Risk Of Ventricular Septal Defect Research Articles

Association of Maternal Dietary Habits and Infant MTHFR Gene Polymorphisms with Ventricular Septal Defect in Offspring: A Case-Control Study.

This study aimed to explore the association of maternal diet, infant MTHFR gene polymorphisms, and their interactions with the risk of ventricular septal defects (VSDs). This case-control study recruited 448 mothers of VSD children and 620 mothers of healthy counterparts. Multivariable-adjusted logistic regression models were constructed to examine the association between maternal dietary habits during the first trimester of gestation, MTHFR gene polymorphisms, and VSD. Gene-environment interaction effects were analyzed through logistic regression models, with false discovery rate p-value (FDR_p) < 0.05. Maternal excessive intake of fermented bean curd (OR = 2.00, 95%CI: 1.59-2.52), corned foods (OR = 2.23, 1.76-2.84), fumatory foods (OR = 1.75, 1.37-2.23), grilled foods (OR = 1.34, 1.04-1.72), and fried foods (OR = 1.80, 1.42-2.27) was associated with an increased risk of VSD. Regular intake of fish and shrimp (OR = 0.42, 0.33-0.53), fresh eggs (OR = 0.58, 0.44-0.75), soy products (OR = 0.69, 0.56-0.85), and dairy products (OR = 0.71, 0.59-0.85) was found to reduce the occurrence of VSD. Moreover, MTHFR gene polymorphisms at rs2066470 (homozygous: OR = 4.28, 1.68-10.90), rs1801133 (homozygous: OR = 2.28, 1.39-3.74), and rs1801131 (heterozygous: OR = 1.75, 1.24-2.47; homozygous: OR = 3.45, 1.50-7.95) elevated offspring susceptibility to VSDs. Furthermore, significant interactions of MTHFR polymorphisms with maternal dietary habits were observed, encompassing corned foods, fermented bean curd, fried foods, and grilled foods. Maternal dietary habits; MTHFR polymorphisms at rs2066470, rs1801131, and rs1801133; and their interactions were significantly associated with the occurrence of VSDs in offspring.

The Risk of Ventricular Septal Defects Associated With Prenatal Marijuana Exposure: A Systematic Review and Meta-Analysis.

With the recent legalization of marijuana across the United States, its usage in pregnant women has increased. The aim of this meta-analysis was to determine if prenatal marijuana use increases the likelihood of ventricular septal defects. The analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search strategy identified 4 case-control studies that were ultimately included in the analysis with a combined 381,621 infant records. Quantitative analysis demonstrated prenatal marijuana usage significantly increases the likelihood of ventricular septal defects (odds ratio = 2.39, 95% confidence interval = 1.11-5.18).

Molecular Genetic Study on HAND2 Gene Promoter in Ventricular Septal Defect.

Ventricular septal defect (VSD), the most common type of congenital heart disease (CHD), is primarily caused by cardiac dysplasia. Heart and neural crest derivatives expressed 2 (HAND2) participates in developing the right heart. The loss of HAND2 expression in humans is closely connected with ventricular septal defects. We used a case-control study to analyze the genetic variations in the HAND2 promoter region in VSD patients and controls. Some statistical analysis methods were used to analyze the association of single nucleotide polymorphisms (SNPs) with VSD. The dual-luciferase reporter assay and electrophoretic mobility shift assay (EMSA) were used to conduct functional analysis and molecular mechanism study of genetic variations. Through sequencing, we identified nine genetic variants in patients with VSD. The SNP rs2276940 G>T and rs2276941 G>A were associated with an increased risk of VSD. The dual-luciferase reporter assay showed that SNP rs2276940 G>T and rs138531627 C>G decreased the transcriptional activity of the HAND2 promoter. Transcription factors (TFs) predicting suggested that all three SNPs may change the binding of TFs. The result of EMSA showed that rs138531627 C>G may create a new binding site for TFs while rs2276940 G>T enhanced the binding affinity for TFs. These results indicated that genetic variants of the HAND2 promoter may increase the risk of VSD, and the molecular mechanism may be the change of the binding affinity of TFs.

