Prenatal Detection of Congenital Heart Diseases Using Echocardiography: 12-Year Results of an Improving Program With 9782 Cases.

Background: A 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. Objectives: To evaluate the effects of this program on the prenatal diagnosis rate (PDR) by echocardiography and termination of pregnancy (TOP). Methods: A 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. Results: The 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. Conclusions: The 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.

Lifelong smoking status, weight gain, and subsequent risk of major adverse cardiovascular events: Long-term follow-up of a middle-aged Chinese population.

OBJECTIVE: The aim of this study was to explore the association of lifelong smoking status with risk of major adverse cardiovascular events (MACE) accounting for weight change in a Chinese cohort. METHODS: The cohort of the People's Republic of China-United States of America (PRC-USA) Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology was established in 1983 to 1984, resurveyed during 1987 to 1988 and 1993 to 1994, and followed up to 2005. A total of 5,849 participants who survived in 1993 to 1994 were classified into never smokers, long-term quitters, short-term quitters, short-term relapsers and new smokers, long-term relapsers and new smokers, and persistent smokers according to the information on lifelong smoking status collected in all three surveys. The associations of lifelong smoking status with MACE in the subsequent 10 years were explored with Cox proportional hazards models. RESULTS: During a median follow-up of 10.2 years, 694 participants had MACE. Compared with persistent smokers, the multivariable-adjusted hazard ratio of developing MACE was 0.83 (95% CI: 0.61-1.12) for short-term quitters, 0.75 (95% CI: 0.54-1.02) for long-term quitters, and 0.68 (95% CI: 0.54-0.85) for never smokers (ptrend = 0.001). In comparison, the hazard ratio was 1.03 (95% CI: 0.77-1.35) for long-term relapsers and new smokers and 0.78 (95% CI: 0.46-1.22) for short-term relapsers and new smokers (ptrend = 0.018). These associations were not significantly altered by further adjusting for weight change in the past 10 years. CONCLUSIONS: Lifelong smoking status is significantly associated with risk of MACE. As time duration increased, health benefit to quitters would become close to that of never smokers, and harms to relapsers and new smokers would become close to that of persistent smokers.

First-Trimester Maternal Folic Acid Supplementation Modifies the Effects of Risk Factors Exposures on Congenital Heart Disease in Offspring.

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.

Maternal exposure to ambient air pollution and congenital heart defects in China.

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.

Using Innovative Machine Learning Methods to Screen and Identify Predictors of Congenital Heart Diseases.

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 (<33.33 s), and elevated glucose levels were the most important predictors and were associated with ranges of 1.17-1.54 relative risks of CHDs. We have developed an online predictive tool for CHDs based on our findings that may help screening and prevention of CHDs. Conclusions: Maternal UA, glucose, and coagulation levels were the most consistent and significant predictors of CHDs. Thresholds below the current clinical definition of "abnormal" for these predictors could be used to help develop CHD screening and prevention strategies.

Maternal folic acid supplementation mediates the associations between maternal socioeconomic status and congenital heart diseases in offspring.

Low maternal socioeconomic status (SES) is considered as a risk factor of congenital heart diseases (CHDs) in offspring. However, the pathways underpinning the SES-CHDs associations are unclear. We assessed if first trimester maternal folic acid supplementation (FAS) is a mediator of the SES-CHDs associations. This case-control study included 8379 CHD cases and 6918 CHD-free controls from 40 participating centers in Guangdong, Southern China, 2004-2016. All fetuses were screened for CHDs using ultrasound and cases were confirmed by echocardiogram. We collected SES and FAS information during face-to-face interview by obstetricians using a structured questionnaire. Low SES was defined as education attainment <12 years, household individual income <3000 Chinese Yuan/person/month or unemployment. FAS referred to at least 0.4 mg of daily folic acid intake over 5 days/week continuously. We used causal mediation analysis to estimate the direct, indirect and proportion mediated by FAS on the SES-CHDs associations adjusted for confounders. Both low maternal income and education were significantly associated with increased risks of CHDs and lower prevalence of FAS. Low maternal FAS prevalence mediated 10% [95%CI:5%,13%] and 3% [95%CI:1%,5%] of the maternal low income-CHDs and the maternal low education-CHDs associations, respectively. In addition, FAS mediated the highest proportion of the associations between income and multiple critical CHDs [46.9%, 95%CI:24.7%,77%] and conotruncal defects [31.5%, 95%CI:17.1%,52.0%], respectively. Maternal FAS partially mediated the SES-CHDs associations, especially among the most critical and common CHDs. Promoting FAS in low SES women of childbearing age may be a feasible intervention to help prevent CHDs.

