KSMU – Obstetrics and Gynecology Dep.Fabio Grubba

A teratogen is an agent that can disturb the development of the embryo or fetus. Teratogens halt the pregnancy or produce a congenital malformation (a birth defect). Classes of teratogens include radiation, maternal infections, chemicals, and drugs

Birth defects are known to occur in 3-5% of all newborns.

They are the leading cause of infant mortality in the United States, accounting for more than 20% of all infant deaths.

They can do direct damage to the fetus, causing abnormal development.

They can compromise the function of the placenta, often by constricting blood vessels and reducing the supply of oxygen and nutrients from the mother to the fetus. This can lead to underdevelopment or low birth weight, which are risk factors for birth defects.

They can trigger forceful uterine contractions, potentially injuring the fetus or prompting premature birth.

Category A Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).

Category B Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Category C Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Category D There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Category X Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

Category N FDA has not classified the drug.

The best course is to prevent teratogen exposure, or reduce the exposure as much as possible.

Prevention is complicated because very often women may not realize they are pregnant until the middle of the period of susceptibility.

Retinoic acid, for example, has a period of susceptibility from days 20-35 after conception—a time when many women might not realize they are pregnant.

Warfarin Pregnancy category - XTrimesters of risk - First, second, and third Associated defects and complications - Deformities of the axial and

appendicular skeleton; also, a hypoplastic nose, eye abnormalities, mental retardation, brachydactyly, and scoliosis

Penicillamine Pregnancy category - DTrimester of risk - Unknown Associated defects and complications - Variable; possible connective-tissue

defects, cerebral palsy, hydrocephalus, skeletal defects, cleft palates, and fetal toxicity (resorptions)

Phenobarbital or methylphenobarbital Pregnancy category - DTrimester of risk – third trimester Associated defects and complications - Phenobarbital or methylphenobarbital

slightly increases the risk of cleft palate or lip and congenital heart disease. These drugs can cause fetal addiction and newborn withdrawal symptoms or newborn hemorrhage

Fluconazole Pregnancy category - C (single dose); D (multiple doses)Trimester of risk - First Associated defects and complications - Craniofacial, skeletal, and cardiac

effects

ACE inhibitors . category C,DTrimesters of risk - First ,second and third trimesters ligohydramnios, intrauterine growth restriction (IUGR), premature labor, and

fetal and neonatal renal failure. Reported birth defects included bony malformations, limb contractures, persistent patent ductus arteriosus, pulmonary hypoplasia, respiratory distress syndrome, prolonged hypotension, neonatal death, fetal calvarial hypoplasia or aplasia, oligohydramnios, and renal anomalies.

Angiotensin II receptor antagonists Pregnancy category - DTrimesters of risk - First, second, and third Associated defects and complications - Hypotension, renal dysplasia, anuria or

oliguria, oligohydramnios, IUGR, pulmonary hypoplasia, patent ductus arteriosus, incomplete ossification of the skull, and intrauterine or neonatal death

Aspirin Pregnancy category - DTrimesters of risk - First, second, and third Associated defects and complications - Unclear; may be associated with an

increased risk of gastroschisisTetracyclines Pregnancy category - DTrimesters of risk - Second and third (20th gestational week or later) Associated defects and complications - Dental staining

Aminoglycosides Pregnancy category DTrimester of risk - Not consistent Some neonates have had hearing defects, whereas others have had

vestibular problems. Some offspring had inner ear damage, whereas others did not.

Benzodiazepines Pregnancy category - D or XTrimesters of risk: The first, second, and third Associated defects and complications - Unclear; potential for isolated

oral cleftCarbamazepine Pregnancy category – D Trimesters of risk - First, second, and third Associated defects and complications - Unique facial appearance and

underdevelopment of the fingers, toes, and nails; developmental delay

Corticosteroids Pregnancy category - CTrimester of risk - First Associated defects and complications - Reduced birth weight,

increased risk of preeclampsia, and increased risk of oral and lip clefts