Incidence and risk factors of congenital ventricular septal defect in Qingdao

Objective: To analyze the incidence and risk factors of ventricular septal defect (VSD) in Qingdao. Methods: A prospective cohort study design was used to include pregnant women who underwent prenatal screening in Qingdao between August 2018 and June 2020 (the whole population coverage). VSD was diagnosed according to the pulse oxygen saturation and heart auscultation, and the final diagnosis was made according to the echocardiography of VSD positive newborns within postnatal day 7. Results: The study included 115 238 live births, among which 388 were diagnosed as VSD, with an incidence of 3.37‰. The results of multivariate logistic regression analysis showed that mother with postgraduate level (OR=1.61, 95%CI: 1.00-2.58, P=0.049) (compared with junior high school and below), preterm birth history (OR=2.90, 95%CI: 1.47-5.70, P=0.002), and pregnancy history of congenital heart disease (OR=5.98, 95%CI: 2.63-14.73, P<0.001) were risk factors for VSD. Compared with female infants, the overall risk of VSD in male infants was relatively low (OR=0.74, 95%CI: 0.60-0.91, P=0.005). Conclusions: The incidence of VSD in Qingdao is 3.37‰. The risk factors of VSD include higher maternal education level, pregnancy history of congenital heart disease and preterm birth history. Moreover, the overall risk of VSD in male infants is low.

Association and Interaction Effect of BHMT Gene Polymorphisms and Maternal Dietary Habits with Ventricular Septal Defect in Offspring.

This study attempted to learn the association between maternal betaine-homocysteine methyltransferase (BHMT) gene polymorphisms, maternal dietary habits, and their interactions with the risk of ventricular septal defects (VSD) in offspring. A total of 426 mothers of VSD children and 740 control mothers were included in the study. Logistic regression was used to evaluate the level of associations and interaction effects. Our study suggested that mothers reporting excessive intake of smoked foods (aOR = 2.44, 95%CI: 1.89–3.13), barbecued foods (aOR = 1.86, 95%CI: 1.39–2.48), fried foods (aOR = 1.93, 95%CI: 1.51–2.46), and pickled vegetables (aOR = 2.50, 95%CI: 1.92–3.25) were at a significantly higher risk of VSD in offspring, instead, mothers reporting regular intake of fresh fruits (aOR = 0.47, 95%CI: 0.36–0.62), fish and shrimp (aOR = 0.35, 95%CI: 0.28–0.44), fresh eggs, (aOR = 0.56, 95%CI: 0.45–0.71), beans (aOR = 0.68, 95%CI: 0.56–0.83), and milk products (aOR = 0.67, 95%CI: 0.56–0.80) were at a lower risk of VSD in offspring. In addition, maternal BHMT gene polymorphisms at rs1316753 (CG vs. CC: aOR = 2.01, 95%CI: 1.43–2.83) and rs1915706 (CT vs. TT: (aOR = 1.81, 95%CI: 1.33–2.46) were significantly associated with increased risk of VSD in offspring. Furthermore, a significant interaction between BHMT polymorphisms and maternal bean intake was identified in the study. In conclusion, Maternal BHMT polymorphisms at rs1316753 and rs1915706, dietary habits as well as their interaction were observed to be significantly associated with the risk of VSD in offspring.

Study of variants associated with ventricular septal defects (VSDs) highlights the unique genetic structure of the Pakistani population

