Diagnosis Of Congenital Heart Defects Research Articles

False-Positive Diagnosis of Congenital Heart Defects at First-Trimester Ultrasound: An Italian Multicentric Study.

Objective. Our objective was to assess the proportion of false-positive CHD cases at the first-trimester evaluation of the fetal heart, performed by experienced operators. Methods. This multicenter retrospective study included of pregnant women with suspicion of CHDs during first-trimester screening for aneuploidies. In all cases, the fetal heart assessments were performed by obstetricians with extensive experience in first-trimester scanning, following an extended protocol proposed by SIEOG national guidelines, which included an axial view of the fetal abdomen and chest to assess visceral situs and evaluation of the four-chamber view (4CV) and three-vessel trachea view (3VTV) with color Doppler. In all suspected cases, fetal echocardiography was offered within 16 and/or at 19-22 weeks' gestation. Results. From a population of 4300 fetuses, 46 CHDs were suspected. Twenty-four cases were excluded from this analysis because the parents opted for early termination of the pregnancies due to associated structural and/or genetic anomalies. For the remaining 22, echocardiography was performed by 16 weeks in 14 cases (64%) and after 16 weeks in 8 cases. In 19 cases (86.4%), a fetal cardiologist confirmed the presence of a CHD. In three cases (13%), the cardiac anatomy was found to be normal at the fetal echocardiography and postnatally. Conclusions. This study shows that the proportion of false-positive cases at the first-trimester ultrasound examination of the fetal heart, performed by experienced operators, may carry a higher risk of false-positive diagnosis than expected. Therefore, this issue must be discussed in instances where a CHD is suspected at the first-trimester screening.

Abstract 4139179: Is Prenatal Diagnosis Responsible for Differences in Timing to Postnatal Intervention for Critical Congenital Heart Defects?

Introduction: The relationships between prenatal diagnosis of congenital heart defects (CHDs) and outcomes are inconsistent. Some studies have shown that compared to postnatal diagnosis, prenatal diagnosis is associated with later surgical timing and worse outcomes. These findings could be due to confounding because more severe CHDs are likelier to be diagnosed on prenatal ultrasonography. To bypass this confounding, we evaluated prenatal diagnosis as a mediator. Aim: To evaluate whether prenatal diagnosis of CHD mediates the association between disease severity and timing to postnatal intervention. Hypothesis: Infants with severe CHD receive intervention sooner than those with mild CHD due to a higher prenatal diagnosis prevalence. Methods: This is a retrospective cohort study of all infants who received their initial cardiac catheterization or surgery between 0-60 days (i.e., critical CHD) at Ann&Robert H. Lurie Children’s Hospital of Chicago (2015-2021). Birthing individuals with inadequate prenatal care were excluded. The primary exposure variable was a three-level categorical variable derived from existing literature, categorizing disease severity based on anatomic factors (mild, moderate, and severe CHD). The outcome was age at intervention, i.e., cardiac catheterization or surgery, whichever occurred sooner, in days. The mediator variable was whether prenatal diagnosis occurred. Control variables included birth weight, sex, surgery during the COVID-19 pandemic, race, ethnicity, birth hospital’s level of perinatal care as designated by Illinois state, presence of a syndrome or non-cardiac abnormality, and insurance status. Results: In total, 429 parent-infant pairs met inclusion criteria; 68.3% had prenatal diagnosis and 28.4% had severe CHD. In adjusted analyses, compared to those with the mild CHD, those with moderate CHD had 40.0% higher probability of prenatal diagnosis (p<0.001) and on average, received intervention 14 days sooner (p=0.001). Those with severe CHD had a 59.5% higher probability of prenatal diagnosis (p<0.001), and on average received intervention 19 days sooner (p<0.001). In a mediation analysis, prenatal diagnosis accounted for 27.2% of the difference in surgical timing between moderate and mild disease, and 29.5% of the difference in surgical timing between severe and mild disease ( Figure 1 ). Conclusion: The relationship between CHD severity and timing to postnatal intervention is partly attributable to prenatal diagnosis.

Population-Based Estimates of the Prevalence of Children With Congenital Heart Disease and Associated Comorbidities in the United States.

