Risk Factors For Congenital Heart Defects Research Articles

Risk factors for isolated congenital heart defects in infants from Western Mexico.

Congenital heart defects (CHDs) are caused by a complex interaction between numerous genetic and environmental risk factors, some of which may differ between different populations. A case-control study was conducted among 1232 newborns, including 308 patients with isolated CHDs (cases) and 924 infants without birth defects (controls), born all during the period 2009-2023 at the Hospital Civil de Guadalajara "Dr. Juan I. Menchaca" (Guadalajara, Mexico). Potential parental risk factors for CHDs were compared using multivariate logistic regression analysis to evaluate the deviance explained by different variables of interest. Consanguinity [adjusted odds ratio (aOR) = 3.3; 95% confidence interval (CI) 1.3-8.5], relatives with CHD (aOR = 8.5; 95% CI 5.3-13.8), maternal first-trimester exposure to diabetes (aOR = 3.5; 95% CI 2.4-5.1), hypertension (aOR = 2.6; 95% CI 1.5-4.4), alcohol consumption (aOR = 1.5; 95% CI 1.0-2.1), and illicit drug use (aOR = 2.4; 95% CI 1.2-5.3), as well as for the paternal history of alcohol consumption (aOR = 1.4; 95% CI 1.0-1.8) and illicit drug use (aOR = 2.7; 95% CI 1.7-4.1), were associated with CHDs. Contrarily, aOR for maternal age ≤19 years (aOR = 0.6; 95% CI 0.4-0.8) and maternal first-trimester coffee consumption (aOR = 0.7; 95% CI 0.5-0.9) have protective odds. Our results suggest that genetic factors, maternal diseases, environmental exposures, and reproductive factors can increase the occurrence of isolated CHDs in our sample, and they are discussed as clues in its pathogenesis.

Abstract We087: The mitochondrial citrate carrier SLC25A1 is a regulator of metabolic reprogramming and morphogenesis in the developing heart

Background: Congenital heart defects (CHDs) are the most common type of birth defect, yet the etiology of most CHDs are unknown. A major genetic risk factor for CHD is 22q11.2 deletion syndrome (22q11.2DS), a multisystem chromosomal microdeletion disorder where ~75% of patients present with CHD. SLC25A1 is a gene found within the 22q11.2DS microdeletion region that encodes for the mitochondrial citrate carrier, an inner membrane transporter that regulates intracellular citrate compartmentalization. Through this role, SLC25A1 is thought to contribute to cytosolic acetyl-CoA availability, and processes like protein acetylation and the epigenetic regulation of gene expression. We have previously found that SLC25A1 is a central gene contributing to the neurodevelopmental presentation of 22q11.2DS and importantly, neuronal mitochondrial function. Because the heart, like the brain, is highly reliant on energy derived from mitochondria, and the developing heart must undergo metabolic maturation whereby metabolism is reprogrammed from primary reliance on glycolysis towards mitochondrial oxidative metabolism, we hypothesized that SLC25A1 plays a key role in the metabolic maturation that is required for proper cardiac development. Objective: Here, we studied the role of Slc25a1 in the developing heart to examine the link between mitochondria and cardiac morphogenesis. Methods and Results: By studying mice with the systemic knockout of SLC25A1, we discovered that Slc25a1 null embryos displayed impaired growth, cardiac malformations, mitochondrial ultrastructural defects and impaired mitochondrial oxygen consumption. Transcriptomics analyses of metabolism-related genes revealed that Slc25a1 deletion causes widespread alterations in metabolic gene expression. Further, metabolic modelling predicted that loss of SLC25A1 downregulates oxidative phosphorylation, while increasing reliance on glucose. Finally, we found that loss of SLC25A1 decreases cardiac H3K9 acetylation levels at promoter regions of dysregulated metabolic genes. Mechanistically, SLC25A1 may regulating mitochondrial function and metabolism through epigenetic control of gene expression to promote metabolic remodeling in the developing heart. Conclusions: Our work suggests that SLC25A1 as an an important mitochondrial regulator of gene expression in the developing heart. Importantly, it positions SLC25A1 as a novel mitochondrial regulator of ventricular morphogenesis as well as cardiac metabolic maturation.

