Major Congenital Heart Disease Research Articles

Clinical implementation of first trimester screening for congenital heart defects.

To examine the feasibility and performance of implementing a standardized fetal cardiac scan at the time of a routine first-trimester ultrasound scan. A retrospective, single-center study in an unselected population between March 2021 and July 2022. A standardized cardiac scan protocol consisting of a four-chamber and 3-vessel trachea view with color Doppler was implemented as part of the routine first-trimester scan. Sonographers were asked to categorize the fetal heart anatomy. Data were stratified into two groups based on the possibility of evaluating the fetal heart. The influence of maternal and fetal characteristics and the detection of major congenital heart disease were investigated. A total of 5083 fetuses were included. The fetal heart evaluation was completed in 84.9%. The proportion of successful scans increased throughout the study period from 76% in the first month to 92% in the last month. High maternal body mass index and early gestational age at scan significantly decreased the feasibility. The first-trimester detection of major congenital heart defects was 7/16, of which four cases were identified by the cardiac scan protocol with no false-positive cases. First-trimester evaluation of the fetal heart by a standardized scan protocol is feasible to implement in daily practice. It can contribute to the earlier detection of congenital heart defects at a very low false positive rate.

Natural History of Secundum ASD in Preterm and Term Neonates: A Comparative Study.

Atrial septal defects(ASDs) are common in neonates. Although past studies suggest ASDs ≥ 3mm in term neonates(TNs) are less likely to close, there is paucity of data regarding the natural history in preterm neonates(PNs), information that would inform surveillance. We sought to compare spontaneous closure rates and need for intervention for ASDs in TNs/near term (≥ 36weeks) versus PNs (< 36weeks). We included all TNs and PNs who underwent echocardiography at ≤ 1month between 2010 and 2018 in our institution with an ASD ≥ 3mm, without major congenital heart disease, and with repeat echocardiogram(s). Spontaneous resolution was defined as size diminution to < 3mm or closure. We included 156 TNs (mean gestational age at birth 38.6 ± 1.4weeks) and 156 PNs (29.6 ± 3.7weeks) with a mean age at follow-up of 16 ± 19 and 15 ± 21months, respectively (p = 0.76). Based on maximum color Doppler diameter, in TNs, ASD resolution occurred in 95% of small (3-5mm), 87% of moderate (5.1-8mm), and 60% of large (> 8mm) defects; whereas, in PNs, resolution occurred in 79% of small, 76% of moderate, and 33% of large ASDs. There was a significant association between size and ASD resolution in TNs (p = 0.003), but not PNs (p = 0.17). Overall, ASD resolution rate was higher in TNs (89%) versus PNs (78%) (p = 0.009), and fewer TNs (1%) compared to PNs (7%) required ASD intervention (p = 0.02). Most ASDs identified in TNs and PNs spontaneously resolve. PNs, however, demonstrate lower ASD resolution and higher intervention rates within all size groups. These data should inform follow-up of affected neonates.

Navigating Neonatal Cardiovascular Emergencies: A Comprehensive Narrative Review on Assessment and Intervention Strategies

Abstract The evaluation and management of congenital heart diseases (CHDs) in neonates are pivotal aspects of pediatric care given the substantial prevalence of this condition. This review emphasizes the urgency of timely recognition and intervention, as a notable proportion of affected neonates face critical illness shortly after birth. The multidisciplinary approach involving neonatologists, pediatricians, and obstetricians is essential to address the diagnostic and therapeutic challenges inherent in neonatal cardiac emergencies. The insights presented herein aim to guide medical practice, enhance early recognition, and ultimately improve outcomes for newborns grappling with critical heart conditions. Key proactive measures advocated include prenatal screening, facilitating early identification of potential cardiac anomalies. Advanced imaging techniques, such as fetal echocardiography, have a crucial role in enabling detailed examinations, contributing to the prenatal diagnosis of major CHDs. The review underscores the importance of preparing medical teams during the prenatal period for potential postnatal complications, emphasizing the necessity of a holistic approach to the care of neonates who survive critical episodes. Continued research and clinical advancements remain imperative to refine strategies and optimize care for this vulnerable patient population. The provided data serve as a valuable guide for healthcare professionals and could improve the outcomes of neonates confronting the challenges of CHD.

Risk of major congenital heart disease in pregestational maternal diabetes is modified by hemoglobin A1c.