Congenital heart defects (CHD) are the most common birth defects and previous estimates report the disease affects 1% of births annually in the United States. To date, CHD prevalence estimates are inconsistent due to varied definitions, data reliant on birth registries, and are geographically limited. These data sources may not be representative of the total prevalence of the CHD population. It is therefore important to derive high-quality, population-based estimates of the prevalence of CHD to help care for this vulnerable population. We performed a descriptive, retrospective 8-year analysis using all-payer claims data from Colorado from 2012 to 2019. Children with CHD were identified by applying International Classification of Diseases-Ninth Revision (ICD-9) and International Classification of Diseases-Tenth Revision (ICD-10) diagnosis codes from the American Heart Association-American College of Cardiology harmonized cardiac codes. We included children with CHD <18 years of age who resided in Colorado, had a documented zip code, and had at least 1 health care claim. CHD type was categorized as simple, moderate, and severe disease. Association with comorbid conditions and genetic diagnoses were analyzed using χ2 test. We used direct standardization to calculate adjusted prevalence rates, controlling for age, sex, primary insurance provider, and urban-rural residence. We identified 1 566 328 children receiving care in Colorado from 2012 to 2019. Of those, 30 512 children had at least 1 CHD diagnosis, comprising 1.95% (95% CI, 1.93-1.97) of the pediatric population. Over half of the children with CHD also had at least 1 complex chronic condition. After direct standardization, the adjusted prevalence rates show a small increase in simple severity diagnoses across the study period (adjusted rate of 11.5 [2012]-14.4 [2019]; P<0.001). The current study is the first population-level analysis of pediatric CHD in the United States. Using administrative claims data, our study found a higher CHD prevalence and comorbidity burden compared with previous estimates.

Genomic insights into prenatal diagnosis of congenital heart defects: value of CNV-seq and WES in clinical practice.

This study aimed to assess the efficiency of CNV-seq and WES in detecting genetic cause of congenital heart disease (CHDs) in prenatal diagnoses and to compare CNV detection rate between isolated and non-isolated CHD cases. We conducted a retrospective study of 118 Chinese fetuses diagnosed with CHD by prenatal ultrasound. Participants underwent CNV-seq and, if necessary, WES to detect chromosomal and single nucleotide variations. The overall detection rate for pathogenic or likely pathogenic chromosomal abnormalities was 16.9%, including 7.6% aneuploidies and 9.3% pathogenic/likely pathogenic copy number variations (CNVs), predominantly 22q11.2 deletion syndrome (54.4%). The sensitivity and specificity of CNV-Seq for detecting P/Lp CNVs were 95% and 100%, respectively. CNV-Seq offered a 6.7% improvement in detecting chromosomal abnormalities over karyotyping. WES further identified significant single nucleotide and small indel variations contributing to CHD in genes such as TMEM67, PLD1, ANKRD11, and PNKP, enhancing diagnostic yield by 14.8% in cases negative for CNVs. Non-isolated CHD cases exhibited higher rates of detectable chromosomal abnormalities compared to isolated cases (32.4% vs. 9.9%, p = 0.005), underlining the genetic complexity of these conditions. The combined use of CNV-seq and WES provides a comprehensive approach to prenatal genetic testing for CHDs, unveiling significant genetic cause that could impact clinical management and parental decision-making. This study supports the integration of these advanced genomic technologies in routine prenatal diagnostics to increase detection diagnostic yields of causal genetic variants associated with CHDs.

Congenital Heart Defects and Concurrent Diagnoses in Influenza Hospitalization in the Pediatric Health Information System Study, 2004-2019.

Influenza is associated with adverse outcomes in children, although modification by additional medical conditions is not well-documented. We aimed to compare outcomes in children with versus without congenital heart defects (CHDs) who were hospitalized for influenza. We retrospectively evaluated patients 1-18y hospitalized for influenza in the Pediatric Health Information (PHIS) databasefrom 2004to2019. Outcomes were compared by CHD presence and then by CHD severity (minor biventricular, major biventricular, and single ventricle disease) using log-binomial regression adjusted for propensity scores accounting for ageat admission, sex, and history of asthma. Outcomes included inpatient mortality, intensive care unit (ICU) admission, mechanical ventilation, and length of stay (LOS) > 12days. To evaluate foreffect modification by genetic diagnoses, analyses were repeated stratified by CHD and genetic diagnosis. Among 55,161 children hospitalized for influenza, 2369 (4.3%) had CHDs, including 963 with minor biventricular, 938 with major biventricular, and 468 with single ventricle CHDs. Adjusting for propensity scores, children with CHDs had higher mortality (4.1% versus 0.9%) compared to those without CHDs (risk ratio [RR] 2.5, 95% confidence interval [CI] 1.9-3.4). Children with CHDs were at higher risk of mechanical ventilation (RR 1.6, 95% CI 1.6-1.7), ICU admission (RR 1.9, 95% CI 1.8-2.1), and LOS > 12days (RR 2.2, 95% CI 2.0-2.3). Compared to those with neither CHD nor genetic condition, children with both had significantly higher risk of all outcomes, with the largest difference for LOS > 12days (RR 2.3, 95% CI 2.0-2.7). Children with CHDs hospitalized for influenza are particularly susceptible to adverse outcomes compared to those without CHDs. Future studies are needed to corroborate findings in light of influenza vaccination.