Association of TGFBR2 gene polymorphisms (rs6785358 and rs764522) with congenital heart disease susceptibility in Egyptians

Aim: Transforming growth factor beta (TGF-β) receptor II (TGFBR2) is a basic constituent of TGF-β signalling pathway and is important in heart development. This study investigates the relationship between TGFBR2 gene variance and congenital heart defects (CHD) among Egyptians. Methods: The study involved 75 CHD-affected subjects and 100 healthy controls. Genotyping of two selected tag single nucleotide polymorphisms (tagSNPs, rs6785358, rs764522) within the TGFBR2 gene was conducted using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) assays. Results: Significant genotype differences were found for rs764522 and rs6785358 (P < 0.05). In the case of rs6785358, the G/G genotype was more prevalent in cases than controls (18.7% vs. 4.0%). This significance was observed in both the codominant model [A/A vs. A/G vs. G/G; odds ratio (OR) = 0.20, 95% confidence interval (CI) = 0.06–0.66, P = 0.0073] and the recessive model (A/A + A/G vs. G/G; OR = 0.19, 95% CI = 0.06–0.60, P = 0.0018). For rs764522, the G/G genotype was more prevalent in cases than controls (21.3% vs. 0.0%). Significant associations were observed in the codominant model (C/C vs. C/G vs. G/G; OR = 0.43, 95% CI = 0.02–0.90, P < 0.0001), as well as in the dominant model (C/C vs. C/G + G/G) and recessive model (C/C + C/G vs. G/G; P < 0.0001). Gender-specific analysis indicated that the C/G genotype was less common in male cases compared to females and controls (OR = 0.24, 95% CI = 0.07–0.84). For rs6785358, the G/G genotype frequency was higher in male cases compared to females and controls (OR = 0.10, 95% CI = 0.01–0.88 and OR = 0.22, 95% CI = 0.05–0.94, respectively). Conclusions: These findings indicate that TGFBR2 gene SNPs (rs6785358 and rs764522) may be risk factors for CHD in Egyptians.

Maternal Blood Group Is a Possible Predictor for Developing Congenital Heart Disease in Turkish Children with Down's Syndrome.

We aimed to evaluate the clinical characteristics and the risk factors for the anomalies of Down's syndrome (DS) patients and reviewed the relation of blood groups of the patients and the mothers with these anomalies. Pediatric patients who were diagnosed with trisomy 21 between 2010 and 2022 were enrolled in this study. The medical records of the DS patients and their parents were retrospectively reviewed. A total of 48 patients applied to our clinic. 24 (50%) patients were diagnosed with congenital heart disease. 21 (43.75%) patients had hypothyroidism. The distribution of individual congenital heart defects (CHDs) was as follows: ventricular septal defect in eight (33.3%) patients, one of which also had patent ductus arteriosus (PDA); atrioventricular septal defects in seven (29.1%) patients; atrial septal defects in four (16.6%) patients, one of which also had patent ducus arteriosus; and PDA in five (20.8%) patients. One (4.2%) patient had tetralogy of Fallot. The incidence of CHD in patients with maternal blood group A was significantly higher than those without CHD, with a prevalence of 63.6 and 21.1%, respectively ( p = 0.020). Binary logistic regression analysis showed that maternal blood group A was a risk factor for CHDs (odds ratio = 6.563; 95% confidence interval: 1.259-34.204; p = 0.025). Although we found that the rate of advanced father age was high in hypothyroidism type, the regression analysis showed that it was not a risk factor. We found that maternal blood group A increased the likelihood of being born with CHDs in DS.

Incidence and Risk Factors of Congenital Heart Diseases in Syndromic Neonates

Congenital heart defects (CHD) are the most common types of major birth defects, leading cause of infant morbidity and mortality. Syndromic babies are more affected by CHD. This observational study was conducted in a tertiary care hospital of military facility in Bangladesh. Eighty syndromic neonates were studied through history, physical examination and investigated for incidence and risk factors for CHD. Out of 80 syndromic neonates 61(76.3%) were found having CHD. Male female ratio was 1.18:1. Average age at diagnosis was 25±1.6 days of age. Down Syndrome (DS) and Congenital Rubella Syndrome (CRS) were the most common syndromes. Ventricular Septal defect (VSD) and Atrial septal defect (ASD) II were the most common CHD. Consanguinity, extracardiac malformations, maternal illness (HTN, DM, Hypothyroidism etc.), both fertility and non-fertility medication are also found to be associated with CHD in Syndromic neonates. CHDs have serious implications and it is important to understand them and how they may affect the child so that appropriate medical and surgical treatment may be provided. So, early detection of CHD in neonate will be able to decrease morbidity as well as mortality. CBMJ 2023 January: Vol. 12 No. 01 P: 17-21

Genetic insights into non-syndromic Tetralogy of Fallot.

