Occurrence Of Congenital Heart Disease Research Articles

Tetralogy of Fallot: Hypoxia, the villain of the story?

Tetralogy of Fallot (ToF) is a cyanotic congenital heart disease, composed of four malformations: persistent communication between the right and the left ventricle, pulmonary stenosis, overriding aorta, and right ventricle hypertrophy. The etiology of this disease is not entirely known as yet, but it has been proposed that the pathology has genetic components. During embryonic development, the fetus is exposed to a physiological hypoxia to facilitate the formation of blood vessels and blood cells through de novo processes. After researching scientific databases on the implications of oxygen on the normal and abnormal development of organs, especially the heart, we were able to propose that oxygen deprivation may be the cause of the disease. During this period, the hypoxia-inducible factor is activated and triggers transcriptional responses that enable adaptation to the hypoxic environment through angiogenic activation. High levels of this protein can alter certain physiological pathways, such as those related to the vascular endothelial growth factor. Research has shown that prolonged oxygen deprivation during embryological development can lead to the occurrence of congenital heart diseases, such as ToF. Studies using animal models have demonstrated that the deficiency or disruption of a protein called "CITED2," which plays an important role in cardiac morphogenesis and its loss, results in the alteration of pluripotent, cardiac, and neural lineage differentiation, thereby disrupting the normal development of the heart and other tissues.

Associations of elevated glucose levels at each time point during OGTT with fetal congenital heart diseases: a cohort study of 72,236 births

BackgroundIt remains unclear how the condition of glucose metabolism during pregnancy affects fetal outcomes. This study aimed to investigate the associations of gestational diabetes mellitus (GDM) and elevated glucose levels at each time point during oral glucose tolerance test (OGTT) with congenital heart disease (CHD) risk in offspring.MethodsWe conducted a retrospective cohort study of mothers with singleton pregnancies of 20 weeks or more registered at Maternal and Child Health Centers in Fujian Province, China. The OGTT results and offspring CHD occurrence were collected. We used logistic regression to analyse the association between elevated blood glucose at each time point during OGTT and CHD.ResultsA total of 71,703 normal and 533 CHD fetuses were included. Compared to the corresponding normal group, women with GDM, elevated blood glucose at different time points in OGTT (0 h ≥ 5.1 mmol/L, 1 h ≥ 10 mmol/L, and 2 h ≥ 8.5 mmol/L) showed an increased risk of CHD in offspring (adjusted OR = 1.41, 1.36, 1.37, and 1.41, all P < 0.05, respectively). Compared to group 1 (normal OGTT 0 h, 1 h and 2 h), the risk of CHD was higher in group 3 (normal OGTT 0 h and abnormal OGTT 1 h or 2 h) and group 4 (abnormal OGTT 0 h, 1 h and 2 h), OR = 1.53 and 2.21, all P < 0.05, respectively. Moreover, we divided participants by advanced maternal age, multipara, assisted reproduction, fetal sex, and others, similar associations were observed in the subgroup analyses.ConclusionElevated blood glucose at different time points during OGTT was associated with CHD in offspring. Fetuses of pregnant women with GDM should be screened for a high risk of CHD.

Charting the Path: Navigating Embryonic Development to Potentially Safeguard against Congenital Heart Defects.

Congenital heart diseases (CHDs) are structural or functional defects present at birth due to improper heart development. Current therapeutic approaches to treating severe CHDs are primarily palliative surgical interventions during the peri- or prenatal stages, when the heart has fully developed from faulty embryogenesis. However, earlier interventions during embryonic development have the potential for better outcomes, as demonstrated by fetal cardiac interventions performed in utero, which have shown improved neonatal and prenatal survival rates, as well as reduced lifelong morbidity. Extensive research on heart development has identified key steps, cellular players, and the intricate network of signaling pathways and transcription factors governing cardiogenesis. Additionally, some reports have indicated that certain adverse genetic and environmental conditions leading to heart malformations and embryonic death may be amendable through the activation of alternative mechanisms. This review first highlights key molecular and cellular processes involved in heart development. Subsequently, it explores the potential for future therapeutic strategies, targeting early embryonic stages, to prevent CHDs, through the delivery of biomolecules or exosomes to compensate for faulty cardiogenic mechanisms. Implementing such non-surgical interventions during early gestation may offer a prophylactic approach toward reducing the occurrence and severity of CHDs.

