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Each year, nearly 40,000 children are born with a Congenital Heart Defect (CHD) in the United States, and 1 in 4 of them are born with a severe CHD requiring surgical intervention within their first year of life (Data and Statistics on Congenital Heart Defects, 2023). About 15% of CHDs are suspected to be due to genetic conditions (Data and Statistics on Congenital Heart Defects, 2023). We reviewed genetic testing trends among individuals with CHDs in Southern Arizona through Current Procedural Terminology (CPT) code analysis and retrospective chart review. We queried CPT codes for genetic testing in data collected by the Arizona Congenital Heart Defects Surveillance across Time And Regions (AZ CHD STAR), an initiative funded through the Centers for Disease Control and Prevention initiative. Out of 37,530 individuals with CHD in Southern Arizona born between 2000 and 2019, 478 (1.27%) underwent genetic testing. We completed medical record abstraction for 441 cases with genetic testing identified from clinical sources, and found genetic test results for 369 (82.9%). Of these 369 cases, 33.3% are individuals with Hispanic ethnicity and 48.8% are individuals with Non-Hispanic White ethnicity. There was a significant difference between the proportions of individuals with a Hispanic background in this study’s cohort compared to the general census data for Southern Arizona (33.3% vs. 43.5%; p value <.001) (QuickFacts: Arizona, 2023). Of all identified testing, individuals with severe CHDs accounted for 80% of total cases and chromosomal microarray was the testing methodology for 56% of all genetic tests. There was a significant difference between abnormal and normal results in severe and non-severe CHD cases for this cohort (chi-squared=11.706, p-value=<0.001), suggesting that abnormal results are more common in individuals with non-severe CHD presentations in this cohort. A majority of testing was performed on individuals with severe CHDs, suggesting that individuals wit

BACKGROUND: Executive functioning (EF) is an umbrella term for various cognitive functions that play a role in monitoring and planning to effectuate goal-directed behavior. The 22q11.2 deletion syndrome (22q11DS), the most common microdeletion syndrome, is associated with a multitude of both somatic and cognitive symptoms, including EF impairments in school-age and adolescence. However, results vary across different EF domains and studies with preschool children are scarce. As EF is critically associated with later psychopathology and adaptive functioning, our first aim was to study EF in preschool children with 22q11DS. Our second aim was to explore the effect of a congenital heart defects (CHD) on EF abilities, as CHD are common in 22q11DS and have been implicated in EF impairment in individuals with CHD without a syndromic origin.METHODS: All children with 22q11DS (n = 44) and typically developing (TD) children (n = 81) were 3.0 to 6.5 years old and participated in a larger prospective study. We administered tasks measuring visual selective attention, visual working memory, and a task gauging broad EF abilities. The presence of CHD was determined by a pediatric cardiologist based on medical records.RESULTS: Analyses showed that children with 22q11DS were outperformed by TD peers on the selective attention task and the working memory task. As many children were unable to complete the broad EF task, we did not run statistical analyses, but provide a qualitative description of the results. There were no differences in EF abilities between children with 22q11DS with and without CHDs.CONCLUSION: To our knowledge, this is the first study measuring EF in a relatively large sample of young children with 22q11DS. Our results show that EF impairments are already present in early childhood in children with 22q11DS. In line with previous studies with older children with 22q11DS, CHDs do not appear to have an effect on EF performance. These findings mi

Jansen de Vries syndrome (JDVS, OMIM: 617450) is a rare neurodevelopmental disorder associated with hypotonia, behavioral features, high threshold to pain, short stature, ophthalmological abnormalities, dysmorphism and occasionally a structural cardiac condition. It is caused by truncating variants of the last and penultimate exons of PPM1D. So far, 21 patients with JVDS have been reported in the literature. Here, we describe four novel cases of JVDS and review the current literature. Notably, our patients 1, 3 and 4 do not have intellectual disability albeit they have significant developmental difficulties. Thus, the phenotype may span from a classic intellectual disability syndrome to a milder neurodevelopmental disorder. Interestingly, two of our patients have received successful growth hormone treatment. Considering the phenotype of all the known JDVS patients, a cardiological consultation is recommended, as at least 7/25 patients showed a structural cardiac defect. Episodic fever and vomiting may associate with hypoglycemia and may even mimic a metabolic disorder. We also report the first JDVS patient with a mosaic gene defect and a mild neurodevelopmental phenotype.

BACKGROUND: Congenital heart defects (CHDs) affect approximately half of individuals with Down syndrome (DS), but the molecular reasons for incomplete penetrance are unknown. Previous studies have largely focused on identifying genetic risk factors associated with CHDs in individuals with DS, but comprehensive studies of the contribution of epigenetic marks are lacking. We aimed to identify and characterize DNA methylation differences from newborn dried blood spots (NDBS) of DS individuals with major CHDs compared to DS individuals without CHDs. METHODS: We used the Illumina EPIC array and whole-genome bisulfite sequencing (WGBS) to quantitate DNA methylation for 86 NDBS samples from the California Biobank Program: (1) 45 DS-CHD (27 female, 18 male) and (2) 41 DS non-CHD (27 female, 14 male). We analyzed global CpG methylation and identified differentially methylated regions (DMRs) in DS-CHD versus DS non-CHD comparisons (both sex-combined and sex-stratified) corrected for sex, age of blood collection, and cell-type proportions. CHD DMRs were analyzed for enrichment in CpG and genic contexts, chromatin states, and histone modifications by genomic coordinates and for gene ontology enrichment by gene mapping. DMRs were also tested in a replication dataset and compared to methylation levels in DS versus typical development (TD) WGBS NDBS samples. RESULTS: We found global CpG hypomethylation in DS-CHD males compared to DS non-CHD males, which was attributable to elevated levels of nucleated red blood cells and not seen in females. At a regional level, we identified 58, 341, and 3938 CHD-associated DMRs in the Sex Combined, Females Only, and Males Only groups, respectively, and used machine learning algorithms to select 19 Males Only loci that could distinguish CHD from non-CHD. DMRs in all comparisons were enriched for gene exons, CpG islands, and bivalent chromatin and mapped to genes enriched for terms related to cardiac and immune functions. Lastly, a greater percent

Background: Higher maternal body mass index (BMI) and abnormal glucose metabolism during early pregnancy are associated with congenital heart defects in the offspring, but the exact mechanisms are unknown. Methods: We evaluated the association between maternal first trimester metabolic profile and transposition of the great arteries (TGA) in the offspring in a matched case–control study with 100 TGA mothers and 200 controls born in Finland during 2004–2014. Cases and controls were matched by birth year, child sex, and maternal age and BMI. Serum samples collected between 10- and 14-weeks of gestation were analyzed for 73 metabolic measures. Conditional logistic regression was used to assess the risk for TGA in the offspring, and a subgroup analysis among mothers with high BMI was conducted. Results: Higher concentrations of four subtypes of extremely large very-low-density lipoprotein (VLDL) particles and one of large VLDL particles were observed in TGA mothers. This finding did not reach statistical significance after multiple testing correction. The pooled odds ratio (OR) of the all metabolic variables was slightly higher in TGA mothers in the subgroup with maternal BMI over 25 (OR 1.25) and significantly higher in the subgroup with maternal BMI over 30 (OR 1.95) compared to the original population (OR 1.18). Conclusions: Our findings indicate that an abnormal maternal early pregnancy metabolic profile might be associated with TGA in the offspring, especially in obese mothers. A trend indicating altered VLDL subtype composition in TGA pregnancies warrants further research.

Ventricular septal defects (VSD) represent the most common congenital heart defect in newborns. We assessed the electrocardiographic characteristics of newborns with VSDs in a general population sample. The Copenhagen Baby Heart Study is a prospective population–based cohort study offering cardiac evaluation of newborns. Echocardiograms and electrocardiograms were obtained within 30 days after birth and systematically analysed. A VSD was identified in 530 newborns (mean age 11 ± 7 days, 42% boys). Newborns with VSDs had a more left-shifted QRS axis (116 ± 34 vs. 120 ± 3°, p = 0.02), and a higher S-wave amplitude in V1 (721 ± 584 vs. 636 ± 549 µV, p = 0.001) than controls. The largest differences were found in newborns with large or perimembraneous VSDs with a higher frequency of left axis deviation, higher S-wave amplitudes in V1, and higher R- and S-wave amplitudes in V6 compared with controls. R-waves in V1 and V6 were significantly associated to left ventricular mass, whereas S-waves in V1 and V6 were dependent on left ventricular end-diastolic diameter on echocardiography. Conclusion: Newborns with VSDs showed significant differences in QRS axis, and R- and S-wave precordial amplitudes compared to matched controls. Perimembranous and large VSDs had the greatest effect on the neonatal ECG., Ventricular septal defects (VSD) represent the most common congenital heart defect in newborns. We assessed the electrocardiographic characteristics of newborns with VSDs in a general population sample. The Copenhagen Baby Heart Study is a prospective population–based cohort study offering cardiac evaluation of newborns. Echocardiograms and electrocardiograms were obtained within 30 days after birth and systematically analysed. A VSD was identified in 530 newborns (mean age 11 ± 7 days, 42% boys). Newborns with VSDs had a more left-shifted QRS axis (116 ± 34 vs. 120 ± 3°, p = 0.02), and a higher S-wave amplitude in V1 (721 ± 584 vs. 636 ± 549 µV, p = 0.001) than controls. The largest differences were found in newborns with large or perimembraneous VSDs with a higher frequency of left axis deviation, higher S-wave amplitudes in V1, and higher R- and S-wave amplitudes in V6 compared with controls. R-waves in V1 and V6 were significantly associated to left ventricular mass, whereas S-waves in V1 and V6 were dependent on left ventricular end-diastolic diameter on echocardiography. Conclusion: Newborns with VSDs showed significant differences in QRS axis, and R- and S-wave precordial amplitudes compared to matched controls. Perimembranous and large VSDs had the greatest effect on the neonatal ECG. What is Known: • Ventricular septal defects in newborns are prevalent and may affect cardiac function and structure. What is New: • The Copenhagen Baby Heart Study is the largest study including a cohort of unselected newborns undergoing postnatal cardiac examination. • We found that newborns with VSD showed significant electrocardiographic differences depending on size and type of VSD compared with healthy newborns.