Congenital heart defects (CHD) include structural abnormalities of the heart or/and great vessels that are present at birth. CHD affects around 1% of all newborns worldwide. Tetralogy of Fallot (TOF) is the most prevalent cyanotic congenital cardiac abnormality, affecting three out of every 10,000 live infants with a prevalence rate of 5–10% of all congenital cardiac defects. The four hallmark characteristics of TOF are: right ventricular hypertrophy, pulmonary stenosis, ventricular septal defect, and overriding aorta. Approximately 20% of cases of TOF are associated with a known disease or chromosomal abnormality, with the remaining 80% of TOF cases being non-syndromic, with no known aetiology. Relatively few TOF patients have been studied, and little is known about critical causative genes for non-syndromic TOF. However, rare genetic variants have been identified as significant risk factors for CHD, and are likely to cause some cases of TOF. Therefore, this review aims to provide an update on well-characterized genes and the most recent variants identified for non-syndromic TOF.

Magnitude of Stress among Parents of Children with Cardiac Malformation in Tertiary Care Hospitals Peshawar

Background: Congenital Heart Defects (CHDs) are inborn anomalies or mal-formations of heart. These are the most common type of birth anomalies, approximately 1-2% babies are delivered with cardiac anomalies all over the world. CHDs are some of these deformities that disturb the lives of effected child as well as parents of the effected child. Studies from Pakistan have only reported incidence and risk factors of CHDs and have not identified their association with parental stress. Aim: The aim of this study was to identify the magnitude of parental stress caused by child diseased status. Methodology: This was a descriptive cross-sectional study. 387 participants was the sample size, calculated through online software open-epi. Every parent fulfilling the inclusion criteria was selected through Consecutive Sampling technique. And, data was collected through an adopted questionnaire. Results: Majorities (60.2%) of the study participants were male. The mean overall score of stress was 64.36 with a Standard Deviation of ±6.24534. A strong association was identified in the category of gender, females were more in stress than the male (Chi-square = 42.66, P < 0.001). Conclusion: The outcomes of the current study show that parents of the CHD diagnosed kids were in stress. There was a major role of demographical variable in the level of outcome variable “stress” among parents of CHD diagnosed children, such as gender, age, income, occupation, and education level.

Accuracy of the Standardized Early Fetal Heart Assessment in Excluding Major Congenital Heart Defects in High-Risk Population: A Single-Center Experience.

To evaluate the ability of standardized early fetal heart assessment (EFHA) that includes the 4-chamber view, outflow tract relationship (OTR), and transverse arches views (TAV) of the great arteries in excluding major congenital heart defects (CHDs) in high-risk populations. This retrospective study included high-risk pregnancies for CHDs undergoing EFHA at 11-14 weeks of gestation. Risk factors for CHDs were diabetes mellitus, a family history of CHDs, a history of a CHD use of teratogenic medications, seizure disorder, assisted reproductive treatment-conceived pregnancy, presence of at least one of the ultrasound markers: enlarged nuchal translucency (>95th percentile), tricuspid regurgitation, and reversed a-wave in the ductus venosus, presence of an extracardiac or a suspected cardiac anomaly, a high-risk first trimester combined screen result, and multiple pregnancies. EFHA consisted of visualization of 4ChV, OTR, and TAV, with and without power Doppler ultrasound. The primary outcome was the negative predictive value of EFHA in excluding major CHDs. EFHA was performed on 1055 fetuses. Of these, 1024 were used for the final analysis. Of these, 94.9% (n=923) were singleton. The most common indication for EFHA was maternal DM (n=231, 22.6%). The sensitivity, specificity, false positive, false negative, and accuracy of EFHA were 93.2%, 99.9%, 1.4%, 0.4%, and 99.5% (P < .0001), respectively, in entire included cases. The performance of EFHA was 88%, 99.9%, 1.4%, 0.4%, and 99.5% (P < .0001) respectively when the terminated cases were excluded. Early fetal heart assessment is feasible for screening for major CHDs in high-risk populations. This approach may be expanded to the general obstetric population.

