Cases Of Congenital Heart Defects Research Articles

A low incidence of preoperative neurosonographic abnormalities in neonates with heart defects

Background and aimTo investigate whether neonates with prenatally detected congenital heart defects (CHD) demonstrate cerebral abnormalities on early preoperative cranial ultrasound (CUS), compared to healthy neonates, and to measure brain structures to assess brain growth and development in both groups. Study design, subjects and outcome measuresProspective cohort study with controls. Between September 2013 and May 2016 consecutive cases of prenatally detected severe isolated CHD were included. Neonatal CUS was performed shortly after birth, before surgery and in a healthy control group. Blinded images were reviewed for brain abnormalities and various measurements of intracranial structures were compared. ResultsCUS was performed in 59 healthy controls and 50 CHD cases. Physiological CUS variants were present in 54% of controls and in 52% of CHD cases. Abnormalities requiring additional monitoring (both significant and minor) were identified in four controls (7%) and five CHD neonates (10%). Significant abnormalities were only identified in four CHD neonates (8%) and never in controls. A separate analysis of an additional 8 CHD neonates after endovascular intervention demonstrated arterial stroke in two cases that underwent balloon atrioseptostomy (BAS). Cerebral measurements were smaller in CHD neonates, except for the cerebrospinal fluid measurements, which were similar to the controls. ConclusionsThe prevalence of significant preoperative CUS abnormalities in CHD cases was lower than previously reported, which may be partially caused by a guarding effect of a prenatal diagnosis. Arterial stroke occurred only in cases after BAS. As expected, neonates with CHD display slightly smaller head size and cerebral growth.

The rate of undetectable genetic causes by Cell-free DNA test in congenital heart defects

Objective The study aimed to estimate the rate of genetic causes that were undetectable by Cell-free DNA (cfDNA) test in prenatally diagnosed congenital heart defect (CHD) cases based on an assumption that cfDNA would accurately detect common aneuploidies including trisomy 21/18/13/45X, and del22q11.2. Methods This study included prenatally diagnosed CHD cases with diagnostic genetic results. The possibility of false-positive/negative results from cfDNA testing was discarded. Thus, cfDNA results would be positive in common aneuploidies or del22q11.2 and negative in normal diagnostic genetic testing results or other genetic conditions. The rate of genetic causes that were undetectable by cfDNA test was estimated for all cases as well as for CHD subgroups. Results Of 302 cases, 98 (34.8%) had a type of genetic abnormalities, with 67 having common aneuploidies or del22q11.2 and 31 having other genetic conditions. The rate of genetic causes that were undetectable by cfDNA test in CHD cases was 13.2% among those with assumingly negative cfDNA screen results and 10.3% among the entire study population. These rates were similar between CHD subgroups (p > .05). The rate of genetic causes that were undetectable by cfDNA test was higher in the non-isolated cases than in the isolated ones among those with assumingly negative-screen results (20.5% and 9.9%, respectively, p = .025). Conclusion In prenatally diagnosed CDH cases, a significant number of chromosomal abnormalities are still identified after diagnostic testing even if cfDNA screen is negative, and thus it is important to extensively counsel patients with negative cfDNA screen carrying a CHD-affected fetus.

Category II Fetal Monitoring in Fetuses With Congenital Heart Defects: Are They Any Different? [06O

