Fetal abnormalities

OXAZOLIDINEDIONES. The oxazolidinediones are used only when other, less-toxic dm have not been effective in controlling the seizure disorder because they have been associated with fetal abnormalities and serious adverse reactions. 

The initial concern for the possible hazard to humans exposed to 2,4,5-T was precipitated by teratologic studies conducted by Bionetics Research Institute under contract from The National Cancer Institute (2). In these studies, large doses of 2,4,5-T were administered to pregnant rats and mice for nine of the 21 days of pregnancy. The incidence of fetal abnormalities was slightly higher in the treated animals than in control animals. Later tests indicated that these abnormalities (cleft palate) may have been caused by 27 8 ppm of 2,3,7,8-tetrachloro-dibenzo-p-dioxin present as a contaminant in the 2,4,5-T sample used in the Bionetic study (3). After the results of the study were made known, the Panel on Herbicides of the President s Science Advisory Committee studied the total 2,4,5-T situation. The report of this committee was published in March, 1971 (4). 

Campbell, S. "The Prenatal Detection of Fetal Abnormality by Ultrasonic Diagnosis" In Birth Defects, Proc. 4th Int. 

Category A Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities. 

Category X Studies, adequate well-controlled or observational, in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. The use of the product is contraindicated in women who are or may become pregnant. 

Certain drugs carry a risk of fetal abnormalities if administered during pregnancy. Match each abnormality with the correct drug. 

Fetal and maternal deaths noted when pregnant rats dosed by gavage at 50-60 mg/kg BW daily during gestation days 6-13. Fetal abnormalities observed when dams given oral dosages of 40-60 mg/kg BW on days 7-16 of gestation... 

Clinical signs and mortality Macroscopic exam + histo on gross lesions Quantitation of corpa lutea and implantation sites Fetal body weights Fetal abnormalities... 

X Studies show fetal abnormalities in animals and humans drug is contraindicated in pregnant women. 

No effect on maternal or fetal survival and no increase in the number of fetal abnormalities were seen after administration in the diet of pregnant mice and rats (up to 300mg/kg/day for 10 days), hamsters (up to 400mg/kg/day for 5 days), or rabbits (up to 400mg/kg/day for 13 days). ... 

Major human fetal abnormalities related to isotretinoin administration in females have been documented. There is an increased risk of spontaneous abortion. In addition, premature births have been reported. 

Category X Studies in animals or humans or advise reaction reports, or both, have demonstrated fetal abnormalities. The risk of use in pregnant women clearly outweighs any possible benefit. 

Ethanol readily passes across the placenta and into the fetal circulation. The fetal alcohol syndrome has three primary features microcephaly, prenatal growth deficiency, and short palpebral fissures Other characteristics include postnatal growth deficiency, fine motor dysfunction, cardiac defects, and anomalies of the external genitalia and inner ear. A definite risk of producing fetal abnormalities occurs when ethanol consumption by the mother exceeds 3 oz daily, the equivalent of about six drinks. 

The strain of animals should be selected from those for which there is adequate background data at the testing laboratory. This is particularly important for interpretation of incidences of fetal abnormalities and variations. 

For statistical analysis, fetal abnormality values belong to two types those where at least 50% of litters have one or more fetuses affected, and those where most litters have no affected fetuses. For the first type, the incidences (percentage of affected fetuses within that litter) are analyzed by the Kruskal-Wallis test (13) for the second type, the number of litters with affected fetuses is compared with the number with no affected fetuses by Fisher s Exact test (14). 

The quote attributed to Andrew Lang he uses statistics as a drunken man uses a lamp post, for support rather than illumination is very appropriate to teratology testing, and particularly to fetal abnormalities. 

All species and strains have a low level of background fetal abnormalities, many of which are of genetic origin. The interpretation must distinguish between a high incidence due to chance, and an increase due to the test substance. It is impossible in this chapter to cover every eventuality, but the following points will serve as a guide. 

Historical control data for embryo-fetal studies at Ricerca Biosciences with CrI 0F1 mouse incidence of external fetal abnormalities... 

Method of classification of fetal abnormalities, e.g., malformation, minor anomaly, variation. 

Methamphetamine passes the blood-brain barrier better than amphetamine, and there is evidence that chronic use of methamphetamine can result in permanent damage to dopamine neurons. Both pass the placental barrier, and there is some evidence that abuse by a pregnant woman can result in fetal abnormalities. Methamphetamine is found in breast milk. The half-life of methamphetamine and amphetamine is about 10 to 13 hours. Some methamphetamine is metabolized to amphetamine, and amphetamine-glucuronide can be detected in urine for about two days. About 50% of methamphetamine is excreted unchanged in the urine over two to three days. 

Dietary administration of 50 mg/kg/day FireMaster BP-6 to mice from gestation days 7 through 18 produced decreased fetal body weight and fetal abnormalities including exencephaly, cleft palate, and hydronephrosis 5 mg/kg/day did not produce significant developmental effects in this study (Corbett et al. 

Changes in membrane permeability might be expected to lead to osmolar imbalance and fetal abnormality. This is hypothetical, as there are no real examples of such a mechanism, although high doses of vitamin A are teratogenic and may cause ultras true tural membrane damage. 

Much recent interest has been aroused by the fact that retinoid compounds, including both retinol and retinoic acid, reduce the incidence of experimentally induced cancer. In addition, 13-czs-retinoic acid taken orally is remarkably effective in treatment of severe cystic acne. s However, both vitamin A and retinoic acid in large doses are teratogenic, i.e., they cause fetal abnormalities. The use of 13-cis-retinoic acid during early phases of pregnancy led to a high incidence of major malformations in infants born.1 11 1... 

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