GATA4 rs61277615, rs73203482, and rs35813172 in Newborns with Transposition of the Great Arteries.

Congenital heart disease is the most common malformative pathology in newborns, with a worldwide incidence at 0.4-5%. We investigated the possible relationship between variations in nucleotide sequences and specific cardiac malformations in the GATA-binding factor 4 (GATA4) exon 1 region by using Sanger sequencing. Forty-four newborns from a third-level neonatal intensive care unit who were diagnosed with nonsyndromic, ductal-dependent congenital heart disease (i.e., transposition of the great arteries or ductal-dependent coarctation of the aorta) were enrolled. Their DNA was extracted using commercial methods and tested using the multiplex ligation-dependent probe amplification (MLPA) technique. The Sanger sequencing for GATA4 exon 1 in the newborns' DNA identified rs61277615, rs73203482, and rs35813172 variants not reported in the ClinVar archive of human variations in newborns previously diagnosed with transposition of the great arteries (n=5) and coarctation of the aorta (n=1). The identification of these novel variants in newborns with transposition of the great arteries or ductal-dependent coarctation of the aorta may be the first step in determining the variants' contribution to the occurrence of congenital heart disease. However, these results may be inconclusive, since the observed variants within GATA4 gene were not previously reported.

Association of maternal methionine synthase reductase gene polymorphisms with the risk of congenital heart disease in offspring: a hospital-based case-control study

Background Evidence suggests that periconceptional folic acid supplementation may prevent congenital heart disease (CHD). Methionine synthase reductase (MTRR) is one of the key regulatory enzymes in the folate metabolic pathway. This study aimed to comprehensively evaluate the association of single nucleotide polymorphisms (SNPs) in the maternal MTRR gene with CHD risk in offspring. Methods A hospital-based case-control study involving 740 mothers of CHD cases and 683 health controls was conducted. Results The study showed that maternal MTRR gene polymorphisms at rs1532268 (C/T vs. C/C: aOR = 1.524; T/T vs. C/C: aOR = 3.178), rs1802059 (G/A vs. G/G: aOR = 1.410; A/A vs. G/G: aOR = 3.953), rs2287779 (G/A vs. G/G: aOR = 0.540), rs16879334 (C/G vs. C/C: aOR = 0.454), and rs2303080 (T/A vs. T/T: aOR = 0.546) were associated with the risk of CHD. And seven haplotypes were observed to be associated with the risk of CHD, T-G-A haplotype (OR = 1.298), C-A-C-C (OR = 4.824) and A-G haplotype (OR = 1.751) were associated with increased risk of CHD in offspring; A-A-A (OR = 0.773), T-A-A (OR = 0.557), G-A-C-C (OR = 0.598) and G-C (OR = 0.740) were associated with decreased risk of CHD in offspring. Conclusions Maternal MTRR gene polymorphisms were associated with CHD in offspring, and its haplotypes have affected the occurrence of CHD. Furthermore, given the complexity and heterogeneity of CHD, the mechanisms by which these factors influence offspring cardiac development remain unknown, and studies in larger samples in an ethnically diverse population are needed.

Polymorphisms in gene UGT1A1 modify the association of prenatal exposure to polycyclic aromatic hydrocarbons with congenital heart diseases risk