Utility of routine screening fetal echocardiogram in pregnancies conceived by in vitro fertilization

To study the incidence and clinical significance of congenital heart defects (CHDs) detected by fetal echocardiography in pregnancies conceived by invitro fertilization (IVF). Cohort study comparing a prospectively maintained database of all fetal echocardiograms from 2012 to 2018 and pooled data from the Connecticut Birth Defects Registry and statewide hospital discharge data. Large tertiary care center. A total of 181,749 live births and 9,252 fetal echocardiograms were analyzed. Fetal echocardiograms in patients with a previous child with a CHD, a family history of CHD, medication exposure, diabetes, anomaly in previous pregnancy, cardiac or other abnormality noted on previous ultrasound, or monochorionic twins were excluded from the final analysis. Treatment with IVF. Incidence of CHD and odds ratios with 95% confidence intervals (CIs). Infant outcomes for cases of CHD were evaluated for clinically significant disease, defined a priori as disease requiring any medical or surgical intervention or continued follow-up with pediatric cardiology. Fetal echocardiography was performed in 2,230 IVF pregnancies, of which 2,040 were without other known risk factors for CHD. The mean gestational age at the time of fetal echocardiography was 22.2 ± 1.4 weeks. The odds ratio for CHD in the IVF group compared with statewide population rates was 1.4 (95% CI 0.9-2.1). CHD was diagnosed in 26 fetuses, of which 21 were clinically insignificant ventricular septal defects. One fetal echocardiogram was concerning for pulmonary stenosis that was not present at birth. Four defects were clinically significant, indicating that 510 fetal echocardiograms were performed for every diagnosis of one clinically significant CHD in the IVF group. The incidence of CHD in IVF pregnancies without other risk factors is not significantly different from baseline population rates, and most CHDs diagnosed by fetal echocardiography in this group are clinically insignificant. Routine screening with fetal echocardiography in all IVF pregnancies provides limited utility beyond routine prenatal care and need not be recommended without the presence of other risk factors.

A Functional Variant Rs492554 Associated With Congenital Heart Defects Modulates SESN2 Expression Through POU2F1.

Hypoxia exposure is responsible for the high incidence of congenital heart defects (CHDs) in high-altitude areas, which is nearly 20 times higher than that in low-altitude areas. However, the genetic factors involved are rarely reported. Sestrin2 (SESN2), a hypoxia stress-inducible gene, protects cardiomyocyte viability under stress; thus, SESN2 polymorphism may be a potential risk factor for CHD. We performed an association study of the SESN2 polymorphisms with CHD risk in two independent groups of the Han Chinese population from two different altitude areas. The allele-specific effects of lead single-nucleotide polymorphisms (SNPs) were assessed by expression quantitative trait locus, electrophoretic mobility shift, and luciferase reporter assays. The molecular mechanism of Sesn2 action against hypoxia-induced cell injury was investigated in embryonic rat-heart-derived H9c2 cells treated with or without hypoxia-mimetic cobalt chloride. SNP rs492554 was significantly associated with reduced CHD risk in the high-altitude population, but not in the low-altitude population. The protective T allele of rs492554 was correlated with higher SESN2 expression and showed a preferential binding affinity to POU2F1. We then identified SNP rs12406992 in strong linkage disequilibrium with rs492554 and mapped it within the binding motif of POU2F1. The T-C haplotype of rs492554-rs12406992 could increase luciferase expression, whereas POU2F1 knockdown effectively suppressed it. Mechanistically, increased Sesn2 protects against oxidative stress and cell apoptosis and maintains cell viability and proliferation. In summary, CHD-associated SNP rs492554 acts as an allele-specific distal enhancer to modulate SESN2 expression via interaction with POU2F1, which might provide new mechanistic insights into CHD pathogenesis.