BACKGROUND: In the palliative pathway of single-ventricle physiology, lymphatic abnormalities on T2-weighted magnetic resonance imaging have been shown after the Glenn operation. It is believed that postsurgical hemodynamic changes contribute to the lymphatic changes.However, little is known about how early these abnormalities occur. Our purpose was to determine if lymphatic abnormalities occur as early as before the Glenn operation. METHODS AND RESULTS: We retrospectively reviewed patients with single-ventricle physiology and a T2-weighted magnetic resonance imaging scan before their Glenn operation (superior cavopulmonary connection) at The Children’s Hospital of Philadelphia from 2012 to 2022. Lymphatic perfusion patterns on T2-magnetic resonance imaging were categorized from type 1 (no supraclavicular T2-signal) to type 4 (supraclavicular, mediastinal, lung parenchymal T2-signal). Types 1 and 2 were considered normal variants. Distribution of lymphatic abnormalities were tabulated, as well as secondary outcomes including chylothorax and mortality. Comparison was done using analysis of variance, Kruskal–Wallis test, and Fisher’s exact test. Seventy-one children were included: 30 with hypoplastic left heart syndrome and 41 with nonhypoplastic left heart syndrome. Lymphatic abnormalities were present before Glenn operation in 21% (type 3) and 20% (type 4), and normal lymphatic perfusion patterns (type 1–2) were seen in 59% of patients. Chylothorax was present in 17% (only types 3 and 4). Pre-Glenn mortality and mortality at any time was significantly increased when having a type 4 lymphatic abnormality compared with types 1 and 2 (P=0.04). CONCLUSIONS: Lymphatic abnormalities can be found on T2-weighted magnetic resonance imaging in children with singleventricle physiology before their Glenn operation. Mortality and chylothorax were more prevalent with advancing grade of lymphatic abnormality.

Children with a Congenital Heart Defect (CHD) need to visit the outpatient clinic regularly their whole lives, often starting from birth. These hospital visits are frequently accompanied by feelings of anxiety and fear, which can have a detrimental impact on a child’s life. In collaboration with the Hospital Hero Foundation and the Willem-Alexander Children’s Hospital, the aim of this project was to design an intervention that reduces children’s feelings (aged four to ten) of fear and anxiety during outpatient visits to the paediatric cardiology department. Employed Methods Throughout the project, the following methodologies were employed: 1. Literature research exploring the background of paediatric hospital-related anxiety and fear, and existing anxiety-and-fear-reducing strategies. 2. Interviews with children (with and without CHD), parents, and paediatric healthcare workers to map the current situation. 3. In-depth observations of the current context of an outpatient visit to the cardiology department. 4. The facilitation of creative sessions to generate ideas and concepts, ultimately resulting in the final design. Home-Based Preparation Home-based preparation was chosen as the leading fear-and-anxiety-reducing strategy. This strategy focuses on providing paediatric patients with information prior to their hospital visit. Due to the developmental and cognitive levels of the defined age group, the responsibility of home-based preparation lies with the caregivers/guardians of the patients. The following main research question was defined: How can design support children (between the ages of four and seven) and their parents in the home-based preparation process of an outpatient visit to the paediatric cardiology department? Research Outcomes Exploring the current preparation touchpoints, practised preparation methods, and the hospital experience from the child’s perspective resulted in the following summari, Design for Interaction | Medisign

Background: The ductus arteriosus is part of the fetal circulation. Normally, the vessel closes during the cardiac transition. Delayed closure is associated with complications. The aim of this study was to evaluate the age-related prevalence of open ductus arteriosus in full-term neonates. Methods: Echocardiograms were collected in the population study, the Copenhagen Baby Heart Study. The present study included full-term neonates with an echocardiogram performed within 28 days after birth. All echocardiograms were reviewed to assess ductus arteriosus patency. Results: A total of 21,649 neonates were included. In neonates examined at day zero and day seven, an open ductus arteriosus was found in 36% and 0.6%, respectively. Beyond day seven, the prevalence remained stable at 0.6%. Conclusion: More than one-third of full-term neonates had an open ductus arteriosus on the first day of life, declining rapidly within the first week and stabilizing below 1% after day seven. Keywords:Congenital heart defect, Patent ductus arteriosus, Ductus arteriosus, Echocardiography, Neonatology, Background: The ductus arteriosus is part of the fetal circulation. Normally, the vessel closes during the cardiac transition. Delayed closure is associated with complications. The aim of this study was to evaluate the age-related prevalence of open ductus arteriosus in full-term neonates. Methods: Echocardiograms were collected in the population study, the Copenhagen Baby Heart Study. The present study included full-term neonates with an echocardiogram performed within 28 days after birth. All echocardiograms were reviewed to assess ductus arteriosus patency. Results: A total of 21,649 neonates were included. In neonates examined at day zero and day seven, an open ductus arteriosus was found in 36% and 0.6%, respectively. Beyond day seven, the prevalence remained stable at 0.6%. Conclusion: More than one-third of full-term neonates had an open ductus arteriosus on the first day of life, declining rapidly within the first week and stabilizing below 1% after day seven.

Ventricular septal defects (VSD) represent the most common congenital heart defect in newborns. We assessed the electrocardiographic characteristics of newborns with VSDs in a general population sample. The Copenhagen Baby Heart Study is a prospective population–based cohort study offering cardiac evaluation of newborns. Echocardiograms and electrocardiograms were obtained within 30 days after birth and systematically analysed. A VSD was identified in 530 newborns (mean age 11 ± 7 days, 42% boys). Newborns with VSDs had a more left-shifted QRS axis (116 ± 34 vs. 120 ± 3°, p = 0.02), and a higher S-wave amplitude in V1 (721 ± 584 vs. 636 ± 549 µV, p = 0.001) than controls. The largest differences were found in newborns with large or perimembraneous VSDs with a higher frequency of left axis deviation, higher S-wave amplitudes in V1, and higher R- and S-wave amplitudes in V6 compared with controls. R-waves in V1 and V6 were significantly associated to left ventricular mass, whereas S-waves in V1 and V6 were dependent on left ventricular end-diastolic diameter on echocardiography. Conclusion: Newborns with VSDs showed significant differences in QRS axis, and R- and S-wave precordial amplitudes compared to matched controls. Perimembranous and large VSDs had the greatest effect on the neonatal ECG., Ventricular septal defects (VSD) represent the most common congenital heart defect in newborns. We assessed the electrocardiographic characteristics of newborns with VSDs in a general population sample. The Copenhagen Baby Heart Study is a prospective population–based cohort study offering cardiac evaluation of newborns. Echocardiograms and electrocardiograms were obtained within 30 days after birth and systematically analysed. A VSD was identified in 530 newborns (mean age 11 ± 7 days, 42% boys). Newborns with VSDs had a more left-shifted QRS axis (116 ± 34 vs. 120 ± 3°, p = 0.02), and a higher S-wave amplitude in V1 (721 ± 584 vs. 636 ± 549 µV, p = 0.001) than controls. The largest differences were found in newborns with large or perimembraneous VSDs with a higher frequency of left axis deviation, higher S-wave amplitudes in V1, and higher R- and S-wave amplitudes in V6 compared with controls. R-waves in V1 and V6 were significantly associated to left ventricular mass, whereas S-waves in V1 and V6 were dependent on left ventricular end-diastolic diameter on echocardiography. Conclusion: Newborns with VSDs showed significant differences in QRS axis, and R- and S-wave precordial amplitudes compared to matched controls. Perimembranous and large VSDs had the greatest effect on the neonatal ECG. What is Known: • Ventricular septal defects in newborns are prevalent and may affect cardiac function and structure. What is New: • The Copenhagen Baby Heart Study is the largest study including a cohort of unselected newborns undergoing postnatal cardiac examination. • We found that newborns with VSD showed significant electrocardiographic differences depending on size and type of VSD compared with healthy newborns.

BACKGROUND: In the palliative pathway of single-ventricle physiology, lymphatic abnormalities on T2-weighted magnetic resonance imaging have been shown after the Glenn operation. It is believed that postsurgical hemodynamic changes contribute to the lymphatic changes.However, little is known about how early these abnormalities occur. Our purpose was to determine if lymphatic abnormalities occur as early as before the Glenn operation. METHODS AND RESULTS: We retrospectively reviewed patients with single-ventricle physiology and a T2-weighted magnetic resonance imaging scan before their Glenn operation (superior cavopulmonary connection) at The Children’s Hospital of Philadelphia from 2012 to 2022. Lymphatic perfusion patterns on T2-magnetic resonance imaging were categorized from type 1 (no supraclavicular T2-signal) to type 4 (supraclavicular, mediastinal, lung parenchymal T2-signal). Types 1 and 2 were considered normal variants. Distribution of lymphatic abnormalities were tabulated, as well as secondary outcomes including chylothorax and mortality. Comparison was done using analysis of variance, Kruskal–Wallis test, and Fisher’s exact test. Seventy-one children were included: 30 with hypoplastic left heart syndrome and 41 with nonhypoplastic left heart syndrome. Lymphatic abnormalities were present before Glenn operation in 21% (type 3) and 20% (type 4), and normal lymphatic perfusion patterns (type 1–2) were seen in 59% of patients. Chylothorax was present in 17% (only types 3 and 4). Pre-Glenn mortality and mortality at any time was significantly increased when having a type 4 lymphatic abnormality compared with types 1 and 2 (P=0.04). CONCLUSIONS: Lymphatic abnormalities can be found on T2-weighted magnetic resonance imaging in children with singleventricle physiology before their Glenn operation. Mortality and chylothorax were more prevalent with advancing grade of lymphatic abnormality.

