Risk of maternal exposure to mixed air pollutants during pregnancy for congenital heart diseases in offspring.

OBJECTIVE: To explore the risk of maternal exposure to mixed air pollutants of particulate matter 1 (PM 1), particulate matter 2.5 (PM 2.5), particulate matter 10 (PM 10) and NO 2 for congenital heart disease (CHD) in offspring, and to estimate the ranked weights of the above pollutants. METHODS: 6038 CHD patients and 5227 healthy controls from 40 medical institutions in 21 cities in Guangdong Registry of Congenital Heart Disease (GRCHD) from 2007 to 2016 were included. Logistic regression model was used to estimate the effect of maternal exposure to a single air pollutant on the occurrence of CHD in offspring. Spearman correlation coefficient was used to analyze the correlation between various pollutants, and Quantile g-computation was used to evaluate the joint effects of mixed exposure of air pollutants on CHD and the weights of various pollutants. RESULTS: The exposure levels of PM 1, PM 2.5, PM 10 and NO 2 in the CHD group were significantly higher than those in the control group (all P<0.01). The correlation coefficients among PM 1, PM 2.5, PM 10 and NO 2 were greater than 0.80. PM 1, PM 2.5, PM 10 and NO 2 exposure were associated with a significantly increased risk of CHD in offspring. Mixed exposure of these closely correlated pollutants presented much stronger effect on CHD than exposure of any single pollutants. There was a monotonic increasing relationship between mixed exposure and CHD risk. For each quantile increase in mixed exposure, the risk of CHD increased by 47% ( OR=1.47, 95% CI: 1.34-1.61). Mixed exposure had greater effect on CHD in the early pregnancy compared with middle and late pregnancy, but the greatest effect was the exposure in the whole pregnancy. The weight of PM 10 is the highest in the mixed exposure (81.3%). CONCLUSIONS: Maternal exposure to the mixture of air pollutants during pregnancy increases the risk of CHD in offspring, and the effect is much stronger than that of single exposure of various pollutants. PM 10 has the largest weights and the strongest effect in the mixed exposure.

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.

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.

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.

[Analysis of environmental risk factors in congenital heart defects].

OBJECTIVE: To explore the environmental risk factors of different categories of congenital heart defects (CHD) and provide evidence for further risk factors and prevention research of CHD phenotypes. METHODS: Data of Guangdong CHD Register Study from 2004 to 2012 were used. In the study, 3 038 CHD cases and 3 038 paired controls from 34 hospitals distributed in 17 cities were registered and related information were collected using uniform, and structured questionnaires. All the CHD phenotypes were coded according to the International Classification of Diseases 10th Revision (ICD-10) and classified into 6 categories according to their pathological features. Univariate analyses were adopted to filter potential risk factors for each category of CHD. Then multivariate conditional Logistic regression was used to calculate the odds ratios of the risk factors for each category of CHD. RESULTS: The risk factors for left-to-right shunt CHD included low (OR=2.63, 95%CI:2.04-3.39) or over birth weight (OR=2.21, 95%CI: 1.47-3.32), premature delivery (OR=1.95, 95%CI: 1.53-2.49), polyembryony (OR=1.99, 95%CI: 1.22-3.26), maternal low education, mother as factory worker (OR=1.62, 95%CI: 1.32-1.98), parity≥2 (OR=1.38, 95%CI: 1.13-1.69), maternal abnormal reproduction history (OR=2.29, 95%CI: 1.75-3.01), fever (OR=2.38, 95%CI: 1.26-4.48), virus infection (OR=1.80, 95%CI: 1.29-2.51), medicine usage (OR=1.73, 95%CI: 1.11-2.69), passive smoking (OR=1.69, 95%CI: 1.26-2.29), chemical agent contact (OR=8.71, 95%CI: 2.33-32.58), living in newly decorated houses (OR=2.56, 95%CI: 1.60-4.09) or room close to the main road (OR=1.40, 95%CI: 1.14-1.72) in the first 3 months of pregnancy and father as factory worker (OR=1.46, 95%CI: 1.23-1.73). The risk factors for pulmonary outflow tract obstruction CHD included low (OR=5.98, 95%CI: 2.88-12.44) or over birth weight (OR=6.56, 95%CI:1.19-36.26), maternal low education, parity≥2 (OR=2.08, 95%CI: 1.03-4.22), virus infection in the first 3 months of pregnancy (OR=4.30, 95%CI: 1.27-13.45). The risk factors for left ventricular outflow tract obstruction CHD included father as factory worker (OR=6.01, 95%CI:1.05-34.59). The risk factors for transposition of the great arteries included low birth weight (OR=12.93, 95%CI:1.14-146.26), maternal low education, mother as factory worker (OR=3.69, 95%CI:1.53-8.91). The risk factors for conditions with intra cardiac mixing of oxygenated and deoxygenated blood included parity=2 (OR=3.45, 95%CI: 1.42-8.38). The risk factors for other CHD included over birth weight (OR=4.87, 95%CI: 1.19-19.94), maternal abnormal reproduction history (OR=2.96, 95%CI: 1.14-7.68), virus infection (OR=4.92, 95%CI: 1.56-15.47), medicine usage (OR=4.90, 95%CI: 1.22-19.77) or passive smoking (OR=10.31, 95%CI: 1.25-85.05) in the first 3 months of pregnancy. CONCLUSION: The environmental risk factors were discrepant among different categories of CHD. Further risk factors study of CHD phenotypes should be performed specially. To prevent CHD, attention should be paid to the risk factors which are related to multi or complex categories of CHD.

