Teratology
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Letter Historical Article
Thalidomide retrospective: what did the clinical teratologist learn?
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In a case-control surveillance program, first trimester medication use was studied in relation to gastroschisis. There were 76 cases of gastroschisis which were compared with 2,142 controls with other major malformations. For pseudoephedrine use, we found a significantly elevated relative risk of 3.2 (95% confidence interval, 1.3-7.7), with adjustment for confounding. ⋯ These positive associations must be considered tentative. They have not been reported previously and should be confirmed independently. Also, acetaminophen, which may be taken for the same indications as salicylates and decongestants, but is not thought to be vasoactive, was associated with gastroschisis, suggesting that identified associations may be due to an underlying maternal illness.
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In total anomalous pulmonary venous return (TAPVR), the intrapulmonary venous plexus has failed to connect to the left atrium, so that the pulmonary veins drain into right atrial tributaries, frequently resulting in early postnatal circulatory distress. The Baltimore-Washington Infant Study (BWIS), a population-based exploratory case-control study of cardiovascular malformations (CVM), identified 41 cases of TAPVR during 1981-1987: 1.5% of all CVM (N = 2659), a regional prevalence of 6.8/100,000 live births. Of the TAPVR infants, 68% were diagnosed as neonates, 88% had surgery, and 51.2% were alive at 1 year of age. ⋯ Total anomalous pulmonary venous return (TAPVR) constitutes a well-defined clinical entity in which the pulmonary veins fail to enter the left atrium and instead drain into the right atrium or its systemic venous tributaries (Neill, '56; Rowe et al., '81). During intrauterine life, the malformation does not compromise the fetal circulation, since the pulmonary arterial resistance is high and the patent foramen ovale provides easy access of right atrial blood to the left side of the heart. At birth, however, the pulmonary vascular resistance begins to fall, and the presence of a severe hemodynamic disturbance becomes increasingly evident (Ferencz et al., '71).(ABSTRACT TRUNCATED AT 400 WORDS)
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The highly toxic, polychlorinated aromatic compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) occurs as a contaminant throughout the environment. Epidemiology studies of populations accidentally exposed to TCDD have failed to identify TCDD as a human teratogen, but these studies are limited by the small numbers of exposed pregnancies and imprecise estimates of exposure. TCDD is highly teratogenic in mice, inducing cleft palate and hydronephrosis. ⋯ The rat shelves respond with altered differentiation at 1 x 10(-8) M and cytotoxicity at 1 x 10(-7) M. All the human shelves respond at 1 x 10(-8) M TCDD with altered differentiation, 1 out of 4 responded at 5 x 10(-11) M, and cytotoxicity occurred at 1 x 10(-7) M. The present data suggest human embryonic palates are less sensitive than those of the C57BL/6N mouse, and that exposure to high levels of TCDD would be required to elicit altered differentiation in the palatal shelf.