The association between pregestational diabetes mellitus (PDM) and risk of congenital heart disease (CHD) is well recognized; however, the importance of glycemic control and other coexisting risk factors during pregnancy is less clear. We sought to determine the relative risk (RR) of major CHD (mCHD) among offspring from pregnancies complicated by PDM and the effect of first-trimester glycemic control on mCHD risk. We determined the incidence of mCHD (requiring surgery within 1 year of birth or resulting in pregnancy termination or fetal demise) among registered births in Alberta, Canada. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c) at < 16 weeks' gestation and other covariates was performed using data from the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted RR (aRR), calculated using log-binomial modeling. Of 1412 cases of mCHD in 594 773 (2.37/1000) births in the study period, mCHD was present in 48/7497 with PDM (6.4/1000; RR, 2.8 (95% CI, 2.1-3.7); P < 0.0001). In the entire cohort, increased maternal age (aRR, 1.03 (95% CI, 1.02-1.04); P < 0.0001) and multiple gestation (aRR, 1.37 (95% CI, 1.1-1.8); P = 0.02) were also associated with mCHD risk, whereas maternal prepregnancy weight > 91 kg was not. The stratified risk for mCHD associated with HbA1c ≤ 6.1%, > 6.1-8.0% and > 8.0% was 4.2/1000, 6.8/1000 and 17.1/1000 PDM/gestational diabetes mellitus births, respectively; the aRR of mCHD associated with PDM and HbA1c > 8.0% was 8.5 (95% CI, 5.0-14.4) compared to those without diabetes and 5.5 (95% CI, 1.6-19.4) compared to PDM with normal HbA1c (≤ 6.1%). PDM is associated with a RR of 2.8 for mCHD, increasing to 8.5 in those with HbA1c > 8%. These data should facilitate refinement of referral indications for high-risk pregnancy screening. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Pediatric ECG-Based Deep Learning to Predict Left Ventricular Dysfunction and Remodeling.

Artificial intelligence-enhanced ECG analysis shows promise to detect ventricular dysfunction and remodeling in adult populations. However, its application to pediatric populations remains underexplored. A convolutional neural network was trained on paired ECG-echocardiograms (≤2 days apart) from patients ≤18 years of age without major congenital heart disease to detect human expert-classified greater than mild left ventricular (LV) dysfunction, hypertrophy, and dilation (individually and as a composite outcome). Model performance was evaluated on single ECG-echocardiogram pairs per patient at Boston Children's Hospital and externally at Mount Sinai Hospital using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC). The training cohort comprised 92 377 ECG-echocardiogram pairs (46 261 patients; median age, 8.2 years). Test groups included internal testing (12 631 patients; median age, 8.8 years; 4.6% composite outcomes), emergency department (2830 patients; median age, 7.7 years; 10.0% composite outcomes), and external validation (5088 patients; median age, 4.3 years; 6.1% composite outcomes) cohorts. Model performance was similar on internal test and emergency department cohorts, with model predictions of LV hypertrophy outperforming the pediatric cardiologist expert benchmark. Adding age and sex to the model added no benefit to model performance. When using quantitative outcome cutoffs, model performance was similar between internal testing (composite outcome: AUROC, 0.88, AUPRC, 0.43; LV dysfunction: AUROC, 0.92, AUPRC, 0.23; LV hypertrophy: AUROC, 0.88, AUPRC, 0.28; LV dilation: AUROC, 0.91, AUPRC, 0.47) and external validation (composite outcome: AUROC, 0.86, AUPRC, 0.39; LV dysfunction: AUROC, 0.94, AUPRC, 0.32; LV hypertrophy: AUROC, 0.84, AUPRC, 0.25; LV dilation: AUROC, 0.87, AUPRC, 0.33), with composite outcome negative predictive values of 99.0% and 99.2%, respectively. Saliency mapping highlighted ECG components that influenced model predictions (precordial QRS complexes for all outcomes; T waves for LV dysfunction). High-risk ECG features include lateral T-wave inversion (LV dysfunction), deep S waves in V1 and V2 and tall R waves in V6 (LV hypertrophy), and tall R waves in V4 through V6 (LV dilation). This externally validated algorithm shows promise to inexpensively screen for LV dysfunction and remodeling in children, which may facilitate improved access to care by democratizing the expertise of pediatric cardiologists.

Anorectal malformations (ARM) and VACTERL association and severity of congenital heart diseases (CHD): Experience of 396 consecutive patients in a tertiary center