Background: The ductus arteriosus is part of the fetal circulation. Normally, the vessel closes during the cardiac transition. Delayed closure is associated with complications. The aim of this study was to evaluate the age-related prevalence of open ductus arteriosus in full-term neonates. Methods: Echocardiograms were collected in the population study, the Copenhagen Baby Heart Study. The present study included full-term neonates with an echocardiogram performed within 28 days after birth. All echocardiograms were reviewed to assess ductus arteriosus patency. Results: A total of 21,649 neonates were included. In neonates examined at day zero and day seven, an open ductus arteriosus was found in 36% and 0.6%, respectively. Beyond day seven, the prevalence remained stable at 0.6%. Conclusion: More than one-third of full-term neonates had an open ductus arteriosus on the first day of life, declining rapidly within the first week and stabilizing below 1% after day seven. Keywords:Congenital heart defect, Patent ductus arteriosus, Ductus arteriosus, Echocardiography, Neonatology, Background: The ductus arteriosus is part of the fetal circulation. Normally, the vessel closes during the cardiac transition. Delayed closure is associated with complications. The aim of this study was to evaluate the age-related prevalence of open ductus arteriosus in full-term neonates. Methods: Echocardiograms were collected in the population study, the Copenhagen Baby Heart Study. The present study included full-term neonates with an echocardiogram performed within 28 days after birth. All echocardiograms were reviewed to assess ductus arteriosus patency. Results: A total of 21,649 neonates were included. In neonates examined at day zero and day seven, an open ductus arteriosus was found in 36% and 0.6%, respectively. Beyond day seven, the prevalence remained stable at 0.6%. Conclusion: More than one-third of full-term neonates had an open ductus arteriosus on the first day of life, declining rapidly within the first week and stabilizing below 1% after day seven.

Objective: The objective of this study was to audit current patient blood management practice in children throughout cardiac surgery and paediatric intensive care unit (PICU) admission. Design: This was a prospective observational cohort study. Setting: This was a single-centre study in the cardiac operating room (OR) and PICU in a major tertiary children's hospital in Australia. Patients: Children undergoing corrective cardiac surgery and requiring admission to PICU for postoperative recovery were included in the study. Measurements and main results: Fifty-six patients and 1779 blood sampling episodes were audited over a 7-month period. The median age was 9 months (interquartile range [IQR] = 1–102), with the majority (n = 30 [54%]) younger than 12 months. The median number of blood sampling episodes per patient per day was 6.6 (IQR = 5.8–8.0) in total, with a median of 5.0 (IQR = 4.0–7.5) episodes in the OR and 5.0 (IQR = 3.4–6.2) episodes per day throughout PICU admission. The most common reason for blood tests across both OR and PICU settings was arterial blood gas analysis (total median = 86%, IQR = 79–96). The overall median blood sampling volume per kg of bodyweight, patient, and day was 0.63 mL (IQR = 0.20–1.14) in total. Median blood loss for each patient was 3.5 mL/kg per patient per day (IQR = 1.7–5.6) with negligible amounts in the OR and a median of 3.6 mL/kg (IQR = 1.7–5.7) in the PICU. The median Cell Saver® transfusion volume was 9.9 mL/kg per patient per day (IQR = 4.0–19.1) in the OR. The overall median volume of other infusion products (albumin 4%, albumin 20%, packed red blood cells) received by each patient was 20.1 mL/kg (IQR = 10.7–36.4) per day. Sampling events and blood loss were positively associated with PICU stay. Conclusions: Patient blood management practices observed in this study largely conform to National Blood Authority guidelines. Further implementation projects and research are needed to accelerate implementation of known effe

Objective: To evaluate corpus callosum (CC) size by neurosonography (NSG) in fetuses with an isolated major congenital heart defect (CHD) and explore the association of CC size with the expected pattern of in-utero oxygen supply to the brain. Methods: A total of 56 fetuses with postnatally confirmed isolated major CHD and 56 gestational-age-matched controls were included. Fetuses with CHD were stratified into two categories according to the main expected pattern of cerebral arterial oxygen supply: Class A, moderately to severely reduced oxygen supply (left outflow tract obstruction and transposition of the great arteries) and Class B, near normal or mildly impaired oxygenated blood supply to the brain (other CHD). Transvaginal NSG was performed at 32–36 weeks in all fetuses to evaluate CC length, CC total area and areas of CC subdivisions in the midsagittal plane. Results: CHD fetuses had a significantly smaller CC area as compared to controls (7.91 ± 1.30 vs 9.01 ± 1.44 mm2; P < 0.001), which was more pronounced in the most posterior part of the CC. There was a significant linear trend for reduced CC total area across the three clinical groups, with CHD Class-A cases showing more prominent changes (controls, 9.01 ± 1.44 vs CHD Class B, 8.18 ± 1.21 vs CHD Class A, 7.53 ± 1.33 mm2; P < 0.05). Conclusions: Fetuses with major CHD had a smaller CC compared with controls, and the difference was more marked in the CHD subgroup with expected poorer brain oxygenation. Sonographic CC size could be a clinically feasible marker of abnormal white matter development in CHD., Peer Reviewed, Postprint (published version)

OBJECTIVE: Hypoplastic left heart syndrome (HLHS) is a congenital disease characterized by an underdevelopment of the anatomical components inside the left heart. Approximately 30% of HLHS newborns will develop tricuspid regurgitation (TR), and it is currently unknown how the valve annulus mechanics and geometry are associated with regurgitation. Thus, we present an engineering mechanics-based analysis approach to quantify the mechanics and geometry of the HLHS-afflicted tricuspid valve (TV), using 4-dimensional echocardiograms. METHODS: Infants born with hypoplastic left heart syndrome (n=8) and healthy newborns (n=4) had their tricuspid valves imaged, and the data was imported to the 3D Slicer. The annular curves were defined at five points in the cardiac cycle. The geometry and deformation (strain) of the TV annulus were calculated to elucidate the mechanics of this critical structure, and compare them between HLHS and normal neonates. RESULTS: For the annular geometry, HLHS-afflicted newborns had significantly larger annular circumferences (20-30%) and anterior-posterior diameters (35-45%) than the healthy patients. From a biomechanics perspective, the HLHS patients had significantly smaller strains in the anterior segments (-0.1±2.6%) during end diastolic and end isovolumetric relaxation (1.7±3.0%) compared to the healthy counterparts (-13.3±2.9% and 6.8±0.9%, respectively). CONCLUSIONS: The image-based analysis in this study may provide novel insights into the geometric and mechanistic differences in the TV annulus between healthy and HLHS newborns. Future longitudinal studies of the biomechanics of TV annulus and other subvalvular structures may inform our understanding of the initiation and development of TR and the design of optimal repairs in this challenging population.

Objectives: The objective of this study was to investigate changes in serum biomarkers of acute brain injury, including white matter and astrocyte injury during chronic foetal hypoxaemia. We have previously shown histopathological changes in myelination and neuronal density in fetuses with chronic foetal hypoxaemia at a level consistent with CHD. Methods: Mid-gestation foetal sheep (110 ± 3 days gestation) were cannulated and attached to a pumpless, low-resistance oxygenator circuit, and incubated in a sterile fluid environment mimicking the intrauterine environment. Fetuses were maintained with an oxygen delivery of 20-25 ml/kg/min (normoxemia) or 14-16 ml/kg/min (hypoxaemia). Myelin Basic Protein and Glial Fibrillary Acidic Protein serum levels in the two groups were assessed by ELISA at baseline and at 7, 14, and 21 days of support. Results: Based on overlapping 95% confidence intervals, there were no statistically significant differences in either Myelin Basic Protein or Glial Fibrillary Acidic Protein serum levels between the normoxemic and hypoxemic groups, at any time point. No statistically significant correlations were observed between oxygen delivery and levels of Myelin Basic Protein and Glial Fibrillary Acidic Protein. Conclusion: Chronic foetal hypoxaemia during mid-gestation is not associated with elevated serum levels of acute white matter (Myelin Basic Protein) or astrocyte injury (Glial Fibrillary Acidic Protein), in this model. In conjunction with our previously reported findings, our data support the hypothesis that the brain dysmaturity with impaired myelination found in fetuses with chronic hypoxaemia is caused by disruption of normal developmental pathways rather than by direct cellular injury.

Background Peripheral muscle factors are presumed to be contributors to the reduced exercise capacity in congenital heart disease (CHD), but the underlying mechanisms are poorly understood. The aim was to investigate if muscle oxygenation, at rest and during exercise, and the resting blood flow in the calf muscle is impaired in adults with complex CHD in comparison to controls. Method Seventy-four adults with complex CHD (35.6 ± 14.3 years, females n = 22 [30%], males n = 52 [70%]) and seventy-four age and sex matched subjects were recruited. Muscle oxygenation was successfully determined using near-infrared spectroscopy on the medial portion of m. gastrocnemius in 63 patients and 67 controls. Measurements were made at rest, during venous occlusion to estimate blood flow (indicated by slope increase of total haemoglobin, HbT), and post arterial occlusion. Additionally, measurements were made at the onset of isotonic unilateral heel-lifts to exhaustion and during recovery post exercise. Results Adults with CHD had a slower desaturation rate at exercise onset (−7.7 ± 4.3%StO2x3.5sec−1 vs. −11.7 ± 5.8%StO2x3.5sec−1, p < 0.001) a slower half recovery time (28.6 ± 21.2s vs. 16.8 ± 11.1s, p < 0.001) and a slower resaturation rate post exercise in comparison to the control subjects (3.9 ± 3.7%StO2x3.5sec−1 vs. 6.1 ± 3.8%StO2x3.5sec−1, p = 0.002). In contrast, there were no differences in muscle oxygen kinetics at rest. Conclusion Slower muscle oxygenation kinetics during muscle exercise found in adults with complex CHD may give insight to the mechanisms for the reduced exercise capacity commonly found in this population. This finding may also provide implications for design of exercise training programs targeting muscle function for these patients.