INTRODUCTION: The majority of literature investigating continuous electronic fetal monitoring (EFM) excludes anomalous fetuses. The objective of this study was to determine if Category II EFM characteristics differed between fetuses with and without congenital heart defects (CHD). METHODS: This was a retrospective IRB-approved cohort study of singleton, term pregnancies admitted for induction or labor with an antenatal diagnosis of fetal CHD between 2017–2019. We excluded fetuses with genetic abnormalities. Cases were matched by race and obesity in a 1:2 ratio to a historic control of term pregnancies with structurally normal fetuses. EFM characteristics in the 1 hour before delivery were extracted. The primary outcome was incidence of Category II EFM features; secondary outcome was total deceleration area (TDA). RESULTS: 47 cases of fetal CHD were matched to 94 controls. There was no difference in advanced maternal age, other baseline demographics, or mode of delivery between groups. Fetuses with CHD were less likely to have prolonged decelerations (6.4 vs 25.5%, P<.01) or any periods of tachycardia (4.3 vs 17.0, p 0.03) compared to normal fetuses. Other Category II features were similar between groups including incidence of recurrent late and variable decelerations and minimal variability. There was no difference in TDA between groups. CONCLUSION: Prolonged decelerations and tachycardia were less common in CHD fetuses. The incidence of other Category II features were similar to nonanomalous fetuses. These results suggest that structural heart defects do not increase the risk of concerning EFM patterns. Future studies should evaluate the risk of acidemia with Category II EFM and CHD.

Maternal dietary fat intake and the risk of congenital heart defects in offspring.

BackgroundFatty acids are crucial in embryologic development, including cardiogenesis. The impact of maternal periconceptional dietary fat intake on the risk of congenital heart defects (CHDs) has not been clearly elucidated. We hypothesized that maternal dietary fat intake during pregnancy is associated with risk of CHDs in offspring.MethodsWe analyzed CHD cases and non-malformed controls from the National Birth Defects Prevention Study, a case-control, multicenter population-based study of birth defects. We used multivariable logistic regression to analyze the association between maternal periconceptional dietary fat intake and occurrence of CHDs.ResultsWe examined 11,393 infants with CHDs (cases) and 11,029 infants without birth defects (controls). Multivariable analysis of maternal dietary fat intake adjusted for maternal energy intake demonstrated modest change in risk for 2 of the 25 CHDs analyzed; otherwise there was no association. Maternal dietary fat intake unadjusted for total energy was associated with increased risk for several CHDs.ConclusionAfter adjusting for total energy intake, maternal periconceptional dietary fat intake has a modest association with risk of a few specific CHDs. If maternal dietary fat intake does impact CHD risk, the effect is minimal.

Special statement: Proposed quality metrics to assess accuracy of prenatal detection of congenital heart defects

Congenital heart defects are a leading cause of neonatal morbidity and mortality. Accurate prenatal diagnosis of congenital heart defects can reduce morbidity and mortality by improving prenatal care, facilitating predelivery pediatric cardiology consultation, and directing delivery to facilities with resources to manage the complex medical and surgical needs of newborns with congenital heart defects. Unfortunately, less than one half of congenital heart defect cases are detected prenatally, resulting in lost opportunities for counseling, shared decision-making, and delivery at an appropriate facility. Quality improvement initiatives to improve prenatal congenital heart defects detection depend on the ability to measure the rate of detection at the level of providers, facilities, or populations, but no standard metric exists for measuring the detection of congenital heart defects at any level. The need for such a metric was recognized at a Cooperative Workshop held at the 2016 Annual Meeting of the Society for Maternal-Fetal Medicine, which recommended the development of a quality metric to assess the rate of prenatal detection of clinically significant congenital heart defects. In this paper, we propose potential quality metrics to measure prenatal detection of critical congenital heart defects, defined as defects with a high rate of morbidity or mortality or that require surgery or tertiary follow-up. One metric is based on a retrospective approach, assessing whether postnatally diagnosed congenital heart defects had been identified prenatally. Other metrics are based on a prospective approach, assessing the sensitivity and specificity of prenatal diagnosis of congenital heart defects by comparing prenatal ultrasound findings with newborn findings. Potential applications, limitations, challenges, barriers, and value for both approaches are discussed. We conclude that future development of these metrics will depend on an expansion of the International Classification of Diseases system to include specific codes that distinguish fetal congenital heart defects from newborn congenital heart defects and on the development of record systems that facilitate the linkage of fetal records (in the maternal chart) with newborn records.