Surgical treatment of a newborn with critical aortic coarctation using palliative stenting: a case report

Introduction. Coarctation of the aorta (CoA) is a congenital severe narrowing of the aortic isthmus, which in turn is often accompanied by impaired organ perfusion or even cardiogenic shock. In newborns with critical CoA in the case of patent ductus arteriosus (PDA) closure, the clinical condition of patients with this congenital heart defect (CHD) sharply worsens and leads to multiple organ failure. In this group of children, mortality ranges from 30 to 50% of infant mortality from CHD. This case demonstrates the positive effect of palliative stenting of a narrowed section of the aorta, which made it possible to safely perform radical surgery for CHD.Case description. Nine-year-old male patient with body weight of 3,5 kg and body length of 53 cm was admitted to the clinic with a diagnosis of CHD: Critical CoA. Secundum atrial septal defect. PDA. Multiple organ failure. Taking into account the severe comorbidity status in the form of multiple organ failure, the high risk of necrotizing enterocolitis, case conference decided to perform a step-by-step CHD treatment as follows: palliative endovascular stenting of critical CoA, followed by radical surgery after stabilization of the patient's condition. The plan was successfully implemented.Conclusion. Сritical CoA stenting can be used as a bridge to radical surgery of the defect in newborns with multiple organ failure. This palliative intervention helps to stabilize the child for up to 3 weeks and more safely perform radical surgery of CoA.

P-772 Assisted reproductive technology and the risk of minor congenital heart defects in the newborn

Abstract Study question Are children conceived through assisted reproductive technology (ART) at higher risk of minor congenital heart defects (CHD) compared with naturally conceived (NC) children? Summary answer Contrary to previous studies children conceived through ART had similar risk of minor CHDs compared with children conceived naturally. What is known already Congenital heart defects (CHD) may precipitate cardiac arrhythmias, lead to thromboembolic events, culminate in heart failure or even sudden cardiac demise. A systematic review and meta-analysis showed an elevated odds ratio (OR) for diagnosis of any CHD among children conceived through in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) compared with NC children. Other studies indicate that ART is associated with an increased arterial blood pressure and vascular dysfunction in the pulmonary and systemic arterial vasculature. This association persists throughout childhood, adolescence, and early adulthood in individuals conceived through ART; this indicates a lasting impact on the cardiovascular circulatory system. Study design, size, duration The present study is a sub-study to the Copenhagen Baby Heart Study (CBHS), a prospective population-based cohort study of &amp;gt; 25 000 children born in the three main maternity wards in Copenhagen, Denmark, in 2016–2018. Transthoracic echocardiography (TTE) was performed on all children within 60 days of delivery and diagnosis of CHD was reviewed by a specialist in paediatric cardiology. Information regarding parental health, pregnancy, delivery, and the newborn was collected through Danish patient registries. Participants/materials, setting, methods This study includes all children conceived by ART in the CBHS (n = 1 784), and a matched group (1:4 by maternal age at birth) of NC children (n = 7 141). Exclusion criteria were genetic or chromosomal syndromes and heart surgery. Minor CHD was defined as an atrial (ASD) or ventricular septum defects (VSD), bicuspid aortic valve, coarctation of the aorta, pulmonary stenosis, or patent ductus arteriosus. We calculated ORs using logistic regression analyses. Main results and the role of chance The mean maternal age at birth was 34.9 (standard deviation [SD] ±4.4) and 35.1 years (SD ± 4.6) and the newborn mean age at TTE was 12.1 (SD ± 9.3) and 12.2 days (SD ± 9.4) in the ART and NC population, respectively. Parental CHD was registered in 40 (2.2 %) children in the ART group and 121 (1.7 %) in the NC group. Overall, 165 (9.2%) children conceived by ART and 611 (8.6%) NC children were diagnosed with a minor CHD. The most prevalent CHDs were VSD and ASD which accounted for 38.8 % and 35.2 % in children with CHD in the ART group, respectively, and 36.8 % and 33.9 % in children with CHD in the NC group. The unadjusted OR for minor CHD was 1.09 (95% CI 0.91–1.30). Adjustments for maternal age and parental CHD did not change the OR. There were no differences in ORs when stratifying by minor CHD type. We stratified by the method of ART: ICSI and IVF and frozen embryo transfer and fresh embryo transfer, and calculated risk of minor CHD comparing the methods and with NC children. We found no difference in any ORs, crude or adjusted. Limitations, reasons for caution Children born preterm, and children with severe minor and major CHDs, were underrepresented in the cohort indicating parents of such children chose not to participate in a research project that would include another hospital visit. Residual confounding is plausible because parental CHD diagnoses were retrieved from patient registries. Wider implications of the findings The number of children conceived through ART is increasing each year and previous research have found an increased risk of CHD in children conceived through ART. Our findings indicate no increased risk of minor CHD, providing comforting and significant information for advising individuals considering or undergoing ART treatment. Trial registration number NCT02753348