Triglyceride to high-density lipoprotein cholesterol ratio and risk of atherosclerotic cardiovascular disease in a Chinese population.

BACKGROUND AND AIMS: Triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio may play a role in predicting cardiovascular events. We aimed to prospectively explore the association between the TG/HDL-C ratio and atherosclerotic cardiovascular disease (ASCVD), ischemic stroke, as well as coronary heart disease (CHD) in a Chinese population. METHODS AND RESULTS: This prospective cohort study included 9368 participants from four Chinese populations in the People's Republic of China-United States of America (PRC-USA) Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology. Over a follow-up period of 20 years, 624 cases of ASCVD events including 458 ischemic stroke events and 166 CHD events were recorded. The relationship between the TG/HDL-C ratio and the endpoints was evaluated through multivariate Cox proportional hazard models adjusted for potential confounding variables, including age, sex, urban or rural residence, northern or southern China, occupational type, education, physical exercise, smoking status, drinking status, body mass index, hypertension, high low-density lipoprotein cholesterol, diabetes, and antihypertensive medication use at baseline. With the lowest TG/HDL-C tertile as the reference, the middle and highest tertiles had the hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.13 (0.91, 1.40), 1.36 (1.10, 1.67) respectively for ASCVD (p for trend = 0.0028), and 1.19 (0.93, 1.54),1.47 (1.15, 1.87) respectively for ischemic stroke (p for trend = 0.0016). However, no significant association was found for CHD events. CONCLUSION: TG/HDL-C ratio was positively associated with the risk of ASCVD and ischemic stroke events in the Chinese population.

Evaluation of interactive effects between paternal alcohol consumption and paternal socioeconomic status and environmental exposures on congenital heart defects.

BACKGROUND: While the maternal risk factors on congenital heart defects (CHDs) have often been assessed, paternal contribution to CHDs, especially the joint effects of paternal risk factors on CHDs remain unknown. This study examined the major impacts of paternal alcohol consumption and its interaction (on multiplicative and additive scales) with paternal socioeconomic status (SES) and environmental exposures on CHDs in China. METHODS: A population-based case-control study involving 4,726 singleton CHDs cases and 4,726 controls (without any malformation and matched on hospital, gender, and gestational age) was conducted in Guangdong, China, 2004-2014. Information on parental demographics, behavioral patterns, disease/medication, and environmental exposures (3 months before pregnancy) was collected through face-to-face interviews. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) while controlling for all parental factors. RESULTS: Paternal alcohol consumption was associated with an increased OR of CHDs (adjusted OR = 2.87, 95% CI: 2.25-3.65). Additionally, paternal smoking, industry occupation, organic solvent contact, virus infection and antibiotic use, living in rural areas, low household income, and migrant status were significantly associated with CHDs (ORs ranged: 1.42-4.44). Significant additive or multiplicative interactions were observed between paternal alcohol consumption and paternal smoking, industrial occupation, and low income on any CHDs (interaction contrast ratio [ICR] = 4.72, 95% CI: 0.96-8.47] and septal defects (ICRs ranged from 2.04 to 2.79, p < .05). CONCLUSIONS: Paternal alcohol consumption and multiple paternal factors were significantly associated with CHDs in China. Paternal smoking and low SES factors modified paternal alcohol consumption-CHDs relationships. Further studies are needed to confirm these findings.

Associations of greenness with gestational diabetes mellitus: The Guangdong Registry of Congenital Heart Disease (GRCHD) study.