ObjectiveCongenital heart diseases (CHD) are the most frequently associated anomalies with anorectal malformations (ARM). Nevertheless, many specific aspects of CHD in ARM patients have yet to be studied. The aims of this study were to evaluate the prevalence and distribution of CHD in neonates-infants with ARM, and to explore whether the severity of ARM, and the presence of VACTERL association, had an impact on CHD rate, severity, and timing at first cardiac surgery. Study designAll consecutive newborn-infants with ARM managed in our tertiary center (January-1999; December-2021) were collected from a prospective database and retrospectively analyzed. Prevalence and distribution of CHD in ARM patients were assessed. Patients were divided into groups depending on ARM severity and presence of VACTERL association. Pairwise comparison for CHD prevalence, severity, and timing at first cardiac surgery was performed between groups. ResultsOf 396 ARM patients identified, those with severe ARM showed a higher number of overall CHD compared to patients with non-severe ARM (36.7 % vs. 25.2 %, p = 0.032). VACTERL + patients had a significantly higher prevalence of CHD (73.4 % vs. 16.4 %; p <0.001) and major CHD (51.7 % vs. 26.9 %; p = 0.008) when compared with VACTERL-patients. Furthermore, VACTERL + patients underwent first cardiac surgery at a significantly younger age than VACTERL-patients (5.2 ± 15.2 months vs. 11.9 ± 6.3, p = 0.039). ConclusionsPatients with severe ARM had a higher number of CHD compared to patients with non-severe ARM. VATERL + patients had significantly more CHD and more severe CHD than VACTERL-patients. Early screening for CHD is strongly recommended in all newborns diagnosed with ARM before surgery. Level of evidenceIII retrospective comparative study.

Temporal trend in hospitalization among patients with congenital heart disease in Denmark: a nationwide study

Abstract Background The survival rate of patients with congenital heart disease (CHD) had increased over the last decades due to improved management. However, the increased survival rate may potentially impact the number of occurrences of late cardiac complications as well as non-cardiovascular diseases requiring hospitalization, and hence warrants further study on this area. Purpose To delineate the temporal trend in hospitalization rate and length of stay (LOS) among patients with major and minor CHD in Denmark from 1977 to 2018 and to investigate the causes of hospitalization. Methods A Danish nationwide, population-based registry study including patients with CHD diagnosis from 1977 to 2018. Patients were categorized as either major or minor CHD, and by age groups (&amp;lt;1, 1-4, 5-17, 18-39, 40-64, ≥65 years). Hospitalization rate was reported as incidence per 100 person-years. Results In this study, 23,386 patients were included with 121,653 hospital admissions. From 1977-1981 to 2012-2018, the overall all-cause hospitalization rate decreased for both major (51.7 [CI: 48.0 -55.7] to 32.8 [CI: 31.0 - 34.7]) and minor CHD patients (28.4 [CI: 26.0 - 31.0] to 22.6 [CI: 21.1 - 24.1]). Median LOS for major CHD decreased from 5 days (IQR: 2 – 11) to 2 days (IQR: 1 – 6), and for minor CHD from 4 days (IQR: 2 – 8) to 2 days (IQR: 1 – 5). However, the trends when looking at specific age groups were different from the trend of overall all-cause hospitalization rate. Figure 1 shows that hospitalization rate had increased significantly for &amp;lt;1-year-olds for major CHD, whereas an increased trend was observed for &amp;lt;1, 40-64 and ≥65 years-olds for minor CHD. In addition, the trends for specific age groups when looking at the most common causes were also different from the trend of all-cause hospitalization rate. For both major and minor CHD, Table 1 shows that the hospitalization rate for &amp;lt;1-year-olds due to respiratory diseases had increased over time, while the hospitalization rate for 40-64-year-olds due to arrythmia had also increased over time. For ≥65-year-olds, significant increase in hospitalization rate for arrythmia was only observed for minor CHD. Conclusion Lower hospitalization rate for major and minor CHD after 1 year old suggests that early intervention of CHD has improved their morbidity during childhood and early adulthood. However, the increased hospitalization rates among &amp;lt;1 year-olds and the elderly suggest that more focus are needed in preventing non-cardiovascular diseases and late cardiac complications for the respective age groups.Figure 1Table 1

Echocardiographic nomograms for left ventricular parameters in 13,454 infants

Abstract Background Cardiac dimensions and function are key parameters in the management of children with cardiopulmonary abnormalities and are important predictors of clinical outcome. In particular, left ventricular (LV) dimensions and function are important predictors of clinical outcome and prognosis. In pediatric echocardiography, nomograms are essential in the separation of normal variation from pathological conditions and ascertaining normal growth. However, data from cohorts of newborns are limited, and current nomograms remain an insufficient approximation of the range of values that should be considered normal. Purpose We developed nomograms and Z scores for two-dimensional echocardiographic measurements of LV structure and function in a large group of healthy newborns. Methods Our study population included newborns from a large population study of newborns (n &amp;gt;25,000) who were born at term to healthy mothers, had a systematic transthoracic echocardiogram (TTE) performed within 30 days of birth, and with no signs of any major congenital heart diseases. We developed nomograms for 10 LV parameters by modelling these parameters as a function of body surface area (BSA) through joint modelling of the mean, standard deviation, skewness, and kurtosis. We then evaluated the impact of infant sex and age at time of echocardiography on the model fit. Results The 13,454 infants in the study population (48.5% females), had a median age of 12 days at TTE for both boys and girls (interquartile range IQR 8–15 and 8–12 days, respectively), and a median BSA of 0.23 m2 (IQR 0.22 m2 - 0.24 m2). All nomograms had acceptable goodness-of-fit within strata of sex. In contrast, model fit was worse for infants examined &amp;lt;7 days of age, compared with those examined from 7 to 30 days of age, necessitating the creation of separate nomograms for the two age groups. Examples of the plotted Z scores of one of the 10 LV parameters is shown in the figure. Conclusions We provide a large normative dataset and Z scores for echocardiographic measures of LV structure and function in neonates. Normative data is crucial in the management of patients with heart disease and these results provide a needed tool for evaluation of LV size and function in the newborn population.Plotted Z scores of the IVSd