Morbidity of congenital heart disease in children with anorectal malformations and related treatment

To investigate the morbidity of congenital heart defects(CHDs) in children with anorectal malformation, and to summarize appropriate treatment. The clinical data and echocardiographic findings of 155 children with congenital anorectal malformations from the Third Affiliated Hospital of Zhengzhou University during January 2016 and October 2019 were reviewed. According to the surgical findings of anorectal malformations, the patients were categorized as the high/intermediate group and the low group; the CHDs were classified as minor CHDs and major CHDs. Multiple logistic regression was used to analyze the correlation of wingspread classification, and extracardiac malformations with the severity of CHDs. Out of 155 children with anorectal malformations, 47 (30.3%) had different types of cardiac structural malformations, including 18 cases of minor CHDs (11.6%) and 29 cases of major CHDs (18.7%). Sixty children (38.7%) had extracardiac malformations, of which 38 cases (24.5%) had a single extracardiac malformation, 15 cases (9.7%) had multiple extracardiac malformations, 6 had trisomy 21 syndrome, and 1 had VATER syndrome. Multivariate logistic regression analysis showed that wingspread classification of anorectal malformation and extracardiac disorders were independent risk factors for major CHDs. The probability of major CHDs in children with high/intermediate anorectal malformation was 4.709 times higher than that with low anorectal malformation (OR=4.709, 95% CI: 1.651-13.432, P<0.01). The probability of major CHDs was 3.85 times higher for increasing each additional grade of extracardiac malformations(without, with single, or multiple malformations) (OR=3.850, 95% CI: 2.065-7.175, P<0.01). According to the presence and severity of CHDs, children with anorectal malformations were classified into three categories: without CHDs, with minor CHDs and with major CHDs, for differential treatment and management. Anorectal malformations would be treated and managed in children without CHDs and with minor CHDs following the original plan; however, children with minor CHDs may require cardiac follow-up after surgery. In children with major CHDs, the personalization tactics were developed based on the principle of emergency first. There were increased perioperative infection rate (P<0.05), longer hospital days (P<0.01), reduced cure rate (P<0.05) and increased mortality (P<0.05) in children with major, compared with those without CHDs and minor CHDs. The morbidity of major CHDs is higher in severe cases with high/intermediate anorectal malformation and acute cases without fistula or with obstructed fistula and cases with multiple congenital disorders. Echocardiography can define the type and severity of CHDs, which are useful to develop the optimal diagnosis and treatment plan for children with anorectal malformation.

Corrigendum. Association between advanced paternal age and congenital heart defects: a systematic review and meta-analysis.

STUDY QUESTION Is there an association between advanced paternal age and congenital heart defects (CHD)? SUMMARY ANSWER Advanced paternal age is associated with a 16% increase in the overall odds of CHD. WHAT IS KNOWN ALREADY CHD are the most common congenital malformations. Several risk factors for CHD have been identified in the literature, but the association between advanced paternal age and CHD remains unclear. STUDY DESIGN, SIZE, DURATION We conducted a systematic literature search on MEDLINE and EMBASE (1960-2019) to identify studies assessing the association between advanced paternal age (≥35 years) and the risk of CHD, unrestrictive of language or sample size. We used a combination of Medical Subject Headings (MeSH) terms and free text words such as 'paternal age', 'paternal factors', 'father's age', 'parental age', 'heart', 'cardiac', 'cardiovascular', 'abnormalities, congenital', 'birth defects', 'congenital malformations' and 'congenital abnormalities'. PARTICIPANTS/MATERIALS, SETTING, METHODS We included observational studies aiming at assessing the association between paternal age and CHD. The included population could be live births, fetal deaths and terminations of pregnancy for fetal anomaly. To be included, studies had to provide either odds ratios (OR) with their 95% confidence interval (CI) or sufficient information to recalculate ORs with 95% CIs per paternal age category. We excluded studies if they had no comparative group and if they were reviews or case reports. Two independent reviewers selected the studies, extracted the data and assessed risk of bias using a modified Newcastle-Ottawa Scale. We used random-effects meta-analysis to produce summary estimates of crude OR. Associations were also tested in subgroups. MAIN RESULTS AND THE ROLE OF CHANCE Of 191 studies identified, we included nine studies in the meta-analysis (9 917 011 participants, including 34 447 CHD), including four population-based studies. Five studies were judged at low risk of bias. Only one population-based study specifically investigated isolated CHD. The risk of CHD was higher with advanced paternal age (summary OR 1.16, 95% CI, 1.07-1.25). Effect sizes were stable in population-based studies and in those with low risk of bias. LIMITATIONS AND REASONS FOR CAUTION The available evidence did not allow to assess (i) the risk of isolated CHD in population-based studies, (ii) the association between paternal age and the risk for specific CHD and (iii) the association between paternal age and CHD after adjustment for other risk factors, such as maternal age. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest that advanced paternal age may be a risk factor for CHD. However, because the association is modest in magnitude, its usefulness as a criterion for targeted screening for CHD seems limited. STUDY FUNDING/COMPETING INTEREST(S) None. PROSPERO REGISTRATION NUMBER CRD42019135061.