BackgroundVentricular septal defects (VSDs) are one of the leading causes of death due to cardiac anomalies during the first months of life. The prevalence of VSD in neonates is reported up to 4%. Despite the remarkable progress in medication, treatment and surgical procedure for VSDs, the genetic etiology of VSDs is still in infancy because of the complex genetic and environmental interactions.MethodsThree hundred fifty subjects (200 VSD children and 150 healthy controls) were recruited from different pediatric cardiac units. Pediatric clinical and demographic data were collected. A total of six variants, rs1017 (ISL1), rs7240256 (NFATc1), rs36208048 (VEGF), variant of HEY2, rs11067075 (TBX5) and rs1801133 (MTHFR) genes were genotyped by tetra-ARMS PCR and PCR–RFLP methods.ResultsThe results showed that in cases, the rs1017 (g.16138A > T) variant in the ISL1 gene has an allele frequency of 0.42 and 0.58 respectively for the T and A alleles, and 0.75 and 0.25 respectively in the controls. The frequencies of the AA, TA and TT genotypes were, 52%, 11% and 37% in cases versus 21%, 8% and 71% respectively in the controls. For the NFATc1 variant rs7240256, minor allele frequency (MAF) was 0.43 in cases while 0.23 in controls. For the variant in the VEGF gene, genotype frequencies were 0% (A), 32% (CA) and 68% (CC) in cases and 0.0%, 33% and 67% respectively in controls. The allele frequency of C and A were 0.84 and 0.16 in cases and 0.83 and 0.17 respectively in controls. The TBX5 polymorphism rs11067075 (g.51682G > T) had an allelic frequency of 0.44 and 0.56 respectively for T and G alleles in cases, versus 0.26 and 0.74 in the controls. We did not detect the presence of the HEY2 gene variant (g.126117350A > C) in our pediatric cohort. For the rs1801133 (g.14783C > T) variant in the MTHFR gene, the genotype frequencies were 25% (CC), 62% (CT) and 13% (TT) in cases, versus 88%, 10% and 2% in controls. The ISL1, NFATc1, TBX5 and MTHFR variants were found to be in association with VSD in the Pakistani pediatric cohort whilst the VEGF and HEY2 variants were completely absent in our cohort.ConclusionWe propose that a wider programme of genetic screening of the Pakistani population for genetic markers in heart development genes would be helpful in reducing the risk of VSDs.

Impact of Hospital Volume on Outcomes of Septal Myectomy for Hypertrophic Cardiomyopathy

BackgroundLeft ventricular outflow tract obstruction is common among symptomatic patients with hypertrophic cardiomyopathy, yet septal reduction by surgical myectomy (septal myectomy [SM]) is performed infrequently in many centers. This study examined the possible relationship between institutional case volume and early outcomes of SM. MethodsThe Society of Thoracic Surgeons Adult Cardiac Surgery Database was queried for patients with hypertrophic cardiomyopathy who underwent SM from January 2012 to December 2019. The study defined center case volume categories as <1, 1 to 4.99, 5 to 9.99, and ≥10 cases performed on average per year. ResultsThe study population included 5935 patients at 481 centers with 933 surgeons. The range of average center volume was <1 to 138 cases per year. Overall early mortality was 2.6%, ventricular septal defect (VSD) occurred in 1.9%, and complete heart block occurred in 9.0%. Concomitant mitral valve (MV) repair was performed in 28.7%, and MV replacement was performed in 17.1%. In multivariable analysis, the lowest annual case volume (average <1 case/y) was consistently associated with greater early mortality (odds ratio [OR], 5.4; CI, 3.0-9.9; P < .001), greater risk of VSD (OR, 9.3; CI ,4.2-20.4; P < .001), increased incidence of complete heart block (OR, 2.0; CI, 1.5-2.7; P < .001), and a higher likelihood of MV replacement (OR, 9.4; CI, 7.5-11.8; P < .001). ConclusionsVolume of SM cases varies widely among institutions reporting to the Society of Thoracic Surgeons Adult Cardiac Surgery Database. There appears to be an important association between surgical experience, as reflected by institutional case volume, and early outcomes, including mortality, as well as the occurrence of VSD, heart block, and MV replacement.

Shorter periconception maternal telomere length and the risk of congenital cardiac outflow defects in the offspring.