Abstract 18941: Pediatric Electrocardiogram-Based Deep Learning to Predict Left Ventricular Dysfunction and Remodeling

Background: Artificial intelligence-enhanced ECG algorithms show promise to detect a range of adult phenotypes, inclusive of ventricular dysfunction and remodeling. However, it remains unclear whether similar approaches provide meaningful and generalizable predictions in children. Methods: We trained a convolutional neural network on paired ECG-echos (≤ 2 days apart) from patients ≤ 18 years old without major congenital heart disease to detect human expert classified greater than mild left ventricular (LV) dysfunction, hypertrophy, and dilation (individually and as a composite outcome). Model performance was assessed by calculating area under the receiver operating curve (AUROC) in an internal test set and external setting (emergency department). Results: The main cohort comprised of 119,787 ECG-echo pairs (61,722 patients; median age 8.3 [IQR, 2.9-13.8] years; 55% male). Training, internal test, and external test sets comprised of 92,377, 24,343, and 3,067 ECG-echo pairs with 8.2%, 7.7%, and 10.0% composite outcome rates, respectively. During internal testing, AUROCs of 0.84 [95% CI, 0.83-0.85], 0.87 [95% CI, 0.85-0.88], 0.86 [95% CI, 0.84-0.87], and 0.84 [95% CI, 0.83-0.86] were achieved for the LV composite outcome, dysfunction, hypertrophy, and dilation, respectively (Figure). During external testing, AUROCs of 0.80 [95% CI, 0.77-0.83], 0.84 [95% CI, 0.80-0.88], 0.77 [95% CI, 0.72-0.82], and 0.86 [95% CI, 0.82-0.89] were achieved, respectively (Figure). Similar model performance was achieved when using quantitative z-score cutoffs for each outcome. Exploratory saliency mapping provides insight into notable ECG components that influence model predictions. Conclusions: Our artificial intelligence-enhanced pediatric ECG algorithm shows promise to inexpensively screen for and diagnose LV dysfunction or remodeling in children. Prospective trials to guide model implementation for supporting clinical decision making are warranted.

Prevalence and detection rate of major congenital heart disease in twin pregnancies in Denmark.

To investigate the national prevalence and prenatal detection rate (DR) of major congenital heart disease (mCHD) in twin pregnancies without twin-to-twin transfusion syndrome (TTTS)-associated CHD in a Danish population following a standardized prenatal screening program. This was a national registry-based study of data collected prospectively over a 10-year period. In Denmark, all women with a twin pregnancy are offered standardized screening and surveillance programs in addition to first- and second-trimester screening for aneuploidies and malformation, respectively: monochorionic (MC) twins every 2 weeks from gestational week 15 and dichorionic (DC) twins every 4 weeks from week 18. The data were retrieved from the Danish Fetal Medicine Database and included all twin pregnancies from 2009-2018, in which at least one fetus had a pre- and/or postnatal mCHD diagnosis. mCHD was defined as CHD requiring surgery within the first year of life, excluding ventricular septal defects. All pregnancy data were pre- and postnatally validated in the local patient files at the four tertiary centers covering the entire country. A total of 60 cases from 59 twin pregnancies were included. The prevalence of mCHD was 4.6 (95% CI, 3.5-6.0) per 1000 twin pregnancies (1.9 (95% CI, 1.3-2.5) per 1000 live births). The prevalences for DC and MC were 3.6 (95%CI, 2.6-5.0) and 9.2 (95%CI, 5.8-13.7) per 1000 twin pregnancies, respectively. The national prenatal DR of mCHD in twin pregnancies for the entire period was 68.3%. The highest DRs were in cases with univentricular hearts (100%) and the lowest with aortopulmonary window, total anomalous pulmonary venous return, Ebstein's anomaly, aortic valve stenosis and coarctation of the aorta (0-25%). Mothers of children with prenatally undetected mCHD had a significantly higher body mass index (BMI) compared to mothers of children with a prenatally detected mCHD (median, 27 kg/m2 and 23 kg/m2 , respectively; P = 0.02). The prevalence of mCHD in twins was 4.6 per 1000 pregnancies and was higher in MC than DC pregnancies. The prenatal DR of mCHD in twin pregnancies was 68.3%. Maternal BMI was higher in cases of prenatally undetected mCHD. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Lower Socioeconomic Status is Associated with an Increased Incidence and Spectrum of Major Congenital Heart Disease and Associated Extracardiac Pathology.

