C ongenital heart defects (CHD) are the most common congenital malformations with an incidence of 0.5% to 1% of live births.1 They also are the first cause of mortality during the first year of life of newborns in developed countries.2 Despite therapeutic advances, CHD are associated with a high proportion of long term morbidity. Among CHD, a large subset involves the outflow tract (OFT). This heterogeneous group of malformations represents 20% to 30% of the CHD diagnosed in newborns.3 Transposition of the great arteries (TGA) accounts for 5% to 7% of all CHD 4 and is one of the most common cyanotic disorder diagnosed in the neonatal period with a prevalence of 0.2 per 1000 live births. The most common form of TGA is the dextro-looped type, which consists in a discordant ventriculoarterial connection implying that the aorta incorrectly arises from the right ventricle in an anterior and right-sided position, whereas the pulmonary artery incorrectly arises from the left ventricle in a posterior and left-sided position. By contrast to the normal heart in which both OFTs and great vessels show a dextral (right handed) spiralization, the great vessels in TGA present with a parallel course lacking normal spiralization. Coarctation Background-Congenital heart defects are the most frequent malformations among newborns and a frequent cause of morbidity and mortality. Although genetic variation contributes to congenital heart defects, their precise molecular bases remain unknown in the majority of patients. Methods and Results-We analyzed, by high-resolution array comparative genomic hybridization, 316 children with sporadic, nonsyndromic congenital heart defects, including 76 coarctation of the aorta, 159 transposition of the great arteries, and 81 tetralogy of Fallot, as well as their unaffected parents. We identified by array comparative genomic hybridization, and validated by quantitative real-time polymerase chain reaction, 71 rare de novo (n=8) or inherited (n=63) copy-number variants (CNVs; 50 duplications and 21 deletions) in patients. We identified 113 candidate genes for congenital heart defects within these CNVs, including BTRC, CHRNB3, CSRP2BP, ERBB2, ERMARD, GLIS3, PLN, PTPRJ, RLN3, and TCTE3. No de novo CNVs were identified in patients with transposition of the great arteries in contrast to coarctation of the aorta and tetralogy of Fallot (P=0.002; Fisher exact test). A search for transcription factor binding sites showed that 93% of the rare CNVs identified in patients with coarctation of the aorta contained at least 1 gene with FOXC1-binding sites. This significant enrichment (P<0.0001; permutation test) was not observed for the CNVs identified in patients with transposition of the great arteries and tetralogy of Fallot. We hypothesize that these CNVs may alter the expression of genes regulated by FOXC1. Foxc1 belongs to the forkhead transcription factors family, which plays a critical role in cardiovascular development in mice. Conclusions-These data suggest that deregulation of FOXC1 or its downstream ge...

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In our experience, despite the presence of several risk factors (growth retardation, chronic hypoxaemia, polycythaemia and left ventricular dysfunction), late repair of TOF was undertaken during childhood in patients from developing countries with no difference in postoperative morbidity and mortality compared with that of timely repair during infancy. These older patients can be discharged sooner. However, patients undergoing late surgery may be at higher risk of complications of right ventricular failure, such as pleural and/or pericardial effusion.

Background: Patent ductus arteriosus (PDA) is a condition frequently found in very preterm infants, and its treatment remains a subject of debate. Furthermore, there are only a few studies available that have examined the impact of these treatments on the neurological outcome of the patient. Objective: To evaluate the neurodevelopmental outcome of PDA treatment on preterm infants born between 24+0 and 28+6 weeks of gestation. Methods: We conducted an observational multicentric cohort study (LIFT Cohort). We compared three groups of patients according to their PDA treatment strategy: medical treatment with ibuprofen, surgical ligation, and no treatment. The neurodevelopmental outcome was assessed with a physical examination and cognitive function evaluation at 2 years of age. A propensity score was used to reduce bias in the analysis. Results: Between 2003 and 2011, 857 infants (91.3%) were evaluated at 2 years of corrected age and included in the analysis: 248 received ibuprofen treatment (29%), 104 had PDA surgical ligation (12%), and 505 did not receive any PDA treatment (59%). Surgical ligation of PDA was significantly associated with neurodevelopmental impairment at 2 years of age (adjusted odds ratio = 2.2; 95% confidence interval: 1.4-3.4). Conclusion: We found an association between PDA surgical ligation and a nonoptimal neurodevelopmental outcome at 2 years of age for preterm infants born before 29 weeks of gestation. These results suggest that if surgical ligation is unavoidable, particular attention should be given to the patient's neurodevelopmental follow-up.

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