What are the teratogenic effects of isotretinoin (Accutane) in pregnancy?

From the Guidelines

Isotretinoin (Accutane) should never be used during pregnancy as it causes severe birth defects, including craniofacial abnormalities, heart defects, central nervous system malformations, thymus gland abnormalities, and intellectual disabilities, with a 20-35% risk of major malformations, especially in the first trimester. The medication's teratogenic effects occur because it is a vitamin A derivative that disrupts normal embryonic development by interfering with neural crest cell migration and differentiation, which are crucial processes in early fetal development 1.

Risks Associated with Isotretinoin Use in Pregnancy

• Craniofacial abnormalities, such as cleft palate, small or absent ears, and facial asymmetry
• Heart defects
• Central nervous system malformations, including hydrocephalus and microcephaly
• Thymus gland abnormalities
• Intellectual disabilities

Recommendations for Women of Childbearing Potential

• Use two effective forms of contraception simultaneously for one month before, during, and for one month after isotretinoin treatment
• Participate in the iPLEDGE program, which includes mandatory pregnancy testing before, during, and after treatment
• Avoid pregnancy for at least one month after discontinuing isotretinoin treatment

Importance of Preconception Counseling

Preconception counseling is crucial for women of childbearing potential who are considering isotretinoin treatment, as it can help prevent unintended pregnancies and reduce the risk of birth defects 1. Women should be educated about the risks associated with isotretinoin use in pregnancy and the importance of using effective contraception and participating in the iPLEDGE program.

Clinical Implications

The use of isotretinoin in pregnancy is associated with significant morbidity and mortality, and its use should be avoided in women of childbearing potential who are not using effective contraception and participating in the iPLEDGE program 1. Clinicians should carefully weigh the benefits and risks of isotretinoin treatment in women of childbearing potential and consider alternative treatments when possible.

From the FDA Drug Label

Isotretinoin must not be used by patients who are or may become pregnant. There is an extremely high risk that life-threatening birth defects will result if pregnancy occurs while taking isotretinoin in any amount, even for short periods of time. Potentially any fetus exposed during pregnancy can be affected There are no accurate means of determining whether an exposed fetus has been affected. Birth defects which have been documented following isotretinoin exposure include abnormalities of the face, eyes, ears, skull, central nervous system, cardiovascular system, and thymus and parathyroid glands. Cases of IQ scores less than 85 with or without other abnormalities have been reported There is an increased risk of spontaneous abortion, and premature births have been reported. Documented external abnormalities include: skull abnormality; ear abnormalities (including anotia, micropinna, small or absent external auditory canals); eye abnormalities (including microphthalmia); facial dysmorphia; cleft palate Documented internal abnormalities include: CNS abnormalities (including cerebral abnormalities, cerebellar malformation, hydrocephalus, microcephaly, cranial nerve deficit); cardiovascular abnormalities; thymus gland abnormality; parathyroid hormone deficiency. In some cases death has occurred with certain of the abnormalities previously noted

The problems that isotretinoin (Acutane) causes in pregnancy include:

• Life-threatening birth defects
• Abnormalities of the face, eyes, ears, skull, central nervous system, cardiovascular system, and thymus and parathyroid glands
• Increased risk of spontaneous abortion
• Premature births
• Documented external abnormalities, such as:
  • Skull abnormality
  • Ear abnormalities
  • Eye abnormalities
  • Facial dysmorphia
  • Cleft palate
• Documented internal abnormalities, such as:
  • CNS abnormalities
  • Cardiovascular abnormalities
  • Thymus gland abnormality
  • Parathyroid hormone deficiency
• Death in some cases 2

From the Research

Problems Caused by Acutane in Pregnancy

• Isotretinoin, the generic name for Acutane, is a known human teratogen that can cause multiple major malformations in fetuses, including craniofacial, cardiac, thymic, and central nervous system malformations 3
• Embryopathy associated with isotretinoin exposure during the first trimester of pregnancy can result in severe birth defects, such as microcephaly, hydrocephalus, and anomalies of the great vessels 4
• The use of isotretinoin during pregnancy has been linked to a high risk of spontaneous abortion, stillbirth, and live births with congenital malformations 5, 4
• Common birth defects associated with isotretinoin exposure include microtia or absence of external ears, as well as central nervous system and cardiovascular system anomalies 4
• Due to its teratogenic effects, isotretinoin is contraindicated in pregnancy, and women of childbearing age are advised to use effective contraception to prevent pregnancy while taking the medication 3, 6