P-769 Congenital heart defects in children born after assisted reproductive technology: A large cohort study from the Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS)

Abstract Study question Are children conceived after assisted reproductive technology (ART) more likely to be born with congenital heart defects (CHDs) than those born after spontaneous conception (SC)? Summary answer Major CHDs and severe CHDs are associated with ART, with a higher risk in both ART-conceived singletons and multiples compared to singletons from SC. What is known already Children born after ART have higher risk of birth defects compared to children born after SC. Among these defects, CHDs hold the highest prevalence, accounting for about 50% of all major birth defects and affecting approximately 1-2% of children in the general population. Several cohort studies and systematic reviews, among these a recent review including 41 studies and in total 25,856 ART children, shows increased risk of CHDs in children born after ART. However, conflicting findings have been reported for specific CHDs. Study design, size, duration This Nordic registry-based cohort study included 7,747,637 liveborn children, with 171,735 conceived after ART. All liveborn children (singletons and multiples) in Denmark (1994–2014), Finland (1990–2014), Norway (1984–2015), and Sweden (1987–2015) were included. National data from ART registries, medical birth registries, patient registries, cause of death registries, and population registries were cross-linked. Participants/materials, setting, methods The International Classification of Diseases (ICD) versions 8, 9, 10 were used for selection of CHDs. Major and severe CHDs were defined according to European Concerted Action on Congenital Anomalies and Twins (EUROCAT). Outcomes were major CHDs, severe CHDs, six hierarchical CHD lesion groups, and ten selected major CHDs. CHD diagnoses were considered prenatally or within the first year of life in Denmark, Finland, Sweden, and prenatally or at birth in Norway. Main results and the role of chance Major CHDs occurred among 1.84% (n = 3159) children born after ART and among 1.15% (n = 86,824) children born after SC, with adjusted odds ratio (AOR) 1.36; 95% CI 1.31–1.41. Risk was highest in multiples, regardless of conception method. Severe CHDs were detected in 0.35% (n = 594) children born after ART and in 0.26% (n = 19,375) children born after SC; AOR 1.30; 95% CI 1.20–1.42. When analysing the risk of CHD for the specific groups of CHDs by the hierarchical classification, children born after ART had higher risk of CHDs than children born after SC for five of the six lesion groups: conotruncal defects, non-conotruncal defects, ventricular septal defect, atrial septal defects, and other CHDs. ART was further associated with an elevated risk in four of ten selected major CHDs. Major CHDs occurred among 1.62% (n = 2059) singletons born after ART and among 1.11% (n = 18,539) singletons born after SC; AOR 1.19; 1.14–1.24. The prevalence of severe CHDs was 0.31% (n = 399) among singletons born after ART and 0.25% (n = 18,539) among singletons born after SC; AOR 1.20; 95% CI 1.09–1.33. In singletons born after ART, no difference was seen between ICSI and IVF or between frozen and fresh embryo transfer for major CHDs or severe CHDs. Limitations, reasons for caution A main limitation in this study is the lack of information on CHDs in miscarriages, pregnancy terminations, and stillbirths. Another limitation is that information on specific techniques used in assisted reproduction was not available from Finland. Lastly, we did not have information on causes of infertility. Wider implications of the findings CHDs, although rare, imply severe risks. Our study reveals an association between ART and major CHDs. While most CHD-affected children survive to adulthood, high morbidity and mortality rates persist in childhood and adulthood. The potential benefit of fetal echocardiography screening in ART pregnancies, beyond routine obstetric ultrasound, remains uncertain. Trial registration number ISRCTN 11780826

Perspectives of Challenges in Counseling for Congenital Heart Defects.

Prior work regarding counseling patients about congenital heart defects (CHD) has focused on their perceptions about accurate communication of cardiac anatomy, and the emotional support received from the provider. The objectives of this study were to identify the additional CHD counseling-specific challenges and areas for future intervention, using a practical communication framework. This is a secondary analysis of qualitative data provided by caretakers of infants who received congenital heart surgery from 2019 to 2020 in the Chicagoland area. While the survey in the primary study pertained to barriers in obtaining prenatal diagnosis, respondents with both prenatal and postnatal diagnosis reported challenges to effective counseling. Qualitative data measuring counseling challenges were collected from semi-structured phone interviews. Thematic analysis was performed using an inductive approach. Themes were organized into five domains using SPIKES (Setting, Perception, Invitation, Knowledge, Empathy, and Summarize/Strategy), a previously validated framework to help clinicians effectively break bad news. Among 160 survey respondents, 35 (21.9%) reported a challenge during CHD counseling that they received. In total, 12 challenges were identified and spanned all six SPIKES domains. The three most common challenges were as follows: perception of repeated imaging studies for accurate diagnosis or management (n = 19, Knowledge), the lack of cardiologist presence at the time of initial CHD detection (n = 8, Setting), and insufficient information provided about the CHD diagnosis (n = 7, Knowledge). Patients perceive counseling as a key component of prenatal diagnosis of CHD and identify the challenges that exist at all stages of the counseling process. These findings suggest that effective counseling extends beyond conveying information about anatomy and prognosis.

Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects

Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. ClinicalTrials.gov Identifier: NCT02133573.

Maternal obesity, interpregnancy weight changes and congenital heart defects in the offspring: a nationwide cohort study

ObjectiveTo evaluate the association between maternal BMI and congenital heart defects (CHDs) in the offspring when including live births, stillbirths, aborted and terminated pregnancies and to investigate if maternal interpregnancy weight changes between the first and second pregnancy influences the risk of foetal CHDs.MethodsA nationwide cohort study of all singleton pregnancies in Denmark from 2008 to 2018. Data were retrieved from the Danish Foetal Medicine Database, which included both pre- and postnatal diagnoses of CHDs. Children or foetuses with chromosomal aberrations were excluded. Odds ratios were calculated with logistic regression models for CHDs overall, severe CHDs and five of the most prevalent subtypes of CHDs.ResultsOf the 547 105 pregnancies included in the cohort, 5 442 had CHDs (1.0%). Risk of CHDs became gradually higher with higher maternal BMI; for BMI 25-29.9 kg/m2, adjusted odds ratio (aOR) 1.17 (95% CI 1.10-1.26), for BMI 30-34.9 kg/m2, aOR 1.21 (95% CI 1.09-1.33), for BMI 35-39.9 kg/m2, aOR 1.29 (95% CI 1.11-1.50) and for BMI ≥ 40 kg/m2, aOR 1.85 (95% CI 1.54-2.21). Data was adjusted for maternal age, smoking status and year of estimated due date. The same pattern was seen for the subgroup of severe CHDs. Among the atrioventricular septal defects (n = 231), an association with maternal BMI ≥ 30 kg/m2 was seen, OR 1.67 (95% CI 1.13-2.44). 109 654 women were identified with their first and second pregnancies in the cohort. Interpregnancy BMI change was associated with the risk of CHDs in the second pregnancy (BMI 2 to < 4 kg/m2: aOR 1.29, 95% CI 1.09-1.53; BMI ≥ 4 kg/m2: aOR 1.36, 95% CI 1.08-1.68).ConclusionThe risk of foetal CHDs became gradually higher with higher maternal BMI and interpregnancy weight increases above 2 BMI units were also associated with a higher risk of CHDs.

Photon-counting computed tomography for paediatric congenital heart defects yields images of high diagnostic quality with low radiation doses at both 70 kV and 90 kV

BackgroundPhoton-counting computed tomography (PCCT) is a new clinical method that may show better diagnostic quality at lower radiation doses than conventional CT.ObjectiveTo investigate the diagnostic quality and radiation dose of paediatric cardiovascular PCCT for diagnosis of congenital heart defects at 70 kV and 90 kV.Materials and methodsThis retrospective assessment included clinical non-gated paediatric PCCT examinations for assessment of congenital heart defects. Radiation doses were recorded, and overall and specific diagnostic quality (1–4) were scored by four paediatric radiologists. Agreement, differences, and trends were assessed by percent rater agreement, intraclass correlation, Mann–Whitney tests, and Jonckheere-Terpstra tests.ResultsSeventy children with congenital heart defects were examined at 70 kV (n = 35; age 2 days–16 years; 63% boys) or 90 kV (n = 35; age 2 days–17 years; 51% boys). All observers gave a median score of 4 (high diagnostic quality) for both 70 kV and 90 kV, with no difference in median values between tube voltages (all P > 0.06). Agreement for overall scores was 66–94% for 70 kV and 60–77% for 90 kV. Agreement for specific scores was 80–97% for 70 kV and 83–89% for 90 kV. Size-dependent dose estimate was 0.68 mGy (0.25–2.02 mGy) for 70 kV and 1.10 mGy (0.58–2.71 mGy; P < 0.001) for 90 kV. Effective dose was 0.30 mSv (0.15–0.82 mSv) for 70 kV and 0.39 mSv (0.22–1.51 mSv; P = 0.01) for 90 kV.ConclusionPaediatric cardiovascular PCCT yields images for congenital heart defects of high diagnostic quality with low radiation dose at both 70 kV and 90 kV.