Introduction Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for the occurrence of congenital heart diseases (CHDs). Genetic susceptibility to PAHs metabolism may modify the exposure–risk relationship. The role of uridine diphosphoglucuronosyl transferase 1A1 (UGT1A1) genetic polymorphisms for modulating the impacts of prenatal PAHs exposure on the risk of CHDs remains to be discovered. Objective The aim of this study was to investigate whether maternal UGT1A1 genetic polymorphisms are associated with fetal susceptibility to CHDs and to assess whether the risk is modified by maternal PAHs exposure. Methods Maternal urinary biomarker of PAHs exposure was determined in 357 pregnant women with CHDs fetuses and 270 controls (pregnant women carrying fetuses without major congenital malformations). Urinary 1-hydroxypyrene-glucuronide (1-OHPG) concentration, a sensitive biomarker for PAHs exposure, was measured using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Maternal single nucleotide polymorphisms (SNPs) in UGT1A1, including rs3755319, rs887829, rs4148323, rs6742078, and rs6717546, were genotyped using an improved multiplex ligation detection reaction (iMLDR) technique. Unconditional logistic regression was performed to determine the impacts of UGT1A1 polymorphisms on the risks of CHDs and their subtypes. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–PAHs exposure interactions. Results None of the selected UGT1A1 polymorphisms was independently associated with the risk of CHDs. The interaction between SNP rs4148323 and PAHs exposure was observed to be associated with CHDs (p< .05). Pregnant women with high-level PAHs exposure and rs4148323 had an increased risk of carrying CHDs fetuses (GA-AA vs. GG: aOR = 2.00, 95% CI = 1.06–3.79). Moreover, the joint effect of rs4148323 and PAHs exposure was found to be significantly associated with risks of septal defects, conotruncal heart defects, and right-sided obstructive malformations. Conclusions Maternal genetic variations of UGT1A1 rs4148323 may modify the association between prenatal PAHs exposure and CHDs risk. This finding needs to be further confirmed in a larger-scale study.

Study of congenital heart diseases among children with Down's syndrome

Background: Congenital heart disease (CHD) is the most common cause for morbidity and mortality among children with Down's syndrome. Methods: This hospital-based descriptive study was conducted on 50 children with Down's syndrome aged &lt;18 years presenting to the department of paediatric medicine at our tertiary care teaching hospital at Tirupati. The prevalence, pattern of congenital heart defects and various factors which are likely to influence the expression of CHD in Down's syndrome are reported. Results: We observed CHD in 27/50 (54%) of patients studied. Ventricular septal defect (n = 40.7%) was s the most common, followed by endocardial cushion defects (n= 29.7%); atrial septal defect, patent ductus arteriosus and tetralogy of Fallot. CHD were more commonly seen in male children (58.6%); karyotyping showed translocation in 30/50 (60%) study subjects. Advanced maternal, paternal age, increased birth order and consanguinity showed a positive association with the occurrence of CHD in children with Down's syndrome. Conclusions: Our observations suggest that routine screening of children with Down's syndrome for cardiac anomalies will help in early diagnosis and early institution of specific treatment.

Effect of maternal pregestational diabetes mellitus on congenital heart diseases.

The increasing population of diabetes mellitus in adolescent girls and women of childbearing age contributes to a large number of pregnancies with maternal pregestational diabetes mellitus. Congenital heart diseases are a common adverse outcome in mothers with pregestational diabetes mellitus. However, there is little systematic information between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring. Literature selection was performed in PubMed. One hundred and seven papers were cited in our review, including 36 clinical studies, 26 experimental studies, 31 reviews, eight meta-analysis articles, and six of other types. Maternal pregestational diabetes mellitus poses a high risk of congenital heart diseases in the offspring and causes variety of phenotypes of congenital heart diseases. Factors such as persistent maternal hyperglycemia, oxidative stress, polymorphism of uncoupling protein 2, polymorphism of adiponectin gene, Notch 1 pathway, Nkx2.5 disorders, dysregulation of the hypoxia-inducible factor 1, and viral etiologies are associated with the occurrence of congenital heart diseases in the offspring of mothers with pregestational diabetes mellitus. Treatment options including blood sugar-reducing, anti-oxidative stress drug supplements and exercise can help to prevent maternal pregestational diabetes mellitus from inducing congenital heart diseases. Our review contributes to a better understanding of the association between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring and to a profound thought of the mechanism, preventive and therapeutic measurements of congenital heart diseases caused by maternal pregestational diabetes mellitus.

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

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. 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. 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%). 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.

Prevalence of Congenital Heart Disease in Chinese Children With Different Birth Weights and Its Relationship to the Neonatal Birth Weight.

