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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fetal injury associated with maternal ethanol ingestion is a major cause of congenital anomalies and mental retardation. Studies with animals suggest that acetaldehyde, the primary hepatic oxidative metabolite of ethanol, may contribute to fetal damage. It is not known, however, whether acetaldehyde reaches the human fetus, either by placental production or transfer. Studies utilizing the perfused human placental cotyledon show that the human placenta oxidizes ethanol to acetaldehyde, releasing it into the fetal perfusate. Moreover, when acetaldehyde is present in the maternal perfusate, it is transferred to the fetal side, reaching approximately 50 percent of the maternal level. These findings suggest that the human placenta may play a pivotal role in the pathophysiology of ethanol-associated fetal injury.
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PMID:Acetaldehyde production and transfer by the perfused human placental cotyledon. 317 52

Suspicion of alcohol's teratogenic potential stretches back many centuries, but it is only recently that solid support for this possibility has been produced. There is now little doubt that alcohol can produce developmental defects, but there are many questions that still remain to be answered concerning the impact of alcohol on the conceptus. One major question that remains to be resolved is why only a small percentage of alcoholic women give birth to children with Fetal Alcohol Syndrome (FAS), whereas other alcoholic women who drink the same amount do not. Another important issue concerns the way in which alcohol produces its effects. Although one of the most likely ways in which alcohol's teratogenic actions are mediated appears to be via hypoxia, other mechanisms such as direct toxicity of alcohol or acetaldehyde may be involved. FAS refers to a pattern of defects in children born to alcoholic women. For a diagnosis of FAS to be made, the patient must have three main characteristics: (1) pre- and postnatal growth retardation (greater than or equal to 2 S.D. for length and weight), (2) facial anomalies, and (3) central nervous system dysfunction Pre- and postnatal growth retardation are the most reliable consequences of fetal alcohol exposure. In many cases, patients with the syndrome weigh less than 2500 g at birth and most do not exhibit postnatal 'catch-up growth' Among the distinctive facial anomalies seen in conjunction with the syndrome are absent-to-indistinct philtrum, epicanthic folds, thin upper lip and short upturned nose. Joint, limb and cardiac anomalies are also often present. Central nervous system dysfunction includes mental retardation, the most serious consequence of in utero alcohol exposure, hyperactivity, sleep disorders and miscellaneous behavioral difficulties. If only one or two of these broad characteristics are present and the mother is suspected of drinking during pregnancy, then a diagnosis of 'possible fetal alcohol syndrome,' or 'partial fetal alcohol syndrome,' or 'fetal alcohol effects,' or 'alcohol-related birth defects' may be made. However, without evidence of maternal drinking during pregnancy, this diagnosis is very tentative, since many of these effects are also observed in conjunction with many other congenital disorders.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prenatal effects of alcohol. 638 8

Signs and symptoms of 108 cases with alcohol embryopathy are presented. In addition to the well-known features (e.g., intrauterine growth retardation, microcephaly, mental retardation and typical craniofacial abnormalities), 29% of the cases had heart defects, 10% had G.U. tract malformations, and 1.8% had spina bifida. Brain malformations of 3 cases and 4 fetuses are described. Auxological measurements demonstrated some catch-up growth for height, but none for head size. Facial anomalies tended to normalize with increasing age. A proposal for classifying alcohol embryopathy (AE) into 3 degrees of severity is presented. Cases with the mild degree showed milder (or no) mental retardation compared to cases with the severe degree. The degree of AE was related to the stage of maternal alcoholism. With increasing severity of maternal alcoholism, the frequency and severity of AE among the offspring increased too. Among siblings, the elder siblings were less affected than the younger. This difference in outcome might be caused by the increasing inability of the alcoholic mothers to metabolize acetaldehyde. It is hypothesized that embryonic disturbance is not as dependent on the amount of daily alcohol consumption as it is on the stage of maternal alcoholism.
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PMID:Alcohol embryopathy: some facts and speculations about pathogenesis. 719 89