Several studies have suggested an inverse relationship between lower socioeconomic status (SES) and the incidence of congenital heart disease (CHD) among live births. We sought to examine this relationship further in a Canada-wide population study, exploring CHD subtypes, trends, and associated noncardiac abnormalities. Infants born in Canada (less Quebec) from 2008 to 2018 with CHD requiring intervention in the first year were identified using ICD-10 codes through the Canadian Institute for Health Information Discharge Abstract Database. Births of CHD patients were stratified by SES (census-based income quintiles) and compared against national birth proportions using X2 tests. Proportions with extracardiac defects (ED) and nonlethal genetic syndromes (GS) were also explored. From 2008 to 2018, 7711 infants born with CHD were included. The proportions of major CHD distributed across SES quintiles were 27.1%, 20.1%, 19.2%, 18.6%, and 15.0% from lowest to highest, with significant differences relative to national birth proportions (22.0%, 20.0%, 20.6%, 20.7%, and 16.7% from lowest (1) to highest (5)) (p < 0.0001). No temporal trends in the CHD proportions across SES categories were observed over the study period. The distribution across SES quintiles was different only for specific CHD subtypes (double-outlet right ventricle (n = 485, p = 0.03), hypoplastic left heart syndrome (n = 547, p = 0.006), heterotaxy (n = 224, p = 0.03), tetralogy of Fallot (n = 1007, p = 0.008), truncus arteriosus (n = 126, p < 0.0001), and ventricular septal defect (n = 1916, p < 0.0001)), with highest proportions observed in the lowest quintile. The proportion of the total population with ED but not GS was highest in lower SES quintiles (< 0.0001) commensurate with increased proportion of CHD. Our study suggests a negative association between SES and certain CHD lesions and ED.

Placental Histopathologic Findings in the Setting of Prenatally Diagnosed Major Congenital Heart Disease

Objectives: Studies suggest an association between placenta and congenital heart disease (CHD). We evaluated placental pathologies associated with major CHD. Methods: A prospective study included fetuses with major CHD, identified by fetal echocardiography. Fetal Doppler of umbilical artery (UA), middle cerebral artery (MCA), and placental histopathology were assessed. Outcome was measured by mortality at one month of age. Results: 21 cases were analyzed. Hypoplastic left heart syndrome was the commonest lesion (23.8%). Significant differences were detected among categories regarding MCA systolic/diastolic (S/D) ratio & pulsatility index (p = 0.023; 0.036), respectively. Placental histopathologies were demonstrated in 18(85.7%), predominately involved fetal malperfusion lesions 16/21(76.2%), especially chorangiosis (33.3%). No significant association was detected between placental histopathological abnormalities and Doppler parameter, diagnostic category, or mortality. Conclusion: The high prevalence of abnormal placental histopathological findings in major fetal CHD provides additional evidence of placental-cardiac interlinkage. No association was detected between abnormal placental histopathology and fetal Doppler measurements or neonatal outcome of CHD.

Fetal congenital heart diseases: Diagnosis by anatomical scans, echocardiography and genetic tests

Objective: To determine the distribution of major fetal congenital heart diseases (CHDs) diagnosed antenatally during routine second-trimester obstetric anatomical scans in an unselected population at a single tertiary centre and to characterise and stratify risk factors, genetic diagnosis and long-term health at 4 years old. Method: A single-centre cohort study of all major fetal CHDs detected on routine obstetric fetal anatomical ultrasound scans between January 2014 and December 2017 was performed in an unselected population. Demographic details, fetal echocardiogram reports, genetic test results, delivery outcomes and postnatal progress were stratified by CHD subtype. Results: Of 20,031 screened pregnancies, 109 pregnancies (0.53%) had major fetal CHDs. The most common subtypes were coarctation of aorta (17.4%), transposition of great arteries (16.5%), and tetralogy of Fallot and univentricular hearts (13.8% each). Of the 60.5% that underwent confirmatory genetic testing—mostly conventional karyotyping and testing for 22q11 microdeletion—about a quarter had abnormalities, of which 22q microdeletion was the most common. We had complete obstetric data in 85 pregnancies (78%), of which 76.5% progressed to live birth. Among these, 92.1% of postnatal echocardiograms concurred with antenatal ones. At 4 years old, 43.2% of offspring had no medical or developmental issues, 20.0% had mild medical or developmental issues, 21.5% had major medical or developmental issues, and 12.3% had deceased. Conclusion: Fetal echocardiograms accurately diagnose CHDs. Future studies should evaluate the roles of chromosomal microarray and next-generation sequencing in diagnosing CHD.

