Lithium
Lithium may produce malformations in 1% of offspring exposed prenatally. The anomalies frequently involve the heart and great vessels, with Ebstein’s anomaly of the tricuspid valve being observed most frequently. The concern regarding lithium exposure is the potentially lethal cardiac defect that occurs at a rate of 1 per 20,000. Exposure late in pregnancy may produce transplacental lithium intoxication with neonatal cyanosis, hypotonia, bradycardia, goiter with hypothyroidism, diabetes insipidus, and polyhydramnios. Additionally, maternal diuresis warrants perinatal dose adjustment to avoid lithium toxicity to neonate and mother.
Diethylstilbestrol
The synthetic estrogen diethylstilbestrol produces structural defects of the genital tract, as well as reproductive problems in prenatally exposed females. Vaginal adenosis has been detected in more than 50% of women whose mothers took this drug before the ninth week of pregnancy. A small percentage of women exposed in utero may develop clear-cell adenocarcinoma of the vagina. A variety of abnormalities of the genitourinary tract have also been observed in as many as 25% of males exposed in utero.
Vitamin A and Its Congeners
Isotretinoin. The vitamin A isomer isotretinoin is a potent teratogen, with serious congenital anomalies reported among approximately 35% of exposed fetuses. The specific congenital anomalies observed after oral administration of isotretinoin during early pregnancy include heart disease, thymic agenesis, microphthalmia, hydrocephalus, microtia, cleft palate, deafness and blindness, and an increased risk of spontaneous abortion.
Tretinoin. Topical tretinoin does not result in an increased risk of congenital anomalies because skin metabolizes the drug and no detectable systemic concentrations result.
Etretinate. Etretinate is an oral agent used to treat psoriasis. Case reports link the use of this agent to birth defects similar to those observed after the use of isotretinoin during pregnancy. Unlike vitamin A and its congeners, etretinate has been detected in serum of patients at therapeutic levels for as long as 7 years after cessation of use. Infants with congenital anomalies similar to those observed with isotretinoin use have been seen when the mothers had ceased use of etretinate up to 18 months before conception.
Drugs and Chemicals Associated with Birth Defects
High-Dose Vitamin A. The Centers for Disease Control and Prevention recently evaluated the use of vitamin A during pregnancy. Daily supplementation with 5,000 IU of vitamin A should be considered the maximum intake before and during pregnancy. A recent report associated maternal use of 15,000 IU or more of this nutrient during pregnancy with a significant risk (about triple the background) of congenital anomalies (eg, renal, craniofacial). This is of particular concern because some nutritional supplements contain 25,000 IU or more in a single dose.
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