BackgroundCongenital cardiac outflow defects (COD) are the largest group of congenital heart defects, with ventricular septal defect (VSD) as the most prevalent phenotype. Increased maternal age, excessive oxidative stress and inflammation are involved in the pathophysiology of COD and enhance telomere length (TL) shortening. We investigated the association between periconception maternal TL and the risk of having a child with COD.MethodsFrom a multicentre case‐control trial, 306 case mothers of a child with COD and 424 control mothers of a child without a congenital malformation were selected. Relative TL was measured by qPCR. Multivariable logistic regression was used to compute crude and adjusted odds ratios, per standard deviation decrease, between maternal T/S ratio and COD and VSD risk. Adjustments were made for maternal age. Additional adjustments were made in a second model.ResultsShorter maternal relative TL was significantly associated with an OR of 1.29 (95% CI 1.04–1.61), p = .02, for the risk of VSD in offspring, which remained significant after an adjustment for maternal age (adjOR 1.25(95% CI 1.01–1.55), p = .04). No association between maternal TL and the risk of overall COD in offspring was observed.ConclusionShorter maternal relative TL is associated with an approximately 1.3‐OR for the risk, per SD in relative TL shortening, of VSD in the offspring. These findings need further confirmation in other studies on the predictive value of maternal TL.

Association of polymorphisms of FOLR1 gene and FOLR2 gene and maternal folic acid supplementation with risk of ventricular septal defect: a case-control study.

It was the first time to examine the role of maternal polymorphisms of FOLR1 gene and FOLR2 gene, as well as their interactions with maternal folic acid supplementation (FAS), in the risk of ventricular septal defect (VSD). A case-control study was conducted with 385 mothers of VSD infants and 652 controls. The exposures of interest were FAS and FOLR1 gene and FOLR2 gene polymorphisms. The logistic regression model was used for accessing the strength of association. After controlling for the potential confounders, women who did not utilize folic acid had a substantially higher risk of VSD (aOR = 2.25; 95% CI: 1.48 to 3.43), compared to those who did. We also observed genetic polymorphisms of FOLR1 gene at rs2071010 (GA vs. GG: aOR = 0.63, 95%CI: 0.45 to 0.88) and rs11235462 (AA vs. TT: aOR = 0.53, 95%CI: 0.33 to 0.84), as well as FOLR2 gene at rs651646 (AA vs. TT: aOR = 0.46, 95%CI: 0.30 to 0.70), rs2298444 (CC vs. TT: aOR = 0.58, 95%CI: 0.36 to 0.91) and rs514933 (TC vs. TT: aOR = 0.57, 95%CI: 0.41 to 0.78) were associated with a lower risk of VSD. Furthermore, there was a statistically significant interaction between maternal FAS and genetic polymorphisms at rs514933 on the risk of VSD (FDR_P = 0.015). The maternal genetic polymorphisms of the FOLR1 gene and FOLR2 gene, as well as FAS and their interactions, were shown to be significantly associated with the risk of VSD in offspring.

Association of Maternal Dietary Habits and MTHFD1 Gene Polymorphisms With Ventricular Septal Defects in Offspring: A Case-Control Study.

ObjectivesThis study aimed at assessing the association between maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene polymorphisms, maternal dietary habits, and their interactions with the risk of ventricular septal defects (VSD) in offspring.MethodsFrom November 2017 to March 2019, a case-control study comprising 360 mothers of VSD cases and 504 mothers of healthy infants was conducted in Han Chinese populations. The main exposures of interest were maternal dietary habits in early pregnancy and MTHFD1 gene polymorphisms. Logistic regression models were used to estimate the main effects and interaction effects.ResultsIt was observed that maternal excessive intake of pickled vegetables (aOR = 1.85, 95%CI: 1.45–2.37), smoked foods (aOR = 1.93, 95%CI: 1.48–2.51), barbecued foods (aOR = 1.74, 95%CI: 1.28–2.36), and fried foods (aOR = 1.68, 95%CI: 1.30–2.17) were associated with a higher risk of VSD in offspring, whereas maternal excessive intake of fresh meat (aOR = 0.61, 95%CI: 0.47–0.79), fish and shrimp (aOR = 0.29, 95%CI: 0.23–0.38), fresh eggs (aOR = 0.54, 95%CI: 0.42–0.70), fresh fruits or vegetables (aOR = 0.44, 95%CI: 0.33–0.60), soy foods (aOR = 0.65, 95%CI: 0.53–0.80), and milk products (aOR = 0.49, 95%CI: 0.40–0.59) could contribute significantly to a lower risk of VSD in offspring. Furthermore, the genetic polymorphisms of maternal MTHFD1 gene at rs1950902 (GA vs. GG: aOR = 0.67, 95%CI: 0.50–0.90) and rs2236222 (GG vs. AA: aOR = 2.75, 95%CI: 1.57–4.83) were significantly associated with the risk of VSD in offspring. In addition, there was a significant interaction effect between maternal dietary habits and MTHFD1 gene polymorphisms on the risk of VSD.ConclusionsMaternal dietary factors, MTHFD1 genetic polymorphisms, and their interactions were all associated with the risk of VSD in offspring. However, further research in diverse ethnic populations and with a larger sample size is warranted to corroborate our findings.Trial RegistrationRegistered in Chinese Clinical Trial Registry Center; registration number, ChiCTR1800016635; registration date, 06/14/2018 (Retrospectively registered); URL of trial registry record, https://www.chictr.org.cn/showproj.aspx?proj=28300.

