Browsing by Author "Jovanovic, Ida (23989306000)"

Small terminal or interstitial deletions involving bands 4q34 and 4q35 have been described in several patients with a relatively mild phenotype such as mild to moderate intellectual disability and minor dysmorphic features. We present a boy born from unrelated parents with a de novo 4q34.1-q35.2 deletion and clinical features resembling 22q11.2 deletion syndrome. To the best of our knowledge, this is the first reported patient with 4q34-q35 deletion and phenotype resembling 22q11.2 deletion syndrome without fifth finger anomalies as a specific feature of 4q- syndrome. G-banding karyotyping disclosed the deletion, which was further delineated by microarray comparative genomic hybridization. Fluorescence in situ hybridization and multiplex ligation-dependent probe amplification analyses did not reveal rearrangements of 22q11.2 region. MLPA confirmed the deletion within the 4q35.2 region. Conclusion: Given the considerable clinical overlaps between the 22q11.2 deletion syndrome and clinical manifestation of the patient described in this study, we propose that region 4q34.1-q35.2 should be considered as another region associated with phenotype resembling 22q11.2 deletion syndrome. We also propose that distal 4q deletions should be considered in the evaluation of patients with phenotypic manifestations resembling 22q11.2 deletion syndrome in whom no 22q11.2 microdeletion was detected, even in the absence of distinctive fifth finger anomalies. Additionally, we underline the importance of applying array CGH that enables simultaneous genome-wide detection and delineation of copy number changes (e.g., deletions and duplications). © 2011 Springer-Verlag.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) represents one of the most common causes of myocardial ischemia in infants and if left untreated results in a high mortality rate. When ALCAPA coexists with other congenital malformations, particularly those associated with pulmonary hypertension, the initial presentation can be quite confusing and is often misinterpreted. We report an infant with ALCAPA associated with scimitar syndrome and aortic coarctation whose clinical course illustrates the complexities and difficulties of management with a successful outcome. © 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc.

Background: The angiotensin-converting enzyme inhibitor (ACEI) enalapril is often administered to infants and young children with heart failure (HF) in various dosing regimens and formulations not adapted for their age. Methods: This prospective, two-center, open-label 8-week study evaluated an age-appropriate formulation of orodispersible minitablets (ODMTs) of enalapril (0.25 mg and 1 mg) in children aged 0 to 6 years with HF due to congenital heart disease. An age/weight-based dosing schedule was followed. Measures of echocardiographic parameters, blood pressure, heart rate, modified Ross score, and biochemistry were obtained over the 8-week period. The following two groups were assessed: ACEI-naïve and ACEI-pretreated patients. Results: In total, 53 children (age range of 0.05 to 4.8 years) were enrolled and 29 were ACEI-naïve. The average enalapril dose was 0.098 mg/kg (0.06–0.17 mg/kg) in the naïve group and 0.15 mg/kg (0.07–0.3 mg/kg) in pretreated patients. After 8 weeks, the modified Ross score and left ventricular diastolic dimension (LVD) z-score showed a significant decrease in both groups (p < 0.005). During 8 weeks follow-up, there were no difference in the z-scores for the systolic blood pressure (p = 0.071) or heart rate (p = 0.146). Conclusions: Pediatric patients treated with ODMTs of enalapril for 8 weeks had favorable improvements in LVD and HF symptoms. © 2024 by the authors.

