Fluorinated steroids do not improve outcome of isolated atrioventricular block.

INTRODUCTION: Congenital atrioventricular block (CAVB) is a rare disorder with a significant morbidity and mortality. Consensus regarding the prescription and efficacy of prenatal corticosteroids is lacking. This nationwide study was initiated to evaluate the effects of prenatal treatment with corticosteroids on the outcome of CAVB in The Netherlands. METHODS: All fetuses identified with isolated congenital AVB-II° or AVB-III° in any of the eight academic fetal heart centers of The Netherlands between 2003 and 2013 were included and reviewed. RESULTS: Fifty-six fetuses were included. Fourteen (25%) fetuses were treated with dexamethasone. We found no differences between the steroid-treated and untreated cases regarding in utero progression of the AVB (63% vs 67% respectively), survival to birth (86% vs 84%), pacemaker implantations (74% vs 58%) or long-term dilated cardiomyopathy (13% vs 17%). Steroid treated fetuses demonstrated more in utero growth restriction (38% vs 11%). CONCLUSION: No benefit from prenatal corticosteroid treatment was demonstrated for fetuses with isolated CAVB in this study. However, we found negative side effects. Our data provide no evidence to support the routine administration of corticosteroids for the treatment of fetal CAVB.

KinCor, a national registry for paediatric patients with congenital and other types of heart disease in the Netherlands: aims, design and interim results.

OBJECTIVE: Studies in children with heart disease have been hampered by a lack of easily identifiable patient groups. Currently, there are few prospective population-based registries covering the entire spectrum of heart disease in children. KinCor is a Dutch national registry for children with heart diseases. This paper presents the aims, design and interim results of the KinCor project. METHODS: All children presenting at a Dutch university medical centre with a diagnosis of heart disease from 2012 onwards were eligible for registration in the KinCor database. Data entry is through a web-based portal. Entry codes have been synchronised with the European Paediatric Cardiac Coding system, allowing coupling with similar databases for adults, such as CONCOR. RESULTS: Between June 2012 and July 2015, 8421 patients were registered (76 % of those eligible). Median age of the patients was 9.8 years, 44.7 % were female; 6782 patients had morphological congenital heart disease. The most prevalent morphological congenital heart defects were ventricular septal defects (18 %), Tetralogy of Fallot (10 %) and transposition of great arteries (9 %). For 42 % of the patients additional diagnoses were registered. Sixty percent of patients had undergone at least one intervention (catheter intervention or surgery). CONCLUSION: The KinCor database has developed into a large registry of data of children with all types of heart disease and continues to grow. This database will provide the opportunity for epidemiological research projects on congenital and other types of heart disease in children. Entry codes are shared with the CONCOR database, which may provide a unique dataset.

Propranolol in a case series of 174 patients with complicated infantile haemangioma: indications, safety and future directions.

BACKGROUND: Infantile haemangioma (IH) is a benign, common and self-limiting tumour of infancy; only a minority of cases need active treatment. Currently, propranolol appears superior to classic treatments. OBJECTIVES: To document in a prospective study indications and side-effects of propranolol for complicated IH in a large patient group. METHODS: Analysis of prospectively collected data was performed on 174 patients with IH treated with propranolol in a tertiary referral centre from September 2008 to January 2012. RESULTS: The group consisted of children with a potentially threatening and/or complicated IH; the girl/boy ratio was 123/51, and the mean age at the start of treatment was 4·8 months. In 173 cases (99·4%), treatment was successful, as assessed nonquantitatively by clinical observation. This striking effect was characterized by immediate cessation of growth, softening, fading of the erythema and rapid induction of regression. The mean duration of treatment was 10·7 months. The most important adverse effects were hypotension (3·4%), wheezing (9·2%), nocturnal restlessness (22·4%) and cold extremities (36·2%). In one patient, propranolol was stopped. In 15 patients it was necessary to reduce the dose, although the lower dose was still effective. CONCLUSIONS: In this study, propranolol was effective and safe in almost all patients with complex IH. Administration of systemic medication to an infant with a benign condition requires careful consideration, as only a minority of patients with IH require an active medical intervention. A shift of the indication of propranolol for IH is evident, expanding its application for life-threatening situations or severe functional impairment to early prevention of disfigurement or cosmetically permanent sequelae. However, the indication for such an active approach should be determined by experienced physicians.

The MTHFR 677C->T polymorphism and the risk of congenital heart defects: a literature review and meta-analysis.

BACKGROUND: Periconceptional folic acid supplementation may protect against congenital heart defects (CHDs). Identification of candidate genes in folate metabolism has suggested that the 677C-->T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene may be particularly associated with the risk of CHDs. AIM: To assess the relationship between MTHFR 677C-->T and CHDs by literature review and meta-analysis. METHODS: Studies were identified by searches of electronic literature for papers focussing on MTHFR 677C-->T and the risk of any type of CHD. Both case-control comparisons and transmission-disequilibrium tests (TDTs) in family-based designs were included. RESULTS: We found 13 eligible studies. Of 10 case-control studies, four focused on the fetal polymorphism, two studied the maternal polymorphism, and a further four investigated both. Three further publications used a family-based association study to assess the effect of the T allele on cardiac development. Overall analysis yielded odds ratios of 1.3 (95%CI 0.97-1.73) and 1.2 (95%CI 0.83-1.74) for fetal and maternal MTHFR TT genotypes, respectively. TDTs revealed no association between fetal 677T allele and CHDs. DISCUSSION: This relatively small meta-analysis found no substantial evidence of increased CHD risk in individuals with MTHFR 677CT and TT genotypes. Heterogeneity regarding population background, study design and type of heart defects complicates the pooling and comparison of the studies. The effect of modification by periconceptional folic acid intake should be taken into account. Further larger studies and well-defined phenotypic subcategory analyses are needed to decide whether the MTHFR 677C-->T polymorphism of the affected child and/or their mother is truly a risk factor for the development of CHDs.

Hyperhomocysteinemia: a risk factor for ischemic stroke in children.

BACKGROUND: Moderate hyperhomocysteinemia is a risk factor for arterial vascular disease and venous thrombosis in adults. We performed a case-control study to assess a possible relation between moderate hyperhomocysteinemia and ischemic stroke in Dutch children (age range, 0 to 18 years). METHODS AND RESULTS: We measured plasma total homocysteine levels (tHcy) in 45 patients with ischemic stroke and in 234 controls. Hyperhomocysteinemia was defined as a tHcy above the 95th percentile regression line for the respective age of the controls. Hyperhomocysteinemia was present in 8 (18%) of the 45 patients with ischemic stroke. The odds ratio was 4.4 (95% CI, 1.7 to 11.6). CONCLUSIONS: We conclude that moderate hyperhomocysteinemia is a risk factor for ischemic stroke in children.