Association between advanced paternal age and congenital heart defects: a systematic review and meta-analysis

Is there an association between advanced paternal age and congenital heart defects (CHD)? Advanced paternal age is associated with a 16% increase in the overall odds of CHD. CHD are the most common congenital malformations. Several risk factors for CHD have been identified in the literature, but the association between advanced paternal age and CHD remains unclear. We conducted a systematic literature search on MEDLINE and EMBASE (1960-2019) to identify studies assessing the association between advanced paternal age (≥35 years) and the risk of CHD, unrestrictive of language or sample size. We used a combination of Medical Subject Headings (MeSH) terms and free text words such as 'paternal age', 'paternal factors', 'father's age', 'parental age', 'heart', 'cardiac', 'cardiovascular', 'abnormalities, congenital', 'birth defects', 'congenital malformations' and 'congenital abnormalities'. We included observational studies aiming at assessing the association between paternal age and CHD. The included population could be live births, fetal deaths and terminations of pregnancy for fetal anomaly. To be included, studies had to provide either odds ratios (OR) with their 95% confidence interval (CI) or sufficient information to recalculate ORs with 95% CIs per paternal age category. We excluded studies if they had no comparative group and if they were reviews or case reports. Two independent reviewers selected the studies, extracted the data and assessed risk of bias using a modified Newcastle-Ottawa Scale. We used random-effects meta-analysis to produce summary estimates of crude OR. Associations were also tested in subgroups. Of 191 studies identified, we included nine studies in the meta-analysis (9917011 participants, including 34447 CHD), including four population-based studies. Five studies were judged at low risk of bias. Only one population-based study specifically investigated isolated CHD. The risk of CHD was higher with advanced paternal age (summary OR 1.16, 95% CI, 1.07-1.25). Effect sizes were stable in population-based studies and in those with low risk of bias. The available evidence did not allow to assess (i) the risk of isolated CHD in population-based studies, (ii) the association between paternal age and the risk for specific CHD and (iii) the association between paternal age and CHD after adjustment for other risk factors, such as maternal age. Our findings suggest that advanced paternal age may be a risk factor for CHD. However, because the association is modest in magnitude, its usefulness as a criterion for targeted screening for CHD seems limited. None. CRD42019135061.

Methyltetrahydrofolate-homocysteine methyltransferase reductase gene and congenital heart defects in Down syndrome

Congenital heart defects (CHD) are the most common abnormalities occurring in 40% -60% of Down syndrome (DS) patients. The 5-methyltetrahydrofolate homocysteine methyl transferase reductase (MTRR) is one of the key regulatory enzymes involved in folate pathway. Disrupted folate pathway due to MTRR polymorphism could be a risk factor for CHD in DS. The aim of the study was to determine the association between polymorphism MTRR 66A&gt; G and CHD in DS. Additionally, the impact of maternal endogenous factors on CHD was analyzed, intake of folate through diet, periconceptional folic acid supplementation, smoking and alcohol drinking. A total of 155 children with DS and 148 their mothers have been enrolled in this study. Genotyping was performed by PCR-RFLP. The frequency of alleles and genotypes of MTRR 66A&gt; G polymorphisms was not significantly different between a group with CHD compared to a group without CHD among DS subjects as well as in their mothers. The mothers with mutated homozygous genotypes who have taken folic acid preparations from the fourth week before pregnancy to eight weeks of pregnancy were more likely to have DS-CHD+ child. The study results suggested that maternal MTRR 66A&gt; G polymorphisms associated with their lifestyle habits such as folic acid intake could altered individual risk for CHD in DS child.