Maternal air pollution exposure associated with risk of congenital heart defect in pre-pregnancy overweighted women

ObjectivesPrenatal exposure to air pollutant has been associated with congenital heart defect (CHD). However, no study has investigated this effect in pre-pregnancy overweighted women. This study aimed to evaluate gestational exposure to particulate pollutant (PM2.5) and gaseous air pollutants (O3 and NO2) on the risk of CHD, and explore the potential effect modifiers including maternal age, pre-pregnancy BMI and pregestational diseases. MethodsIn this birth cohort study, a total of 63,213 pregnant women in Foshan, China were initially recruited and followed from their first hospital visit for pregnancy to delivery during 2015–2019. CHD cases were confirmed by the records in hospital- and population- based birth defect surveillance systems. Air pollutant exposures were estimated by the daily concentrations measured in air monitoring stations in each participant's residential county. Mixed-effects regression models, adjusted for potential confounding factors were applied to estimate the associations between air pollutant and CHD during the first three months of the pregnancy. ResultsA total of 985 (1.6%) newborns were identified as CHD cases. For each 10 μg/m3 increase in ambient O3 during the 1st month, the OR values for CHD were 1.03 (95% CI: 0.94, 1.13) in pre-pregnancy normal weighted women and 1.24 (95% CI: 1.01, 1.53) in pre-pregnancy overweighted women. For each 10 μg/m3 increase in NO2 during the 3rd month, the OR values for CHD were 1.09 (95% CI: 1.01, 1.18) in pre-pregnancy normal weighted women and 1.27 (95% CI: 1.07, 1.51) in pre-pregnancy overweighted women. No significant associations were found between PM2.5 exposure and CHD in our analysis. ConclusionsThis study demonstrates that gaseous air pollutants (O3 and NO2) exposure during the cardiac embryogenesis period is associated with an increased risk of CHD, particularly for pre-pregnancy overweighted women.

The 3-vessel view as a means of screening for conotruncal malformations

Prenatal detection of fetal anomalies allows the adequate counseling of the parents regarding the pregnancy and the neonatal prognosis. This is especially true in the case of congenital heart defects where counseling the parents is essential, given the high neonatal mortality of such anomalies. Conotruncal malformations are made up of a wide variety of congenital heart defects with abnormal ventriculoarterial connections and represent up to 30% of all cases of congenital heart defects. The most common types of conotruncal malformations are tetralogy of Fallot, transposition of great arteries, double outlet right ventricle, common arterial trunk, but numerous anatomical variants exist. The 3-vessel view can be used as an alternative to the ventricular outflow tract views to detect conotruncal malformations and may be used as a screening test. To test this hypothesis, we evaluated the 3-vessel view in both normal cases and cases of conotruncal malformations. As expected, in the 30 normal cases we reviewed, all the criteria for a normal 3-vessel view were met. In the 15 cases of conotruncal malformations (tetralogy of Fallot, transposition of great arteries, double outlet right ventricle, common arterial trunk) that we investigated, at least one criterion for a normal 3-vessel view was not met. This goes to show the utility the 3-vessel view can have in the screening for conotruncal malformations

