Docosahexaenoic acid (DHA, 22:6n‐3), the major polyunsaturated fatty acid accumulated in the brain during development, has been implicated in learning and memory, but underlying cellular mechanisms are not clearly understood. Here, we demonstrate that DHA significantly affects hippocampal neuronal development and synaptic function in developing hippocampi. In embryonic neuronal cultures, DHA supplementation uniquely promoted neurite growth, synapsin puncta formation and synaptic protein expression, particularly synapsins and glutamate receptors. In DHA‐supplemented neurons, spontaneous synaptic activity was significantly increased, mostly because of enhanced glutamatergic synaptic activity. Conversely, hippocampal neurons from DHA‐depleted fetuses showed inhibited neurite growth and synaptogenesis. Furthermore, n‐3 fatty acid deprivation during development resulted in marked decreases of synapsins and glutamate receptor subunits in the hippocampi of 18‐day‐old pups with concomitant impairment of long‐term potentiation, a cellular mechanism underlying learning and memory. While levels of synapsins and NMDA receptor subunit NR2A were decreased in most hippocampal regions, NR2A expression was particularly reduced in CA3, suggesting possible role of DHA in CA3‐NMDA receptor‐dependent learning and memory processes. The DHA‐induced neurite growth, synaptogenesis, synapsin, and glutamate receptor expression, and glutamatergic synaptic function may represent important cellular aspects supporting the hippocampus‐related cognitive function improved by DHA.

Background-Left ventricular noncompaction is a cardiomyopathy characterized by excessive trabeculation of the left ventricle, progressive myocardial dysfunction, and early mortality. Left ventricular noncompaction has a heterogeneous clinical presentation that includes arrhythmia and sudden cardiac death. Methods and Results-We retrospectively reviewed all children diagnosed with left ventricular noncompaction at TexasChildren's Hospital from January 1990 to January 2009. Patients with congenital cardiac lesions were excluded. Two hundred forty-two children were diagnosed with isolated left ventricular noncompaction over the study period. Thirtyone (12.8%) died, and 13 (5.4%) were received a transplant. One hundred fifty (62%) presented with or developed cardiac dysfunction. The presence of cardiac dysfunction was strongly associated with mortality (hazard ratio, 11; P<0.001).ECG abnormalities were present in 87%, with ventricular hypertrophy and repolarization abnormalities occurring most commonly. Repolarization abnormalities were associated with increased mortality (hazard ratio, 2.1; P=0.02). Eighty children (33.1%) had an arrhythmia, and those with arrhythmias had increased mortality (hazard ratio, 2.8; P=0.002). Forty-two (17.4%) had ventricular tachycardia, with 5 presenting with resuscitated sudden cardiac death. In total, there were 15 cases of sudden cardiac death in the cohort (6.2%). Nearly all patients with sudden death (14 of 15) had abnormal cardiac dimensions or cardiac dysfunction. No patient with normal cardiac dimensions and function without preceding arrhythmias died. Conclusions-Left ventricular noncompaction has a high mortality rate and is strongly associated with arrhythmias in children. Preceding cardiac dysfunction or ventricular arrhythmias are associated with increased mortality. Children with normal cardiac dimensions and normal function are at low risk for sudden death. Brescia et al Mortality and Pediatric LVNC 2203the ventricular cavity, as demonstrated by color Doppler; and (3) a 2-layered structure of the endocardium with a noncompacted to compacted ratio >2.0. 8 Patients were included in the cohort only if both echocardiogram reviewers agreed on the diagnosis. Patients with LVNC and associated congenital heart disease or known metabolic syndromes (nonisolated LVNC) were excluded. Only patients primarily followed up at Texas Children's Hospital for LVNC were included; patients referred for isolated second opinions or only seen for single visits (without longitudinal follow-up) were excluded. The present study was approved by the Baylor College of Medicine Institutional Review Board, and individual consent was waived. Medical records were reviewed to document clinical presentation and course. Serial echocardiograms were analyzed for measures of systolic function (shortening fraction and ejection fraction), and cardiac dimensions were measured by M-mode echocardiography. Ejection fraction was calculated by the Simpson biplane method. Cardiac systolic dysfunction was defined as an...

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In children with isolated HCM managed primarily with exercise restriction and medication, cardiac death occurred infrequently. Non-SCD or transplant was at least as common as SCD. Extreme left ventricular hypertrophy and blunted blood pressure response to exercise were associated with an increased risk of non-SCD.