ObjectiveThis study aimed to examine the prevalence and the related risk factors of congenital heart disease (CHD) in children with different birth weights in China and the relationship between the subtypes of CHD and birth weight (BW).MethodsThis study conducted a cross-sectional survey on the data collected in the children’s congenital heart disease database (CHDD) established in China. This database contained data from one Grade A, Level III Children’s Public Hospital in Zhengzhou, Henan. The study included all the children and their parents in the database from 2014 to 2020 as the study subjects, and the missing data were processed by means of imputation. Diagnoses of CHD were coded using the International Classification of Diseases version 10 (ICD-10), and subtypes were classified by the codes Q20 to Q26. We reported the prevalence of CHD based on birth weight and gestational age and analyzed the related risk factors for children with CHD in different birth weight groups and factors for children of the same birth weight groups between the CHD groups and the non-CHD groups. The generalized linear model was used to assess the association between the subtypes of CHD and BW by establishing three adjusting models, and the data were stratified for further analysis by urban-rural and infant gender.ResultsA total of 42,814 children were identified as having CHD among 5,071,799 live children; the overall prevalence of CHD was 8.44 per 1,000 live births during 2014–2020; and the three subtypes with the highest prevalence of CHD were atrial septal defect (ASD) (2.75‰), ventricular septal defect (VSD) (2.57‰), and patent foramen ovale (PFO) (1.12‰). The prevalence of CHD was 18.87‰ in the group with BW <1,500 g, 12.84‰ in the group with BW 1,500–2,500 g, 8.24‰ in the group with BW 2,500–4,000 g, and 4.80‰ in the group with BW ≥4,000 g. The prevalence of CHD was 16.62‰ in the small for gestational age (SGA) group, 6.99‰ in the appropriate for gestational age (AGA) group, and 6.40‰ in the larger for gestational age (LGA) group. Parental factors such as drinking, smoking, viral infections, peri-pregnancy exposure to radioactive substances, low family monthly expenditure, and low Apgar scores at 1 and 5 min were related to the increased risk of CHD in the offspring. Parental supplementation of folic acid and exercise during the peri-pregnancy period could reduce the risk of CHD in the offspring. The results of Model 3 adjusting for confounding variables showed that infants with ASD had a birth weight 461 g lower (95% CI: −1,085, –128), infants with VSD had a birth weight 426 g lower (95% CI: –932, –120), infants with tetralogy of Fallot (TOF) had a birth weight 532 g lower (95% CI: –987, –168), and without classification, infants with CHD had a birth weight 973 g lower (95% CI: –1,502, –204).ConclusionIn very low birth weight (VLBW) and low birth weight (LBW) infants, CHDs are more prevalent than in the general live-born population. Moreover, some peri-pregnancy factors of parents are closely related to the occurrence of CHD in offspring; different types of heart defects can lead to LBW. Therefore, if the fetus is found to have a heart defect during the prenatal examination, the mother should pay more attention to maintaining weight and ensuring that the fetus is within the normal weight range, thereby increasing the postpartum survival rate, reducing complications, and promoting children’s health.

Association between maternal exposure to indoor air pollution and offspring congenital heart disease: a case\u2013control study in East China

BackgroundPrevious research suggested an association between maternal exposure to ambient air pollutants and the risk of congenital heart disease (CHD). However, the effect of individual prenatal exposure to indoor air pollutants on CHD occurrence was not reported.MethodsWe performed a hospital-based case–control study to investigate the association between personal air pollution exposure during pregnancy and the risk of CHD in offspring. A total of 44 cases and 75 controls were included from two hospitals in East China. We investigated maternal and residential environmental characteristics using a questionnaire and obtained personal indoor air samples to assess particulate matter (PM) and volatile organic compounds (VOCs) from 22–30 gestational weeks. Formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOCs), PM2.5, and PM10 were assessed. Logistic regression was performed to assess associations and interactions between individual indoor air pollutants and CHD after adjusting for confounders. The potential residential environmental factors affecting the risks of indoor air pollutants on CHD were also assessed.ResultsMedian TVOC (0.400 vs. 0.005 mg/m3, P < 0.001) exposure levels in cases were significantly higher than controls. A logistic regression model adjusted for confounders revealed that exposure to high levels of indoor TVOCs (AOR 7.09, 95% CI 2.10–23.88) during pregnancy was associated with risks for CHD and the occurrence of some major CHD subtype in offspring. These risk effects were enhanced in pregnant women living in a newly renovated house but were mitigated by household use of smoke ventilators when cooking. We observed a positive interaction of maternal exposure to TVOCs and PM2.5 and the risk for CHD.ConclusionsMaternal exposure to indoor VOCs and PMs may increase the risk of giving birth to foetuses with CHD.