Risk factors for congenital heart defects in two populations residing in the same geographic area: a long-term population-based study, Southern Israel

Congenital Heart Defects (CHD) are the most common structural defects of newborns. Southern Israel's population is comprised of Jews (75%) and Arab-Bedouins (25%). The latter has a high rate of consanguinity and low abortion rate compared with the Jewish population, which led us to suspect a higher CHD prevalence in this population. Our aim was to compare maternal risk factors that are associated with CHD in these populations. All births during 1991-2011 in Soroka University Medical Center (n = 247, 289) with 6078 newborns having CHD were included. To account for same-woman deliveries, general estimating equation models adjusted for ethnicity, gender and birth number were used. The total prevalence of CHD was 24.6/1000 live births, with 21.4 and 30 among Jewish and Bedouin populations, respectively, (p = 0.001). Multi-variant analysis of risk factors for CHD revealed that risk factors common to both populations included conception with fertility medications, sibling CHD, maternal CHD, diabetes mellitus, hypertension and anaemia. Risk factors that were specific for the Bedouin population were - maternal age over 35 years, recurrent pregnancy loss and in vitro fertilisation. However, sibling CHD was more common as a CHD risk factor in the Jewish compared with the Bedouin population (Adjusted OR 10.23 versus 3.19, respectively). The prevalence of CHD is higher in both the Bedouin and Jewish populations than previously reported. Several maternal factors were associated with CHD specifically for a certain population. Risk factors for CHD vary in populations residing in the same geographic area.

The non‐genetic paternal factors for congenital heart defects: A systematic review and meta‐analysis

BackgroundAdvances have been made in identifying genetic etiologies and maternal risk factors of congenital heart defects (CHDs), while few literatures are available regarding paternal risk factors for CHDs. Thus, we aim to conduct a meta‐analysis and systematic review about the non‐genetic paternal risk factors for CHDs.MethodsWe searched the PubMed, MEDLINE, and Cochrane Library online databases and identified 31 studies published between 1990 and 2018 according to the inclusion criteria. Paternal risk factors were divided into subgroups, and summarized odd ratios (OR) were calculated.ResultsPaternal age between 24 and 29 years decreased the risk of CHDs in the offspring (OR = 0.90 [0.82, 0.98]), while paternal age ≥ 35 years old increased the risk of CHDs (35‐39 years old: OR = 1.14 [1.09, 1.19], and ≥ 40 years: OR = 1.27 [1.14, 1.42]). Paternal cigarette smoking increased the risk of CHDs in a dose‐dependent way. Paternal wine drinking (OR = 1.47 [1.05, 2.07]) and exposure to chemical agents or drugs (OR = 2.15 [1.53, 3.02]) also increased the risk of CHDs. Some specific paternal occupations were also associated with increased risk for CHDs or CHD subtypes including factory workers, janitors, painters, and plywood mill workers.ConclusionsThis meta‐analysis and systematic review suggested that advanced paternal age, cigarette smoking, wine drinking, exposure to chemical agents or drugs and some specific occupations were associated with an increased risk of CHDs. More measures should be taken to reduce occupational and environment exposures. At the same time, fertility at certain age and establishment of healthy life habits are strongly recommended.

Epidemiology and major subtypes of congenital heart defects in Hunan Province, China.

Congenital heart defects (CHDs) are the most common birth defects (BDs) and account for nearly one-third of all BDs. The aim of this article was to investigate the epidemiology and major subtypes of CHDs in Hunan Province, China in the last 5 years.CHD surveillance data from 2012 to 2016 were collected from 52 registered hospitals in Hunan. The prevalence rates of CHDs, incidence rates of CHDs combined with other BDs, and rates of termination of pregnancy (TOP) for CHDs among different regions, infant sexes, and maternal ages were calculated for both early fetuses (<28 weeks of gestation) and perinatal infants (PIs) (between 28 weeks of gestation and 7 days after birth). Both the constituent ratio and prevalence rates were computed among subtypes.CHDs were found in 6289 out of 673,060 births. The overall prevalence was 93.44 per 10,000 PIs, with 19.27 and 74.17 per 10,000 in early fetuses and PIs, respectively. The risks of CHDs were higher in infants from urban areas than those from rural areas during the whole gestation and were higher in male infants than in female infants during the perinatal period. The total prevalence of CHDs increased significantly with maternal age (χ2 trend = 141.84, P < .05). Among fetuses in early gestation, there were 288 cases (22.21%) of CHDs combined with other BDs and 1292 cases (99.61%) of TOP for CHD. The 3 major subtypes of CHDs were ventricular septal defect (VSD) (22.06%), Tetralogy of Fallot (TOF) (9.43%), and atrioventricular septal defect (AVSD) (6.69%). Among PIs, there were 1541 cases (30.87%) of CHD diagnosed before delivery and 1184 cases (76.83%) were TOP. The 3 major subtypes were atrial septal defect (ASD) (42.81%), patent ductus arteriosus (PDA) (16.07%), and VSDs (15.21%).The total prevalence of CHD in Hunan Province and the rate of TOP for CHD was high, especially for early-gestation fetuses. Pregnancies in urban women, male PIs, and maternal age were the risk factors for CHDs. Among early-gestation fetuses, the most common types were VSD, TOF, and ASD, and among PIs, the most common types were ASD, PDA, and VSD.