Objectives: This study was conducted to determine the effects of carvedilol adjunct to standard treatment on left ventricular function (LVF), estimated as ejection fraction (EF) and fractional shortening (FS) on echocardiography, in children with idiopathic dilated cardiomyopathy (DCM). A secondary end point was to characterize the antioxidant potential of carvedilol. Methods: Hospitalized children aged ≤16 years with clinically stable DCM and advanced congestive heart failure (HF) with modified New York Heart Association Classification for Children (NYHAC) functional classes II to IV and EF <40% were enrolled in this prospective, 12-month, 2-center, open-label study. Oral carvedilol was added to a standard regimen of an angiotensin-converting enzyme inhibitor, a diuretic, and digoxin in a dose-escalation design. Systolic and diastolic blood pressure (BP), heart rate (HR), and modified NYHAC were assessed before (baseline) and at 1, 3, 6, and 12 months of adjunct carvedilol treatment. EF and FS were analyzed before and at 6 and 12 months of carvedilol treatment. At each study visit, tolerability was assessed in terms of adverse events (AEs), treatment emergent signs and symptoms, physical examination including vital sign measurement (BP, HR, and body temperature), and laboratory analysis. Antioxidative enzyme activity was evaluated by measuring erythrocyte copper/zinc superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activity at baseline and 1, 3, 6, and 12 months of adjunct carvedilol treatment. For assessment of antioxidative enzyme activity, a control group comprised 29 age-matched healthy children. Results: Twenty-one children (12 boys, 9 girls; age range, 7 months to 16 years; 100% white) completed the study. Four patients discontinued carvedilol at the beginning of the study due to severe arrhythmia which required amiodarone therapy (2 patients), bradycardia and hypotension (1), and bronchospasm (1). Carvedilol (0.4 mg/kg/d in children ≤62.5 kg or 25 mg/d in children >62.5 kg) was associated with significant decreases from baseline in systolic BP (130 [4] vs 123 [3] mm Hg; P < 0.05), diastolic BP (85 [4] vs 77 [4] mm Hg; P < 0.05), and HR (81 [4] vs 65 [4] bpm; P < 0.001) after the first month of addition to standard therapy. At 6 months, there were significant improvements from baseline in EF (37.2% [2.4%] vs 50.2% [2.3%]; P < 0.001) and FS (18.37% [2.00%] vs 23.58% [0.90%]; P < 0.001). Modified NYHAC class was significantly improved in 80% of children (2.9 vs 2.3; P < 0.001) at 12 months. The highest dose of carvedilol (0.8 mg/kg/d in children ≤62.5 kg or 50 mg/d in children >62.5 kg) was well tolerated in all 21 children. No serious AEs that necessitated study drug discontinuation (tiredness, headache, vomiting) were observed. At baseline, mean (SE) erythrocyte SOD activity (2781 [116] vs 2406 [102] U/g Hb; P < 0.05) and GR activity (5.3 [0.3] vs 3.0 [0.2] μmol nicotinamide adenine dinucleotide phosphate [NADPH]/min/g Hb; P < 0.001) were significantly higher in children with DCM who received standard therapy compared with healthy controls.CAT activity (12.7[0.9] vs 18.5 [1.0]U/g Hb; P < 0.001) was significantly lower, while GSH-Px was unchanged. At 6 and 12 months of therapy, carvedilol plus standard treatment was associated with significant decreases from baseline in SOD (2516 [126] and 2550 [118], respectively, vs 2781 [116] U/g Hb; both, P<0.001) and GR (4.7 [0.3] and 4.1 [0.2], respectively, vs 5.3 [0.2] μmol NADPH/min/g Hb; P < 0.05 and P < 0.001) and increased CAT (16.9 [1.0] and 16.4 [0.7], respectively, vs 12.7 [0.9] U/g Hb; both, P < 0.001). Conclusions: These pediatric patients with DCM treated for 12 months with carvedilol (up to 0.8 mg/kg/d in children ≤62.5 kg or 50 mg/d in children >62.5 kg) were found to have significant improvements in LVF and symptoms of HF. Twelve months of carvedilol therapy was associated with antioxidant enzyme activities near those observed in healthy children. © 2008 Excerpta Medica Inc.