Gestational Leucylation Suppresses Embryonic T-Box Transcription Factor 5 Signal and Causes Congenital Heart Disease.

Dysregulated maternal nutrition, such as vitamin deficiencies and excessive levels of glucose and fatty acids, increases the risk for congenital heart disease (CHD) in the offspring. However, the association between maternal amino‐acid levels and CHD is unclear. Here, it is shown that increased leucine levels in maternal plasma during the first trimester are associated with elevated CHD risk in the offspring. High levels of maternal leucine increase embryonic lysine‐leucylation (K‐Leu), which is catalyzed by leucyl‐tRNA synthetase (LARS). LARS preferentially binds to and catalyzes K‐Leu modification of lysine 339 within T‐box transcription factor TBX5, whereas SIRT3 removes K‐Leu from TBX5. Reversible leucylation retains TBX5 in the cytoplasm and inhibits its transcriptional activity. Increasing embryonic K‐Leu levels in high‐leucine‐diet fed or Sirt3 knockout mice causes CHD in the offspring. Targeting K‐Leu using the leucine analogue leucinol can inhibit LARS activity, reverse TBX5 K‐Leu modification, and decrease the occurrence of CHD in high‐leucine‐diet fed mice. This study reveals that increased maternal leucine levels increases CHD risk in the offspring through inhibition of embryonic TBX5 signaling, indicating that leucylation exerts teratogenic effects during heart development and may be an intervening target of CHD.

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.

Precise Dose of Folic Acid Supplementation Is Essential for Embryonic Heart Development in Zebrafish

Simple SummaryFolic acid is an essential vitamin for human beings. It has become a consensus to supplement folic acid during pregnancy. It is reported that 15~20% of people in the world supplement folic acid excessively. We found that excessive folic acid supplementation or insufficient folic acid intake could lead to abnormal heart development in zebrafish embryos. We elucidated the mechanism of folic acid on early cardiac development for the first time. These results provide a scientific basis for the important reasonable supplement dose of folic acid. At the same time, we constructed zebrafish mutants with abnormal folate metabolism, which provide a novel biological model for the study of folate acid metabolism.Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. Moreover, we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid and mthfr−/− mutant all gave rise to early pericardial edema and cardiac defect at 3 days post fertilization (dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5 dpf. The expression levels of cardiac marker genes hand2, gata4, and nppa changed in the abnormality of folate metabolism embryos and mthfr−/− mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. Furthermore, our results reveal that folic acid has a dose-dependent effect on early cardiac development. Precise dosage of folic acid supplementation is crucial for the embryonic development of organisms.

Epidemiological Aspects, Prenatal Screening and Diagnosis of Congenital Heart Defects in Beijing.

Background: In China, congenital heart disease (CHD) is the most common birth defect type, with approximately 13,000 new cases annually. This study aimed to investigate high-risk factors, prenatal screening and prenatal diagnosis as a basis for clinical decisions.Methods: All CHD cases identified from 2018 to 2020 were obtained from the Beijing city birth defect surveillance system and prenatal diagnosis institutions. The prenatal CHD diagnosis was confirmed by fetal echocardiography and amniotic fluid or cord blood genetic examination. Chi-square, odds ratio (OR), 95% confidence interval (CI), and univariate and multivariate logistic analyses were used to explore the high-risk factors, prenatal screening and prenatal diagnosis of CHD. Results: In total, 6,786/594,860 fetuses with CHD were diagnosed by prenatal echocardiography. The average incidence of CHD was 11.4 per 1,000 births, with an increase of 30.7 per 1,000 births from 2018 to 2020 (P < 0.05); the average incidence of complex CHD (CCHD) was 2.02 per 1,000 births, with no significant change from 2018 to 2020 (P > 0.05). Women age ≥35 years (OR 1.06, 95% CI 0.77–1.46) was at higher risk of having babies with CHD than women aged 21–34 years. Overall, CHD incidence increased with maternal age (OR1.03, 95% CI 1.02–1.03). Additionally, women who had a non-local household registration (OR 1.16, 95% CI 1.10–1.22) or had diabetes mellitus (DM) (OR 1.16, 95% CI 0.96–1.25) were at higher risk of CHD. As an independent factor, CCHD was related to maternal age, DM, fetal gender, and maternal education level (all P < 0.05). The prenatal ultrasound screening detection rate of CCHD was 97.59%, which was far higher than that of total CHD (51.67%) (P < 0.001). The prenatal ultrasound diagnosis rate of CCHD was higher than that of simple CHD (P < 0.001), but the coincidence rate in the ultrasound diagnosis of CCHD was lower than that of simple CHD (P < 0.001). Prenatal genetic testing revealed chromosomal abnormalities in 25.62% (279/1089) of CHD cases with indications for a prenatal diagnosis.Conclusions: Maternal age, household registration and DM were related to CHD occurrence. Prenatal ultrasound screening is a highly effective method for CCHD diagnosis, and CHD fetuses should be closely evaluated to exclude chromosomal abnormalities.

