Gestational drug exposure

Only in special circumstances will the determination of embryo levels of drug add meaningfully to the assessment of human risk from a drug. In such studies, even if it is found that the embryo is not exposed, the lack of exposure of the embryo would not necessarily indicate an invalid study or increased human risk since there may also be no exposure in human embryos. When embryo level studies are conducted, the selection of day(s) of gestation to harvest embryos is severely restricted by the sensitivity of the assay. Often, the earliest day that allows the collection of sufficient tissue for assay is gestational Day 10 or 11. 

An unusual condition that has been tentatively ascribed to clomiphene is persistence of the hyperplastic primary vitreous, that is fetal ophthalmic tissue that normally resolves before birth. If more than a trace of the material persists, ocular complications, including cataract and retinal detachment, can result. In a case reported from Canada, there had been an estimated 3 weeks of exposure to high doses of clomiphene (100 mg/day) after gestation, and the child s vision was severely impaired (20). This is probably not a mere chance association, since several cases of visual defects of various types after exposure to clomiphene have been described before, and in some animal studies the drug does adversely affect ocular development. 

The impact of prenatal exposure to cocaine on fetal growth and fetal head circumference has been studied in 476 African-American neonates, including 253 full-term infants prenatally exposed to cocaine (with or without alcohol, tobacco, or marijuana) and 223 non-cocaine exposed infants (147 drug-free, 76 exposed to alcohol, tobacco, or marijuana) (300). The cocaine-associated deficit in fetal growth was 0.63 standard deviations and for gestational age 0.33 standard deviations. There were also cocaine-associated deficits in birth weight and length, but no evidence of a disproportionate effect on head circumference. 

Since 1987, and the first report of fetal cocaine exposure by Parton etal., ° 10 papers have presented data on gestational exposure revealed by hair analysis. The most important results " ° are presented in Table 2. All the reports have clearly demonstrated that the hair analysis technique is better able to detect previous drug use than is the standard urinalysis. However, hair analysis cannot completely replace urine testing, since drug use occurring only in the recent few days would not be detectable by hair analysis, yet would be detectable through urinalysis. 

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