Objectives: This study was conducted to determine the effects of carvedilol adjunct to standard treatment on left ventricular function (LVF), estimated as ejection fraction (EF) and fractional shortening (FS) on echocardiography, in children with idiopathic dilated cardiomyopathy (DCM). A secondary end point was to characterize the antioxidant potential of carvedilol. Methods: Hospitalized children aged ≤16 years with clinically stable DCM and advanced congestive heart failure (HF) with modified New York Heart Association Classification for Children (NYHAC) functional classes II to IV and EF <40% were enrolled in this prospective, 12-month, 2-center, open-label study. Oral carvedilol was added to a standard regimen of an angiotensin-converting enzyme inhibitor, a diuretic, and digoxin in a dose-escalation design. Systolic and diastolic blood pressure (BP), heart rate (HR), and modified NYHAC were assessed before (baseline) and at 1, 3, 6, and 12 months of adjunct carvedilol treatment. EF and FS were analyzed before and at 6 and 12 months of carvedilol treatment. At each study visit, tolerability was assessed in terms of adverse events (AEs), treatment emergent signs and symptoms, physical examination including vital sign measurement (BP, HR, and body temperature), and laboratory analysis. Antioxidative enzyme activity was evaluated by measuring erythrocyte copper/zinc superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activity at baseline and 1, 3, 6, and 12 months of adjunct carvedilol treatment. For assessment of antioxidative enzyme activity, a control group comprised 29 age-matched healthy children. Results: Twenty-one children (12 boys, 9 girls; age range, 7 months to 16 years; 100% white) completed the study. Four patients discontinued carvedilol at the beginning of the study due to severe arrhythmia which required amiodarone therapy (2 patients), bradycardia and hypotension (1), and bronchospasm (1). Carvedilol (0.4 mg/kg/d in children ≤62.5 kg or 25 mg/d in children >62.5 kg) was associated with significant decreases from baseline in systolic BP (130 [4] vs 123 [3] mm Hg; P < 0.05), diastolic BP (85 [4] vs 77 [4] mm Hg; P < 0.05), and HR (81 [4] vs 65 [4] bpm; P < 0.001) after the first month of addition to standard therapy. At 6 months, there were significant improvements from baseline in EF (37.2% [2.4%] vs 50.2% [2.3%]; P < 0.001) and FS (18.37% [2.00%] vs 23.58% [0.90%]; P < 0.001). Modified NYHAC class was significantly improved in 80% of children (2.9 vs 2.3; P < 0.001) at 12 months. The highest dose of carvedilol (0.8 mg/kg/d in children ≤62.5 kg or 50 mg/d in children >62.5 kg) was well tolerated in all 21 children. No serious AEs that necessitated study drug discontinuation (tiredness, headache, vomiting) were observed. At baseline, mean (SE) erythrocyte SOD activity (2781 [116] vs 2406 [102] U/g Hb; P < 0.05) and GR activity (5.3 [0.3] vs 3.0 [0.2] μmol nicotinamide adenine dinucleotide phosphate [NADPH]/min/g Hb; P < 0.001) were significantly higher in children with DCM who received standard therapy compared with healthy controls.CAT activity (12.7[0.9] vs 18.5 [1.0]U/g Hb; P < 0.001) was significantly lower, while GSH-Px was unchanged. At 6 and 12 months of therapy, carvedilol plus standard treatment was associated with significant decreases from baseline in SOD (2516 [126] and 2550 [118], respectively, vs 2781 [116] U/g Hb; both, P<0.001) and GR (4.7 [0.3] and 4.1 [0.2], respectively, vs 5.3 [0.2] μmol NADPH/min/g Hb; P < 0.05 and P < 0.001) and increased CAT (16.9 [1.0] and 16.4 [0.7], respectively, vs 12.7 [0.9] U/g Hb; both, P < 0.001). Conclusions: These pediatric patients with DCM treated for 12 months with carvedilol (up to 0.8 mg/kg/d in children ≤62.5 kg or 50 mg/d in children >62.5 kg) were found to have significant improvements in LVF and symptoms of HF. Twelve months of carvedilol therapy was associated with antioxidant enzyme activities near those observed in healthy children. © 2008 Excerpta Medica Inc.