Background Peripheral muscle factors are presumed to be contributors to the reduced exercise capacity in congenital heart disease (CHD), but the underlying mechanisms are poorly understood. The aim was to investigate if muscle oxygenation, at rest and during exercise, and the resting blood flow in the calf muscle is impaired in adults with complex CHD in comparison to controls. Method Seventy-four adults with complex CHD (35.6 ± 14.3 years, females n = 22 [30%], males n = 52 [70%]) and seventy-four age and sex matched subjects were recruited. Muscle oxygenation was successfully determined using near-infrared spectroscopy on the medial portion of m. gastrocnemius in 63 patients and 67 controls. Measurements were made at rest, during venous occlusion to estimate blood flow (indicated by slope increase of total haemoglobin, HbT), and post arterial occlusion. Additionally, measurements were made at the onset of isotonic unilateral heel-lifts to exhaustion and during recovery post exercise. Results Adults with CHD had a slower desaturation rate at exercise onset (−7.7 ± 4.3%StO2x3.5sec−1 vs. −11.7 ± 5.8%StO2x3.5sec−1, p < 0.001) a slower half recovery time (28.6 ± 21.2s vs. 16.8 ± 11.1s, p < 0.001) and a slower resaturation rate post exercise in comparison to the control subjects (3.9 ± 3.7%StO2x3.5sec−1 vs. 6.1 ± 3.8%StO2x3.5sec−1, p = 0.002). In contrast, there were no differences in muscle oxygen kinetics at rest. Conclusion Slower muscle oxygenation kinetics during muscle exercise found in adults with complex CHD may give insight to the mechanisms for the reduced exercise capacity commonly found in this population. This finding may also provide implications for design of exercise training programs targeting muscle function for these patients.

Background Peripheral muscle factors are presumed to be contributors to the reduced exercise capacity in congenital heart disease (CHD), but the underlying mechanisms are poorly understood. The aim was to investigate if muscle oxygenation, at rest and during exercise, and the resting blood flow in the calf muscle is impaired in adults with complex CHD in comparison to controls. Method Seventy-four adults with complex CHD (35.6 ± 14.3 years, females n = 22 [30%], males n = 52 [70%]) and seventy-four age and sex matched subjects were recruited. Muscle oxygenation was successfully determined using near-infrared spectroscopy on the medial portion of m. gastrocnemius in 63 patients and 67 controls. Measurements were made at rest, during venous occlusion to estimate blood flow (indicated by slope increase of total haemoglobin, HbT), and post arterial occlusion. Additionally, measurements were made at the onset of isotonic unilateral heel-lifts to exhaustion and during recovery post exercise. Results Adults with CHD had a slower desaturation rate at exercise onset (−7.7 ± 4.3%StO2x3.5sec−1 vs. −11.7 ± 5.8%StO2x3.5sec−1, p < 0.001) a slower half recovery time (28.6 ± 21.2s vs. 16.8 ± 11.1s, p < 0.001) and a slower resaturation rate post exercise in comparison to the control subjects (3.9 ± 3.7%StO2x3.5sec−1 vs. 6.1 ± 3.8%StO2x3.5sec−1, p = 0.002). In contrast, there were no differences in muscle oxygen kinetics at rest. Conclusion Slower muscle oxygenation kinetics during muscle exercise found in adults with complex CHD may give insight to the mechanisms for the reduced exercise capacity commonly found in this population. This finding may also provide implications for design of exercise training programs targeting muscle function for these patients.

Background Peripheral muscle factors are presumed to be contributors to the reduced exercise capacity in congenital heart disease (CHD), but the underlying mechanisms are poorly understood. The aim was to investigate if muscle oxygenation, at rest and during exercise, and the resting blood flow in the calf muscle is impaired in adults with complex CHD in comparison to controls. Method Seventy-four adults with complex CHD (35.6 ± 14.3 years, females n = 22 [30%], males n = 52 [70%]) and seventy-four age and sex matched subjects were recruited. Muscle oxygenation was successfully determined using near-infrared spectroscopy on the medial portion of m. gastrocnemius in 63 patients and 67 controls. Measurements were made at rest, during venous occlusion to estimate blood flow (indicated by slope increase of total haemoglobin, HbT), and post arterial occlusion. Additionally, measurements were made at the onset of isotonic unilateral heel-lifts to exhaustion and during recovery post exercise. Results Adults with CHD had a slower desaturation rate at exercise onset (−7.7 ± 4.3%StO2x3.5sec−1 vs. −11.7 ± 5.8%StO2x3.5sec−1, p < 0.001) a slower half recovery time (28.6 ± 21.2s vs. 16.8 ± 11.1s, p < 0.001) and a slower resaturation rate post exercise in comparison to the control subjects (3.9 ± 3.7%StO2x3.5sec−1 vs. 6.1 ± 3.8%StO2x3.5sec−1, p = 0.002). In contrast, there were no differences in muscle oxygen kinetics at rest. Conclusion Slower muscle oxygenation kinetics during muscle exercise found in adults with complex CHD may give insight to the mechanisms for the reduced exercise capacity commonly found in this population. This finding may also provide implications for design of exercise training programs targeting muscle function for these patients.

Unguarded mitral valve orifice is a rare disease with only 7 described cases in the literature. We describe the first known case of unguarded mitral valve orifice with normal segmental cardiac anatomy, severe left ventricular dilatation and dysfunction, aortic atresia, and atrial flutter. (Level of Difficulty: Advanced.).

Purpose: In this study we aimed to establish the genetic cause of a myriad of cardiovascular defects prevalent in individuals from a genetically isolated population, who were found to share a common ancestor in 1728. Methods: Trio genome sequencing was carried out in an index patient with critical congenital heart disease (CHD); family members had either exome or Sanger sequencing. To confirm enrichment, we performed a gene-based association test and meta-analysis in two independent validation cohorts: one with 2685 CHD cases versus 4370. These controls were also ancestry-matched (same as FTAA controls), and the other with 326 cases with familial thoracic aortic aneurysms (FTAA) and dissections versus 570 ancestry-matched controls. Functional consequences of identified variants were evaluated using expression studies. Results: We identified a loss-of-function variant in the Notch target transcription factor-encoding gene HEY2. The homozygous state (n = 3) causes life-threatening congenital heart defects, while 80% of heterozygous carriers (n = 20) had cardiovascular defects, mainly CHD and FTAA of the ascending aorta. We confirm enrichment of rare risk variants in HEY2 functional domains after meta-analysis (MetaSKAT p = 0.018). Furthermore, we show that several identified variants lead to dysregulation of repression by HEY2. Conclusion: A homozygous germline loss-of-function variant in HEY2 leads to critical CHD. The majority of heterozygotes show a myriad of cardiovascular defects.

Darstellung des Themas: Jährlich kommen in der Schweiz 600 bis 800 Kinder mit einem angeborenen Herzfehler zur Welt, wovon etwa 250 eine Operation benötigen. Die Lebenserwartung dieser Kinder hat sich dank operativen Fortschritten verbessert. Trotzdem ist die postoperative Phase für die Eltern des betroffenen Kindes eine emotionale Achterbahnfahrt. Fragestellung: «Wie erleben Eltern, deren Kind an einem angeborenen Herzfehler leidet, die postoperative Phase im akutstationären Setting?» Methode: Es wurde eine systematisierte Literaturrecherche in den pflegewissenschaftlichen Datenbanken «CINAHL Complete» und «PubMed» sowie per Schneeballsystem durchgeführt. Acht qualitative Studien wurden zusammengefasst, kritisch gewürdigt und auf ihre Evidenz geprüft. Anschliessend erfolgte ein Theorie-Praxis-Transfer. Relevante Ergebnisse: Aus den einbezogenen Studien konnten drei Hauptkategorien mit ihren jeweiligen Subthemen identifiziert werden: das Erleben, die Beziehungen und die Copingstrategien. Es hat sich herausgestellt, dass das Erleben der Eltern ein komplexes Geschehen ist und sie mit unzälligen intensiven Emotionen konfrontiert sind. Schlussfolgerung: Eltern, deren Kind an einem angeborenen Herzfehler leidet, sind diversen psychosozialen Belastungen ausgesetzt und benötigen eine ganzheitliche Betreuung im Sinne eines familienzentrierten Ansatzes durch die Pflegefachpersonen in der postoperativen Phase im akutstationären Setting.

Pulmonary vasodilator therapy is still often an off-label treatment for pulmonary hypertension in children. The aim of this nationwide register-based study was to assess patient characteristics and strategies for pulmonary vasodilator therapy in young Swedish children. Prescription information for all children below seven years of age at treatment initiation, between 2007 and 2017, was retrieved from the National Prescribed Drug Register, and medical information was obtained by linkage to other registers. All patients were categorized according to the WHO classification of pulmonary hypertension. In total, 233 patients had been prescribed pulmonary vasodilators. The treatment was initiated before one year of age in 61% (N = 143). Sildenafil was most common (N = 224 patients), followed by bosentan (N = 29), iloprost (N = 14), macitentan (N = 4), treprostinil (N = 2) and riociguat (N = 2). Over the study period, the prescription rate for sildenafil tripled. Monotherapy was most common, 87% (N = 203), while 13% (N = 20) had combination therapy. Bronchopulmonary dysplasia (N = 82, 35%) and/or congenital heart defects (N = 156, 67%) were the most common associated conditions. Eight percent (N = 18) of the patients had Down syndrome. Cardiac catheterization had been performed in 39% (N = 91). Overall mortality was 13% (N = 30) during the study period. This study provides an unbiased overview of national outpatient use of pulmonary vasodilator therapy in young children. Few cases of idiopathic pulmonary arterial hypertension were found, but a large proportion of pulmonary hypertension associated with congenital heart defects or bronchopulmonary dysplasia. Despite treatment, mortality was high, and additional pediatric studies are needed for a better understanding of underlying pathologies and evidence of treatment effects.

