Fetal Alcohol Syndrome Diagnosis, Epidemiology, Prevention, and Treatment (1996) / Chapter Skim
Currently Skimming:
2 Issues in Research on Fetal Drug Effects
2 Issues in Research on Fetal Drug Effects
Pages 33-51
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 33... ...
The neurotoxic properties of these compounds have generally been confirmed in animal studies. Based on their effects, these agents can be divided into two classes of neurotoxicants: some are teratogens in that they produce CNS malformations with associated neurobehavioral dysfunction (e.g., alcohol, methylmercury)
|
From page 35... ...
and a variety of other alcohol-related effects in children exposed during prenatal life. Of all the substances of abuse, including heroin, cocaine, and marijuana, alcohol produces by far the most serious neurobehavioral effects in the fetus.
|
From page 36... ...
Prenatal exposure to tobacco is clearly linked to low birth weight. Although reports from the mid 1980s suggested that the use of cocaine during pregnancy increased the risk of genitourinary tract malformations, abruptio placenta, intrauterine growth retardation, sudden infant death syndrome as well as a number of postnatal neurobehavioral deficits, subsequent reports largely failed to replicate these initial observations (see Hutchings, 1993 and accompanying commentaries)
|
From page 37... ...
At any time in the total span of development, these ongoing processes can be subtly deflected, severely perturbed, or abruptly halted, resulting in death or abnormal development. Furthermore, although the effects of exposure during specific stages or "critical periods" of development are probably best documented for the anatomical or dysmorphogenic effects of various teratogenic agents, data on stage-specific effects on growth and functional deficits are increasing, particularly in relation to prenatal alcohol exposure.
|
From page 38... ...
Most cell types appear to be vulnerable to alcohol-induced cell death, but neuronal cell populations may be particularly vulnerable. Exposure on gestation days 7 and 8 in mice was shown to result in craniofacial defects similar to those seen in FAS (e.g., micrognathia, low-set ears, short philtrum, cleft palate, cleft lip)
|
From page 39... ...
In mouse models, prenatal alcohol exposure on gestation day 15 or 18 was shown to result in dose-dependent decreases in fetal body weight, decreased brain DNA (deoxyribonucleic acid) synthesis, and delayed neonatal reflexive behaviors (Ciociola and Gautieri, 1988~.
|
From page 40... ...
The majority of studies using rodent models have focused on the period of the embryo, which is the primary period of organogenesis. These studies have shown that some mouse strains appear to be particularly sensitive to the teratogenic effects of both acute and chronic alcohol exposure, whereas other strains appear to be less sensitive to alcohol's teratogenic effects (Cassells et al., 1987; Chernoff, 1977~.
|
From page 41... ...
) reported line differences in fetal growth, dysmorphology, behavioral deficits, and mortality that cannot be explained by differences in maternal weight gain, duration of alcohol exposure, or blood alcohol levels (Gilliam et al., 1987; 1989a,b)
|
From page 42... ...
Both thalidomide and isotretinoin are examples of compounds that produce gross structural malformations in the offspring at levels that are pharmacologically active in the mother (lowest observable effect level, LOEL) but are below the dose that produces maternal toxicity.
|
From page 43... ...
In two early studies using mouse models, dose-response effects were observed for malformations induced by prenatal alcohol exposure. Chernoff (1977)
|
From page 44... ...
A particular dose of alcohol administered in multiple feedings over 24 hours has significantly fewer adverse effects than the same dose condensed and administered over a shorter period of time: That is, the more concentrated the pattern of alcohol administration, the higher are the maximum blood alcohol levels achieved and the more severe is the interference with brain growth. Thus, the pattern of alcohol exposure is important because of the resultant blood alcohol concentrations.
|
From page 45... ...
This latter observation was confirmed in follow-up studies in which animals exposed to peak maternal blood alcohol levels of >140 mg/dl once per week in the first six weeks of gestation had the same degree of developmental delay as animals exposed to the same dosages nearly throughout gestation. Thus, measurable teratogenic effects from weekly exposures to alcohol occurred only at intoxicating doses.
|
From page 46... ...
Clearly, further investigation is needed on the role of prostaglandin in mediating the teratogenic effects of alcohol and on the possible use of PG inhibitors in attenuating alcohol-related birth defects. A series of studies by Wainwright and colleagues investigated the possibility that adverse effects of fetal alcohol exposure on brain development might be mediated in part by an alcohol-induced reduction of available long-chain polyunsaturated fatty acids to the developing brain (Wainwright et al., 1990a,b)
|
From page 47... ...
Although one cannot directly extrapolate from findings in animals to the clinical setting, the present data certainly indicate one possible direction for future research on the treatment of children exposed to alcohol prenatally. A MULTIFACTORIAL MODEL The data presented above clearly indicate that the teratogenic effects of prenatal alcohol exposure can be influenced by numerous factors, both biological and environmental.
|
From page 48... ...
Determination of the proximate teratogen of the mouse fetal alcohol syndrome: Teratogenicity of ethanol and acetaldehyde. Toxicology and Applied Pharmacology 1984; 72:355-363.
|
From page 49... ...
The effects of the timing of ethanol exposure during the brain growth spurt on the number of cerebellar Purkinje and granule cell nuclear profiles. Alcoholism: Clinical and Experimental Research 1993; 17:610-622.
|
From page 50... ...
Experimental Fetal Alcohol Syndrome:Proposed pathogenic basis for a variety of associated facial and brain anomalies. American Journal of Medical Genetics 1992; 44:168176.
|
From page 51... ...
Sulik KK, Johnston MC, Webb MA. Fetal alcohol syndrome: Embryogenesis in a mouse model.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.