Risk Of Congenital Heart Defects Research Articles

Maternal Body Mass Index and Risk of Congenital Heart Defects in Infants: A Dose-Response Meta-Analysis.

Objective The exact shape of the dose-response relationship between maternal body mass index (BMI) and the risk of congenital heart defects (CHDs) in infants has not been clearly defined yet. This study aims to further clarify the relationship between maternal obesity and the risk of CHDs in infants by an overall and dose-response meta-analysis. Methods PubMed, Embase, and Web of Science databases were searched to identify all related studies. The studies were limited to human cohort or case-control studies in English language. Random-effect models and dose-response meta-analysis were used to synthesize the results. Heterogeneity, subgroup analysis, sensitivity analysis, and publication bias were also assessed. Results Nineteen studies with 2,416,546 participants were included in our meta-analysis. Compared with the mothers with normal weight, the pooled relative risks (RRs) of infants with CHDs were 1.08 (95% CI=1.03-1.13) in overweight and 1.23 (95% CI=1.17-1.29) in obese mothers. According to the findings from the linear meta-analysis, we observed an increased risk of infants with CHDs (RR=1.07, 95% CI=1.06-1.08) for each 5 kg/m2 increase in maternal BMI. A nonlinear relationship between maternal BMI and risk of infants with CHDs was also found (p=0.012). Conclusion The results from our meta-analysis indicate that increased maternal BMI is related to increased risk of CHDs in infants.

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.

Prenatal exposure to nitrate in drinking water and the risk of congenital anomalies

BackgroundNitrate is a common water contaminant that has been associated with birth defects, although the evidence is limited. The purpose of this study was to examine whether maternal consumption of nitrate through drinking water is associated with an increased risk of congenital anomalies. MethodsThe study included a total of 348,250 singletons births from the state of Missouri between January 1, 2004 and December 31, 2008. Individual-level birth defect data and maternal and child characteristics were obtained from the Missouri birth defects registry and state vital statistics records. Outcomes were linked with county-specific monthly estimates of the nitrate concentration in finished water, based on data collected for compliance with the Safe Drinking Water Standard. Poisson models were fit to examine the association between nitrate exposure and birth defects. Average nitrate exposure during the first trimester and over 12 months prior to birth were modeled as continuous variables. Sensitivity analyses included restriction of the sample to counties with <20% and <10% private well usage to reduce exposure misclassification as well as limiting the analyses to residents of rural counties only to account for potential confounding by urbanicity. ResultsEstimated water concentrations of nitrate were generally low and below the Environmental Protection Agency’s maximum contaminant level of 10 mg/L. Nitrate exposure was associated with a significantly increased risk of limb deficiencies (RR for 1 mg/L (RR1) = 1.26, 95% CI = 1.05, 1.51) in models without well restriction. Nitrate was also weakly associated with an increased risk of congenital heart defects (RR1 = 1.13, 95%CI = 0.93, 1.51) and neural tube defects (RR1 = 1.18, 95%CI = 0.93, 1.51) in models with well restriction (<10%). ConclusionThe positive associations found between nitrate exposure via drinking water and congenital abnormalities are largely consistent with some previous epidemiologic studies. The results of this study should be interpreted with caution given limitations in our ability to estimate exposures and the lack information on some risk factors for congenital abnormalities. Our findings may have serious policy implications given that exposure levels in our study were well below current EPA standards for nitrate in drinking water.

Maternal voluntary exercise mitigates oxidative stress and incidence of congenital heart defects in pre-gestational diabetes.

