro-n-dodecanoic acid [PFDoA, aOR (95% CI) = 6.82(1.75, 26.61)] were associated with conotruncal defects. Effect estimates also suggested associations for higher maternal 6 m-PFOS and PFDA concentrations with ventricular septal defect. However, we did not observe these associations in cord blood. Conclusion: These exploratory findings suggested that gestational exposure to most PFAS, especially linear PFOS, 6 m-PFOS, PFDA, and PFDoA, was associated with greater risks for septal and conotruncal defects. However, a larger, adequately powered study is needed to confirm our findings, and to more comprehensively investigate the potential teratogenic effects of other more recently introduced PFAS, and on associations with individual CHD subtypes.

Background: Evidence of maternal exposure to ambient air pollution on congenital heart defects (CHD) has been mixed and are still relatively limited in developing countries. We aimed to investigate the association between maternal exposure to air pollution and CHD in China. Method: This longitudinal, population-based, case-control study consecutively recruited fetuses with CHD and healthy volunteers from 21 cities, Southern China, between January 2006 and December 2016. Residential address at delivery was linked to random forests models to estimate maternal exposure to particulate matter with an aerodynamic diameter of ≤ 1 µm (PM1), ≤2.5 µm, and ≤10 µm as well as nitrogen dioxides, in three trimesters. The CHD cases were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia ultrasound. The CHD subtypes were coded using the International Classification Diseases. Adjusted logistic regression models were used to assess the associations between air pollutants and CHD and its subtypes. Results: A total of 7055 isolated CHD and 6423 controls were included in the current analysis. Maternal air pollution exposures were consistently higher among cases than those among controls. Logistic regression analyses showed that maternal exposure to all air pollutants during the first trimester was associated with an increased odds of CHD (e.g., an interquartile range [13.3 µg/m3] increase in PM1 was associated with 1.09-fold ([95% confidence interval, 1.01–1.18]) greater odds of CHD). No significant associations were observed for maternal air pollution exposures during the second trimester and the third trimester. The pattern of the associations between air pollutants and different CHD subtypes was mixed. Conclusions: Maternal exposure to greater levels of air pollutants during the pregnancy, especially the first trimester, is associated with higher odds of CHD in offspring. Further longitudinal well-designed studies are warranted to confirm our findings.

Background: Proximity to greenness has shown protective effects on coronary heart diseases by limiting exposure to environmental hazards, encouraging physical activity, and reducing mental stress. However, no studies have previously evaluated the impacts of greenness on congenital heart defects (CHDs). We examined the association between maternal residential greenness and the risks of CHDs. Methods: We conducted a case-control study (8042 children with major CHDs and 6887 controls without malformations) in 21 cities in Southern China, 2004 – 2016. CHDs cases were diagnosed and verified by obstetrician, pediatrician, or pediatric cardiologists, within one year. We estimated maternal residential greenness using satellite-derived normalized difference vegetation index (NDVI) in zones of 500 meters (m) and 1000 m surrounding participants’ residences. Logistic regression models were used to assess NDVI-CHD relationships adjusting for confounders. Results: Interquartile range NDVI increases within 500 m or 1000 m were associated with odds ratios (OR) of 0.95 (95% confidence interval (CI): 0.92, 0.98) and 0.94 (95%CI: 0.91, 0.97) for total CHDs respectively. Air pollutants mediated 52.1% of the association. We also identified a protective threshold at 0.21 NDVI on CHD. Similar protective effects from greenness were found in most CHDs subtypes. The protective associations were stronger for fall, urban or permanent residents, higher household income maternal age ≤35 years of age, and high maternal education (ORs: ranged from 0.85 to 0.96). Conclusion: Our findings suggest a beneficial effect of maternal residential greenness on CHDs. Further studies are needed to confirm our findings, which will help to refine preventive health and urban design strategies.

Background Maternal folic acid supplementation (FAS) reduces the risk of neural tube defects in offspring. However, its effect on congenital heart disease (CHDs), especially on the severe ones remains uncertain. This study aimed to assess the individual and joint effect of first‐trimester maternal FAS and multivitamin use on CHDs in offspring. Methods and Results This is a case‐control study including 8379 confirmed CHD cases and 6918 controls from 40 healthcare centers of 21 cities in Guangdong Province, China. Adjusted odds ratios (aORs) of FAS and multivitamin use between CHD cases (overall and specific CHD phenotypes) and controls were calculated by controlling for parental confounders. The multiplicative interaction effect of FAS and multivitamin use on CHDs was estimated. A significantly protective association was detected between first‐trimester maternal FAS and CHDs among offspring (aOR, 0.69; 95% CI, 0.62–0.76), but not for multivitamin use alone (aOR, 1.42; 95% CI, 0.73–2.78). There was no interaction between FAS and multivitamin use on CHDs (P=0.292). Most CHD phenotypes benefited from FAS (aORs ranged from 0.03–0.85), especially the most severe categories (ie, multiple critical CHDs [aOR, 0.16; 95% CI, 0.12–0.22]) and phenotypes (ie, single ventricle [aOR, 0.03; 95% CI, 0.004–0.21]). Conclusions First‐trimester maternal FAS, but not multivitamin use, was substantially associated with lower risk of CHDs, and the association was strongest for the most severe CHD phenotypes. We recommend that women of childbearing age should supplement with folic acid as early as possible, ensuring coverage of the critical window for fetal heart development to prevent CHDs.