Maternal trichloroethylene exposure and metabolic gene polymorphisms may interact during fetal cardiovascular malformation

This study aimed to analyze the potential association between trichloroethylene (TCE) exposure and congenital heart disease (CHD) and to explore the effect of metabolic enzyme gene polymorphisms on heart development. A multicenter case-control study was conducted. The trichloroethylene concentrations were measured by UPLC-MSMS in urine. Fourteen SNPs in the GSTA1, GSTP1, MPO, NAT1, NAT2, CYP1A1, CYP1A2, CYP2E1 and EPHX1 genes were genotyped using an improved multiplex ligation detection reaction (iMLDR) technique. A total of 283 cases and 331 controls with maternal urine and/or venous blood were included in the present study. The median NAcDCVC was 7.65 ng/mL in the case group and 7.43 ng/mL in the control group. There was no significant difference in the NAcDCVC concentration between the CHD subtypes and controls (P > 0.05). The GA/AA of GSTA1 rs3957357 could increase the risk of CHDs under the dominant model (aOR = 2.26, 95 % CI: 1.31, 3.90), but other SNPs were not associated with CHDs (P > 0.05). GA or AA genotypes of GSTA1 rs3957357 with lower levels of TCE exposure were 3.53 times at risk relative to mothers carrying the wild type genotype. In conclusion, maternal exposure to trichloroethylene alone is not associated with the occurrence of fetal CHD and CHD subtypes. Maternal GSTA1 rs3957357 may increase the risk of CHD in offspring. TCE exposure and metabolic gene polymorphisms probably interact with each other to induce fetal cardiovascular malformation, but larger sample size studies are needed to confirm this hypothesis.

High maternal blood lipid levels during early pregnancy are associated with increased risk of congenital heart disease in offspring.

IntroductionThis study aimed to investigate whether maternal blood lipid levels during early pregnancy are associated with the occurrence of congenital heart disease (CHD) in their offspring.Material and methodsIn this single‐center case–control study, mothers of offspring with CHD (n = 230) and without CHD (n = 381) were included. Maternal lipid levels were determined on fasting blood samples taken in the first trimester. Relevant demographic and clinical data were extracted from the medical records. Maternal lipid profile was compared between the two groups, and regression analysis was performed to evaluate the association between lipid profile and CHD risk in offspring.ResultsCompared with the control group, levels of triglyceride, apolipoprotein‐A1, and apolipoprotein‐B in early pregnancy were significantly higher in the CHD group. Multivariate analyses showed that triglyceride (odds ratio [OR] 2.46, 95% CI 1.62–3.73, p < 0.01), total/high‐density lipoprotein cholesterol (OR 2.10, 95% CI 1.07–4.13, p = 0.03), and apolipoprotein‐A1 (OR 2.73, 95% CI 1.16–6.40, p = 0.02) were positively associated with CHD risk in offspring.ConclusionsElevated maternal lipid profile was associated with increased risk of CHD in offspring.

