Although the full potential for fetal harm is undefined for many medications, the Food and Drug Administration determines "best guess" safety profiles for most drugs.
In 1979, the United States Food and Drug Administration (FDA) introduced a set of guidelines that established safety profiles that defined the risks for fetal injury caused by pharmaceutical agents used in this country.
These pregnancy safety categories outline the potential for fetal harm only; they are not intended to delineate the risks to nursing infants.
FDA use-in-pregnancy ratings are summarized below:
- Category A: Studies in pregnant women show no risk (i.e., long-term experience with a drug following its approval has shown no evidence of human fetal harm; the few drugs that are included in this category have been on the market for many years and have been used in a large number of pregnant women)
- Category B: Animal studies show no risk, but human data are insufficient; or animal studies show toxicity, but human studies show no risk (post-marketing use – sometimes including “off label” use in pregnant women – shows no evidence of fetal harm in humans; category B medications appear to be safe during pregnancy, but may not have enjoyed a long period of use on the U.S. market or in a large number of pregnant women)
- Category C: Animal studies show toxicity, human data are insufficient, but clinical benefit may exceed risk (a “no-man’s-land” category; a theoretical risk of human harm can be extrapolated from animal studies, but the need to use the medication may outweigh theoretical risks)
- Category D: There is evidence of human risk, but clinical benefits may outweigh risk (i.e., the mother may require the medication for her wellbeing in spite of a real risk to her infant; usually, if a physician prescribes such a drug during pregnancy, no other medication is available that demonstrates similar benefits but less risk)
- Category X: There is evidence of fetal abnormalities in humans, and risk exceeds benefits (i.e., the medication should never be used during pregnancy)
Drugs Associated with Adverse Effects During Pregnancy
Classes of drugs – and representative examples – that can cause fetal harm include:
Antimicrobials (antibiotics, antifungals, antiparasitics, etc.)
- Aminoglycosides (gentamicin, tobramycin, amikacin, etc.): damage to fetal ears, resulting in deafness. Category D
- Chloramphenicol: hemolytic anemia in fetuses and mothers with G6PD deficiency; “gray baby” syndrome (ashen color, limpness, low blood pressure and body temperature, shock). Category C
- Primaquine (anti-malarial): hemolytic anemia in fetuses and mothers with G6PD deficiency. Category C
- Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, etc.): possible bone and tendon abnormalities. Category C
- Sulfa drugs (except sulfasalazine): if given late in pregnancy, neonatal jaundice and/or kernicterus (central nervous system damage due to high bilirubin levels); possible hemolytic anemia. Category C
- Tetracycline: bone growth abnormalities; delayed tooth enamel development and permanently yellowed teeth. Category D
Anticoagulants (blood thinners)
- Heparin: maternal osteoporosis after prolonged exposure (>6 months). Category C
- Warfarin (Coumadin): fetal optic atrophy (blindness); facial abnormalities; mental retardation. Category X
Anticonvulsants
- Carbamazepine (Tegretol), Phenobarbital: congenital malformations; bleeding abnormalities in the newborn. Category D
- Phenytoin (Dilantin): congenital malformations (cleft lip and palate, genitourinary abnormalities, heart defects); bleeding abnormalities in the newborn. Category D
- Valproate (Depakene): major congenital malformations of the limbs, spine, heart, and face. Category D
Blood Pressure Medications
- ACE inhibitors (Captopril, Zestril, Vasotec, Accupril, Lotensin, etc.): head and facial malformations, kidney failure, limb abnormalities, and underdeveloped lungs. Category D
- Beta-blockers (Propranolol, timolol, metoprolol, etc.): possible fetal growth retardation; cardiac rhythm disturbances; blood sugar abnormalities. Category C
- Thiazide diuretics (hydrochlorothiazide, etc.): fetal growth retardation; neonatal electrolyte disturbances; low platelet count. Category D
Chemotherapeutic Agents
- Busulfan, chlorambucil, cyclophosphamide, mercaptopurine, and methotrexate: fetal growth retardation, head and facial malformations, spinal defects, ear defects, and clubfoot. Category D, (except methotrexate, which is Category X)
Medications for Psychiatric Conditions
- Diazepam (Valium): neonatal respiratory depression and possible withdrawal syndrome. Category D
- Lithium: neonatal lethargy, hypothyroidism, flaccidity, diabetes insipidus, and failure to thrive. Category D
Pain Medications
- Opioids (narcotics): neonatal withdrawal in infants of addicted mothers. Category C
- Aspirin and other nonsteroidal anti-inflammatories: delayed onset of labor; fetal kernicterus; vascular abnormalities (premature closing of ductus arteriosus); jaundice; neonatal hemorrhage. Category D
Hormones
- Danazol, synthetic progestins (except at low doses, as in birth control pills): masculinization of female fetuses’ genitals. Category X
Thyroid Medications
- SSKI: fetal goiter, which may be large enough to obstruct neonatal airway
- Methimazole, propylthiouracil, triiodothyronine: fetal goiter
- Radioactive iodine: depending on trimester, either destruction of the fetal thyroid or severe fetal hyperthyroidism
- All are Category D
Vaccines
- All live-virus vaccines (measles, mumps, rubella, polio, chickenpox, yellow fever, etc.) may potentially infect the placenta and developing fetus; they should be avoided
Vitamin K may cause hemolytic anemia in women or fetuses with G6PD deficiency
(Adapted from Drugs with Adverse Effects During Pregnancy in The Merck Manual, 18th Edition. 2006:2174-77)
Given the wide variety of medications that can cause fetal anomalies and maternal illness, no pregnant woman should take any medication without the knowledge of her physician or midwife.
The copyright of the article Drugs to Avoid During Pregnancy in Prenatal Health is owned by Stephen Allen Christensen. Permission to republish Drugs to Avoid During Pregnancy in print or online must be granted by the author in writing.
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