Gestational diabetes mellitus (GDM) is associated with adverse short- and long-term health outcomes among mothers and their offspring. GDM affects 0.6%-15% of pregnancies worldwide and its incidence is increasing. However, intervention strategies are lacking for GDM. Previous studies indicated a protective association between greenspace and type 2 diabetes mellitus (T2DM), while few studies have explored the association between greenness and GDM. This study aimed to investigate the association between residential greenness and GDM among women from 40 clinical centers in Guangdong province, south China. The study population comprised 5237 pregnant mothers of fetuses and infants without birth defects, from 2004 to 2016. There were n = 157 diagnosed with GDM according to World Health Organization criteria. We estimated residential greenness using the Normalized Difference Vegetation Index (NDVI), derived from satellite imagery using a spatial-statistical model. Associations between greenness during pregnancy and GDM were assessed by confounder-adjusted random effects log-binomial regression models, with participating centers as the random effect. One interquartile increments of NDVI250m, NDVI500m and NDVI1000m were associated with 13% (RR = 0.87, 95%CI: 0.87-0.87), 8% (RR = 0.92, 95%CI: 0.91-0.92) and 3% (RR = 0.97, 95%CI: 0.97-0.97) lower risks for GDM, respectively. However, NDVI3000m was not significantly associated with GDM (RR = 0.96, 95%CI: 0.78-1.19). The risk for GDM decreased monotonically with greater NDVI. The protective effect of greenness on GDM was stronger among women with lower socioeconomic status and in environments with a lower level air pollutants. Our results suggest that greenness might provide an effective intervention to decrease GDM. Greenness and residential proximity to greenspace should be considered in community planning to improve maternal health outcomes.

First-Trimester Maternal Folic Acid Supplementation Reduced Risks of Severe and Most Congenital Heart Diseases in Offspring: A Large Case-Control Study.

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.

Maternal residential greenness and congenital heart defects in infants: A large case-control study in Southern China.

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.

Arterial switch operation: A double cohort study of 20 years’ outcomes of 571 patients in a single center / 中国胸心血管外科临床杂志

@#Objective    To define the patient characteristics and perioperative management, and to define the mortality and its risk factors after arterial switch operation (ASO). Methods    We conducted a bidirectional cohort study with 571 consecutive patients undergoing ASO from 1997 to 2016 in our hospital. We enrolled patients who underwent ASO before 2012 retrospectively and after 2012 prospectively and followed up all the patients prospectively. Demographic characteristics, clinical information and mortality of these patients were summarized. Joinpoint regression analysis was used to identify the time trend of the overall mortality. Kaplan-Meier survival analysis was used to evaluate the mid- and long-term survival rate after ASO. Cox proportional hazards regression models were used to explore the potential factors associated with mortality. The cumulative incidence of complications after ASO was predicted using competing risk models. Results    Several aspects of patients’ characteristics and perioperative management in our center differed from those in the developed countries. The overall mortality and in-hospital mortality after ASO was 16.3% and 15.1%, respectively. The overall cumulative survival rate at 5, 10 and 15 years after ASO was 83.3%, 82.8% and 82.8%, respectively. A significant decrease of overall mortality from 1997 to 2016 was observed. Independent risk factors of mortality included earlier ASO (1997-2006), single or intramural coronary anatomy and longer cardiopulmonary bypass time. Ten years after ASO, re-intervention, arrhythmia, pulmonary and anastomotic stenosis were the most common complications with a cumulative incidence over 10%. Conclusion    Significant improvements in the results of the ASO were observed and the postoperative mortality rate is close to reports from developed countries. Nonetheless, we have identified the need for further improvement in the early and late postoperative periods after ASO. Pulmonary stenosis, anastomotic stenosis and arrhythmia should be paid attention to during the long-term follow-up after ASO.

Fasting glucose and its association with 20-year all-cause and cause-specific mortality in Chinese general population.

OBJECTIVE: The aim of this study was to explore the relationship between fasting glucose levels and all-cause and cause-specific mortality in Chinese population. METHODS: The role of fasting blood glucose levels as a predictor of all-cause and cause-specific mortality was estimated in 9930 participants from four Chinese general populations with a 20-year follow-up. Multivariate Cox proportional hazard models were used to identify the relationship between fasting glucose and mortality. RESULTS: There were 1471 deaths after a median follow-up of 20.2 years (a total of 187,374 person-years), including 310 cardiovascular deaths, 581 cancer deaths, and 580 other-cause deaths. After adjustment for age, sex, urban or rural, northern or southern of China, types of work, education level, physical exercise, smoking status, drinking status, body mass index, systolic blood pressure, and serum total cholesterol at baseline, the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in the fasting blood glucose categories of <60, 60-69, 70-79, 90-99, 100-109, 110-125, and ≥126 mg/dl were 1.38 (1.04-1.84), 1.20 (1.01-1.43), 1.18 (1.03-1.36), 1.18 (0.99-1.41), 1.48 (1.16-1.88), 1.17 (0.84-1.62), and 2.23 (1.72-2.90), respectively, in contrast to the reference group (80-89 mg/dl). The HRs and 95% CIs for cardiovascular disease mortality in these groups were 2.58 (1.44-4.61), 1.41 (0.95-2.10), 1.56 (1.15-2.11), 1.29 (0.88-1.89), 1.36 (0.78-2.37), 1.05 (0.52-2.11), and 2.73 (1.64-4.56), respectively. CONCLUSIONS: Both low and high fasting glucose were significantly associated with increased risk of all-cause and cardiovascular mortality in Chinese general population.