Parental consanguinity increases the risk of congenital malformations

Introduction: Congenital malformation is a physical or structural abnormality present either prenatally or after birth. These anomalies are either primary or secondary malformation. Primary malformations adversely affect body functions, however, the secondary malformations are the structural defects which may have less or no effect on body functions. Primary congenital anomalies show marked variations globally with respect to prevalence. The aim of the current study was to further add to the scientific evidences on the pattern and prevalence of congenital anomalies in cousins and non-cousins’ marriages in Khyber Pakhtunkhwa. Material and Methods: Data of 200 patients (divided into two groups) was collected by convenience sampling through cross-sectional survey. Group-I consisted of 100 gravidas who were diagnosed with anomalous foetus either hydrocephalous, anencephaly or cleft lip/palate and Group-II comprised of infants with inborn heart defects were selected. Results: The study shows 68% consanguineous and 32% non-consanguineous marriages. Hydrocephalous shows the highest rate of incidence (55%) followed by anencephaly (40%) cleft lip/palate (5%), Ventricular Septal Defect (43%), Atrial Septal Defect (29%), Patent Ductus Arteriosus (16%) and Tetralogy of Fallot (12%). The relative risk of hydrocephalus and anencephaly in consanguineous and non-consanguineous marriage was 0.98 while the relative risk of Ventricular Septal Defect and Patent Ductus Arteriosus was 1.1. Rate of miscarriages was comparatively high in cousin marriages. Frequency of CM was higher in multigravida compared to primigravida. Detection rate of hydrocephalus was highest in second trimester, cleft lip/palate in third trimester and anencephaly in first trimester. Conclusion: Parental consanguinity is one of the major risk factors for structural, neurological and cardiac anomalies.

Ondansetron use in the first trimester of pregnancy and the risk of neonatal ventricular septal defect.

Literature is divided regarding the risk of neonatal ventricular septal defect (VSD) associated with first trimester ondansetron use in pregnancy. We evaluated the risk of VSD associated with first trimester exposure to intravenous or oral ondansetron in 33 677 deliveries at Magee-Womens Hospital in Pittsburgh, PA (2006-2014). Using log-binomial regression, we evaluated the risk: (1) in the full cohort, (2) using propensity score designs with both matching and inverse probability weighting and (3) utilizing clustered trajectory analysis evaluating the role of dose. Sensitivity analyses assessed the association between ondansetron and all recorded birth defects in aggregate. A total of 3733 (11%) pregnancies were exposed to ondansetron in the first trimester (dose range: 2.4-1008 mg). Ondansetron was associated with increased risk of VSD with risk ratios ranging from 1.7 [95% confidence interval (CI) 1.0-2.9] to 2.1 (95% CI 1.1-4.0) across methods. Risks correspond to one additional VSD for approximately every 330 pregnancies exposed in the first trimester. The association was dose-dependent with increased risk in women receiving highest cumulative doses compared with lowest doses [adjusted risk ratio: 3.2 (95% CI 1.0-9.9)]. The association between ondansetron and congenital malformations was diluted as the outcome included additional birth defects. First trimester ondansetron use is associated with an increased risk of neonatal VSD potentially driven by higher doses. This risk should be viewed in the context of risks attributable to severe untreated nausea and vomiting of pregnancy.