Women with pre‐gestational diabetes have a higher risk of producing children with congenital heart defects (CHDs), caused predominantly by hyperglycemia‐induced oxidative stress. In this study, we evaluated if exercise during pregnancy could mitigate oxidative stress and reduce the incidence of CHDs in the offspring of diabetic mice. Female mice were treated with streptozotocin to induce pre‐gestational diabetes, then mated with healthy males to produce offspring. They were also given access to running wheels 1 week before mating and allowed to exercise voluntarily until E18.5. Heart morphology, gene expression, and oxidative stress were assessed in foetal hearts. Maternal voluntary exercise results in a significantly lower incidence of CHDs from 59.5% to 25%. Additionally, diabetes‐induced defects in coronary artery and capillary morphogenesis were also lower with exercise. Myocardial cell proliferation and epithelial‐mesenchymal transition at E12.5 was significantly lower with pre‐gestational diabetes which was mitigated with maternal exercise. Cardiac gene expression of Notch1, Snail1, Gata4 and Cyclin D1 was significantly higher in the embryos of diabetic mice that exercised compared to the non‐exercised group. Furthermore, maternal exercise produced lower reactive oxygen species (ROS) and oxidative stress in the foetal heart. In conclusion, maternal exercise mitigates ROS and oxidative damage in the foetal heart, and results in a lower incidence of CHDs in the offspring of pre‐gestational diabetes. Exercise may be an effective intervention to compliment clinical management and further minimize CHD risk in mothers with diabetes.

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.

Metal nickel exposure increase the risk of congenital heart defects occurrence in offspring: A case-control study in China.

Background:Previous studies have investigated heavy metal exposure could increase the occurrence of congenital heart defects (CHDs). However, there are limited data regarding the relationship between exposure to nickel and CHDs occurrence in offspring. The aim of this study was to analyze the association between nickel exposure in mothers and the risk of CHDs in offspring.Materials and methods:To explore the association of nickel exposure and occurrence of CHD, a case-control study with 490 controls and 399 cases with CHDs in China were developed. The concentrations of nickel in hair of pregnant woman and fetal placental tissue were measured and used a logistic regression analysis to explore the relationship between nickel exposure and risk of CHD.Results:The median concentrations of nickel were 0.629 ng/mg, P < .05 (adjusted odds ratio [aOR], 1.326; 95% CI, 1.003–1.757) and 0.178 ng/mg, P < .05 (aOR, 2.204; 95% CI, 0.783–6.206), in maternal hair and in fetal placental tissue in the CHD group, respectively. Significant differences in the level of nickel in hair were also found in the different CHD subtypes including septal defects (P < .05), conotruncal defects (P < .05), right ventricular outflow tract obstruction (P < .01), and left ventricular outflow tract obstruction (P < .05). Dramatically different nickel concentrations in fetal placenta tissue were found in cases with other heart defects (P < .05).Conclusions:The finding suggested that the occurrence of CHDs may be associated with nickel exposure.

Excess VEGF‐A disrupts tubular heart formation and cardiac blood flow dynamics

Vascular Endothelial Growth Factor (VEGF) plays a critical role during heart development. Clinical evidence shows that maternal conditions that modify VEGF signaling in utero, such as high altitude hypoxia and maternal diabetes, are correlated with an increased risk of congenital heart defects. While VEGF is essential for vasculogenesis and angiogenesis, its role during early heart tube formation is not fully understood. During early embryogenesis, paired endocardial tubes fuse into a single linear heart tube, which ultimately transforms into a four‐chambered heart. To better understand the role of VEGF in heart tube fusion, we studied how an early transient dysregulation of VEGF, produced by adding exogenous VEGF‐A right before tube fusion, affects heart tube formation and the onset of blood flow in the heart, leading to congenital heart defects.To enable longitudinal studies of heart development, and determine effects on early and late cardiac formation events, we developed an in ovo quail model of early transient VEGF dysregulation. We chose quail due to ease of access and monitoring during development. We applied recombinant human VEGF165 (rhVEGF165; VEGF‐A isoform) to quail embryos in ovo at Hamburger‐Hamilton (HH) stage 8 (~29 hours incubation) just before heart tube fusion (500ng in a 5μL drop on top of the embryo). Control embryos (vehicle applied at HH8) were also prepared. Eggs were then resealed and re‐incubated for an additional 13hrs (approximately HH11, early tubular heart); 22hrs (around HH14, early beating tubular heart); or 10 days (HH38, fully formed heart); to study how a short, transient, early exposure to excess VEGF‐A impacts cardiac formation.We found both early and late cardiac deficiencies after transient VEGF exposure at HH8. Around HH11, the newly formed tubular heart presented three distinct phenotypes when exposed to early VEGF excess: 1. Wider and shorter than normal heart tubes; 2. Heart tubes with multiple ridges (abnormal folds and protrusions); and 3. Lack of heart tube. Total number of malformed hearts accounted for 70% (n = 21/30) in VEGF‐treated embryos versus 27% (n = 6/22) in controls. Around HH14, when the heart is beating, we measured blood flow and cardiac wall mechanics. We found that heart tubes that were significantly wider than normal (~30%) after VEGF‐treatment, had about 30% increase in maximum flow velocity (n = 3), and their heart tubes failed to completely close the lumen to avoid backflow. When the heart was fully formed, at HH38, microCT images revealed four malformation phenotypes: 1. Ventricular septal defect (VSD); 2. Right ventricular hypoplasia; 3. Hearts that were both shorter and wider than normal; and 4. Aortic arch anomalies. Total number of malformed hearts accounted for 28% (n = 9/32) of surviving VEGF‐treated embryos; and 14% (4/28) surviving control embryos. Our data highlight that VEGF‐A is involved in shaping the geometrical characteristics of the early heart tube, and thus the onset of blood flow dynamics, together affecting mature heart formation.Support or Funding InformationNIH R01 HL094570; AHA 16GRNT29840002; OHSU Presidential Bridge Fund.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Parental smoking and the risk of congenital heart defects in offspring: An updated meta-analysis of observational studies.