Urinary sodium excretion and risk of cardiovascular disease in the Chinese population: a prospective study.

The effect of dietary sodium (salt) on cardiovascular disease (CVD) has been debated for a long time. The present study aims to explore whether salt intake affects the risk of cardiovascular disease in the Chinese population. Data from a prospective cohort study that included 954 men and women aged 35-59 years at baseline from four urban and rural population samples in China were used. Each participant collected their overnight urine for three consecutive days during two seasons to estimate sodium intake. CVD events, including incidences of coronary heart disease (CHD), stroke, and death from CVD, and all-cause mortality were tested by Cox proportional hazards models. After a median of 18.6 years of follow-up, CVD events occurred in 81 (8.5%) participants, including 20 CHD and 64 stroke events. All-cause deaths occurred in 149 (15.6%) participants, including 31 CVD-related deaths, 56 cancer-related deaths and 62 other-cause deaths. The hazard ratios and 95% confidence intervals for CVD events in each of the sodium excretion tertiles were 1.00, 1.66 (0.79-3.47) and 3.04 (1.46-6.34), P for trend = 0.001. This trend was also found for stroke incidence (P for trend < 0.001). The cardiovascular mortality risk increased as the sodium excretion levels rose after adjusting for confounding factors (P for trend = 0.043). However, this trend was not significant after adjusting for the baseline systolic blood pressure and antihypertensive medication use (P for trend = 0.171). No significant associations were found between sodium excretion and all-cause, cancer-related or other-cause mortality. High urinary sodium excretion was independently associated with an increased risk of cardiovascular disease in the general Chinese population.

Ideal cardiovascular health metrics and its association with 20-year cardiovascular morbidity and mortality in a Chinese population.

BACKGROUND: The American Heart Association (AHA) developed a simplified assessment tool based on seven ideal cardiovascular health (CVH) metrics, but the relationship between the AHA defined ideal CVH metrics and cardiovascular risk in Chinese population has not been well estimated. METHODS: The baseline survey were conducted among 938 Chinese men and women from four urban and rural population samples in China, aged 35-59 years in 1983-1984. The cohort was followed up for multiple cardiovascular endpoints up to 2005. Cox proportional hazard models were used to test the associations accounting for multiple covariates. Outcomes were collected in 1987-2005 and data analysed in 2017. RESULTS: During a median of 20.3 years follow-up, 68 non-fatal CVD events and 139 deaths (29 CVD deaths) occurred. The multivariable adjusted HRs and 95% CIs for all CVD in the groups with three and 4-7 ideal CVH metrics were 0.59 (95% CI 0.33 to 1.04) and 0.24 (95% CI 0.12 to 0.47), when the group with 0-2 ideal CVH metrics as the reference. Results also showed that participants with 4-7 ideal CVH metrics had a 54% (95% CI 24% to 72%) lower risk of all-cause mortality in comparison with those with 0-2 ideal metrics. CONCLUSIONS: The number of ideal CVH metrics was inversely associated with the risk of cardiovascular morbidity and mortality in this Chinese general population.

Perinatal and early postnatal outcomes for fetuses with prenatally diagnosed d-transposition of the great arteries: a prospective cohort study assessing the effect of standardised prenatal consultation.