Associations between maternal social support and stressful life event with ventricular septal defect in offspring: a case-control study

BackgroundPrevious studies suggested that maternal subjective feeling of stress seemed to be involved in the incidence of congenial heart disease in offspring. To better understand the findings, our study would discuss the relationships of maternal exposure to stressful life event and social support, which are more objective and comprehensive indicators of stress, around periconceptional period with the risk of ventricular septal defect (VSD), the most popular subtype of congenital heart disease.MethodsA hospital-based case-control study was conducted through June, 2016 to December, 2017. We collected maternal self-reports of 8 social support questions in 3 aspects and 8 stressful life events among mothers of 202 VSD cases and 262 controls. Social support was categorized into low, medium high, and high (higher is better), and stressful life event was indexed into low, medium low, and high (higher is worse). Logistic regression models were applied to estimate adjusted odds ratios and 95% confidence intervals (95% CI).ResultsThe adjusted odds ratio of high stressful life event was 2.342 (95% CI: 1.348, 4.819) compared with low stressful life event. After crossover analysis, compared with low event & high support, the adjusted odds ratio of low event & low support, high event & high support, and high event & low support were 2.059 (95% CI: 1.104, 3.841), 2.699 (95% CI: 1.042, 6.988) and 2.781 (95% CI: 1.033, 7.489), respectively.ConclusionsIn summary, we observed an increased risk of VSD when pregnant women exposed to stressful life events, however, social support could, to some extent, reduce the risk of stressful life event.

Spatial variations in ambient ultrafine particle concentrations and risk of congenital heart defects

BackgroundCardiovascular malformations account for nearly one-third of all congenital anomalies, making these the most common type of birth defects. Little is known regarding the influence of ambient ultrafine particles (<0.1 μm) (UFPs) on their occurrence. ObjectiveThis population-based study examined the association between prenatal exposure to UFPs and congenital heart defects (CHDs). MethodsA total of 158,743 singleton live births occurring in the City of Toronto, Canada between April 1st 2006 and March 31st 2012 were identified from a birth registry. Associations between exposure to ambient UFPs between the 2nd and 8th week post conception when the foetal heart begins to form and CHDs identified at birth were estimated using random-effects logistic regression models, adjusting for personal- and neighbourhood-level covariates. We also investigated multi-pollutant models accounting for co-exposures to PM2.5, NO2 and O3. ResultsA total of 1468 CHDs were identified. In fully adjusted models, UFP exposures during weeks 2 to 8 of pregnancy were not associated with overall CHDs (Odds Ratio (OR) per interquartile (IQR) increase = 1.02, 95% CI: 0.96–1.08). When investigating subtypes of CHDs, UFP exposures were associated with ventricular septal defects (Odds Ratio (OR) per interquartile (IQR) increase = 1.13, 95% CI: 1.03–1.33), but not with atrial septal defect (Odds Ratio (OR) per interquartile (IQR) increase = 0.89, 95% CI: 0.74–1.06). ConclusionThis is the first study to evaluate the association between prenatal exposure to UFPs and the risk of CHDs. UFP exposures during a critical period of embryogenesis were associated with an increased risk of ventricular septal defect.

Statin exposure during first trimester of pregnancy is associated with fetal ventricular septal defect

BackgroundA growing number of young women are exposed to statins during their first trimester of pregnancy. The goal of this study is to examine if first trimester statin exposure is associated with an increase in risk of fetal congenital cardiac anomalies. MethodsIn a cohort of 379,238 pregnancies, we examined the risk of fetal congenital cardiac anomalies in association with maternal exposure to statin therapy during the first trimester of pregnancy using logistic regression models and propensity score matching methods. Results280 women were exposed to statins. Congenital cardiac anomalies were present in 14 (5.0%) of pregnancies exposed to statin and 5282 (1.4%) of non-exposed pregnancies. First-trimester statin exposure was associated with an increased risk of ventricular septal defect (adjusted odds ratio [OR] 3.3, 95% confidence interval [CI]l 1.8–6.0, p < 0.001). This association was confirmed in an analysis using a propensity score-matched cohort (OR 4.7, 95% CI 2.0–10.8, p < 0.001). ConclusionsExposure to statins during the first trimester of pregnancy is associated with fetal ventricular septal defect.