Objective: The incidence of the 22q11.2 microdeletion among children who have at least two out of five major clinical criteria for 22q11.2 deletion syndrome. Design: Prospective study. Setting: University Children’s Hospital in Belgrade, Serbia between 2005 and 2014. Participants: 57 patients with clinical characteristics of 22q11.2 deletion syndrome. Methods: Standard G-banding cytogenetic analysis was performed in all children, and the 22q11.2 genomic region was examined using fluorescence in situ hybridization (FISH). For patients with no deletion detected by FISH, multiplex ligationdependent probe amplification (MLPA) analysis was also done in order to detect cryptic deletions of this region and to analyze other genomic loci associated with phenotypes resembling the syndrome. A selected group of patients diagnosed to have 22q11.2 microdeletion by FISH underwent MLPA testing in order to characterize the size and position of deletion. Outcome Measure: The frequency of 22q11.2 microdeletion among children with at least two of the five major characteristics of 22q11.2 deletion syndrome (heart malformations, facial dysmorphism, T-cell immunodeficiency, palatal clefts and hypocalcemia/hypoparathyroidism) Results: Typical 22q11.2 microdeletion was detected in 42.1% of patients; heart malformation were identified in all of them, facial dysmorphism in 79.2%, immunological problems in 63.6%, hypocalcemia in 62.5% and cleft palate in 8.3%. Conclusions: A higher detection rate compared to one-feature criterion is obtained when at least two major features of 22q11.2 deletion syndrome are taking into consideration. The criteria applied in this study could be considered by centers in lowincome countries. © 2016, Indian Academy of Pediatrics.

Objective To characterise heart failure (HF) maintenance pharmacotherapy for children across Europe and investigate how angiotensin-converting enzyme inhibitors (ACE-I) are used in this setting. Methods A Europe-wide web-based survey was conducted between January and May 2015 among European paediatricians dedicated to cardiology. Results Out of 200-eligible, 100 physicians representing 100 hospitals in 27 European countries participated. All participants reported prescribing ACE-I to treat dilated cardiomyopathy-related HF and 97% in the context of congenital heart defects; 87% for single ventricle physiology. Twenty-six per cent avoid ACE-I in newborns. Captopril was most frequently selected as first-choice for newborns (73%) and infants and toddlers (66%) and enalapril for children (56%) and adolescents (58%). Reported starting and maintenance doses varied widely. Up to 72% of participants follow formal creatinine increase limits for decision-making when up-titrating; however, heterogeneity in the cut-off points selected existed. ACE-I formulations prescribed by 47% of participants are obtained from more than a single source. Regarding symptomatic HF maintenance therapy, 25 different initial drug combinations were reported, although 79% select a regimen that includes ACE-I and diuretic (thiazide and/or loop), 61% ACE-I and aldosterone antagonist; 44% start with beta-blocker, 52% use beta-blockers as an add-on drug. Of the 89 participants that prescribe pharmacotherapy to asymptomatic patients, 40% do not use ACE-I monotherapy or ACE-I-beta-blocker two-drug only combination. Conclusions Despite some reluctance to use them in newborns, ACE-I seem key in paediatric HF treatment strategies. Use in single ventricle patients seems frequent, in apparent contradiction with current paediatric evidence. Disparate dosage criteria and potential formulation-induced variability suggest significant differences may exist in the risk-benefit profile children are exposed to. No uniformity seems to exist in the drug regimens in use. The information collected provides relevant insight into real-life clinical practice and may facilitate research to identify the best therapeutic options for HF children. © 2019 BMJ Publishing Group Limited.

Background: Little evidence exists to support pharmacotherapeutic strategies for heart failure management in paediatrics. A recent Europe-wide survey suggests that this translates into substantial variability in clinical practice.Objective: To conduct a formal discussion among an expert group of paediatric cardiology physicians on controversial aspects regarding the pharmacotherapy of children heart failure, facilitate consensus, and highlight areas of agreement and disagreement.Methods: A two-round modified Delphi process was conducted between July and August 2015. Topics addressed were predominantly selected from the results of a previous Europe-wide survey. Fourteen statements were presented for discussion grouped under three categories; Angiotensin-converting-enzyme-inhibitors: Considerations for optimal dosage; Angiotensin-converting-enzyme-inhibitors for the management of CHDs; Neurohumoral antagonists for the management of dilated cardiomyopathy-related heart failure.Results: A total of 13 paediatricians dedicated to cardiology from across Europe and the United States of America completed the study; of them, 92% had a working experience in the field of more than 10 years and were working in a specific paediatric cardiology unit. Agreement on the acceptance/rejection of 11 statements was achieved. Results show agreement on the importance of a set of topics relevant to the standardisation of the therapy as well as consensus upon specific therapeutic attitudes.Conclusions: We have found areas of common thinking and motivation, which can provide a means of triggering scientific collaboration. Our results might also contribute to disseminate available paediatric evidence and promote reducing unjustified variability in everyday practice. Until solid evidence is available, other research methods can contribute to advancing the goal of safe and effective paediatric heart failure pharmacotherapy. © Cambridge University Press 2019.