BACKGROUND: The aim of this study was to explore perinatal and early postnatal outcomes in fetuses with prenatally diagnosed d-transposition of the great arteries and impacts of standardised prenatal consultation. METHODS: All fetuses with prenatally diagnosed d-transposition of the great arteries prospectively enrolled at South China cardiac centre from 2011 to 2015. Standardised prenatal consultation was introduced in 2013 and comprehensive measures were implemented, such as establishing fetal CHD Outpatient Consultation Service, performing standard prenatal consultation according to specifications, and establishing a multidisciplinary team with senior specialists performing in-person consultations. Continuous follow-up investigation was conducted. Perinatal and postnatal outcomes were compared before and after consultation including live birth, elective termination of pregnancy, spontaneous fetal death, stillbirths, referral for surgery, and survival. RESULTS: In all, 146 fetuses were enrolled with 41 (28%) lost to follow-up. Among 105 remaining fetuses, 29 (28%) were live births and 76 (72%) were terminated. After consultation, live birth rate was higher (50 versus 33%) and termination rate was lower (50 versus 76%), although there was no statistical significance. Excluding three live births without postnatal d-transposition of the great arteries, 65% (17/26) underwent arterial switch operation within 30 days. A total of three in-hospital deaths occurred and during the 10-month follow-up period, one death was observed. In one case, the switch procedure was performed at 13 months and the infant survived. Out of eight infants without arterial switch operation, two died. CONCLUSIONS: Live birth rate increased after consultation; however, termination remained high. Combining termination, patients without arterial switch operation, and operative mortality, outcomes of d-transposition of the great arteries infants can be improved. Standard consultation, multidisciplinary collaboration, and improved perinatal care are important to improve outcomes.

Does maternal environmental tobacco smoke interact with social-demographics and environmental factors on congenital heart defects?

Congenital heart defects (CHDs) are a major cause of death in infancy and childhood. Major risk factors for most CHDs, particularly those resulting from the combination of environmental exposures with social determinants and behaviors, are still unknown. This study evaluated the main effect of maternal environmental tobacco smoke (ETS), and its interaction with social-demographics and environmental factors on CHDs in China. A population-based, matched case-control study of 9452 live-born infants and stillborn fetuses was conducted using the Guangdong Registry of Congenital Heart Disease data (2004-2014). The CHDs were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia tomography/catheterization. Controls were randomly chosen from singleton newborns without any malformation, born in the same hospital as the cases and 1:1 matched by infant sex, time of conception, and parental residence (same city and town to ensure sufficient geographical distribution for analyses). Face-to-face interviews were conducted to collect information on demographics, behavior patterns, maternal disease/medication, and environmental exposures. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals of ETS exposure on CHDs while controlling for all risk factors. Interactive effects were evaluated using a multivariate delta method for maternal demographics, behavior, and environmental exposures on the ETS-CHD relationship. Mothers exposed to ETS during the first trimester of pregnancy were more likely to have infants with CHD than mothers who did not (aOR = 1.44, 95% CI 1.25-1.66). We also observed a significant dose-response relationship when mothers were exposed to ETS and an increasing number of risk factors and CHDs. There were greater than additive interactions for maternal ETS and migrant status, low household income and paternal alcohol consumption on CHDs. Maternal low education also modified the ETS-CHD association on the multiplicative scale. These findings may help to identify high-risk populations for CHD, providing an opportunity for targeted preventive interventions.

Associations between toxic and essential trace elements in maternal blood and fetal congenital heart defects.

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.

Incidence of Congenital Heart Disease: The 9-Year Experience of the Guangdong Registry of Congenital Heart Disease, China.

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.

Risk factors of different congenital heart defects in Guangdong, China.

BACKGROUND: Limited studies have evaluated the risk factors for congenital heart defects (CHDs) in China and compared them for different types of CHDs. This study examined risk factors between isolated and multiple CHDs as well as among CHDs subtypes in Guangdong, Southern China. METHODS: This population-based case-control study included 4,034 pairs of case and control infants enrolled in the Guangdong Registry of CHD study, 2004-2013. Multivariate logistic regression was used to compute adjusted odds ratios (ORs) while simultaneously controlling for confounders. RESULTS: Multiple maternal environmental exposures, including living in newly renovated rooms, residential proximity to main traffic, paternal smoking, and maternal occupation as manual worker, were significantly associated with CHDs with ORs ranging 1.30-9.43. Maternal perinatal diseases (including maternal fever, diabetes, influenza, and threatened abortion), maternal medication use (antibiotic use), advanced maternal age, low socioeconomic status, and paternal alcohol intake were also significantly associated with CHDs, with ORs ranging 1.60-3.96. Isolated CHDs and multiple defects have different profiles of risk factors, while subtype of CHD shares common risk factors. CONCLUSION: These results suggest that maternal environmental exposures/occupation and perinatal diseases/medication use were dominant risk factors associated with CHDs in Southern China. Isolated and multiple CHDs may have different etiologic factors.