162: Congenital cardiac defects and placental vascular malperfusion

There is growing evidence that abnormal early angiogenesis impacts pathogenesis of maternal hypertensive disorders, fetal growth restriction and congenital heart defects (CHD). The aim of this retrospective case control study is to assess the frequency of placental vascular malperfusion in congenital heart defects. Singleton pregnancies with isolated fetal CHD and delivery after 32 weeks that necessitated intervention with catheterization and or surgery in the first year of life were recruited from the Pediatric Cardiology database from April 2016 to April 2019. A control group without any congenital anomalies or diabetes, chronic hypertension, gestational hypertension, or preeclampsia were recruited from the Pathology data base. CHD was classified as groups: 1. right single ventricle morphology, 2. left single ventricle morphology, 3. transposition of the great vessels (TGA), 4. other conotruncal CHD, and 5. other CHD. Placental histopathology was classified as fetal vascular malperfusion (FVM), maternal vascular malperfusion (MVM), both FVM and MVM and neither. Chi square and t test were used as appropriate for statistical analysis. There were 37 patients and 45 controls included in the study. The CHD group had a decreased birth weight (BW) as compared to the control group. Placental vascular malperfusion and fetal vascular malperfusion were significantly increased in the CHD cases (33 % vs 62 %, Table 1). When compared to other CHD groups combined, CHD Groups 1 and 2 had a trend for any vascular malperfusion (80% vs 50%, p=0.09), (Table 2). Placental malperfusion overall and FVM were increased in CHD. These findings suggest interactions of the fetal cardiac and placental development pathways.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Genetic Variants at the rs4720169 Locus of TBX20 and the rs12921862 Locus of AXIN1 May Increase the Risk of Congenital Heart Defects in the Mexican Population: A Pilot Study.

Background: Congenital heart defects (CHDs) are the most common type of birth defects and a major cause of infant mortality. Although knowledge of genetic risk variants for CHDs is scarce, most cases of CHDs are considered to be due to multifactorial inheritance. Objective: To analyze the association of 14 single nucleotide polymorphic variants previously associated with a risk of CHDs in a Mexican population with isolated CHDs. Materials and Methods: DNA samples obtained from healthy subjects and from subjects with isolated atrial, ventricular, or atrioventricular septal defects living in Northeastern Mexico were analyzed by real time-polymerase chain reaction for allelic discrimination of genetic variants of the genes TBX1, TBX20, ASTX-18-AS1, AXIN1, MTHFR, NKX2.5, BMP4, and NFATc1. The odds ratios (ORs) for allele and genotype frequencies and inheritance models were obtained. Results: Forty-two patients and 138 controls were included. Two variants were found to confer a risk of CHDs: variant rs4720169 of TBX20 in which the OR for the heterozygous state was 1.88 (95% confidence interval [CI]: 1.12-3.14, p = 0.010), whereas the OR for the homozygous state was 3.82 (95% CI: 1.18-12.3, p = 0.010); and variant rs12921862 of AXIN1 in which the OR for the heterozygous state was 4.15 (95% CI: 2.42-7.10; p ≤ 0.001), whereas the OR for the homozygous state was 9.2 (95% CI: 1.31-64.7, p = 0.008) for allele A. Conclusion: Genetic variants of the TBX20 and AXIN1 genes confer a significantly increased risk of congenital septal heart defects in a population from Northeastern Mexico.

Cortical development in fetuses with congenital heart defects using an automated brain-age prediction algorithm.

Congenital heart defects are associated with neurodevelopmental delay. It is hypothesized that fetuses affected by congenital heart defect have altered cerebral oxygen perfusion and are therefore prone to delay in cortical maturation. The aim of this study was to determine the difference in fetal brain age between consecutive congenital heart defect cases and controls in the second and third trimester using ultrasound. Since 2014, we have included 90 isolated severe congenital heart defect cases in the Heart And Neurodevelopment (HAND)-study. Every 4weeks, detailed neurosonography was performed in these fetuses, including the recording of a 3D volume of the fetal brain, from 20weeks onwards. In all, 75 healthy fetuses underwent the same protocol to serve as a control group. The volumes were analyzed by automated age prediction software which determines gestational age by the assessment of cortical maturation. In total, 477 volumes were analyzed using the age prediction software (199 volumes of 90 congenital heart defect cases; 278 volumes of 75 controls). Of these, 16 (3.2%) volume recordings were excluded because of imaging quality. The age distribution was 19-33weeks. Mixed model analysis showed that the age predicted by brain maturation was 3days delayed compared with the control group (P=.002). This study shows that fetuses with isolated cases of congenital heart defects show some delay in cortical maturation as compared with healthy control cases. The clinical relevance of this small difference is debatable. This finding was consistent throughout pregnancy and did not progress during the third trimester.

Maternal risk factors for congenital heart defects in infants with Down syndrome from Western Mexico.