Effect of assessing velocity time integral at different locations across ventricular outflow tracts when calculating cardiac output in neonates

This study aims to evaluate the effect of assessing velocity time integral at different locations across ventricular outflow tracts for calculating cardiac output (CO) in neonates. Velocity time integral (VTI) and CO were measured at 3 different locations across right and left ventricular outflow tracts using transthoracic echocardiography in healthy term neonates without any major congenital heart disease. ANOVA with Bonferroni correction was used to determine the differences between the VTI and CO sampled at these three locations. Forty-one neonates met inclusion criteria with mean gestational age of 38.6 ± 1 weeks and mean birth weight of 3155 ± 463 g. The median hours after birth when echocardiography was obtained was 23 h (range 11–68 h after birth). Left CO were 121 ± 30 mL/kg/min, 155 ± 38 mL/kg/min, and 176 ± 36 mL/kg/min measured below the valve, hinges of the valve, and tip of the valve, respectively. Right CO were 197 ± 73 mL/kg/min, 270 ± 83 mL/kg/min, and 329 ± 104 mL/kg/min measured below the valve, hinges of the valve, and tip of the valve, respectively. A statistically significant difference (P < 0.001) was found in the VTI and CO measured at the 3 different locations across both left and right ventricular outflow tracts. Conclusions: There is a significant difference in measurements of VTI and CO depending on the location of Doppler gate sampling across the ventricular outflow tracts. Consistency and precision in Doppler gate location are essential for measuring VTI and calculating CO while assessing changes in hemodynamic status in critically ill infants.What is Known:• Targeted Neonatal Echocardiography is increasingly applied to measure cardiac output in critically ill neonates and serial assessments are performed to assess the trend in changes in cardiac output.• Noninvasive measurement using velocity time integral to calculate cardiac output is commonly performed. However, location of Doppler sample gate to measure ventricular outflow tract velocity time integral is not consistent.What is New:• Statistically significant changes in measured velocity time integral and cardiac output are noted based on the location of Doppler gate sampling.• To monitor the cardiac output for trending, it is important to be consistent with regards to the location of the Doppler sample gate to assess changes in cardiac output in critically ill newborns.

Long-Term Postnatal Follow-Up in Monochorionic TTTS Twin Pregnancies Treated with Fetoscopic Laser Surgery and Complicated by Right Ventricular Outflow Tract Anomalies.

Right ventricular outflow tract anomalies (RVOTAs), such as pulmonary stenosis (PS), pulmonary atresia (PA), and pulmonary insufficiency (PI), are typical cardiac anomalies in monochorionic twins, and they are complicated by twin-to-twin transfusion syndrome (TTTS). The aim of this study was to conduct a long-term postnatal cardiological evaluation of prenatal RVOTAs in monochorionic diamniotic twin pregnancies complicated by TTTS and treated with fetoscopic laser surgery (FLS) and to analyze possible prenatal predictors of congenital heart disease (CHD). Prenatal RVOTAs were retrospectively retrieved from all TTTS cases treated with FLS in our unit between 2009 and 2019. Twenty-eight prenatal cases of RVOTAs (16 PI, 10 PS, 2 PA) were observed out of 335 cases of TTTS. Four cases did not reach the postnatal period. CHD was present in 17 of the remaining 24 cases (70.8%), with 10 being severe (58.8%; 10/17); nine cases of PS required balloon valvuloplasty, and one case required biventricular non-compaction cardiomyopathy. The risk of major CHD increased with prenatal evidence of PS and decreased with the gestational age at the time of TTTS and with the prenatal normalization of blood flow across the pulmonary valve. Despite treatment with FLS, the majority of monochorionic diamniotic twin pregnancies complicated by TTTS with prenatal RVOTAs had CHD at long-term follow-up.

Pregnancy loss in major fetal congenital heart disease: incidence, risk factors and timing.

