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Drugs and Chemicals Associated with Birth Defects

Major congenital anomalies are observed in about 3% of all births. Maternal exposure to drugs or environmental chemicals may be responsible for 4-6% of these anomalies, or approximately 1 in 400 liveborn infants.

Whether birth defects occur in a conceptus exposed to a potentially teratogenic agent depends in large part on two factors: 1) gestational timing of the exposure and 2) the genetic makeup of the conceptus and the mother. Morphogenetic stage of the organism's development is a key factor in susceptibility to a potential teratogen. Exposure to a teratogenic agent.

Drugs and Chemicals

Epidemiologic studies have determined that most drugs commonly used during pregnancy (eg, aspirin, acetaminophen, metronidazole, caffeine, phenothiazines) are not associated with an increased risk of congenital anomalies. However, based on anecdotal evidence, maternal hyper-thermia seems to be associated with congenital anomalies when the fever persists.

Hormonal Agents

Danazol and other androgenic hormone agents may produce clitoral enlargement or labioscrotal fusion in the female fetus when they are given before 13 weeks of gestation. Recent studies, however, have failed to demonstrate a significant relationship.


Warfarin and other coumarin-derived anticoagulants inhibit the synthesis of vitamin K-dependent coagulation factors, and use during gestation can produce major and minor congenital anomalies.

Antithyroid Drugs

Thyroid medications such as propylthiouracil, methimazole, and iodide cross the placenta and may occasionally produce transient fetal hypothyroidism and goiter. Infants exposed to methimazole in utero.


Each of the commonly used anticonvulsant medications has been implicated as teratogenic, but there is no clear consensus concerning which one has the most teratogenic potential (see "Seizure Disorders," page 4). Diphenylhydantoin may produce a syndrome characterized by abnormal facies, microcephaly, growth deficiency, mental retardation, and hypoplastic nails and distal phalanges in as many as 10% of exposed offspring. However, as many as 30% of exposed newborns may demonstrate some aspects of the syndrome. Intrauterine exposure to diphenylhydantoin is also associated with a three- to fourfold increase.

Both valproic acid and carbamazepine have been associated with NTDs. Exposure during embryogenesis poses approximately a 1% risk of spina bifida to exposed fetuses. Specific syndromes have been described.

Trimethadione and paramethadione have been associated with abnormalities similar to those observed with the hydantoins. The risk for congenital anomalies or spontaneous abortion is 60-80%.


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.


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.

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.

Tretinoin. Topical tretinoin does not result in an increased risk of congenital anomalies because skin metabolizes the drug.

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.

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.

Occupational and Environmental Agents

Pregnant women may be occupationally or environmentally exposed to a variety of chemicals that are associated with poor reproductive outcomes, including spontaneous abortion, low birth weight, neurologic abnormalities, and congenital anomalies.

Ionizing Radiation

Embryonic or fetal radiation exposure usually results from diagnostic radiologic studies. Diagnostic radiation usually exposes the conceptus to less than 5 cGy (5 rads), depending.

Social and Illicit Drugs


Maternal alcohol ingestion during pregnancy may result in a recognizable pattern of congenital anomalies known as fetal alcohol syndrome. Fetal alcohol syndrome features include prenatal and postnatal growth restriction, characteristic facial anomalies (ie, short palpebral fissures, microphthalmia, indistinct or absent philtrum, thin upper lip, midfacial hypoplasia), microcephaly, joint contractures, and cardiac defects. Fetal alcohol syndrome is associated postnatally with mental retardation, hyperactivity.


Smoking tobacco poses a threat to reproductive function and pregnancy outcome in women. The prevalence of smoking among adults has decreased from approximately 40% in 1965 to approximately 25% in the 1990s, with a similar decrease.

The pregnant smoker may be at increased risk for the spontaneous abortion of an otherwise normal fetus, fetal death associated with placental abruption or placenta previa, preterm delivery, and PROM. A dose-response relationship has been shown.


Marijuana, the most frequently used illicit drug, has been associated with poor perinatal outcome in some studies but not in others. It is particularly difficult to identify the effects of a single illicit drug on perinatal outcome because the lifestyle associated.


Cocaine (street names "coke;' "snow;' "lady;' and "gold dust") use is a major public health concern. Use of cocaine in the 1970s was primarily limited to the intranasal route. In the 1980s, a decrease in the street cost and wider availability of cocaine resulted in an increasing prevalence of intravenous and smoked ("free-base" or "crack") routes of use. Consequently, the prevalence of cocaine-associated medical complications.

Other Illicit Drugs

Maternal use of heroin, methadone, methamphetamine, or phencyclidine may produce a neonatal withdrawal syndrome characterized by increased muscle tone, tremors.