Background: Peripheral muscle factors are presumed to be contributors to the reduced exercise capacity incongenital heart disease (CHD), but the underlying mechanisms are poorly understood. The aim was to investigate if muscle oxygenation, at rest and during exercise, and the resting blood flow in the calf muscle is impaired in adults with complex CHD in comparison to controls. Method: Seventy-four adults with complex CHD (35.6 ± 14.3 years, females n = 22 [30%], males n = 52 [70%]) and seventy-four age and sex matched subjects were recruited. Muscle oxygenation was successfully determined using near-infrared spectroscopy on the medial portion of m. gastrocnemius in 63 patients and 67 controls. Measurements were made at rest, during venous occlusion to estimate blood flow (indicated by slope increase of total haemoglobin, HbT), and post arterial occlusion. Additionally, measurements were made at the onset of isotonic unilateral heel-lifts to exhaustion and during recovery post exercise. Results: Adults with CHD had a slower desaturation rate at exercise onset (-7.7 ± 4.3%StO2x3.5sec-1 vs. -11.7 ± 5.8%StO2x3.5sec-1, p < 0.001) a slower half recovery time (28.6 ± 21.2s vs. 16.8 ± 11.1s, p < 0.001) and a slower resaturation rate post exercise in comparison to the control subjects (3.9 ± 3.7%StO2x3.5sec-1 vs. 6.1 ± 3.8%StO2x3.5sec-1, p = 0.002). In contrast, there were no differences in muscle oxygen kinetics at rest. Conclusion: Slower muscle oxygenation kinetics during muscle exercise found in adults with complex CHD may give insight to the mechanisms for the reduced exercise capacity commonly found in this population. This finding may also provide implications for design of exercise training programs targeting muscle function for these patients.

Pulmonary vasodilator therapy is still often an off-label treatment for pulmonary hypertension in children. The aim of this nationwide register-based study was to assess patient characteristics and strategies for pulmonary vasodilator therapy in young Swedish children. Prescription information for all children below seven years of age at treatment initiation, between 2007 and 2017, was retrieved from the National Prescribed Drug Register, and medical information was obtained by linkage to other registers. All patients were categorized according to the WHO classification of pulmonary hypertension. In total, 233 patients had been prescribed pulmonary vasodilators. The treatment was initiated before one year of age in 61% (N = 143). Sildenafil was most common (N = 224 patients), followed by bosentan (N = 29), iloprost (N = 14), macitentan (N = 4), treprostinil (N = 2) and riociguat (N = 2). Over the study period, the prescription rate for sildenafil tripled. Monotherapy was most common, 87% (N = 203), while 13% (N = 20) had combination therapy. Bronchopulmonary dysplasia (N = 82, 35%) and/or congenital heart defects (N = 156, 67%) were the most common associated conditions. Eight percent (N = 18) of the patients had Down syndrome. Cardiac catheterization had been performed in 39% (N = 91). Overall mortality was 13% (N = 30) during the study period. This study provides an unbiased overview of national outpatient use of pulmonary vasodilator therapy in young children. Few cases of idiopathic pulmonary arterial hypertension were found, but a large proportion of pulmonary hypertension associated with congenital heart defects or bronchopulmonary dysplasia. Despite treatment, mortality was high, and additional pediatric studies are needed for a better understanding of underlying pathologies and evidence of treatment effects.

Background: Peripheral muscle factors are presumed to be contributors to the reduced exercise capacity incongenital heart disease (CHD), but the underlying mechanisms are poorly understood. The aim was to investigate if muscle oxygenation, at rest and during exercise, and the resting blood flow in the calf muscle is impaired in adults with complex CHD in comparison to controls. Method: Seventy-four adults with complex CHD (35.6 ± 14.3 years, females n = 22 [30%], males n = 52 [70%]) and seventy-four age and sex matched subjects were recruited. Muscle oxygenation was successfully determined using near-infrared spectroscopy on the medial portion of m. gastrocnemius in 63 patients and 67 controls. Measurements were made at rest, during venous occlusion to estimate blood flow (indicated by slope increase of total haemoglobin, HbT), and post arterial occlusion. Additionally, measurements were made at the onset of isotonic unilateral heel-lifts to exhaustion and during recovery post exercise. Results: Adults with CHD had a slower desaturation rate at exercise onset (-7.7 ± 4.3%StO2x3.5sec-1 vs. -11.7 ± 5.8%StO2x3.5sec-1, p < 0.001) a slower half recovery time (28.6 ± 21.2s vs. 16.8 ± 11.1s, p < 0.001) and a slower resaturation rate post exercise in comparison to the control subjects (3.9 ± 3.7%StO2x3.5sec-1 vs. 6.1 ± 3.8%StO2x3.5sec-1, p = 0.002). In contrast, there were no differences in muscle oxygen kinetics at rest. Conclusion: Slower muscle oxygenation kinetics during muscle exercise found in adults with complex CHD may give insight to the mechanisms for the reduced exercise capacity commonly found in this population. This finding may also provide implications for design of exercise training programs targeting muscle function for these patients.

Pulmonary vasodilator therapy is still often an off-label treatment for pulmonary hypertension in children. The aim of this nationwide register-based study was to assess patient characteristics and strategies for pulmonary vasodilator therapy in young Swedish children. Prescription information for all children below seven years of age at treatment initiation, between 2007 and 2017, was retrieved from the National Prescribed Drug Register, and medical information was obtained by linkage to other registers. All patients were categorized according to the WHO classification of pulmonary hypertension. In total, 233 patients had been prescribed pulmonary vasodilators. The treatment was initiated before one year of age in 61% (N = 143). Sildenafil was most common (N = 224 patients), followed by bosentan (N = 29), iloprost (N = 14), macitentan (N = 4), treprostinil (N = 2) and riociguat (N = 2). Over the study period, the prescription rate for sildenafil tripled. Monotherapy was most common, 87% (N = 203), while 13% (N = 20) had combination therapy. Bronchopulmonary dysplasia (N = 82, 35%) and/or congenital heart defects (N = 156, 67%) were the most common associated conditions. Eight percent (N = 18) of the patients had Down syndrome. Cardiac catheterization had been performed in 39% (N = 91). Overall mortality was 13% (N = 30) during the study period. This study provides an unbiased overview of national outpatient use of pulmonary vasodilator therapy in young children. Few cases of idiopathic pulmonary arterial hypertension were found, but a large proportion of pulmonary hypertension associated with congenital heart defects or bronchopulmonary dysplasia. Despite treatment, mortality was high, and additional pediatric studies are needed for a better understanding of underlying pathologies and evidence of treatment effects.

Background: Peripheral muscle factors are presumed to be contributors to the reduced exercise capacity incongenital heart disease (CHD), but the underlying mechanisms are poorly understood. The aim was to investigate if muscle oxygenation, at rest and during exercise, and the resting blood flow in the calf muscle is impaired in adults with complex CHD in comparison to controls. Method: Seventy-four adults with complex CHD (35.6 ± 14.3 years, females n = 22 [30%], males n = 52 [70%]) and seventy-four age and sex matched subjects were recruited. Muscle oxygenation was successfully determined using near-infrared spectroscopy on the medial portion of m. gastrocnemius in 63 patients and 67 controls. Measurements were made at rest, during venous occlusion to estimate blood flow (indicated by slope increase of total haemoglobin, HbT), and post arterial occlusion. Additionally, measurements were made at the onset of isotonic unilateral heel-lifts to exhaustion and during recovery post exercise. Results: Adults with CHD had a slower desaturation rate at exercise onset (-7.7 ± 4.3%StO2x3.5sec-1 vs. -11.7 ± 5.8%StO2x3.5sec-1, p < 0.001) a slower half recovery time (28.6 ± 21.2s vs. 16.8 ± 11.1s, p < 0.001) and a slower resaturation rate post exercise in comparison to the control subjects (3.9 ± 3.7%StO2x3.5sec-1 vs. 6.1 ± 3.8%StO2x3.5sec-1, p = 0.002). In contrast, there were no differences in muscle oxygen kinetics at rest. Conclusion: Slower muscle oxygenation kinetics during muscle exercise found in adults with complex CHD may give insight to the mechanisms for the reduced exercise capacity commonly found in this population. This finding may also provide implications for design of exercise training programs targeting muscle function for these patients.

Unguarded mitral valve orifice is a rare disease with only 7 described cases in the literature. We describe the first known case of unguarded mitral valve orifice with normal segmental cardiac anatomy, severe left ventricular dilatation and dysfunction, aortic atresia, and atrial flutter. (Level of Difficulty: Advanced.).

