AIMS: Recent studies have suggested a possible association between maternal use of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy and cardiovascular anomalies. The aim of the present study was to evaluate the teratogenic risk of paroxetine and fluoxetine.\ud \ud METHODS: This multicentre, prospective, controlled study evaluated the rate of major congenital anomalies after first-trimester gestational exposure to paroxetine, fluoxetine or nonteratogens.\ud \ud RESULTS: We followed up 410 paroxetine, 314 fluoxetine first-trimester exposed pregnancies and 1467 controls. After exclusion of genetic and cytogenetic anomalies, there was a higher rate of major anomalies in the SSRI groups compared with the controls [paroxetine 18/348 (5.2%), fluoxetine 12/253 (4.7%) and controls 34/1359 (2.5%)]. The main risk applied to cardiovascular anomalies [paroxetine 7/348 (2.0%), crude odds ratio (OR) 3.47, 95% confidence interval (CI) 1.13, 10.58; fluoxetine 7/253 (2.8%), crude OR, 4.81 95% CI 1.56, 14.71; and controls 8/1359 (0.6%)]. On logistic regression analysis only cigarette smoking of >or=10 cigarettes day(-1) and fluoxetine exposure were significant variables for cardiovascular anomalies. The adjusted ORs for paroxetine and fluoxetine were 2.66 (95% CI 0.80, 8.90) and 4.47 (95% CI 1.31, 15.27), respectively.\ud \ud CONCLUSION: This study suggests a possible association between cardiovascular anomalies and first-trimester exposure to fluoxetine

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SUMMARY The left anterior descending coronary artery of four dogs and the right common carotid artery of 15 rabbits were subjected to 40-60% reduction in transluminal diameter for 1 hour by partial ligation with suture thread. Scanning electron microscopic examination of the luminal surface of these vessels revealed endothelial craters and balloons, fragmentation and desquamation on the proximal slope of the constriction. Platelet attachment to exposed subendothelial tissues was clearly evident, and microthrombi were seen at the point of maximum constriction. Blood flow, as measured by electromagnetic flow probe, was virtually unchanged upon partial ligation. In control studies, where a second ligature was placed proximal to and before the first to reduce blood flow to the distal constriction site substantially or totally, endothelial desquamation was found in only one of 14 animals, and the number of craters and balloons was significantly reduced. We suggest that endothelial damage and thrombus formation may occur at the site of focal arterial constriction even when the reduction in transluminal diameter is insufficient to alter substantially the rate of flow.THE THREAT posed by coronary vasospasm for the initiation of myocardial ischemia or infarction is assumed to depend on the degree to which the reduction in transluminal diameter results in the interference with coronary blood flow. Further, it is thought that the thrombosis that may accompany vasospasm is a result of the grossly reduced blood flow secondary to a critical vascular constriction and that the interaction of platelets with a damaged vascular wall, with the ensuing release reaction, may further potentiate the coronary spasm." 2 In the present report we present evidence from scanning electron microscopic (SEM) studies that indicates that marked endothelial damage, extensive platelet deposition and thrombus formation may occur at the site of a focal arterial constriction even when the reduction in transluminal diameter is insufficient to alter flow substantially. MethodsFifteen New Zealand white rabbits (3.1 ± 0.4 kg, mean ± SD) were anesthetized with sodium pentobar- The RCCA of five rabbits and the LAD of two dogs were focally constricted 1 cm proximal to the probe by partial ligation with suture thread (0-cotton) to achieve a 50% reduction in transluminal diameter ( fig. 1). The desired degree of luminal constriction was achieved by the apposition of two points on the suture thread; the distance between these points was calculated from the vascular circumference, with the wall thickness (0.1 mm) considered negligible. The diameters were confirmed during SEM examination and varied from 40-60% luminal reduction. Group 2In a second group of five rabbits and two dogs, a second ligature was placed 1 cm proximal and immediately before the first ( fig. 1)