Profile of congenital heart disease in Pediatric population: two years' experience at a teaching hospital

Background: CHDs (Congenital heart defects) are a major morbidity and mortality cause in children with a substantial worldwide health burden. Therefore, this is significant for determining their spectrum as well as identifies treatable heart defects. Aims: To study the CHD's profile in a semi urban along with rural community between age group 0 to 12 years and study different forms and frequency of occurrence of congenital heart diseases in selected cases using echocardiography as diagnostic tool. Methods: In this retrospective study, case records of 154 cases of proven cases of CHD were analyzed in detail. The relative frequency of occurrence of each acyanotic and cyanotic CHD has been noted in selected cases. The study period was between January 2015 to December 2016. Results: Of 154 cases analyzed ventricular septal defect has been found the mainly diagnosis.42 cases were detected to have ventricular septal defect followed in frequency by tetralogy of fallot which was echocardiography diagnosis in 38 cases. PDA followed by ASD were the next common acyanotic congenital heart diseases detected. In cyanotic cases, TOF was followed by transposition pathology complex. Males outnumbered females. Conclusion:We observed that CHD's profile was comparable to the published literature in our population. CHGs are widespread in our set-up, and echocardiographic early CHD detection is a safe and reliable method to diagnose CHD in children,which significantly enhances the assessment of critically sick children

Profile of congenital heart disease in Pediatric population: two years' experience at a teaching hospital

Background: CHDs (Congenital heart defects) are a major morbidity and mortality cause in children with a substantial worldwide health burden. Therefore, this is significant for determining their spectrum as well as identifies treatable heart defects. Aims: To study the CHD's profile in a semi urban along with rural community between age group 0 to 12 years and study different forms and frequency of occurrence of congenital heart diseases in selected cases using echocardiography as diagnostic tool. Methods: In this retrospective study, case records of 154 cases of proven cases of CHD were analyzed in detail. The relative frequency of occurrence of each acyanotic and cyanotic CHD has been noted in selected cases. The study period was between January 2015 to December 2016. Results: Of 154 cases analyzed ventricular septal defect has been found the mainly diagnosis.42 cases were detected to have ventricular septal defect followed in frequency by tetralogy of fallot which was echocardiography diagnosis in 38 cases. PDAfollowed by ASD were the next common acyanotic congenital heart diseases detected. In cyanotic cases, TOF was followed by transposition pathology complex. Males outnumbered females. Conclusion:We observed that CHD's profile was comparable to the published literature in our population. CHGs are widespread in our set-up, and echocardiographic early CHD detection is a safe and reliable method to diagnose CHD in children, which significantly enhances the assessment of critically sick children.

Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring

BackgroundAlthough many studies showed that the risk of congenital heart disease (CHD) was closely related to genetic factors, the exact pathogenesis is still unknown. Our study aimed to comprehensively assess the association of single nucleotide polymorphisms (SNPs) of maternal MTHFR gene with risk of CHD and its three subtypes in offspring.MethodsA case–control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed.ResultsOur study showed that genetic polymorphisms of maternal MTHFR gene at rs4846052 and rs1801131 were significantly associated with risk of CHD in the homozygote comparisons (TT vs. CC at rs4846052: OR = 7.62 [95%CI 2.95–19.65]; GG vs. TT at rs1801131: OR = 5.18 [95%CI 2.77–9.71]). And six haplotypes of G–C (involving rs4846048 and rs2274976), A–C (involving rs1801133 and rs4846052), G–T (involving rs1801133 and rs4846052), G–T–G (involving rs2066470, rs3737964 and rs535107), A–C–G (involving rs2066470, rs3737964 and rs535107) and G–C–G (involving rs2066470, rs3737964 and rs535107) were identified to be significantly associated with risk of CHD. Additionally, we observed that a two-locus model involving rs2066470 and rs1801131 as well as a three-locus model involving rs227497, rs1801133 and rs1801131 were significantly associated with risk of CHD in the gene–gene interaction analyses. For three subtypes including atrial septal defect, ventricular septal defect and patent ductus arteriosus, similar results were observed.ConclusionsOur study indicated genetic polymorphisms of maternal MTHFR gene were significantly associated with risk of fetal CHD in the Chinese population. Additionally, there were significantly interactions among different SNPs on risk of CHD. However, how these SNPs affect the development of fetal heart remains unknown, and more studies in different ethnic populations and with a larger sample are required to confirm these findings.