Fetuses with congenital heart disease (CHD) are at increased risk of pregnancy loss compared with the general population. We aimed to assess the incidence, timing and risk factors of pregnancy loss in cases with major fetal CHD, overall and according to cardiac diagnosis. This was a retrospective, population-level cohort study of fetuses and infants diagnosed with major CHD between 1997 and 2018 identified by the Utah Birth Defect Network (UBDN), excluding cases with termination of pregnancy and minor cardiovascular diagnoses (e.g. isolated aortic/pulmonary pathology and isolated septal defects). The incidence and timing of pregnancy loss were recorded, overall and according to CHD diagnosis, with further stratification based on presence of isolated CHD vs additional fetal diagnosis (genetic diagnosis and/or extracardiac malformation). Adjusted risk of pregnancy loss was calculated and risk factors were assessed using multivariable models for the overall cohort and prenatal diagnosis subgroup. Of 9351 UBDN cases with a cardiovascular code, 3251 cases with major CHD were identified, resulting in a study cohort of 3120 following exclusion of cases with pregnancy termination (n = 131). There were 2956 (94.7%) live births and 164 (5.3%) cases of pregnancy loss, which occurred at a median gestational age of 27.3 weeks. Of study cases, 1848 (59.2%) had isolated CHD and 1272 (40.8%) had an additional fetal diagnosis, including 736 (57.9%) with a genetic diagnosis and 536 (42.1%) with an extracardiac malformation. The observed incidence of pregnancy loss was highest in the presence of mitral stenosis (< 13.5%), hypoplastic left heart syndrome (HLHS) (10.7%), double-outlet right ventricle with normally related great vessels or not otherwise specified (10.5%) and Ebstein's anomaly (9.9%). The adjusted risk of pregnancy loss was 5.3% (95% CI, 3.7-7.6%) in the overall CHD population and 1.4% (95% CI, 0.9-2.3%) in cases with isolated CHD (adjusted risk ratio, 9.0 (95% CI, 6.0-13.0) and 2.0 (95% CI, 1.0-6.0), respectively, based on the general population risk of 0.6%). On multivariable analysis, variables associated with pregnancy loss in the overall CHD population included female fetal sex (adjusted odds ratio (aOR), 1.6 (95% CI, 1.1-2.3)), Hispanic ethnicity (aOR, 1.6 (95% CI, 1.0-2.5)), hydrops (aOR, 6.7 (95% CI, 4.3-10.5)) and additional fetal diagnosis (aOR, 6.3 (95% CI, 4.1-10)). On multivariable analysis of the prenatal diagnosis subgroup, years of maternal education (aOR, 1.2 (95% CI, 1.0-1.4)), presence of an additional fetal diagnosis (aOR, 2.7 (95% CI, 1.4-5.6)), atrioventricular valve regurgitation ≥ moderate (aOR, 3.6 (95% CI, 1.3-8.8)) and ventricular dysfunction (aOR, 3.8 (95% CI, 1.2-11.1)) were associated with pregnancy loss. Diagnostic groups associated with pregnancy loss were HLHS and variants (aOR, 3.0 (95% CI, 1.7-5.3)), other single ventricles (aOR, 2.4 (95% CI, 1.1-4.9)) and other (aOR, 0.1 (95% CI, 0-0.97)). Time-to-pregnancy-loss analysis demonstrated a steeper survival curve for cases with an additional fetal diagnosis, indicating a higher rate of pregnancy loss compared to cases with isolated CHD (P < 0.0001). The risk of pregnancy loss is higher in cases with major fetal CHD compared with the general population and varies according to CHD type and presence of additional fetal diagnoses. Improved understanding of the incidence, risk factors and timing of pregnancy loss in CHD cases should inform patient counseling, antenatal surveillance and delivery planning. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

P-774 Congenital Heart Disease in Children Born after Assisted Reproductive Technology: A Nordic Cohort Study.

Abstract Study question Do children conceived after assisted reproductive technology (ART) have a higher risk of Congenital Heart Disease (CHD) in comparison with children born after spontaneous conception? Summary answer Children born after ART have a higher risk of a major CHD compared with children born after spontaneous conception. What is known already It is well-known that children born after ART have higher risk of birth defects compared to children born after spontaneous conception. Congenital heart disease (CHD) is the most common birth defect, accounting for almost 50% of all major birth defects. Several cohort studies and systematic reviews have also found an increased risk of CHD in children born after ART, a recent review included 41 studies and 25 856 ART children covering CHDs in ART children. Conflicting results have been reported for specific CHDs. Study design, size, duration This Nordic registry-based cohort study from CoNARTaS (Committee of Nordic ART and Safety) included 171 774 live births born after use of ART and 7 772 474 live births born after spontaneous conception during a study period of up to three decades (Denmark 1994-2014, Finland 1990-2014, Norway 1984-2015, and Sweden 1985-2015). National data from ART registries, medical birth registries, malformation registries, patient registries, cause of death registries, and population registries were crosslinked. Participants/materials, setting, methods International Classification of Diseases (ICD) versions 8, 9, 10 were used for CHD codes at birth and up to one year of age. Major CHDs were defined according to European Concerted Action on Congenital Anomalies and Twins (EUROCAT). According to EUROCAT, 26 of the major CHDs were considered as severe. All major CHDs were further classified into six different groups in a hierarchical order. Minor CHDs as well as stillbirths and pregnancy terminations were excluded. Main results and the role of chance Data from Sweden included a total of 3 228 526 singletons and multiples; 62 243 children conceived after use of ART and 3 166 283 children after spontaneous conception. Among ART children, 2.27% (n = 1411) were diagnosed with any major non-chromosomal CHD during their first year of life, corresponding figures for children born after spontaneous conception was 1.43% (n = 45 310) (Odds Ratio [OR] 1.60; 95% Confidence Interval (CI) 1.51 to 1.69, p &amp;lt; 0.0001). Severe CHD occurred in 0.40% (n = 249) in the ART group and 0.31% (n = 9 795) in the spontaneous conception group (OR 1.29; 95% CI 1.14 to 1.47, p &amp;lt; 0.0001). Ventricular septal defect was the most common CHD, 0.97% (n = 603) in the ART vs 0.64% (n = 20 343) in the spontaneous conception group (OR 1.51; 95% CI 1.39 to 1.64, p &amp;lt; 0.0001), followed by atrial septal defect; 0.84% (n = 525) in the ART and 0.42% (n = 13 363) in the spontaneous conception group (OR 2.00; 95% CI 1.83 to 2.19, p &amp;lt; 0.0001). Limitations, reasons for caution This analysis included only non-adjusted Swedish data. Further analysis will include Danish, Finnish, and Norwegian data with adjustments, and subgroup analysis on singletons and multiples. No data are available on prenatal diagnosis, or pregnancies not ending to a live birth. A skewed distribution in these outcomes might introduce a bias. Wider implications of the findings Pregnancies conceived after use of ART may benefit from screening with fetal echocardiography. Although most children with CHD reach adulthood, the mortality rate is still high for this group during the first years of life. Early detection with antenatal diagnosis and pre/postnatal intervention may be beneficial and improve the outcome. Trial registration number Not applicable