Fetal premature atrial contractions: natural course, risk factors and adverse outcome.

Fetal premature atrial contractions (PAC) are usually benign but may be associated with congenital heart defect (CHD) and tachyarrhythmia, which in turn carry a risk of cardiac failure and fetal death. We aimed to explore the frequency of adverse outcome and to identify risk factors for tachyarrhythmia in pregnancies complicated by fetal PAC. This was a retrospective cohort study of fetuses diagnosed with PAC at two academic centers in Amsterdam, The Netherlands, between 2007 and 2022. Cases with a congenital anomaly and those with a prior diagnosis of CHD or other arrhythmias were excluded. M-mode and Doppler tracings were reanalyzed and the frequency of PAC was recorded. The incidence of the following adverse outcomes was examined: underlying CHD not identified at the 20-week fetal anomaly scan, tachyarrhythmia, other arrhythmia, administration of antiarrhythmic therapy and death. Risk factors for tachyarrhythmia were analyzed using odds ratios (OR). In 24.1% of 1439 referred cases, PAC resolved before confirmation at the fetal medicine unit (FMU). Of the 939 included cases with confirmed PAC, the total incidence of adverse outcome was 6.8% (64/939). CHD was diagnosed in 14 (1.5% (95% CI, 0.9-2.5%)) cases, of which eight were diagnosed prenatally and six postnatally. Compared with baseline, the incidence of CHD was higher in the presence of fetal PAC (OR, 1.8 (95% CI, 1.0-3.3); P = 0.034). Tachyarrhythmia occurred prenatally and/or postnatally in 32 (3.4%) cases, of which eight (25.0%) showed signs of cardiac failure, and in 23 (71.9%) cases, antiarrhythmic therapy was required. No cases of tachyarrhythmia led to fetal or infant death. Risk factors for tachyarrhythmia were PAC with short runs of supraventricular tachycardia (OR, 98.7), blocked PAC (OR, 30.3), PAC in bigeminy (OR, 21.8), frequent PAC (one per 5-10 beats) (OR, 6.9), signs of cardiac failure (OR, 14.2) and the presence of a foramen ovale aneurysm (OR, 5.0). PAC are generally benign and often resolve spontaneously. However, fetuses with an irregular heart rhythm should be referred for advanced ultrasonography, which should focus on classifying the type of PAC and risk of adverse outcome. When risk factors for tachyarrhythmia are identified, weekly fetal heart-rate monitoring is advised until resolution of the PAC. In the absence of risk factors, standard obstetric care may be sufficient, with additional instructions to report reduced fetal movements. Should tachyarrhythmia or cardiac failure develop, referral back to the FMU is indicated. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Imaging of congenital heart defects with a focus on magnetic resonance imaging and computed tomography

Due to advances in diagnostics and therapy, the survival rate of patients with congenital heart defects is continuously increasing. The aim of this review is to compare various imaging modalities that are used in the diagnosis of congenital heart defects. Transthoracic echocardiography is the imaging method of choice in the presence of acongenital heart defect because of its wide availability and non-invasiveness. It can be complemented by transesophageal echocardiography, cardiac catheterization, computed tomography (CT), and magnetic resonance imaging (MRI) of the heart and vessels close to the heart. The radiation exposure of CT examinations of the heart is continuously decreasing because of improved technologies. MRI is also being continuously optimized, e.g., by the acquisition of MR angiographies without contrast medium application or athin three-dimensional (3D) visualization of the entire heart with the possibility of reconstruction in all spatial planes (whole-heart technique) as well as 2D to 4D flow. Due to the complexity of congenital heart defects and the variety of possible pathologies, the choice of imaging modality and its exact performance has to be coordinated in an interdisciplinary context and individually adapted.

Fetal cardiac screening: 1st trimester and beyond.

Congenital heart defects (CHD) are the most common birth defect and a leading cause of infant morbidity and mortality. CHD often occurs in low-risk pregnant patients, which underscores the importance of routine fetal cardiac screening at the time of the 2nd trimester ultrasound. Prenatal diagnosis of CHD is important for counseling and decision-making, focused diagnostic testing, and optimal perinatal and delivery management. As a result, prenatal diagnosis has led to improved neonatal and infant outcomes. Updated fetal cardiac screening guidelines, coupled with technological advancements and educational efforts, have resulted in increased prenatal detection of CHD in both low- and high-risk populations. However, room for improvement remains. In recent years, fetal cardiac screening for specific high-risk populations has started in the 1st trimester, which is a trend that is likely to expand over time. This review discusses fetal cardiac screening throughout pregnancy.

From phenotype to mechanism: Prenatal spectrum of NKAP mutation-related disorder and its pathogenesis inducing congenital heart disease.