AIMS: Orofacial clefts (OFC) are a heterogeneous group of birth defects arising in about 1.7/1000 newborns. They can occur with other congenital anomalies, including heart defects. We aim to describe a population with orofacial clefts and associated cardiac anomalies.METHODS: Retrospective study of patients attended in the Cleft Lip and Palate Multidisciplinary Group outpatient clinic at Hospital Universitario São João, Porto-Portugal. Medical records from January 1992 through December 2018 were reviewed. Patients were divided into four groups according to the Spina classification: cleft lip (CL), cleft lip and palate (CLP), isolated cleft palate (CP) and atypical cleft (AC). Further categorization included gender, affected relatives, associated congenital anomalies and syndromes.RESULTS: From the 588 patients included, 77 (13%) presented cardiac anomalies. Of those with orofacial cleft and cardiac anomalies, 53% were males and 17% had known affected relatives. CP was the most common cleft among patients with cardiac anomaly (~56%). Additional congenital anomalies were found in 89.7% of patients, namely facial defects, central nervous system, renal and skeletal malformations. A recognizable syndrome was identified in 61.5%, being Pierre-Robin the most common (n=22), followed by 22q11.2 microdeletion (n=9). Both additional congenital anomalies and recognizable syndromes were significantly more prevalent in patients with heart disease (p<0.05). The main groups of cardiac anomalies were left-to-right shunt (n=47) and right ventricular outflow tract obstruction (n=14). From these, 26 had a ventricular septal defect, 15 atrial septal defect and seven patients had tetralogy of Fallot. Five patients had dysrhythmias.CONCLUSIONS: Due to the high prevalence of cardiac anomalies in the cleft population, a routine cardiac evaluation should be performed in all these patients., INTRODUÇÃO: As fendas lábio-palatinas são um grupo heterogêneo de defeitos congênitos que ocorrem em cerca de 1,7 / 1000 recém-nascidos. Eles podem ocorrer com outras anomalias congênitas, incluindo defeitos cardíacos. O nosso objetivo é descrever uma população com fendas lábio-palatinas e anomalias cardíacas associadas.MÉTODOS: Estudo retrospectivo de doentes seguidos pelo Grupo Multidisciplinar de Fendas Lábio-Palatinas no Hospital Universitário São João, Porto-Portugal. Foram analisados os prontuários médicos de janeiro de 1992 a dezembro de 2018. Os doentes foram divididos em quatro grupos, de acordo com a classificação de Spina: fenda labial (CL), fenda labial e palatina (CLP), fenda palatina isolada (PC) e fenda atípica (CA). Outras categorizações incluíram sexo, parentes afetados, anomalias e síndromes congênitas associadas.RESULTADOS: Dos 588 pacientes incluídos, 77 (13%) apresentaram anomalias cardíacas. Daqueles com fenda e anomalias cardíacas, 53% eram do sexo masculino e 17% tinham parentes afetados. A PC foi a fenda mais comum entre os doentes com anomalia cardíaca (aproximadamente 56%). Anomalias congénitas adicionais, como defeitos faciais, malformações do sistema nervoso central, renais e esqueléticas foram encontradas em 89,7%. Síndromes foram identificadas em 61,5%, sendo Pierre-Robin a mais comum (n = 22), seguida pela microdeleção 22q11.2 (n = 9). Anomalias congénitas adicionais e a presença de uma síndrome genética foram significativamente mais prevalentes em doentes com doença cardíaca associada (p <0,05). Os principais grupos de anomalias cardíacas foram shunt da esquerda para a direita (n = 47) e obstrução da via de saída do ventrículo direito (n = 14). Destes, 26 apresentaram comunicação interventricular, 15 comunicação interauricular e sete pacientes apresentaram tetralogia de Fallot. Cinco pacientes apresentaram disritmias.CONCLUSÕES: Devido à elevada prevalência de anomalias cardíacas na população de doentes com Fenda Lábio-Palatina, acon

Background Peripheral muscle factors are presumed to be contributors to the reduced exercise capacity in congenital heart disease (CHD), but the underlying mechanisms are poorly understood. The aim was to investigate if muscle oxygenation, at rest and during exercise, and the resting blood flow in the calf muscle is impaired in adults with complex CHD in comparison to controls. Method Seventy-four adults with complex CHD (35.6 ± 14.3 years, females n = 22 [30%], males n = 52 [70%]) and seventy-four age and sex matched subjects were recruited. Muscle oxygenation was successfully determined using near-infrared spectroscopy on the medial portion of m. gastrocnemius in 63 patients and 67 controls. Measurements were made at rest, during venous occlusion to estimate blood flow (indicated by slope increase of total haemoglobin, HbT), and post arterial occlusion. Additionally, measurements were made at the onset of isotonic unilateral heel-lifts to exhaustion and during recovery post exercise. Results Adults with CHD had a slower desaturation rate at exercise onset (−7.7 ± 4.3%StO2x3.5sec−1 vs. −11.7 ± 5.8%StO2x3.5sec−1, p < 0.001) a slower half recovery time (28.6 ± 21.2s vs. 16.8 ± 11.1s, p < 0.001) and a slower resaturation rate post exercise in comparison to the control subjects (3.9 ± 3.7%StO2x3.5sec−1 vs. 6.1 ± 3.8%StO2x3.5sec−1, p = 0.002). In contrast, there were no differences in muscle oxygen kinetics at rest. Conclusion Slower muscle oxygenation kinetics during muscle exercise found in adults with complex CHD may give insight to the mechanisms for the reduced exercise capacity commonly found in this population. This finding may also provide implications for design of exercise training programs targeting muscle function for these patients.

Purpose: In this study we aimed to establish the genetic cause of a myriad of cardiovascular defects prevalent in individuals from a genetically isolated population, who were found to share a common ancestor in 1728. Methods: Trio genome sequencing was carried out in an index patient with critical congenital heart disease (CHD); family members had either exome or Sanger sequencing. To confirm enrichment, we performed a gene-based association test and meta-analysis in two independent validation cohorts: one with 2685 CHD cases versus 4370. These controls were also ancestry-matched (same as FTAA controls), and the other with 326 cases with familial thoracic aortic aneurysms (FTAA) and dissections versus 570 ancestry-matched controls. Functional consequences of identified variants were evaluated using expression studies. Results: We identified a loss-of-function variant in the Notch target transcription factor-encoding gene HEY2. The homozygous state (n = 3) causes life-threatening congenital heart defects, while 80% of heterozygous carriers (n = 20) had cardiovascular defects, mainly CHD and FTAA of the ascending aorta. We confirm enrichment of rare risk variants in HEY2 functional domains after meta-analysis (MetaSKAT p = 0.018). Furthermore, we show that several identified variants lead to dysregulation of repression by HEY2. Conclusion: A homozygous germline loss-of-function variant in HEY2 leads to critical CHD. The majority of heterozygotes show a myriad of cardiovascular defects.

Darstellung des Themas: Jährlich kommen in der Schweiz 600 bis 800 Kinder mit einem angeborenen Herzfehler zur Welt, wovon etwa 250 eine Operation benötigen. Die Lebenserwartung dieser Kinder hat sich dank operativen Fortschritten verbessert. Trotzdem ist die postoperative Phase für die Eltern des betroffenen Kindes eine emotionale Achterbahnfahrt. Fragestellung: «Wie erleben Eltern, deren Kind an einem angeborenen Herzfehler leidet, die postoperative Phase im akutstationären Setting?» Methode: Es wurde eine systematisierte Literaturrecherche in den pflegewissenschaftlichen Datenbanken «CINAHL Complete» und «PubMed» sowie per Schneeballsystem durchgeführt. Acht qualitative Studien wurden zusammengefasst, kritisch gewürdigt und auf ihre Evidenz geprüft. Anschliessend erfolgte ein Theorie-Praxis-Transfer. Relevante Ergebnisse: Aus den einbezogenen Studien konnten drei Hauptkategorien mit ihren jeweiligen Subthemen identifiziert werden: das Erleben, die Beziehungen und die Copingstrategien. Es hat sich herausgestellt, dass das Erleben der Eltern ein komplexes Geschehen ist und sie mit unzälligen intensiven Emotionen konfrontiert sind. Schlussfolgerung: Eltern, deren Kind an einem angeborenen Herzfehler leidet, sind diversen psychosozialen Belastungen ausgesetzt und benötigen eine ganzheitliche Betreuung im Sinne eines familienzentrierten Ansatzes durch die Pflegefachpersonen in der postoperativen Phase im akutstationären Setting.

BACKGROUND: Children operated on for a simple congenital heart defect (CHD) are at risk of neurodevelopmental abnor-malities. Abnormal cortical development and folding have been observed in fetuses with CHD. We examined whether sulcal folding patterns in adults operated on for simple CHD in childhood differ from those of healthy controls, and whether such differences are associated with neuropsychological outcomes. METHODS AND RESULTS: Patients (mean age, 24.5 years) who underwent childhood surgery for isolated atrial septal defect (ASD; n=33) or ventricular septal defect (VSD; n=30) and healthy controls (n=37) were enrolled. Sulcal pattern similarity to healthy controls was determined using magnetic resonance imaging and looking at features of sulcal folds, their intersulcal relationships, and sulcal graph topology. The sulcal pattern similarity values were tested for associations with comprehensive neuropsychological scores. Patients with both ASD and VSD had decreased sulcal pattern similarity in the left hemisphere compared with controls. The differences were found in the left temporal lobe in the ASD group and in the whole left hemisphere in the VSD group (P=0.033 and P=0.039, respectively). The extent of abnormal left hemispheric sulcal pattern similarity was associated with worse neuropsychological scores (intelligence, executive function, and visuospatial abilities) in the VSD group, and special educational support in the ASD group. CONCLUSIONS: Adults who underwent surgery for simple CHD in childhood display altered left hemisphere sulcal folding pat-terns, commensurate with neuropsychological scores for patients with VSD and special educational support for ASD. This may indicate that simple CHD affects early brain development. REGISTRATION: URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03871881.

Pulmonary vasodilator therapy is still often an off-label treatment for pulmonary hypertension in children. The aim of this nationwide register-based study was to assess patient characteristics and strategies for pulmonary vasodilator therapy in young Swedish children. Prescription information for all children below seven years of age at treatment initiation, between 2007 and 2017, was retrieved from the National Prescribed Drug Register, and medical information was obtained by linkage to other registers. All patients were categorized according to the WHO classification of pulmonary hypertension. In total, 233 patients had been prescribed pulmonary vasodilators. The treatment was initiated before one year of age in 61% (N = 143). Sildenafil was most common (N = 224 patients), followed by bosentan (N = 29), iloprost (N = 14), macitentan (N = 4), treprostinil (N = 2) and riociguat (N = 2). Over the study period, the prescription rate for sildenafil tripled. Monotherapy was most common, 87% (N = 203), while 13% (N = 20) had combination therapy. Bronchopulmonary dysplasia (N = 82, 35%) and/or congenital heart defects (N = 156, 67%) were the most common associated conditions. Eight percent (N = 18) of the patients had Down syndrome. Cardiac catheterization had been performed in 39% (N = 91). Overall mortality was 13% (N = 30) during the study period. This study provides an unbiased overview of national outpatient use of pulmonary vasodilator therapy in young children. Few cases of idiopathic pulmonary arterial hypertension were found, but a large proportion of pulmonary hypertension associated with congenital heart defects or bronchopulmonary dysplasia. Despite treatment, mortality was high, and additional pediatric studies are needed for a better understanding of underlying pathologies and evidence of treatment effects.