Risk Factors for Ventricular Septal Defects in Murmansk County, Russia: A Registry-Based Study.

Cardiovascular malformations are one of the most common birth defects among newborns and constitute a leading cause of perinatal and infant mortality. Although some risk factors are recognized, the causes of cardiovascular malformations (CVMs) remain largely unknown. In this study, we aim to identify risk factors for ventricular septal defects (VSDs) in Northwest Russia. The study population included singleton births registered in the Murmansk County Birth Registry (MCBR) between 1 January 2006 and 31 December 2011. Infants with a diagnosis of VSD in the MCBR and/or in the Murmansk Regional Congenital Defects Registry (up to two years post-delivery) constituted the study sample. Among the 52,253 infants born during the study period there were 744 cases of septal heart defects (SHDs), which corresponds to a prevalence of 14.2 [95% confidence interval (CI) of 13.2–15.3] per 1000 infants. Logistic regression analyses were carried out to identify VSD risk factors. Increased risk of VSDs was observed among infants born to mothers who abused alcohol [OR = 4.83; 95% CI 1.88–12.41], or smoked during pregnancy [OR = 1.35; 95% CI 1.02–1.80]. Maternal diabetes mellitus was also a significant risk factor [OR = 8.72; 95% CI 3.16–24.07], while maternal age, body mass index, folic acid and multivitamin intake were not associated with increased risk. Overall risks of VSDs for male babies were lower [OR = 0.67; 95% CI 0.52–0.88].

Does septal thickness influence outcome of myectomy for hypertrophic obstructive cardiomyopathy?

Patients with hypertrophic obstructive cardiomyopathy and basal septal thickness <18 mm are often considered unsuitable candidates for myectomy. Mitral valve (MV) replacement is frequently performed instead. We aimed to determine whether septal thickness affects outcomes and adequacy of myectomy. Clinical and echocardiographic data were reviewed for 1486 consecutive adult patients with hypertrophic obstructive cardiomyopathy who underwent transaortic septal myectomy from January 2005 through December 2014. Comparisons between patients, grouped by septal thickness (<18 mm, n = 369; 18-21 mm, n = 612 and >21 mm, n = 505), were performed with the Kruskal-Wallis and the Pearson χ2 tests and semiparametric analysis of covariance. Median group ages were 57, 57 and 54 years (P = 0.007); men comprised 50.4%, 56.7% and 62.0%, respectively (P = 0.003). Intrinsic MV disease was present in 5.9%, 5.2% and 4.6%, respectively (P = 0.80). All patients underwent transaortic septal myectomy. Additional mitral procedures were performed in 7.6%, 7.8% and 8.1%, respectively (P = 0.90). Reasons for MV surgery included intrinsic MV disease (66.7%), residual mitral regurgitation (30.8%) and residual gradient (2.6%). All groups had postoperative gradient relief (median reduction: 51, 54 and 50 mmHg; P = 0.11). Ventricular septal defect occurred in 4 patients (0.3%), and risk did not differ by group (P = 0.24). Adequate relief of left ventricular outflow tract obstruction can be achieved via transaortic septal myectomy without concomitant MV procedures when septal thickness is < 18 mm, and the risk of ventricular septal defect is minimal. Concomitant MV repair/replacement should be reserved for patients with intrinsic MV disease or inadequate relief of mitral regurgitation/left ventricular outflow tract obstruction following adequate extended septal myectomy.

Population Study Confirms Serum Proteins' Change and Reveals Diagnostic Values in Congenital Ventricular Septal Defect.