Atrioventricular septal defects (AVSDs) have been identified as intriguingly infrequent among Hispanics with Down syndrome (DS) born in the United States. The aim of this study was to evaluate the effect of possible maternal risk factors in the presence of congenital heart defects (CHDs) in Mexican infants with DS. A total of 231 live birth infants born with DS during 2009-2018 at the "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara (Guadalajara, Mexico) were ascertained in a case-control study. Patients with DS with any major CHD were included as cases and those without major CHD as controls. Potential risk factors were analyzed using logistic regression. Of eligible infants with DS, 100 (43.3%) had ≥1 major CHDs (cases) and were compared with a control group of 131 infants (56.7%) with DS without CHDs. Prevalent CHDs were ostium secundum atrial septal defects (ASDs) (46.9%), ventricular septal defects (27.3%), and AVSDs (14%). Lack of folic acid supplementation before pregnancy had a significant risk for CHDs in infants with DS (adjusted odds ratio [aORs] = 2.9 (95% confidence interval [95% CI]: 1.0-8.6) and in the analysis by subtype of CHDs, also, for the occurrence of ASDs (aOR = 11.5, 95% CI: 1.4-94.4). Almost half of the infants with DS in our sample had CHDs, being ASD the commonest subtype and AVSD the rarest. Our ethnic background alone or in concomitance with observed nutritional disadvantages seems to contribute differences in CHD subtype rates in our DS patients.

The Combined Use of Ultrasound and Fetal Magnetic Resonance Imaging for a Comprehensive Fetal Neurological Assessment in Fetal Congenital Cardiac Defects: Scientific Impact Paper No. 60.

Heart problems are common in newborn babies, affecting approximately 5-10 in 1000 babies. Some are more serious than others, but most babies born with heart problems do not have other health issues. Of those babies who have a serious heart problem, almost 1 in 4 will have heart surgery in their first year. In the UK, pregnant women are offered a scan at around 20weeks to try and spot any heart problems. In most cases there is not a clear reason for the problem, but sometimes other issues, such as genetic conditions, are discovered. In recent years the care given to these babies after they are born has improved their chances of surviving. However, it is recognised that babies born with heart problems have a risk of delays in their learning and development. This may be due to their medical condition, or as a result of surgery and complications after birth. In babies with heart problems, there is a need for more research on ultrasound and magnetic resonance imaging (MRI) to understand how the brain develops and why these babies are more likely to have delays in learning and development. This paper discusses the way ultrasound and MRI are used in assessing the baby's brain. Ultrasound is often used to spot any problems, looking at how the baby's brain develops in pregnancy. Advances in ultrasound technologies have made this easier. MRI is well-established and safe in pregnancy, and if problems in the brain have been seen on ultrasound, MRI may be used to look at these problems in more detail. While it is not always clear what unusual MRI findings can mean for the baby in the long term, increased understanding may mean parents can be given more information about possible outcomes for the baby and may help to improve the counselling they are offered before their baby's birth.

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.

Fetuses with Isolated Congenital Heart Defects Show Normal Cerebral and Extracerebral Fluid Volume Growth: A 3D Sonographic Study in the Second and Third Trimester

Objective: The aim of our study is to explore whether the cerebral growth is delayed in fetuses with congenital heart defects (CHD) in the second and early third trimester. Methods: A prospective cohort study was conducted in 77 CHD cases, with 75 healthy controls. 3D cerebral volume acquisition was performed sequentially. The volumes of the fetal hemicerebrum and extracerebral fluid were compared by linear regression analysis, and the Sylvian fissure was measured. Results: Between 19 and 32 weeks of gestation, 158 measurements in cases and 183 measurements in controls were performed (mean 2.2/subject). The volume growth of the hemicerebrum (R² = 0.95 vs. 0.95; p = 0.9) and the extracerebral fluid (R² = 0.84 vs. 0.82, p = 0.9) were similar. Fetuses with abnormal oxygen delivery to the brain have a slightly smaller brain at 20 weeks of gestation (p = 0.02), but this difference disappeared with advancing gestation. CHD cases demonstrated a slightly shallower Sylvian fissure (mean ratio 0.146 vs. 0.153; p = 0.004). Conclusions: Our study shows no differences in cerebral growth, studied in an unselected cohort, with successive cases of isolated CHD. Even in the severest CHD cases, cerebral size is similar in the early third trimester. The cause and meaning of a shallower Sylvian fissure is unclear; possibly, it is a marker for delayed cerebral maturation or it might be an expression of decreasing amount of extracerebral fluid.