Although previous reviews confirmed maternal active smoking was significantly associated with risk of fetal congenital heart defects (CHDs), association between maternal passive smoking and paternal smoking and risk of CHDs is inconclusive nowadays; furthermore, a complete overview is lacking. A meta-analysis of observational studies was conducted to assess the risk of CHDs associated with maternal active and passive smoking and paternal smoking. Seven electronic databases were searched for qualified research up to June 2018. We summarized study characteristics and the summary risk estimates were calculated using either the random-effect model or fixed-effect model. Sensitivity and subgroup analysis were carried out to identify the potential heterogeneity moderators. One hundred and twenty-five studies involving 137,574 CHDs cases in 8,770,837 study participants were included. Overall, maternal active (risk ratio (RR) = 1.25; 95% confidence interval (CI): 1.16-1.34; p < 0.01) and passive (RR = 2.24, 95% CI: 1.81-2.77; p < 0.01) smoking as well as paternal active smoking (RR = 1.74, 95% CI: 1.48-2.06; p < 0.01) were significantly associated with CHDs risk. For specific CHD subtypes, our study showed that maternal active smoking was significantly associated with risk of atrial septal defect (RR = 1.27, 95% CI: 1.02-1.59; p = 0.03) and right ventricular outflow tract obstruction (RR = 1.43, 95% CI: 1.04-1.97; p = 0.03). Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. Maternal active smoking, maternal passive smoking as well as paternal smoking all increased the risk of CHDs in offspring. Preventing parental smoking during peri-pregnancy is a priority for CHDs prevention.

Association Between Maternal Folic Acid Supplementation and Congenital Heart Defects in Offspring in Birth Cohorts From Denmark and Norway.

BackgroundEvidence linking individual‐level maternal folic acid supplementation to offspring risk of congenital heart defects is lacking. We investigated whether folic acid supplementation in early pregnancy reduces offspring risk of heart defects in 2 large birth cohort studies.Methods and ResultsWomen recruited in early pregnancy within the DNBC (Danish National Birth Cohort), 1996–2003, and MoBa (Norwegian Mother and Child Cohort Study), 2000–2009, were followed until delivery. Information on periconceptional intake of folic acid and other supplements was linked with information on heart defects from national registers. Among 197 123 births, we identified 2247 individuals with heart defects (114/10 000). Periconceptional (4 weeks before through 8 weeks after conception) use of folic acid plus other supplements (54.8%), folic acid only (12.2%), and non–folic acid supplements (5.0%) were compared with no supplement use (28.0%); the adjusted relative risks of heart defects were 0.99 (95% CI, 0.80–1.22), 1.08 (95% CI, 0.93–1.25), and 1.07 (95% CI, 0.97–1.19), respectively. For initiation of folic acid in the preconception period weeks −4 to −1 (33.7%) and the postconception periods 0 to 4 weeks (15.5%), 5 to 8 weeks (17.8%), and 9 to 12 weeks (4.6%), compared with no or late folic acid intake (29.1%), relative risks of heart defect were 1.11 (95% CI, 1.00–1.25), 1.09 (95% CI, 0.95–1.25), 0.98 (95% CI, 0.86–1.12), and 0.97 (95% CI, 0.78–1.20), respectively. Relative risks of severe defects, conotruncal defects, and septal defects showed similar results.ConclusionsFolic acid was not associated with offspring risk of heart defects, including severe defects, conotruncal defects, or septal defects.