[Cut-off values of waist circumference for central obesity in Chinese adults].

OBJECTIVE: To investigate the appropriate cut-off values of waist circumference(WC)for central obesity and severe central obesity in Chinese adults. METHODS: A total of 10 265 participants aged 35-69 years from the cross-sectional survey of the PRC-USA Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology between 1993 and 1994 with integral data were included. Each integer unit in centimeters of WC in a given range was used as the cut-off point to detect clustering of risk factors, which was defined as an individual with 2 or more risk factors including hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia and low levels of high-density lipoprotein cholesterol. Sensitivity, specificity and distance from the receiver operating characteristic (ROC) curves to the upper left corner of the ROC graph were calculated. The WC value corresponding to the point on the ROC curve nearest to the upper left corner was considered as the optimal cut-off value for central obesity and the value corresponding to the point with specificity of 90% or more was considered as the optimal cut-off for severe central obesity. RESULTS: The mean WC was (80.5 ± 9.9) cm in men and (77.8 ± 10.0) cm in women; 18.1% (890/4 921) of men and 14.5% (776/5 344) of women were identified with two or more major risk factors. Based on the ROC curve analysis, the optimal value of WC to detect clustering of risk factors was ≥ 84 cm for men and ≥ 80 cm for women, and the shortest distance to the upper left corner was 0.430 and 0.450, respectively. The cut-off values of WC to detect clustering of risk factors with specificity of 90% or more were ≥ 93 cm and ≥ 91 cm for men and women, respectively. CONCLUSION: The cut-off points of WC for central obesity and severe central obesity in Chinese adults obtained from this study are equal or similar to the WC cut-off values proposed by the Guidelines for Prevention and Control of Overweight and Obesity in Chinese Adults.

[Long term trends of blood lipid and glucose change in Guangzhou urban and rural natural population].

OBJECTIVE: To observe the long term trends of blood lipid and glucose change in Guangzhou urban and rural natural population. METHODS: We cross-sectionally studied individuals 35 to 65 years of age (50% male) from People' Republic of China-United States cardiovascular and cardiopulmonary epidemiology research study using random sampling design in Guangzhou Shipyard and Panyu Dashi Town (Dashi Street and Luopu Street now) in 1983 and 1984 (n = 4 548), 1998 (n = 1 593), 2004 (n = 2 095)and 2011 (n = 1 692). Prevalence of dyslipidemia and pathoglycemia were standardized to the WHO world standard population. Blood lipid and glucose levels were compared in this cohort during the 28 years. RESULTS: (1) The age adjusted mean average levels of blood lipid and glucose and the standardized prevalence rate of dyslipidemia and increased blood glucose as well as cardiovascular risk factors were significantly higher in the urban than in the rural residents and higher in male than in female participants (P < 0.01 or 0.05).(2) The age adjusted mean level of blood total cholesterol (TC), triglyceride (TG), glucose and high density lipoprotein cholesterol (HDL-C) increased from 1983/1984 to 2004 year in both urban and rural residents, and trended to be stable or decreased thereafter.(3) Standardized prevalence of multiple cardiovascular risk factors, such as high blood TG, low HDL-C, blood lipid disorder, fasting blood glucose level and diabetes, steadily increased from 1983/1984 to 2004 and this increasing trend was slowed or reversed thereafter, except the prevalence rate of high blood TC. CONCLUSIONS: Except for high blood TC, the prevalence of multiple cardiovascular risk factors, such as high blood TG, low HDL-C, higher fasting blood glucose and diabetes, tended to be under control after 2004 in this cohort. Further efforts are warranted to strengthen this positive trend in the natural population.