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.

889: Utility of Noninvasive Prenatal Testing (NIPT) in evaluation of Congenital Heart Defects (CHD)

NIPT side steps many of the issues associated with invasive fetal testing, and has become a popular screening tool in assessing chromosome abnormalities when fetal anomalies are identified. Our clinical experience suggested NIPT has low yield in fetuses with heart defects. This study describes the utility of NIPT in specific classes of congenital heart disease. Retrospective chart analysis identified pregnancies with isolated (I) or non-isolated (NI) fetal CHD. Inclusion criteria: confirmed cardiac diagnosis, prenatal NIPT results known, abnormal postnatal chromosome results. CHDs were classified based on their embryological development: 1) hypoplastic left heart (HLH); 2) transposition of great arteries (TGA); 3) truncus arteriosus (TA); 4) conotruncal defects (CT); 5) atrioventricular septal defect (AVSD); 6) muscular septal defects (mVSD); 7) right aortic arch (RAA); 8) coarctation of aorta (CoA)/interrupted aortic arch (IAA); and, 9) right sided defects. Utility of NIPT was defined as the chance NIPT could provide a causative diagnosis for the CHD ( T21, T18, T13, 45,X, triploidy, del22q11.2) to the patient to supplant invasive testing in confirmed (I) and (NI) CHD groups Eighty two babies with abnormal chromosomes were studied, 57 with isolated defects and 25 with both cardiac and extracardiac abnormality. Table 1 shows the percentage of cases predicted accurately by NIPT, ordered by CHD class. The highest utility of NIPT in (I) and (NI) cases was in cases with TA or AVSD, 100% and 94.4%, respectively. NIPT gave no valuable information in isolated HPLH, TGA, or RAA. Overall yield of NIPT was 64% for isolated CHD, 70.7% for non-isolated cases. Genetic conditions not identified by NIPT in NI CHD cases include microarray abnormalities and single gene conditions (Noonan syndrome). Two cases of aortic coarctation were diagnosed with mosaic Turner syndrome; the technology of NIPT may be limited in mosaic cases. NIPT has satisfactory (although not complete) utility in AVSD and CT abnormalities more often associated with standard aneuploidies. A low-risk result from NIPT does not eliminate microarray abnormality for all other types of CHD and is not reliable enough to substitute for invasive fetal testing. Invasive procedures have modest associated risks, but the additional information they provide may be key for families and healthcare providers. The CHD category is an important factor to consider if NIPT is offered as an option.

Expression profile of maternal circulating microRNAs as non-invasive biomarkers for prenatal diagnosis of congenital heart defects

ObjectiveThe discovery of cell free fetal microRNAs (miRNAs) in maternal circulation has opened up novel probabilities for non-invasive prenatal diagnosis. This study aims to investigate circulating miRNAs as potential biomarkers in the serum of pregnant women with congenital heart defect (CHD) fetuses. MethodA total of 110 pregnant women including 50 CHD cases and 60 healthy controls were included in this study. miRNA microarray followed by real-time PCR was used to explore miRNA expression. Receiver operating characteristic (ROC) curves were calculated to assess the diagnostic capability of miRNAs for fetal CHDs. Results38 Serum miRNAs were revealed to be differentially expressed in the CHD group as compared to control group via microarray. Among these, nine down-regulated and three up-regulated miRNAs were validated by real-time PCR. Ten of these miRNAs were rapidly reduced in the normal maternal serum after delivery as compared to before delivery. In particular, we identified a biomarker panel consisting of four miRNAs (miR-142-5p, miR-1275, miR-4666a-3p and miR-3664-3p) capable of distinguishing CHDs from controls (area under the ROC curve (AUC), 0.920; p < 0.0001). ConclusionThe discovery of these dysregulated pregnancy-associated miRNAs in maternal serum may be potential biomarkers for non-invasive prenatal diagnosis of fetal CHDs.