Background: Peripheral muscle factors are presumed to be contributors to the reduced exercise capacity incongenital heart disease (CHD), but the underlying mechanisms are poorly understood. The aim was to investigate if muscle oxygenation, at rest and during exercise, and the resting blood flow in the calf muscle is impaired in adults with complex CHD in comparison to controls. Method: Seventy-four adults with complex CHD (35.6 ± 14.3 years, females n = 22 [30%], males n = 52 [70%]) and seventy-four age and sex matched subjects were recruited. Muscle oxygenation was successfully determined using near-infrared spectroscopy on the medial portion of m. gastrocnemius in 63 patients and 67 controls. Measurements were made at rest, during venous occlusion to estimate blood flow (indicated by slope increase of total haemoglobin, HbT), and post arterial occlusion. Additionally, measurements were made at the onset of isotonic unilateral heel-lifts to exhaustion and during recovery post exercise. Results: Adults with CHD had a slower desaturation rate at exercise onset (-7.7 ± 4.3%StO2x3.5sec-1 vs. -11.7 ± 5.8%StO2x3.5sec-1, p < 0.001) a slower half recovery time (28.6 ± 21.2s vs. 16.8 ± 11.1s, p < 0.001) and a slower resaturation rate post exercise in comparison to the control subjects (3.9 ± 3.7%StO2x3.5sec-1 vs. 6.1 ± 3.8%StO2x3.5sec-1, p = 0.002). In contrast, there were no differences in muscle oxygen kinetics at rest. Conclusion: Slower muscle oxygenation kinetics during muscle exercise found in adults with complex CHD may give insight to the mechanisms for the reduced exercise capacity commonly found in this population. This finding may also provide implications for design of exercise training programs targeting muscle function for these patients.

Pulmonary vasodilator therapy is still often an off-label treatment for pulmonary hypertension in children. The aim of this nationwide register-based study was to assess patient characteristics and strategies for pulmonary vasodilator therapy in young Swedish children. Prescription information for all children below seven years of age at treatment initiation, between 2007 and 2017, was retrieved from the National Prescribed Drug Register, and medical information was obtained by linkage to other registers. All patients were categorized according to the WHO classification of pulmonary hypertension. In total, 233 patients had been prescribed pulmonary vasodilators. The treatment was initiated before one year of age in 61% (N = 143). Sildenafil was most common (N = 224 patients), followed by bosentan (N = 29), iloprost (N = 14), macitentan (N = 4), treprostinil (N = 2) and riociguat (N = 2). Over the study period, the prescription rate for sildenafil tripled. Monotherapy was most common, 87% (N = 203), while 13% (N = 20) had combination therapy. Bronchopulmonary dysplasia (N = 82, 35%) and/or congenital heart defects (N = 156, 67%) were the most common associated conditions. Eight percent (N = 18) of the patients had Down syndrome. Cardiac catheterization had been performed in 39% (N = 91). Overall mortality was 13% (N = 30) during the study period. This study provides an unbiased overview of national outpatient use of pulmonary vasodilator therapy in young children. Few cases of idiopathic pulmonary arterial hypertension were found, but a large proportion of pulmonary hypertension associated with congenital heart defects or bronchopulmonary dysplasia. Despite treatment, mortality was high, and additional pediatric studies are needed for a better understanding of underlying pathologies and evidence of treatment effects.

Background: Peripheral muscle factors are presumed to be contributors to the reduced exercise capacity incongenital heart disease (CHD), but the underlying mechanisms are poorly understood. The aim was to investigate if muscle oxygenation, at rest and during exercise, and the resting blood flow in the calf muscle is impaired in adults with complex CHD in comparison to controls. Method: Seventy-four adults with complex CHD (35.6 ± 14.3 years, females n = 22 [30%], males n = 52 [70%]) and seventy-four age and sex matched subjects were recruited. Muscle oxygenation was successfully determined using near-infrared spectroscopy on the medial portion of m. gastrocnemius in 63 patients and 67 controls. Measurements were made at rest, during venous occlusion to estimate blood flow (indicated by slope increase of total haemoglobin, HbT), and post arterial occlusion. Additionally, measurements were made at the onset of isotonic unilateral heel-lifts to exhaustion and during recovery post exercise. Results: Adults with CHD had a slower desaturation rate at exercise onset (-7.7 ± 4.3%StO2x3.5sec-1 vs. -11.7 ± 5.8%StO2x3.5sec-1, p < 0.001) a slower half recovery time (28.6 ± 21.2s vs. 16.8 ± 11.1s, p < 0.001) and a slower resaturation rate post exercise in comparison to the control subjects (3.9 ± 3.7%StO2x3.5sec-1 vs. 6.1 ± 3.8%StO2x3.5sec-1, p = 0.002). In contrast, there were no differences in muscle oxygen kinetics at rest. Conclusion: Slower muscle oxygenation kinetics during muscle exercise found in adults with complex CHD may give insight to the mechanisms for the reduced exercise capacity commonly found in this population. This finding may also provide implications for design of exercise training programs targeting muscle function for these patients.

BACKGROUND: Children operated on for a simple congenital heart defect (CHD) are at risk of neurodevelopmental abnor-malities. Abnormal cortical development and folding have been observed in fetuses with CHD. We examined whether sulcal folding patterns in adults operated on for simple CHD in childhood differ from those of healthy controls, and whether such differences are associated with neuropsychological outcomes. METHODS AND RESULTS: Patients (mean age, 24.5 years) who underwent childhood surgery for isolated atrial septal defect (ASD; n=33) or ventricular septal defect (VSD; n=30) and healthy controls (n=37) were enrolled. Sulcal pattern similarity to healthy controls was determined using magnetic resonance imaging and looking at features of sulcal folds, their intersulcal relationships, and sulcal graph topology. The sulcal pattern similarity values were tested for associations with comprehensive neuropsychological scores. Patients with both ASD and VSD had decreased sulcal pattern similarity in the left hemisphere compared with controls. The differences were found in the left temporal lobe in the ASD group and in the whole left hemisphere in the VSD group (P=0.033 and P=0.039, respectively). The extent of abnormal left hemispheric sulcal pattern similarity was associated with worse neuropsychological scores (intelligence, executive function, and visuospatial abilities) in the VSD group, and special educational support in the ASD group. CONCLUSIONS: Adults who underwent surgery for simple CHD in childhood display altered left hemisphere sulcal folding pat-terns, commensurate with neuropsychological scores for patients with VSD and special educational support for ASD. This may indicate that simple CHD affects early brain development. REGISTRATION: URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03871881.

We present a case of a 20-year-old man with tetralogy of Fallot status post-repair with a transannular patch and left pulmonary artery reconstruction at age 1 and subsequent pulmonary valve replacement with bioprosthetic valve 3 years ago. A transthoracic echocardiogram revealed severe bioprosthetic valve insufficiency. Cardiac magnetic resonance with 4-dimensional flow revealed a paravalvular leak. (Level of Difficulty: Intermediate.).

Organogenesis involves integration of myriad cell types, each progressing through successive stages of lineage specification, proliferation and differentiation. Establishment of unique gene networks within each cell drives fate determination and behavior, and mutations of the transcription factors that drive such networks can result in birth defects. Congenital heart malformations are the most common defects, and are caused by disruption of discrete subsets of progenitors that contribute to distinct cardiac structures. However, determining the transcriptional changes in individual cells that lead to organ-level defects in the heart has not been tractable. Here, we employed single-cell transcriptomics to interrogate early cardiac progenitor cells as they become specified during normal and abnormal cardiogenesis. We identified novel cell-type specific genes and uncovered additional heterogeneity within wild-type progenitor compartments. A network-based computational method that predicts lineage specifying transcription factors identified Hand2 as a specifier of outflow tract cells but not right ventricular cells, despite failure of right ventricular formation in Hand2-null mice. Temporal single-cell transcriptome analysis of Hand2-null embryos revealed failure of outflow tract myocardium specification, whereas right ventricular myocardium was appropriately specified, but exhibited differentiation defects and failed to migrate into the developing heart. We found dysregulation of retinoic acid signaling that was associated with posteriorization of anterior cardiac progenitors in Hand2-null mutant hearts and ectopic atrial gene expression in outflow tract cells and right ventricle precursors. This work reveals transcriptional determinants in individual cells that specify cardiac progenitor cell fate and differentiation, and exposes mechanisms of disrupted cardiac development and single-cell resolution, providing a framework to investigate congenital heart defects.

Organogenesis involves integration of myriad cell types, each progressing through successive stages of lineage specification, proliferation and differentiation. Establishment of unique gene networks within each cell drives fate determination and behavior, and mutations of the transcription factors that drive such networks can result in birth defects. Congenital heart malformations are the most common defects, and are caused by disruption of discrete subsets of progenitors that contribute to distinct cardiac structures. However, determining the transcriptional changes in individual cells that lead to organ-level defects in the heart has not been tractable. Here, we employed single-cell transcriptomics to interrogate early cardiac progenitor cells as they become specified during normal and abnormal cardiogenesis. We identified novel cell-type specific genes and uncovered additional heterogeneity within wild-type progenitor compartments. A network-based computational method that predicts lineage specifying transcription factors identified Hand2 as a specifier of outflow tract cells but not right ventricular cells, despite failure of right ventricular formation in Hand2-null mice. Temporal single-cell transcriptome analysis of Hand2-null embryos revealed failure of outflow tract myocardium specification, whereas right ventricular myocardium was appropriately specified, but exhibited differentiation defects and failed to migrate into the developing heart. We found dysregulation of retinoic acid signaling that was associated with posteriorization of anterior cardiac progenitors in Hand2-null mutant hearts and ectopic atrial gene expression in outflow tract cells and right ventricle precursors. This work reveals transcriptional determinants in individual cells that specify cardiac progenitor cell fate and differentiation, and exposes mechanisms of disrupted cardiac development and single-cell resolution, providing a framework to investigate congenital heart defects.