Glutamine enhances pneumococcal growth under methionine semi-starvation by elevating intracellular pH.

Introduction: Bacteria frequently encounter nutrient limitation in nature. The ability of living in this nutrient shortage environment is vital for bacteria to preserve their population and important for some pathogenic bacteria to cause infectious diseases. Usually, we study how bacteria survive after nutrient depletion, a total starvation condition when bacteria almost cease growth and try to survive. However, nutrient limitation may not always lead to total starvation. Methods: Bacterial adaptation to nutrient shortage was studied by determining bacterial growth curves, intracellular pH, intracellular amino acid contents, gene transcription, protein expression, enzyme activity, and translation and replication activities. Results: No exogenous supply of methionine results in growth attenuation of Streptococcus pneumoniae, a human pathogen. In this paper, we refer to this inhibited growth state between ceased growth under total starvation and full-speed growth with full nutrients as semi-starvation. Similar to total starvation, methionine semi-starvation also leads to intracellular acidification. Surprisingly, it is intracellular acidification but not insufficient methionine synthesis that causes growth attenuation under methionine semi-starvation. With excessive glutamine supply in the medium, intracellular methionine level was not changed, while bacterial intracellular pH was elevated to ~ 7.6 (the optimal intracellular pH for pneumococcal growth) by glutamine deamination, and bacterial growth under semi-starvation was restored fully. Our data suggest that intracellular acidification decreases translation level and glutamine supply increases intracellular pH to restore translation level, thus restoring bacterial growth. Discussion: This growth with intracellular pH adjustment by glutamine is a novel strategy we found for bacterial adaptation to nutrient shortage, which may provide new drug targets to inhibit growth of pathogenic bacteria under semi-starvation.

Maternal serum neonicotinoids during early-mid pregnancy and congenital heart diseases in offspring: An exploratory study.

Experimental evidence has indicated a correlation between in-utero exposure to neonicotinoid pesticides (NEOs) and adverse birth outcomes in mammals. However, the distribution of NEO exposure during human pregnancy, as well as its association with congenital heart diseases (CHDs), the most common birth defects, are unclear. Our purpose was to explore the distribution of and contributing factors to NEO exposure in pregnant women during early-mid pregnancy and to assess the associations between NEOs and CHDs. This nested case-control study was conducted within an ongoing prospective birth cohort study and enrolled 141 CHD singletons and their 282 individually matched controls. Six "parent" NEOs and three NEO metabolites were measured in maternal serum collected at an average gestational age of 16 weeks, using liquid chromatography-tandem mass spectrometry. Logistic regression was used to quantify the NEOs-CHDs associations and explore potential contributing factors to serum NEO levels in controls. N-desmethyl acetamiprid (N-dm-ACE) and imidacloprid (IMI) were the most frequently detected NEOs, found in 100% and 20% of maternal sera, respectively. We did not find a statistically significant association between total NEOs and overall CHDs. However, there was a trend towards a higher risk of septal defects with greater serum NEOs (ORs ranged from 1.80 to 2.36), especially nitro-containing NEOs represented by IMI. Pregnant women with lower education had elevated serum total NEOs compared to women with higher education (OR = 48.39, 95% CI: 23.48-99.72). Pregnant women were primarily exposed to N-dm-ACE and IMI during early-mid pregnancy. Gestational exposure to NEOs may be associated with an increased risk of septal defects, but the evidence is limited at present. Education is a potential contributing factor to NEO exposure in pregnant women. Larger and more precise studies with longitudinal biospecimen collection, are recommended to validate our exploratory findings.

[Risk factors of congenital heart defects in fetal and infants born from 2004 to 2011 in Guangdong].