Association of maternal disease and medication use with the risk of congenital heart defects in offspring: a case-control study using logistic regression with a random-effects model.

Objective To examine the association between maternal diseases and congenital heart defects (CHDs) and to evaluate whether those associations vary with corresponding medication use. Methods A multi-hospital case-control study conducted from February 2010 to December 2014 analysed 916 controls and 1236 cases. Participating mothers were asked whether they suffered from influenza, common cold, herpes and threatened abortion or had used corresponding medication during the periconception period or the early pregnancy period. We used a random-effects logistic regression model to compute the odds ratios (ORs), adjusted odds ratios (AORs) and 95% confidence intervals (CIs) while controlling for potential confounders. Results Compared with the results for mothers with no exposure, there were significant associations between maternal diseases with medication non-use and CHDs in the aggregate, including influenza (AOR, 1.83; 95% CI, 1.13-2.95), common cold (AOR, 2.05; 95% CI, 1.60-2.64) and herpes (AOR, 7.00; 95% CI, 2.15-22.84). There was no significant association between medication users and offspring with any subtype of CHDs, except that maternal common cold with medication use slightly increased the risk of the specific subtype, namely, isolated cardiac defects. However, an association was observed between maternal threatened abortion and medication and isolated cardiac defects (AOR, 1.33; 95% CI, 1.01-1.75). Conclusion Maternal influenza, common cold, herpes and threatened abortion from 3 months before pregnancy through the first trimester were associated with an increased risk of congenital heart disease in offspring. The teratogenic effect of these conditions may be attenuated by medication use, except for threatened abortion.

Novel mutations of AXIN2 identified in a Chinese Congenital Heart Disease Cohort

Congenital heart defects (CHDs), the most common congenital human birth anomalies, involves complex genetic factors. Wnt/β-catenin pathway is critical for cardiogenesis and proved to be associated with numerous congenital heart abnormities. AXIN2 has a unique role in Wnt/β-catenin pathway, as it is not only an important inhibitor but also a direct target of Wnt/β-catenin pathway. However, whether AXIN2 is associated with human CHDs has not been reported. In our present study, we found a differential expression of Axin2 mRNA during the development of mouse heart, indicating its importance in mouse cardiac development. Then using targeted next-generation sequencing, we found two novel case-specific rare mutations [c.28 C > T (p.L10F), c.395 A > G (p.K132R)] in the sequencing region of AXIN2. In vitro functional analysis suggested that L10F might be a loss-of-function mutation and K132R is a gain-of-function mutation. Both mutations disrupted Wnt/β-catenin pathway and failed to rescue CHD phenotype caused by Axin2 knockdown in zebrafish model. Collectively, our study indicates that rare mutations in AXIN2 might contribute to the risk of human CHDs and a balanced canonical Wnt pathway is critical for cardiac development process. To our knowledge, it is the first study of AXIN2 mutations associated with human CHDs, providing new insights into CHD etiology.

Intake of sucrose-sweetened soft beverages during pregnancy and risk of congenital heart defects (CHD) in offspring: a Norwegian pregnancy cohort study.