[No abstract available]

22q11.2 microdeletion is the most common microdeletion in humans. The purpose of this study was to evaluate postoperative outcome in children with 22q11.2 microdeletion who had undergone complete surgical correction of a congenital heart defect. The study included 34 patients who underwent complete correction of conotruncal heart defects. Of these, 17 patients diagnosed with 22q11.2 microdeletion represent the investigated group. Another 17 patients without 22q11.2 microdeletion represent the control group. Investigated and control groups differ significantly for total length of stay in the hospital (average 37.35 and 14.12 days, respectively); length of postoperative stay in the intensive care unit (average 10.82 and 6.76 days, respectively); sepsis (eight and two patients, respectively); administration of antibiotics (15 and seven patients, respectively); duration of antibiotic therapy (average 17.65 and 14.59 days, respectively); occurrence of hypocalcemia (16 and 0 patients, respectively); and initiation of peroral nutrition during the postoperative course (average 10.29 and 3.88 days, respectively). No difference was found for duration of ventilatory support (average 6.12 and 4.24 days, respectively), administration of total parenteral nutrition, and postoperative mortality rate. The study results suggest that genotype of 22q11.2 microdeletion affects postoperative outcome after cardiac surgery. Possible targets for intervention in postoperative intensive care management are prevention and treatment of systemic infections, monitoring, and treatment of hypocalcemias, rational administration of antibiotics and careful planning of nutrition. Consequently, this could shorten patients’ intensive care stay and overall duration of hospitalization. © 2017, Springer Science+Business Media, LLC.

Malposition of the branch pulmonary arteries is a rare malformation with two forms. In the typical form, pulmonary arteries cross each other as they proceed to their respective lungs. The lesser form is characterised by the left pulmonary artery ostium lying directly superior to the ostium of the right pulmonary artery, without crossing of the branch pulmonary arteries. Malposition of the branch pulmonary arteries is often associated with other congenital heart defects and extracardiac anomalies, as well as with 22q11.2 microdeletion. We report three infants with crossed pulmonary arteries and one adolescent with lesser form of the malformation. The results suggest that diagnosis of malposition of the branch pulmonary arteries could be challenging if based solely on echocardiography, whereas modern imaging technologies such as contrast computed tomography and magnetic resonance angiography provide reliable establishment of diagnosis. In addition, we performed the first molecular characterisation of the 22q11.2 region among patients with malposition of the branch pulmonary arteries and revealed a 3-megabase deletion in two out of four patients. © 2012 Cambridge University Press.

Ultrasound is the screening modality of choice for the fetal imaging. However, there are circumstances in which an alternative imaging technique is needed for additional information regarding fetal anatomy and pathology as well as different maternal conditions. Magnetic resonance imaging (MRI) is being increasingly used as correlative imaging modality in pregnancy because it uses no ionizing radiation, provides excellent soft-tissue contrast, and has multiple planes for reconstruction and large field of view, allowing better depiction of anatomy in fetuses with large or complex anomalies. In this review, we attempted to identify strengths and weaknesses of each modality both from the literature and our own working experience, and to propose to some practical recommendations on when to use which imaging modality. Both ultrasonography and MRI are operator-dependant and neither technique obviates the need for thorough knowledge of normal and abnormal anatomy. In early pregnancy, and where repeated assessment is needed, ultrasound has the obvious advantage. In circumstances where ultrasound examination is difficult, as in the obese patient or severe oligohydramnion, better images might be obtained by MRI examination. MRI might also identify early fetal ischemic lesions after an insult, such as maternal trauma or death of a monochorionic co-twin. From the published literature, it would appear that MRI may provide additional diagnostic information to that given by ultrasound in 25 to 55% of cases, which in turn may have influence on parental counseling and/or management of affected pregnancies. Individual circumstances and expertise influence the accuracy of both modalities. Ultrasound and MRI should be performed to the highest possible standard, and the final diagnosis should be made in a multidisciplinary setting.