OBJECTIVE: To analyze the risk factors of congenital heart defects (CHD) in fetal and infants born from 2004 to 2011 in Guangdong province. METHODS: Babies with CHD aged from 28th week of gestation to 1 year old postnatal from July 1 2004 to December 31 2011 were registered in Guangdong CHD monitoring network with 34 participating units. Totally 2568 CHD cases were included, and 1: 1 matched with a normal control cohort by gender, living district and birth date (time span within 3 months).Exposed information of mother and father at pre-pregnancy and early pregnancy was collected. Post collinearity diagnostics analysis, univariate analysis results were included in a multivariate analysis model with forward stepwise conditional logistic regression. RESULTS: Multivariate conditional logistic regression analysis showed that high risk factors for CHD included low birth weight infant (OR = 5.34, P < 0.01), macrosomia (OR = 1.67, P < 0.05), low per capita income (0-1200 yuan, OR = 1.68, P < 0.01), exposure to chemical agent at early pregnancy (OR = 19.72, P < 0.01), floating population (OR = 2.13, P < 0.01), abnormal reproductive history (OR = 3.18, P < 0.01), exposure to passive smoking (OR = 2.59, P < 0.01), suffering from fever (OR = 3.74, P < 0.01), equal to or more than twice parity (OR = 1.45, P < 0.01), living in a newly (within six months)-decorated-apartment (OR = 2.74, P < 0.01), suffering from virus infection (OR = 2.08, P < 0.01), rural residence (OR = 1.33, P < 0.01), living in an apartment within 50 meters of major traffic road (OR = 1.52, P < 0.01), syphilis infection at early pregnancy (OR = 13.06, P < 0.05) and father's drinking habit at pre-pregnancy (OR = 1.57, P < 0.05). CONCLUSION: Numerous risk factors for CHD in fetal and infants of Guangdong province are indicated by our results, comprehensive intervention should be considered in pre-pregnancy and early pregnancy to reduce the risk of CHD.

[Current prevalence rate of congenital heart disease in 12 month-old and younger infants among four regions of Guangdong province].

OBJECTIVE: To summarize prevalence rate and region distribution of congenital heart disease (CHD) in 12-month-old and younger infants among four regions of Guangdong province, China. METHODS: Data from Guangdong CHD monitoring network including 34 monitoring units covering different geographic regions were analyzed. Professional training on screening and diagnosing CHD was provided to each work group member to improve the diagnosis level. CHD infants under or aged 12 months detected in the monitoring unit were included. CHD was diagnosed by fetus and infants echocardiography. RESULTS: From July 2004 to December 2010, 383 281 perinatal were registered and 3263 cases of CHD were detected in the 34 member units of Guangdong CHD monitoring network [total prevalence rate of CHD: 0.851% (3263/383 281), male prevalence rate: 0.868% (1799/207 347), female prevalence rate:0.828% (1456/175 843)].Stillbirth CHD prevalence rate was significantly higher than livebirth CHD prevalence rate [10.627% (676/6361) vs. 0.686% (2587/376 920), P < 0.01]. The total prevalence of CHD was significantly higher in Pearl River Delta region [0.906% (2826/311 823)] than in other regions [0.611% (437/71 458), P < 0.01]. Ventricular septal defect [39.93% (1033/2587) in livebirth] was the most dominant CHD, followed by patent ductus arteriosus [29.84% (772/2587)] and secundum atrial septal defect [13.76% (356/2587)]. CONCLUSIONS: The present data indicate that the prevalence of CHD in Guangdong is at the medium-upper level of the country associated with high stillbirth rate. The dominant type of CHD is ventricular septal defect. CHD prevalence is higher in the Pearl River Delta region than in other regions.

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.

Adverse trends of cardiovascular risk factors among low risk populations (1983-1994)--a cohort study of workers and farmers in Guangzhou, China.

BACKGROUND: The levels and trends of cardiovascular risk factors vary greatly throughout China. We examine 10-year trends of cardiovascular risk factors (1983-1994) and the factors related to these trends among low-risk cohorts of workers and farmers in Guangzhou, China. METHODS: This is a cohort study of 3,131 workers and 3,493 farmers aged 25-64 years at baseline with 10 years of follow-up. We performed a longitudinal analysis to account for the aging of the cohorts and the repeated measures of the same individual. RESULTS: At baseline the prevalence of overweight (including obese) ranged from 1.0% to 11.8%, hypertension ranged from 3.8% to 10.5%, and mean serum total cholesterol (TC) ranged from 155.4 mg/dl to 187.2 mg/dl. Although prevalence of smoking declined, blood pressure levels and body mass index (BMI) increased significantly, and lipid profiles changed unfavorably during the 10-year follow-ups. The prevalence of hypertension increased from 5.0 percentage points (female farmers) to 12.3 percentage points (male farmers). Mean TC increased significantly (e.g., +22.8 mg/dl and +17.0 mg/dl in male and female farmers, respectively). In the longitudinal data analyses, increase in BMI was associated with increase in blood pressure levels and TC. Significant adverse trends of risk factors persisted after adjustment for aging, education, BMI, smoking, and alcohol intake. CONCLUSION: Urgent action is needed to prevent and reverse the unhealthy trends occurring among these low risk Chinese workers and farmers.

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.

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 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.

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.

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.

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.