Studies report increased risk of congenital heart defects (CHD) in the offspring of mothers with diabetes, where high blood glucose levels might confer the risk. We explored the association between intake of sucrose-sweetened soft beverages during pregnancy and risk of CHD. Prospective cohort data with 88,514 pregnant women participating in the Norwegian Mother and Child Cohort Study was linked with information on infant CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. Risk ratios were estimated by fitting generalized linear models and generalized additive models. The prevalence of children with CHD was 12/1000 in this cohort (1049/88,514). Among these, 201 had severe and 848 had non-severe CHD (patent ductus arteriosus; valvular pulmonary stenosis; ventricular septal defect; atrial septal defect). Only non-severe CHD was associated with sucrose-sweetened soft beverages. The adjusted risk ratios (aRR) for non-severe CHD was 1.30 (95% CI 1.07-1.58) for women who consumed 25-70ml/day and 1.27 (95% CI 1.06-1.52) for women who consumed ≥ 70ml/day when compared to those drinking ≤ 25ml/day. Dose-response analyses revealed an association between the risk of non-severe CHD and the increasing exposure to sucrose-sweetened soft beverages, especially for septal defects with aRR = 1.26 (95% CI 1.07-1.47) per tenfold increase in daily intake dose. The findings persisted after adjustment for maternal diabetes or after excluding mothers with diabetes (n = 19). Fruit juices, cordial beverages and artificial sweeteners showed no associations with CHD. The findings suggest that sucrose-sweetened soft beverages may affect the CHD risk in offspring.

Congenital Heart Defects in Children Born to Women with Systemic Lupus Erythematosus in Dubai, a Nested Case-Control Study pf Ajch Patient Records between 2015-2017

It has been speculated by some studies that the exposure to systemic lupus erythematosus (SLE) in utero may lead to the development of congenital heart defects (CHD) in the growing fetus. The evidence we have on the truth of this correlation is weak and needs to be elucidated. We determined to study whether children who are born to women with SLE have an increased risk of CHD when compared to children born to women without SLE.

Interaction between MTHFR Polymorphisms and Maternal Age Increases the Risk of Congenital Heart Defects in Down Syndrome

Interaction between MTHFR Polymorphisms and Maternal Age Increases the Risk of Congenital Heart Defects in Down Syndrome

Сongenital diseases of the heart among newborn children: genetic aspects

Congenital heart defects are a heterogeneous group of diseases that occur as isolation or a part of multiple birth defects, gene disorders or chromosomal abnormalities. Chromosomal abnormalities and its underlying syndromes are the cause of 6 to 36% of cases of congenital heart defects. Monogenic etiology is proven in about 8% of cases, and the main group - about 90% of the congenital heart defects is the result of an unfavorable combination of genetic predisposition and external factors. The causes of early neonatal infant mortality are dominated by incompatible birth defects: almost 26% of perinatal and neonatal deaths are associated with congenital child pathology. Heart defects compose about 30% of all birth defects. They rank first place among the diseases that lead to perinatal mortality and early disability. World statistics show that the incidence of birth defects in the world is 9 per 1000 newborns, in Europe - 8/1000, which is 4 times more frequent than neural tube defects and 6 times higher than chromosomal abnormalities. In Ukraine, about 5,000 children with congenital heart defects are born each year, and the total number of those children on dispensary records reaches more than 45,000. Knowledge about the prevalence of birth defects in the region is needed to develop new information markers of the risk of congenital pathology of the circulatory system for women of reproductive age. Data on the incidence of congenital heart defects of fetuses and newborns in the region will allow the creation of a database for follow-up studies, which will facilitate the timely identification of pregnant women at risk. This will improve the prognosis of pregnancy, reduce the level of perinatal pathology, which will have a significant medical and social effect. The data obtained will allow to create preconditions for improvement of approaches to the definition of risk groups of perinatal pathology, perfection of specialized care for pregnant women with risk of congenital heart defects of the fetus.

