Genetic Disorders and the Fetus. Группа авторов
Source: Modified from Barr et al. 2007. 470
Accurate bioanalytical methods facilitate discovery of drugs of abuse, such as cocaine, in AF. This is important given that, in one study, some 17 percent of mothers denying cocaine use had a positive maternal or newborn specimen.500 These methods enable monitoring of drugs of abuse not only in AF, but also in vernix caseosa, cord blood or tissue, meconium, urine, hair, nails, sweat, and saliva.501
An improved method to measure cocaine and norcocaine was developed and employed to show a significant correlation between the presence of cocaine metabolites in neonates' urine and symptoms of acute cocaine intoxication.502, 503 Multiple studies504–506 have shown no evidence of teratogenicity, although increased risk of placental abruption and premature rupture of membranes was observed.506 A 2011 meta‐analysis found association between cocaine exposure and preterm birth, low birthweight, and small for gestational age infants.507
In women treated during pregnancy with fluvoxamine, sertraline, and venlafaxine, antidepressant and metabolite concentrations were detectable in the AF.508, 509 No adverse effects of the medication were reported. The presence of these antidepressants in AF suggests that fetal exposure is continual and may occur via placental passage, fetal swallowing, and fetal lung absorption.
Omtzigt et al.510 report on three women with epilepsy who were taking long‐term valproate. They measured the concentrations of the parent compound and 13 of its metabolites in AF, maternal serum, and 24‐hour maternal urine samples. AF concentrations of valproate and its metabolites correlated with, but were much lower than, total valproate concentrations as well as with unbound valproate concentrations in maternal serum. The AF may act as a deep compartment, with slow appearance and disappearance of valproate and its main metabolites. In pregnancies associated with fetal NTDs (n = 55) significantly higher daily doses of valproate were used and higher levels of valproate were found in maternal serum. However, the metabolite patterns in maternal serum, 24‐hour urine samples, and AF did not show significant differences in pregnancies with NTDs.
Ethanol, a well known teratogen, causes fetal alcohol spectrum disorders in up to 5 percent of children in the United States and Europe.511 Ethanol enters the fetal compartment freely but is eliminated very slowly: “While the fetus has the ability to metabolize some ethanol, removal from the fetal‐maternal unit relies primarily on maternal metabolic capacity. The alcohol elimination rate from the fetal compartment is approximately 3% to 4% of the maternal rate.”512
The vast majority of human cancers are thought to have environmental origins, whereas about 60 percent of congenital malformations have unrecognized causes. Since carcinogenesis and teratogenesis may share common pathways involved in cellular growth proliferation, migration, and differentiation, it is worrisome that many toxicants found in AF, meconium, or cord blood must reflect their entry into the fetal environment471 (see Tables 3.5 and 3.6). For example, bisphenol A (BPA), an estrogenic endocrine‐disrupting chemical used in the plastics industry, is found in AF.514 BPA reportedly affects preimplantation and alters postnatal development,515 and experimental evidence in rats suggests BPA interferes with amelogenesis.516 Given the importance of thyroid hormone in brain development, the realization that BPA acts as a thyroid hormone receptor antagonist517 evokes concern.