Mental retardation, hydrocephalus, and agenesis of the corpus callosum are observed both in fetal alcohol syndrome (FAS) and in children with mutations in the gene for the cell adhesion molecule L1. We studied the effects of ethanol on cell-cell adhesion in mouse fibroblasts transfected with human L1. L1-transfected fibroblasts exhibited increased cell-cell adhesion compared with wild-type or vector-transfected controls. Ethanol potently and completely inhibited L1-mediated adhesion both in transfected L cells and NIH/3T3 cells. Half-maximal inhibition was observed at 7 mM ethanol, a concentration achieved in blood and brain after ingesting one alcoholic beverage. In contrast, ethanol did not inhibit the adhesion of fibroblasts transfected with vector alone or with N-CAM-140. L1-mediated cell-cell adhesion was inhibited with increasing potency by n-propanol and n-butanol, but was not inhibited at all by n-alcohols of 5 to 8 carbons, acetaldehyde, or acetate, suggesting that ethanol interacts directly with a small hydrophobic pocket within L1. Phenylalanine, teratogenic anticonvulsants, and high concentrations of glucose did not inhibit L1-mediated cell-cell adhesion. Ethanol also inhibited potently the heterotypic adhesion of rat cerebellar granule cells to a monolayer of L1-transfected NIH/3T3 cells, but had no effect on their adhesion to N-CAM-140 or vector-transfected NIH/3T3 cells. Because L1 plays a role in both neural development and learning, ethanol inhibition of L1-mediated cell-cell interactions could contribute to FAS and ethanol-associated memory disorders.
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PMID:Alcohol inhibits cell-cell adhesion mediated by human L1. 860 70

Much information has emerged over the years concerning the teratogenicity of acute and chronic alcohol exposure during pregnancy. Both alcohol and its primary metabolite, acetaldehyde, are teratogenic. Exposure during pregnancy may lead to fetal alcohol syndrome (FAS), and this is said to occur in a substantial proportion of infants born to mothers who are chronic, heavy daily drinkers. Such infants usually survive to birth but are mentally retarded, often display growth retardation and additionally display a characteristic range of clinical features, principally craniofacial abnormalities and neurological damage. We have recently been interested in the effect of exposure of pregnant female mice to a single high level of alcohol during pregnancy, equivalent to an episode of 'binge' drinking, on the optic nerve, and believe that our findings, which are outlined in the first part of this review, may shed important light on the pathogenesis of some of the ocular features characteristically seen in infants with this syndrome. What is not generally appreciated, is that exposure to alcohol and other 'spindle-active' substances that have a similar action on the meiotic spindle apparatus during the menstrual cycle before conception can induce chromosome segregation errors in the ovulated oocyte. The successful fertilization of such eggs consequently results in the production of aneuploid embryos, which have a very high chance of being spontaneously aborted during the first trimester of pregnancy. Those relatively few aneuploid conceptuses that survive to term invariably show moderate to severe degrees of mental retardation, craniofacial and other abnormalities, as well as having a significantly reduced life expectancy. The findings from our experimental studies that have been carried out in mice draw attention to important principles which are of general applicability to the situation in the human. These findings, and our conclusions drawn from them, are discussed in detail in the second part of this review.
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PMID:The teratogenic effects of alcohol following exposure during pregnancy, and its influence on the chromosome constitution of the pre-ovulatory egg. 910 5

The methylmercury exposure of patients with congenital or infantile Minamata disease is known only from a small number of analyses of umbilical cords. Four laboratories in Japan have analyzed a total of 176 samples of umbilical cord tissue obtained from Minamata. The highest concentrations were seen in cord tissue from children born during 1950-1965, i.e., the peak period of acetaldehyde production in Minamata before installation of waste water treatment. Twenty-four samples from patients diagnosed with Minamata disease showed a median mercury concentration of 1.63 microg/g and differed significantly from levels seen in cord tissue from control children. However, children diagnosed with mental retardation had mercury concentrations in cord that were intermediate between the two other groups. Using regression coefficients obtained at a study conducted at the Faroe Islands, the median cord mercury concentration from the children with Minamata disease is estimated to correspond to about 216 microg/L cord blood and 41 microg/g in maternal hair. Based on correlations reported in the literature, the median daily mercury intake of the women whose children developed Minamata disease can then be estimated at about 225 microg. Although these children had fully developed Minamata disease, the estimates of median mercury levels are only four to five times higher than current mercury exposure limits.
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PMID:Methylmercury dose estimation from umbilical cord concentrations in patients with Minamata disease. 960 Aug 2