Maternal Overweight and Obesity and Risk of Congenital Heart Defects

BackgroundCongenital heart defects are more frequent in offspring of mothers with overweight or obesity. However, associations between maternal overweight and obesity, and risks of complex and specific heart defects are not clear. ObjectivesThis study sought to analyze associations between maternal overweight and obesity severity and rates of complex and specific heart defects. MethodsThis was a population-based cohort study in Sweden, including 2,050,491 live singleton infants born between 1992 and 2012. Data on maternal and infant characteristics, and diagnoses of congenital heart defects were retrieved from nationwide registries. Maternal body mass index (BMI) was categorized as underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5 to <25 kg/m2), overweight (BMI 25 to <30 kg/m2), obesity class I (BMI 30 to <35 kg/m2), class II (BMI 35 to <40 kg/m2), and class III (BMI ≥40 kg/m2). Outcomes included complex heart defects (tetralogy of Fallot, transposition of the great arteries, atrial septal defects [ASD], aortic arch defects, and single-ventricle heart) and subgroups of specific heart defects diagnosed up to 5 years of age. The authors calculated adjusted prevalence rate ratios (PRRs) with 95% confidence intervals. ResultsA total of 28,628 (1.40%, N = 2,050,491) children had at least 1 congenital heart defect. PRRs of aortic arch defects increased with maternal obesity severity. Compared with offspring of normal weight mothers, PRRs of aortic arch defects and transposition of the great arteries were doubled in offspring of mothers with severe obesity. PRRs of ASD and persistent ductus arteriosus in term infants increased with maternal BMI. ConclusionsPRRs of aortic branch defects, ASD, and persistent ductus arteriosus increase with maternal obesity severity.

236: Micro RNA expression profile in pregnant women complicated fetuses with muscular ventricular septal defects

Ventricular septal defects (VSD) account for 20% of congenital heart defects (CHDs) and the pathogenesis and molecular mechanism have not been elucidated. MicroRNAs (miRs) are small single-stranded, non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Recent research demonstrated that miRs help regulate embryonic cardiac development, cardiac mophogenesis, and cardiomyocyte growth and differentiation and are closely related to the occurrence of CHDs. This study aimed to measure differences in miR expression in maternal serum in patients complicated with fetal muscular VSD. This was a prospective study including fetuses at risk for CHD (pregestational diabetes, anticonvulsant use, or history of cardiac defects) during 2nd trimester echocardiographic examination. Fetuses without cardiac abnormalities were marked as control. Fetuses with isolated mVSD were marked as abnormal. Maternal venous serum was collected, RNA extracted, and an expression profile of 797 human miRs was measured using NanoString nCounter technology as counts (molecules/100ng RNA). Expression levels of >2fold increase or <50% decrease compared to control were considered up- or downregulated, respectively. Placental-derived miRs within the entire expression profile were also evaluated separately. miRs profiling was obtained in 6 controls and 7 mVSDs cases. Expression levels ranged from 3-198 counts, indicating relatively low expression. The median count did not vary between normal (20.7) and mVSD (21.4). Of the 797, 12 miRs were significantly upregulated (Fig. 1) and 36 miRs downregulated (P<0.01 for both). There were no differences in expression among the 114 known placentally-derived miRs between groups. This study identifies a select serum miR expression profile in women with mVSD fetuses in the 2nd trimester that differs from women with normal fetuses. This approach may provide a quantitative screening tool for confirming fetal CHDs diagnosed by echocardiography. This will be valuable as a biomarker approach for early detection of fetal CHDs in the first trimester to aid diagnosis by fetal echocardiography.

Detecting moderate or complex congenital heart defects in adults from an electronic health records system.