NKAP mutations are associated with Hackmann-Di Donato-type X-linked syndromic intellectual developmental disorder (MRXSHD, MIM: #301039). Here, we elucidate the potential prenatal manifestation of NKAP mutation-associated disorder for the first time, alongside revealing the relationship between NKAP mutations and congenital heart defect (CHD) in the Chinese population. An NKAP mutation (NM_024528.4: c.988C>T, p.Arg330Cys) was identified in two foetuses presenting with CHD. Subsequent mechanistic exploration revealed a marked downregulation of NKAP transcription within HEK293T cells transfected with NKAP p.R330C. However, no significant change was observed at the protein level. Moreover, the mutation led to a dysregulation in the transcription of genes associated with cardiac morphogenesis, such as DHRS3, DNAH11 and JAG1. Additionally, our research determined that NKAP p.R330C affected Nkap protein intra-nuclear distribution, and binding with Hdac3. Summarily, our study strengthens NKAP mutations as a cause of CHD and prompts the reclassification of NKAP p.R330C as likely pathogenic, thereby establishing a prospective prenatal phenotypic spectrum that provides new insight into the prenatal diagnosis of CHD. Our findings also provide evidence of NKAP p.R330C pathogenicity and demonstrate the potential mechanism by which p.R330C dysregulates cardiac developmental gene transcription by altering Nkap intra-nuclear distribution and obstructing the interaction between Nkap and Hdac3, thereby leading to CHD.

Use of polygenic and clinical risk scores in wide spectrum congenital heart malformations: a diagnostic and therapeutic perspective

Worldwide, congenital heart defects (CHDs) are a leading cause of mortality and morbidity. Globally, the annual prevalence rate of CHDs is about 1.5 million. It is one of the most common life-threatening congenital malformations, with a visible difference between high-income countries (HICs) and developing countries. This difference may be attributed to the diagnostic facilities and interventions.1 Moreover, the use of genetic and clinical risk scores is less studied in this field compared to other diagnostic and therapeutic approaches. Thus, we comprehensively review the available literature on adult and pediatric syndromic or non-syndromic CHDs and propose limitations and future directions in this field. Risk factors for this fatal disease include genetic and environmental factors.2,3 Risk stratification based on prenatal diagnosis with genetic counseling has shown better clinical outcomes. The modified World Health Organization (mWHO) guidelines are among the first proposed for risk stratification based on clinical scores.4 The combination of polygenic risk scores (PRS) and clinical risk evaluation has been adopted in various populations as better diagnostic and therapeutic approaches for various diseases, including coronary artery disease,5 diabetes,6 obesity,7 and cancers.8,9 However, unlike these diseases, polygenic risk scores are rarely used for the genetic diagnosis of CHD patients. The clinical utility of polygenic risk scores for CHDs is still in the early stages and requires validation studies in different cohorts. Incorporating PRS into the clinical setting may improve CHD diagnosis and therapeutic strategies.10 Recently, an initial attempt was made to determine the clinical utility of polygenic risk scores in a large dataset of the European cohort. Data from this study suggested a high potential for PRS in distinguishing between clinical phenotypes (mild, moderate, and severe) of congenital heart malformations.11 Furthermore, this hypothesis was tested in patients with transposition of the great arteries (TGA) to assess the utility of risk stratification after arterial switch operation. The cumulative risk score was computed for single nucleotide polymorphisms (SNPs) that reached the threshold statistical significance of p&lt;1×10−5 in the initial analysis. Combined clinical and polygenic risk scores showed improved risk stratification in mild, moderate, and severe TGA phenotypes.12 Similarly, in another European cohort, the risk allele frequency was higher in the diseased group compared to the control group. However, statistical analysis suggested a non-significant association with p&gt;0.05. Interestingly, combined risk scores constructed for selected SNPs showed a significant association with the disease with a p-value of 0.002. This evidence further supports the hypothesis that the cumulative effect of polymorphisms has better diagnostic and therapeutic efficacy than individual SNPs.13 There are certain limitations to its clinical use. Firstly, social stigma and lack of awareness regarding this disease are major hurdles. Secondly, there is a need to recruit a large number of samples from different populations to validate the clinical utility of PRS. Additionally, a lack of resources in developing countries also contributes to fatal outcomes. We recommend conducting large cohort studies in different ethnic groups to predict better risk associations, develop better therapeutic strategies, and formulate management guidelines.