ISUOG Practice Guidelines (updated): fetal cardiac screening.

ISUOG Practice Guidelines (updated): fetal cardiac screening.

ARE LOW BIRTH WEIGHT AND MAJOR CONGENITAL HEART DISEASES CONTRAINDICATIONS FOR THORACOSCOPIC REPAIR OF ESOPHAGEAL ATRESIA WITH TRACHEOESOPHAGEAL FISTULA?

BACKGROUND Thoracoscopic repair of esophageal atresia (EA) with tracheoesophageal fistula (TEF) is becoming an increasingly widespread technique; there is still controversy about its indication in certain patients. Our objective is to analyze if potential risk factors such as major congenital heart disease (CHD) or low birth weight are a limitation to this approach. METHODS Retrospective study (2017-2021) of patients with EA and distal TEF who underwent thoracoscopic repair were included. Patients with low birth weight <2000g or major congenital heart disease were compared to the rest. RESULTS Twenty-five patients underwent thoracoscopic surgery. Nine patients (36%) had major CHD. Five of them (20%) were low birth weight <2000g and only 8% presented both risk factors (2/25). There were no differences in terms of operative time, conversion rate, tolerance evaluated with gasometric parameters (pO2, pCO2, pH) or complications (anastomotic leak and stricture, both early or during follow-up) in patients with major CHD and LBW (1473 ± 319g vs 2664 ± 402g). One conversion to thoracotomy was performed in a baby weighing 1050 g due to anesthetic intolerance. There was no recurrence of TEF. One patient died at the age of 9 months, due to major uncorrectable heart disease. CONCLUSIONS Thoracoscopic repair of EA/TEF is feasible technique in patients with CHD or LBW, with similar results to other patients. The complexity of this technique warrants individualizing the indication in each case.

Third Trimester Umbilical Arterial Pulsatility Index is Associated with Neurodevelopmental Outcomes at 2-Years in Major Congenital Heart Disease

Major congenital heart disease (CHD) is associated with impaired neurodevelopment (ND), partly from prenatal insults. In this study we explore associations between 2nd and 3rd trimester umbilical (UA) and middle cerebral artery (MCA) pulsatility index (PI = systolic-diastolic velocities/mean velocity) in fetuses with major CHD and 2-year ND and growth outcomes. Eligible patients included those with a prenatal diagnosis of CHD from 2007 to 2017 without a genetic syndrome who underwent previously defined cardiac surgeries and 2-year biometric and ND assessments in our program. UA and MCA-PI Z-scores at fetal echocardiography were examined for relationships with 2-year Bayley Scales of Infant and Toddler Development and biometric Z-scores. Data from 147 children was analyzed. Second and 3rd trimester fetal echocardiograms were performed at 22.4 ± 3.7 and 34.7 ± 2.9weeks (mean ± SD), respectively. Multivariable regression analysis showed an inverse relationship between 3rd trimester UA-PI for all CHD and cognitive -1.98 (-3.37, -0.59), motor -2.57 (-4.15, -0.99), and language -1.67 (-3.3, -0.03) (effect size and 95th confidence interval) ND domains (p < 0.05), with the strongest relationships in the single ventricle and hypoplastic left heart syndrome subgroups. No association was found for 2nd trimester UA-PI or any trimester MCA-PI and ND or between UA or MCA-PI and 2-year growth parameters. Increased 3rd trimester UA-PI, reflecting an altered late gestation fetoplacental circulation, relates to worse 2-year ND in all domains.