Congenital heart defects according to the types of the risk factors – a single center experience

Objective: The main aim of this study was to compare the prevalence of congenital heart defects (CHDs) between pregnant women with and those without the risk factors. The secondary aim was to determine the influence of the specific risk factors, divided into subgroups, on the development of the CHD.Methods: The presented results were obtained over the course of a 15-year study between years 2002 and 2016. Fetal echocardiography was performed as a planned screening examination during the second trimester of gravidity. A total of 35,831 singleton pregnancies were examined at our center. Risk factors for the development of CHDs were analyzed and divide into the following groups: (i) maternal age ≥35 years; (ii) mother-related risk factors; (iii) pregnancy- and fetus-related risk factors; (iv) pregnancy after in vitro fertilization (IVF); (v) history of CHDs in the first-degree family member; (vi) history of CHDs in the second-degree family member; and (vii) positive genetic family history.Results: The risk factors were identified in 25% (8990/35,831) of pregnancies. In total, CHDs were detected in 1.1% (394/35,831) of fetuses. The prevalence rate of CHDs was higher in the pregnancies with than in those without the risk factors (2.5% [221/8990] versus 0.6% [173/26,841]; p < .0001). The presence of pregnancy- and fetus-related risk factors (odds ratio [OR], 6.5; 95% confidence interval [CI], 4.3–9.7) and pregnancy after IVF (OR, 2.8; 95% CI, 1.5–5.2) were found to be independent risk factors of CHDs.Conclusions: The presence of specific risk factors is related to the increasing prevalence of CHDs. Pregnancy- and fetus-related risk factors and in vitro fertilization were found to be the independent risk factors of CHD.

Maternal exposure to ambient PM10 during pregnancy increases the risk of congenital heart defects: Evidence from machine learning models

Previous research suggested an association between maternal exposure to ambient air pollutants and risk of congenital heart defects (CHDs), though the effects of particulate matter ≤10μm in aerodynamic diameter (PM10) on CHDs are inconsistent. We used two machine learning models (i.e., random forest (RF) and gradient boosting (GB)) to investigate the non-linear effects of PM10 exposure during the critical time window, weeks 3–8 in pregnancy, on risk of CHDs. From 2009 through 2012, we carried out a population-based birth cohort study on 39,053 live-born infants in Beijing. RF and GB models were used to calculate odds ratios for CHDs associated with increase in PM10 exposure, adjusting for maternal and perinatal characteristics. Maternal exposure to PM10 was identified as the primary risk factor for CHDs in all machine learning models. We observed a clear non-linear effect of maternal exposure to PM10 on CHDs risk. Compared to 40μgm−3, the following odds ratios resulted: 1) 92μgm−3 [RF: 1.16 (95% CI: 1.06, 1.28); GB: 1.26 (95% CI: 1.17, 1.35)]; 2) 111μgm−3 [RF: 1.04 (95% CI: 0.96, 1.14); GB: 1.04 (95% CI: 0.99, 1.08)]; 3) 124μgm−3 [RF: 1.01 (95% CI: 0.94, 1.10); GB: 0.98 (95% CI: 0.93, 1.02)]; 4) 190μgm−3 [RF: 1.29 (95% CI: 1.14, 1.44); GB: 1.71 (95% CI: 1.04, 2.17)]. Overall, both machine models showed an association between maternal exposure to ambient PM10 and CHDs in Beijing, highlighting the need for non-linear methods to investigate dose-response relationships.

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.