Prenatal exposure to toxic trace elements, including heavy metals, is an important public health concern. Few studies have assessed if individual and multiple trace elements simultaneously affect cardiac development. The current study evaluated the association between maternal blood lead (Pb), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), and selenium (Se) levels and congenital heart defects (CHDs) in offspring. This hospital-based case-control study included 112 case and 107 control infants. Maternal peripheral blood draw was made during gestational weeks 17–40 and used to determine trace element levels by inductively coupled plasma mass spectrometry. Multivariable logistic regression was used to assess associations and interactions between individual and multiple trace elements and fetal CHDs, adjusted for maternal age, parity, education, newborn gender, migrant, folic acid or multivitamin intake, cigarette smoking, maternal prepregnancy body mass index, and time of sample collection. Control participants had medians of 2.61μg/dL Pb, 1.76μg/L Cd, 3.57μg/L Cr, 896.56μg/L Cu, 4.17μg/L Hg, and 186.47μg/L Se in blood. In a model including all measured trace elements and adjusted for confounders, high levels of maternal Pb (OR=12.09, 95% CI: 2.81, 51.97) and Se (OR=0.25, 95% CI: 0.08, 0.77) were harmful and protective predictors of CHDs, respectively, with positive and negative interactions suggested for Cd with Pb and Se with Pb, respectively. Similar associations were detected for subgroups of CHDs, including conotruncal defects, septal defects, and right ventricle outflow tract obstruction. Our results suggest that even under the current standard for protecting human health (10μg/dL), Pb exposure poses an important health threat. These data can be used for developing interventions and identifying high-risk pregnancies. Keywords: Heart anomalies, Teratogen, Trace elements, Risk factor, Environment

This study aimed to examine effect modification of maternal risk factor exposures and congenital heart disease (CHD) by maternal folic acid supplementation (FAS)/non-FAS. We included 8379 CHD cases and 6918 CHD-free controls from 40 clinical centers in Guangdong Province, Southern China, 2004–2016. Controls were randomly chosen from malformation-free fetuses and infants and frequency matched to the echocardiogram-confirmed cases by enrollment hospital and year of birth. We used multiple regression models to evaluate interactions between FAS/non-FAS and risk factors on CHDs and major CHD categories, adjusted for confounding variables. We detected statistically significant additive and multiplicative interactions between maternal FAS/non-FAS and first-trimester fever, viral infection, and threatened abortion on CHDs. An additive interaction on CHDs was also identified between non-FAS and living in a newly renovated home. We observed a statistically significant dose-response relationship between non-FAS and a greater number of maternal risk factors on CHDs. Non-FAS and maternal risk factors interacted additively on multiple critical CHDs, conotruncal defects, and right ventricular outflow tract obstruction. Maternal risk factor exposures may have differential associations with CHD risk in offspring, according to FAS. These findings may inform the design of targeted interventions to prevent CHDs in highly susceptible population groups.

There are 16.5 million newborns in China annually. However, the incidence of congenital heart disease (CHD) has not been evaluated. In 2004, we launched an active province-wide hospital-based CHD registry in the Guangdong Province of southern China. In this study, we examined the incidence of CHD and its subtypes from 2004 to 2012 and compared our findings to the literature. Our results indicate there is an increasing trend of CHD incidence. The increase in incidence occurred mainly for single lesion and the most common subtypes (e.g., ventricular or atrial septal defect, patent ductus arteriosus). There were no increases found for multiple lesions or more complex subtypes. The proportion of CHD cases that were detected early (e.g., 1 week) increased over time. The incidence of CHD stabilized in 2010-2012 with the average cumulative incidences of 9.7, 9.9, and 11.1 per 1,000 live births at 1 week, 1 month, and 1 year, respectively. The incidences of CHD subtypes were comparable with recent international results. The data did not support previous reports that Asian children have a higher incidence of pulmonary outflow obstructions and lower incidence of transposition of the great arteries. However, there was a lower incidence of left ventricular outflow tract obstructions observed in our series. The increase in CHD incidence observed over time was due to improved detection and diagnosis. The true incidence of CHD in China was approximately 11.1 per 1,000 live births, which is higher than previously reported.

Background: Research on fetal congenital heart defect (CHD) mostly focuses on etiology and mechanisms. However, studies on maternal complications or pathophysiology are limited. Our objective was to determine whether vascular dysfunction exists in pregnant women carrying a fetus with congenital heart defects. Methods: We conducted a case-control study. 27 cases of pregnant women carrying a fetus with major CHD admitted to our hospital for delivery between April 2021 and August 2022 were selected. Every case was matched with about 2 pregnant complication-free controls without fetal abnormalities. The proangiogenic and anti-angiogenic factors and pregnancy outcomes were compared. Results: The proangiogenic factors include vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). The anti-angiogenic factors involve soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng). No differences were found in maternal plasma concentrations of PlGF, VEGF, and sFlt-1 between case-control groups when analyzed at 36 weeks ≤ gestational age (GA) < 39 weeks and 39 weeks ≤ GA ≤ 41 weeks. The concentrations of sEng in maternal plasma in the fetal CHD group were significantly higher than those in the control group: 0.60 (0.77) vs. 0.32 (0.26) ng/ml at 36 weeks ≤ GA < 39 weeks, p = 0.001 and 0.75 (0.55) vs. 0.28 (0.27) ng/ml at 39 weeks ≤ GA ≤ 41 weeks, p < 0.001. Conclusion: Vascular dysfunction exists in pregnant women with fetal congenital heart defects, manifesting significantly elevated sEng concentration at delivery. [ABSTRACT FROM AUTHOR]