The Role of SHROOM3 in Congenital Heart Disease

Background and Hypothesis: Congenital heart defects (CHD) are the most common, and most frequently fatal birth defects, but most etiology remains unknown. We identified a patient with CHD and implicated a gene called SHROOM3. SHROOM3 binds Dishevelled2 which is the central cytoplasmic component of both canonical and noncanonical Wnt/planar cell polarity (PCP) signaling pathways. PCP drives cell movement and is important to embryogenesis and disruption causes CHD. We hypothesize CHD can result from SHROOM3-loss-of-function due to PCP disruption.&#x0D; Project Methods: To interrogate SHROOM3’s role in CHD and PCP we utilized an established in vivo SHROOM3-loss-of-function model, Shroom3 gene trap mice (Shroom3gt). We also utilized a loss-of-function model for PCP membrane component VANGL2, (Vangl2+/-). We assayed genetic interaction between Shroom3 and Vangl2 during cardiac development by crossing singly heterozygous null mice to produce compound heterozygous embryos, harvested embryos, and performed histologic analysis for cardiac defects. We also utilized a human in vitro SHROOM3-loss-of-function model, a CRISPR-Cas9 edited SHROOM3 knockout HELA cell line. We assayed cell movement using a scratch assay.&#x0D; Results: Compound heterozygous Shroom3+/gt;Vangl2+/- embryos had a three fold increase in heart defects compared to singly heterozygous Shroom3+/gt;Vangl2+/+ or Shroom3+/+;Vangl2+/- embryos (3 of 19 or 15.7%, versus 1 of 17 or 5.2%, and 1 of 19 or 4.8%, respectively), demonstrating a trend towards genetic interaction between SHROOM3 and VANGL2/PCP during cardiac development. The scratch assays demonstrated cell movement defects due to SHROOM3-loss-of-function consistent with increased cell movement.&#x0D; Conclusion and Potential Impact: We demonstrate SHROOM3 interacts with Wnt/PCP during cardiac development. Further interrogation of SHROOM3’s role in Wnt signaling will provide insight into the mechanisms by which a novel CHD candidate participates in cardiogenesis and will improve CHD diagnosis, management, and therapeutic development.

Patient-reported barriers to prenatal diagnosis of congenital heart defects: A mixed-methods study.

To ascertain patient-reported, modifiable barriers to prenatal diagnosis of congenital heart defects (CHDs). This was a mixed-methods study among caretakers of infants who received congenital heart surgery from 2019 to 2020 in the Chicagoland area. Quantitative variables measuring sociodemographic characteristics and prenatal care utilization, and qualitative data pertaining to patient-reported barriers to prenatal diagnosis were collected from electronic health records and semi-structured phone surveys. Thematic analysis was performed using a convergent parallel approach. In total, 160 caretakers completed the survey, 438 were eligible for survey, and 49 (31%) received prenatal care during the COVID-19 pandemic. When comparing respondents and non-respondents, there was a lower prevalence of maternal Hispanic ethnicity and a higher prevalence of non-English/Spanish-speaking households. Of all respondents, 34% reported an undetected CHD on ultrasound or echocardiogram, while 79% reported at least one barrier to prenatal diagnosis related to social determinants of health. Among those social barriers, the most common were difficulty with appointment scheduling (n=12, 9.5%), far distance to care/lack of access to transportation (n=12, 9.5%) and difficulty getting time off work to attend appointments (n=6, 4.8%). The latter two barriers were correlated. While technical improvements in the detection of CHDs remain an important area of research, it is equally critical to produce evidence for interventions that mitigate barriers to prenatal diagnosis due to social determinants of health.

Association Between Maternal Factors in Early Pregnancy and Congenital Heart Defects in Offspring: The Japan Environment and Children's Study.

Background Many prenatal factors are reported to be associated with congenital heart defects (CHD) in offspring. However, these associations have not been adequately examined using large-scale birth cohorts. Methods and Results We evaluated a data set of the Japan Environmental and Children's Study. The primary outcome was a diagnosis of CHD by age 2 years. We defined the following variables as exposures: maternal baseline characteristics, fertilization treatment, maternal history of diseases, socioeconomic status, maternal alcohol intake, smoking, tea consumption, maternal dietary intake, and maternal medications and supplements up to 12 weeks of gestation. We used multivariable logistic regression analysis to assess the associations between various exposures and CHD in offspring. A total of 91 664 singletons were included, among which 1264 (1.38%) had CHD. In multivariable analysis, vitamin A supplements (adjusted odds ratio [aOR], 5.78 [95% CI, 2.30-14.51]), maternal use of valproic acid (aOR, 4.86 [95% CI, 1.51-15.64]), maternal use of antihypertensive agents (aOR, 3.80 [95% CI, 1.74-8.29]), maternal age ≥40 years (aOR, 1.59 [95% CI, 1.14-2.20]), and high maternal hemoglobin concentration in the second trimester (aOR, 1.10 per g/dL [95% CI, 1.03-1.17]) were associated with CHD in offspring. Conclusions Using a Japanese large-scale birth cohort study, we found 6 maternal factors to be associated with CHD in offspring.