We present a case of a 20-year-old man with tetralogy of Fallot status post-repair with a transannular patch and left pulmonary artery reconstruction at age 1 and subsequent pulmonary valve replacement with bioprosthetic valve 3 years ago. A transthoracic echocardiogram revealed severe bioprosthetic valve insufficiency. Cardiac magnetic resonance with 4-dimensional flow revealed a paravalvular leak. (Level of Difficulty: Intermediate.).

Objective: To investigate the impact of feeding mode on neurodevelopmental outcomes in children with congenital heart defects. Design: A retrospective cohort study of 208 children with congenital heart disease (CHD), who had surgery from 1 January 2013 until 31 December 2016 at Texas Children’s Hospital, Houston, TX, US. Settings: University Hospital, Developmental Outcome Clinic. Outcomes measures: Standardized cognitive scores were assessed with Capute Scales and motor development with Revised Gesell Developmental Schedules. We analyzed anthropometrics, mode of feeding, surgical complexity, syndrome, and gender as predictors of developmental outcomes at four time points: hospital discharge, and 6, 12, and 24 months of age. Results: Mode of feeding is associated with neurodevelopmental outcome in children with CHD. Children on enteral feeding tubes had significantly lower developmental quotient (DQ) scores in cognition, communication, and motor function at 12 and 24 months compared to orally fed children. There were greater proportions of developmental delays (DQ < 70) in enteral tube fed children at the 6, 12, and 24 months visits. Further, there was a strong association between presence of enteral feeding tube, syndrome, and developmental outcome. Greater surgical complexity, weight gain and ethnicity were not associated with the developmental outcomes. Conclusions: Our findings suggest that the presence of an enteral feeding tube following corrective congenital heart surgery are at increased risk of neurodevelopmental delays at 12 and 24 months.

The purpose of this study was to illuminate pediatric nurses' (PNs) perceptions of support for families with a child with a congenital heart defect. The study used a qualitative design with narrative interviews with eight PNs in Northern Sweden, and the interview data were analyzed with content analysis. The analysis revealed that the nurses perceive that letting the parents be involved in their child's care is of great importance in supporting the families. Although they have a paternalistic attitude to the families, they also stated that nurses should inform the parents about the care of the child, create a good relationship with the family, and build trust among all parties involved.

BackgroundThe teratogenic effects of immunomodulatory and certain antimicrobial therapies are described in small rodents and humans. While the described teratogenic effects in small rodents have been extrapolated to make conclusions about its use in the pregnant dam, teratogenic effects of prednisone and doxycycline have not yet been reported in the dog. Here we report and describe midline defects observed in a litter of golden retriever puppies exposed to mid-gestational immunosuppressive and antimicrobial therapy.Case presentationTwenty-one days into gestation, the dam of a litter of eight golden retriever puppies was administered prednisone, doxycycline, and tramadol as treatment for immune-mediated polyarthritis. The individuals in the litter were subsequently diagnosed with a variety of midline defects and congenital cardiac defects. This case series describes the variety of identified defects and presents a descriptive account of complex congenital abnormalities that are likely secondary to teratogenic effects of one or more drugs administered during gestation. The available puppies, dam, and grand dam underwent thorough physical examination, complete echocardiogram, and where indicated, advanced imaging with various surgical corrections when possible. Numerous midline congenital defects and congenital heart disease were identified in the puppies evaluated. Ultimately 5 of 8 puppies born to the dam were presented for thorough evaluation. The midline defects include: gastroschisis (1), peritoneopericardial diaphragmatic hernias (4, PPDH), umbilical hernia (4), unilateral cryptorchidism (1 of 4 males), cleft palate (1), renal agenesis (1), renal abnormalities (1), sternal and vertebral abnormalities (3), remnant liver lobe (1) and malformations consistent with ductal plate malformations with congenital hepatic fibrosis (1). The congenital cardiac defects include: ventricular septal defect (4, VSD) and subaortic stenosis (4, SAS). The presence of greater than one

The clinical case of a 3.5-month-old girl with Down syndrome (regular trisomy), who was born from the mother with a mosaic form of this syndrome, is presented. The child has the characteristic Down syndrome phenotype and congenital heart defect. The surgical operation was performed — ligation of the open ductus arteriosus. Given the increased risk of complications due to congenital heart defect and health status, all children with this syndrome should be provided a genetic examination, geneticist and cardiologist consultations, and screening echocardiography. The article will familiarize paediatricians, cardiologists, family doctors and other specialists with the family case of Down syndrome and the results of surgical correction of congenital heart disease. Early echocardiographic screening and surgery significantly increase the duration and quality of life of these children., Представлено клиническое наблюдение девочки 3,5 месяцев с синдромом Дауна (регулярная трисомия), родившейся от матери c мозаичной формой данного синдрома. У ребенка наблюдались характерный фенотип синдрома Дауна и наличие врожденного порока сердца. Проведена хирургическая операция — перевязка открытого артериального протока. Учитывая повышенный риск осложнений, обусловленных врожденным пороком сердца и состоянием здоровья, всем детям с данным синдромом должны проводиться генетическое обследование, консультации генетика, кардиолога и скрининг-эхокардиографии. Статья ознакомит врачей-педиатров, кардиологов, семейных врачей и других специалистов с семейным случаем синдрома Дауна и результатами хирургической коррекции врожденного порока сердца. Ранний эхокардиографический скрининг и своевременное хирургическое вмешательство значительно повышают продолжительность и качество жизни этих детей., Наведено клінічне спостереження дівчинки 3,5 місяців із синдромом Дауна (регулярна трисомія), що народилася від матері з мозаїчною формою даного синдрому. У дитини спостерігалися притаманний синдрому Дауна фенотип та наявність природженої вади серця. Проведена хірургічна операція — перев’язка відкритої артеріальної протоки. Враховуючи підвищений ризик ускладнень, обумовлених природженою вадою серця та станом здоров’я, усім дітям з даним синдромом повинні проводитися генетичне обстеження, консультації генетика, кардіолога і скринінг-эхокардіографії. Стаття ознайомить лікарів-педіатрів, кардіологів, сімейних лікарів та інших спеціалістів з родинним випадком синдрому Дауна та результатами хірургічної корекції природженої вади серця. Ранній ехокардіографічний скринінг та своєчасне хірургічне втручання значно підвищують тривалість та якість життя цих дітей.

BackgroundThe teratogenic effects of immunomodulatory and certain antimicrobial therapies are described in small rodents and humans. While the described teratogenic effects in small rodents have been extrapolated to make conclusions about its use in the pregnant dam, teratogenic effects of prednisone and doxycycline have not yet been reported in the dog. Here we report and describe midline defects observed in a litter of golden retriever puppies exposed to mid-gestational immunosuppressive and antimicrobial therapy.Case presentationTwenty-one days into gestation, the dam of a litter of eight golden retriever puppies was administered prednisone, doxycycline, and tramadol as treatment for immune-mediated polyarthritis. The individuals in the litter were subsequently diagnosed with a variety of midline defects and congenital cardiac defects. This case series describes the variety of identified defects and presents a descriptive account of complex congenital abnormalities that are likely secondary to teratogenic effects of one or more drugs administered during gestation. The available puppies, dam, and grand dam underwent thorough physical examination, complete echocardiogram, and where indicated, advanced imaging with various surgical corrections when possible. Numerous midline congenital defects and congenital heart disease were identified in the puppies evaluated. Ultimately 5 of 8 puppies born to the dam were presented for thorough evaluation. The midline defects include: gastroschisis (1), peritoneopericardial diaphragmatic hernias (4, PPDH), umbilical hernia (4), unilateral cryptorchidism (1 of 4 males), cleft palate (1), renal agenesis (1), renal abnormalities (1), sternal and vertebral abnormalities (3), remnant liver lobe (1) and malformations consistent with ductal plate malformations with congenital hepatic fibrosis (1). The congenital cardiac defects include: ventricular septal defect (4, VSD) and subaortic stenosis (4, SAS). The presence of greater than one

Children and adolescents with a congenital heart defect (ConHD) frequently undergo painful or frightening medical procedures and hospitalizations. They often need multiple invasive procedures at a very young age and require regular checkups during their entire life. From other pediatric populations, it is known that these kinds of experiences can result in acute stress reactions and even in post-traumatic stress disorder (PTSD) in the long-term. PTSD and also subthreshold PTSD can lead to serious (psychosocial) impairment. However, limited information is available about PTSD in children with ConHD. Therefore, the aim of this review is to provide a summary of the current literature on post-traumatic stress (PTS) in children and adolescents with ConHD describing the prevalence of PTSD and its predictors/correlates. This review indicates that a range of 12-31% of children undergoing cardiac surgery develop PTSD. A range of 12-14% shows elevated post-traumatic stress symptoms (PTSS). These findings are comparable to those of hospitalized children without ConHD. Noteworthy, most studies used varying self-report questionnaires to measure PTSD and only one study used a semistructured interview. Although all studies point in the same direction of elevated PTSD and PTSS, systematic research is necessary to be able to draw firm conclusions. At present, as far as we know, in most clinics treating patients with ConHD, there is no regular screening for PTS in children with ConHD. In the reviewed literature, there is strong consensus that screening for PTSS and (preventive) psychological care for children and adolescents with ConHD is urgently needed.