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.

The Exposure Science Aspects of the Re-Envisioning of the (U.S.) National Library of Medicine's Toxicology and Environmental Health Resources

Background/Objective: High ambient temperature is shown to influence birth outcomes, however, few studies have assessed heat&amp;#8217;s effect during the fetal development period on congenital heart defects (CHDs), especially in transitional seasons. We examined and compared the associations between extreme heat and CHD phenotypes in summer and spring, assessed their geographical differences, and compared different heat indicators.Methods: We identified all 5,848 CHD cases and 5,742 controls (without major structural defects) from the National Birth Defects Prevention Study, a United States (U.S.) multicenter population-based case-control study. Extreme heat events (EHEs) were defined by using 95th (EHE95) or 90th (EHE90) percentile of daily maximum temperature and its frequency and duration during postconceptional weeks 3-8. We used a two-stage Bayesian hierarchical model to examine both regional and study-wide associations. Exposure odds ratios (ORs) were calculated using multivariate logistic regression analyses, while controlling for potential confounding factors.Results: Overall, we observed no consistent relationships between maternal EHE exposure and CHDs in most regions. However, we found that 3-11 days of EHE90 in both summer and spring was significantly associated with ventricular septal defects (VSDs) study-wide (ORs ranged: 2.17-3.24). EHE95 in spring were significantly associated with conotruncal defects and VSDs in the South (ORs: 1.23-1.78). Most EHE indicators in spring were significantly associated with increased septal defects (VSDs and atrial septal defects (ASDs)) in the Northeast.Conclusion: While generally null results were found, longer heat durations were associated with increased risks for VSDs and ASDs, mainly in the South and Northeastern U.S., as well as transitional months in spring when using multiple heat indicators. Further research is needed to confirm our findings.

Functionally significant, novel GATA4 variants are frequently associated with Tetralogy of Fallot.

Transcription factor GATA4 is known to play crucial role during heart development, regulating expression of several other key cardiogenic factors. Various GATA4 mutations are reported in familial as well as sporadic cases of congenital heart defects (CHDs). To estimate the prevalence and pathogenic potential of GATA4 variants in our CHD cohort, we have screened 285 CHD cases along with 200 controls by Sanger sequencing and identified 9 genetic variants (c.23C>A; p.Ala8Asp, c.25G>A; p.Ala9Thr, c.223G>T; p.Ala75Ser, c.383A>T; p.Glu128Val, c.397A>T; p.Ser133Cys, c.682T>A; p.Trp228Arg, c.1064C>G; p.Thr355Ser, c.1073G>C; p.Ser358Thr, and c.1220C>A; p.Pro407Gln) in 22 unrelated CHD probands (frequency:7.72%). Five of these are novel and located in the N-terminal transactivation domain (TAD) and first zinc finger domain. Majority C-terminal domain variants are polymorphic. Two of the TAD variants p.Glu128Val, p.Ser133Cys, and a first zinc finger variant p.Trp228Arg, impair combinatorial synergy of NKX2-5, SRF, and TBX5, suggesting potential role of these domains in GATA4 interactions with these factors. Decreased DNA-binding affinity with EMSA also supports this observation. Homology modeling and tertiary structure comparison show conformational changes in these variants. Interestingly, GATA4 variants are more frequently associated with ToF (45%; P=0.0046) and PS (22.7%; P<0.0001) in spite of abundance of septal defects in our study cohort.