This study was designed to validate thrombospondin 1 (TSP-1), vascular endothelial-cadherin complex (VE-cad), insulin-like growth factor 2 (IGF-2), and amyloid precursor protein (APP) and assess their diagnostic value in ventricular septal defect (VSD). We investigated the serum levels of TSP-1, VE-cad, IGF-2, and APP by enzyme-linked immunosorbent assay in a hospital-based case-control study that included 40 VSD children and 40 healthy controls. Logistic regression analysis was applied to evaluate the relationship of the proteins and VSD, and receiver operating characteristic (ROC) curve was used to assess the diagnostic value of the significant proteins. The serum levels of TSP-1, VE-cad, and IGF-2 were significantly higher in VSD patients than those in healthy controls (p<0.05). Multivariate logistic regression analysis demonstrated that high levels of TSP-1, VE-cad, and IGF-2 were significantly associated with an increased risk of VSD [TSP-1 (OR 26.91, 95% CI 6.60-72.66, p<0.001), VE-cad (OR 11.91, 95% CI 3.90-36.36, p<0.001), IGF-2 (OR 3.25, 95% CI 1.25-8.43, p=0.015)]. Areas under the ROC curve for TSP-1, VE-cad, and IGF-2 were 0.985, 0.838, and 0.658, respectively. These data demonstrated that TSP-1, VE-cad, and IGF-2 were significantly associated with risk of VSD and manifested diagnostic values, which may provide new evidence for understanding the etiology and promote the early diagnosis and prevention of VSD.

Associations of GATA4 genetic mutations with the risk of congenital heart disease: A meta-analysis.

Background:GATA4 gene is a cardiac transcriptional factor playing important role in cardiac formation and development. Three GATA4 gene mutations, 99 G>T, 487 C>T, and 354 A>C, have been reported in congenital heart disease (CHD). Therefore, a meta-analysis was performed to explore the associations between 99 G>T, 487 C>T, or 354 A>C mutations and the risk of CHD.Methods:We searched the relevant studies in electronic databases, including ISI Science Citation Index, Embase, PubMed, CNKI, and Wan fang, from January 2006 to March 2016. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the associations between 99 G>T, 487 C>T, or 354 A>C mutations and the risk of CHD.Results:A total of 11 studies including 2878 CHD cases and 3339 controls were evaluated. There was no significant association between GATA4 99 G>T (OR = 1.22, 95% CI = 0.74–2.01, P = .43) or 487 C>T (OR = 1.16, 95% CI = 0.48–2.78, P = .74) mutations and the risk of CHD, whereas GATA4 354 A>C (OR = 1.49, 95% CI = 1.15–1.93, P = .003) mutation was significantly associated with CHD risk. Subgroup analysis was further performed for GATA4 99 G>T, 487 C>T, and 354 A>C mutations based on sample size and ethnicity, and no significant association between GATA4 99 G>T or 487 C>T mutations and the risk of CHD was found in all subgroups, whereas GATA4 354 A>C mutation was significantly associated with CHD risk in large-sample-size and Asian subgroups. However, subgroup analysis by types of CHD indicated that there was no significant association between GATA4 354 A>C mutation and the risk of ventricular septal defects.Conclusions:Our findings suggested that GATA4 99 G>T and 487 C>T mutations may not be related to the incidence of CHD. However, GATA4 354 A>C mutation was significantly associated with CHD risk.

TCF21 rs12190287 Polymorphisms Are Associated with Ventricular Septal Defects in a Chinese Population.

TCF21 knockout mice display cardiac defects, including ventricular septal defects (VSDs). Functional rs12190287 polymorphisms located within the 3' untranslated region (3'-UTR) of TCF21 were associated with a risk of coronary heart disease in the European and Eastern populations. However, whether rs12190287 polymorphisms in the TCF21-3'UTR confer predisposition to congenital heart disease (CHD) is unclear. A case-control study was designed consisting of 781 nonsyndromic VSD patients and 867 non-CHD control subjects. The genotype frequency of rs12190287 polymorphisms was determined by real-time polymerase chain reaction. There were significant differences in the genotype and allele frequencies of rs12190287 between the cases and controls in a Chinese population. Allele G of rs12190287 was significantly associated with an increased risk of VSD in a Chinese population. Our results demonstrate that rs12190287 polymorphisms confer predisposition to VSDs in the Chinese population studied here.