http://repub.eur.nl/res/aut/3432/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/14622/ 2008-10-01T00:00:00Z Background: With the exception of studies on folic acid, little evidence is available concerning other nutrients in the pathogenesis of congenital heart defects (CHDs). Fatty acids play a central role in embryonic development, and the B-vitamins riboflavin and nicotinamide are co-enzymes in lipid metabolism. Aim of the study: To investigate associations between the maternal dietary intake of fats, riboflavin and nicotinamide, and CHD risk in the offspring. Methods: A case-control family study was conducted in 276 mothers of a child with a CHD comprising of 190 outflow tract defects (OTD) and 86 non-outflow tract defects (non-OTD) and 324 control mothers of a non-malformed child. Mothers filled out general and food frequency questionnaires at 16 months after the index-pregnancy, as a proxy of the habitual food intake in the preconception period. Nutrient intakes (medians) were compared between cases and controls by Mann-Whitney U test. Odds ratios (OR) for the association between CHDs and nutrient intakes were estimated in a logistic regression model. Results: Case mothers, in particular mothers of a child with OTD, had higher dietary intakes of saturated fat, 30.9 vs. 29.8 g/d; P < 0.05. Dietary intakes of riboflavin and nicotinamide were lower in mothers of a child with an OTD than in controls (1.32 vs. 1.41 mg/d; P < 0.05 and 14.6 vs. 15.1 mg/d; P < 0.05, respectively). Energy, unsaturated fat, cholesterol and folate intakes were comparable between the groups. Low dietary intakes of both riboflavin (<1.20 mg/d) and nicotinamide (<13.5 mg/d) increased more than two-fold the risk of a child with an OTD, especially in mothers who did not use vitamin supplements in the periconceptional period (OR 2.4, 95%CI 1.4-4.0). Increasing intakes of nicotinamide (OR 0.8, 95%CI 0.7-1.001, per unit standard deviation increase) decreased CHD risk independent of dietary folate intake. Conclusions: A maternal diet high in saturated fats and low in riboflavin and nicotinamide seems to contribute to CHD risk, in particular OTDs. http://repub.eur.nl/res/pub/29139/ 2008-08-01T00:00:00Z OBJECTIVE: To investigate whether the association between the maternal methylation status as reflected by low S-adenosylmethionine and high S-adenosylhomocysteine, is detrimental for cardiogenesis and congenital heart disease (CHD) in the offspring. METHODS: As part of a case-control study in the western part of the Netherlands, we evaluated 231 mothers of children with CHD and 315 control mothers of nonmalformed children. The total case group was analyzed and stratified into isolated (n=180) and nonisolated CHDs (n=51). The latter subgroup was further subdivided into Nonsyndromic (n=20), Down Syndrome (n=19), and Other Syndromes (n=12). A multivariable general linear model was used to test for differences between the case groups and controls. All analyses were adjusted for current B vitamin supplement use. RESULTS: Plasma total homocysteine was significantly different between the total case group (median, range 10.3, 4.0-43.8, P=.026) and the nonisolated cases (11.1, 5.5-43.8, P=.006) compared with the controls (10.0, 5.3-42.0). The subgroup of Down Syndrome presented significantly higher total homocysteine and S-adenosylhomocysteine levels and a lower S-adenosylmethionine/S-adenosylhomocysteine ratio than controls. CONCLUSION: Maternal hyperhomocysteinemia, and not hypomethylation, is a risk factor for having a child with CHD. Maternal hypomethylation, however, seems to be associated with offspring having CHD and Down syndrome. http://repub.eur.nl/res/pub/8313/ 2002-01-01T00:00:00Z BACKGROUND: In patients with the tetralogy of Fallot, QRS prolongation predicts malignant ventricular arrhythmias. QRS prolongation may result from right ventricular dilatation. The relation of ECG markers to biventricular wall mass and volumes has not been assessed. OBJECTIVE: To investigate the relations of surface ECG markers of depolarisation and repolarisation to right and left ventricular volume and biventricular wall mass. METHODS: 37 Fallot patients (mean (SD) age 17 (9) years) were studied 14 (8) years after surgical repair; 34 had important pulmonary regurgitation. Left and right ventricular size was assessed from tomographic magnetic resonance imaging (MRI), and the amount of pulmonary regurgitation by velocity mapping MRI. QT, QRS, and JT duration and interlead dispersion markers were derived from a standard 12 lead ECG. RESULTS: Mean QRS duration was significantly prolonged (133 (31) v 91 (11) ms in controls), as were dispersion of QRS (36 (17) v 20 (6) ms), QT interval (87 (48) v 42 (20) ms), and JT interval (93 (48) v 42 (19) ms). Biventricular volumes were increased (right ventricular end diastolic volume, 129 (41) v 70 (9) ml/m(2); left ventricular end diastolic volume, 83 (16) v 69 (10) ml/m(2)), as was right ventricular wall mass (24 (7) v 17 (2) g/m(2)). QRS duration correlated best with right ventricular mass (r = 0.55, p < 0.01). CONCLUSIONS: In patients operated on for tetralogy of Fallot and with pulmonary regurgitation, ECG predictors of ventricular arrhythmias are influenced by several mechanical factors that may occur simultaneously. These include increased right ventricular volume, but also increases in left ventricular volume and in right and left ventricular wall mass. http://repub.eur.nl/res/pub/9997/ 2002-01-01T00:00:00Z OBJECTIVE: The purpose of the present study was to determine the symptomatology, diagnostic procedures, and therapeutic strategies of patients with an isolated unilateral absence of a pulmonary artery (UAPA). BACKGROUND: Isolated UAPA is a rare anomaly. Some case reports exist, but the best diagnostic and therapeutic approaches to these patients remain unclear. METHODS: A retrospective analysis was made of 108 cases reported between 1978 and 2000. The database of the National Library of Medicine (MEDLINE) was used to identify cases that were published in any language from 1978 onward. RESULTS: Of the 108 patients identified, 14 were asymptomatic. The median age was 14 years (range, 0.1 to 58 years). Most patients had symptoms such as frequent pulmonary infections (37%), dyspnea or limited exercise tolerance (40%), or hemoptysis (20%). Pulmonary hypertension was present in 44% of the patients. Surgical procedures were performed in 17% of patients, and the overall mortality rate was 7%. CONCLUSION: Only a few patients with isolated UAPA remain asymptomatic during follow-up. The diagnosis can be made by chest radiograph, echocardiography, CT scan, and MRI. Hilar arteries can be shown by cardiac catheterization and pulmonary venous wedge angiography. This is important since revascularization may improve pulmonary hypertension. The avoidance of high altitudes and pregnancy may further improve outcomes.