The prevalence of moderate or complex (moderate-complex) congenital heart defects (CHDs) among adults is increasing due to improved survival, but many patients experience lapses in specialty care or their CHDs are undocumented in the medical system. There is, to date, no efficient approach to identify this population. To develop and assess the performance of a risk score to identify adults aged 20-60 years with undocumented specific moderate-complex CHDs from electronic health records (EHR). We used a case-control study (596 adults with specific moderate-complex CHDs and 2384 controls). We extracted age, race/ethnicity, electrocardiogram (EKG), and blood tests from routine outpatient visits (1/2009 through 12/2012). We used multivariable logistic regression models and a split-sample (4: 1 ratio) approach to develop and internally validate the risk score, respectively. We generated receiver operating characteristic (ROC) c-statistics and Brier scores to assess the ability of models to predict the presence of specific moderate-complex CHDs. Out of six models, the non-blood biomarker model that included age, sex, and EKG parameters offered a high ROC c-statistic of 0.96 [95% confidence interval: 0.95, 0.97] and low Brier score (0.05) relative to the other models. The adult moderate-complex congenital heart defect risk score demonstrated good accuracy with 96.4% sensitivity and 80.0% specificity at a threshold score of 10. A simple risk score based on age, sex, and EKG parameters offers early proof of concept and may help accurately identify adults with specific moderate-complex CHDs from routine EHR systems who may benefit from specialty care.

Increased maternal Body Mass Index is associated with congenital heart defects: An updated meta-analysis of observational studies

PurposeTo review and summarize the epidemiologic evidence on the association of maternal Body Mass Index (BMI) with risk of congenital heart defects (CHDs) and to assess the possible dose-response patterns. MethodsSix electronic databases were searched for eligible studies up to April 2018. The summary risk estimates were calculated using either the fixed-effect models or random-effect models. A dose-response meta-analysis was also performed to capture the shape of the observed association. Subgroup and sensitivity analysis were conducted to explore the potential heterogeneity moderators. ResultsTwenty-nine studies involving 99,205 CHDs cases among 6,467,422 participants were included in the meta-analysis. Mothers who were overweight (odds ratio [OR] = 1.07; 95% confidence intervals [CI]: 1.00–1.13) and obese (OR = 1.32; 95% CI: 1.21–1.43) had a significantly higher risk of total CHDs in their offspring when compared with those with normal weight. When obesity was further divided into class I (OR = 1.15; 95% CI: 1.11–1.20), class II (OR = 1.26; 95% CI: 1.18–1.34) and class III (OR = 1.42; 95% CI: 1.33–1.51) obesity, a significantly increased risk of total CHDs persisted. Different risks for specific CHD phenotypes were also found in different BMI categories. Furthermore, a nonlinear dose-response relationship between maternal BMI and risk of total CHDs was observed. Subgroup and sensitivity analyses identified the most relevant heterogeneity moderators. ConclusionThe increased maternal BMI is associated with the risk of developing CHDs in offspring. Severe obesity can play an independent role in the observed association, but the effect may be mediated by diabetes mellitus. Preventing obesity or excessive weight gain is a priority for CHDs prevention.

Applicability of Standardized Early Fetal Heart Examination in the Obese Population.

This study aimed to evaluate the impact of obesity on early evaluation of fetal cardiac landmarks using a standardized examination method at the time of nuchal translucency scan. This was a cross-sectional study of an ongoing prospective cohort at high risk for congenital heart defects. We used a standardized examination protocol using 2-dimensional sonography with power Doppler in the evaluation of fetal cardiac landmarks consisting of 4-chamber view, outflow tract relationship, and transverse arches view. The study population was stratified based on maternal body mass index into nonobese (<30 kg/m2 ) and obese (≥30 kg/m2 ). Groups were compared in terms of satisfactory evaluation of fetal cardiac landmarks, transvaginal sonography use, and scan times required for the evaluations. Subanalysis was performed by further categorizing obesity into nonmorbid obesity (30.0-39.9 kg/m2 ) and morbid obesity (≥40 kg/m2 ). A total of 190 patients were evaluated. Of these, 48.4% (n = 92) were obese. The most common indication for fetal cardiac assessment was maternal pregestational diabetes mellitus (42.6%). Transvaginal sonography was utilized in one nonobese woman (1.4%) and 11 obese women (12%) (P = .002). The satisfactory evaluation of 4-chamber view, outflow tract relationship, transverse arches view, and all views were not significantly different between groups (P > .05). The scan time was about 5 minutes longer in the obese group compared with nonobese group (P = .020). Obesity does not hamper early evaluation of fetal cardiac landmarks around the time of nuchal translucency scan. However, obese patients are more likely to require transvaginal examinations.