• Clinical science

Teratogenesis

Summary

Teratogenesis plays an important role in neonatology and is a common cause of intellectual disability. Teratogens are environmental factors that result in permanent structural or functional malformations or death of the embryo or fetus. Many congenital malformations are of unknown origin, but known teratogens include drugs, maternal illnesses and infections, metal toxicity, and physical agents (e.g., radiation). The fetus is most susceptible in the 3rd–8th weeks of pregnancy during organogenesis in the embryonic period; after 8 weeks, growth and function are affected. The earlier the exposure to the teratogenic agent in utero, the more severe the defects are in the embryo/fetus. However, the individual response to teratogens is highly varied and depends on genetic susceptibility and severity of the exposure.

See “Pharmacotherapy during pregnancy” for more information on teratogenic drugs during pregnancy.

See “Congenital TORCH infections” for more information on teratogenic infectious agents.

Overview

  • Teratogen: an environmental factor that causes a permanent structural or functional abnormality, growth restriction, or death of the embryo or fetus
  • Effects depend on multiple factors
    • The pharmacological properties, dose, and regimen of drug exposure determine the risk of developing teratogenic birth defects.
    • Stage of pregnancy in which exposure occurs
Stage in pregnancy Significance
Preimplantation phase
Embryonic phase
Phase of fetal growth and maturation
  • Second and third trimesters
  • Period of fetal growth and maturation
  • Can lead to deficits in organ function, intellect, behavior, or minor structural malformations

Maternal illnesses

Pregestational diabetes mellitus or gestational diabetes mellitus [2][3]

Diabetic embryopathy

Diabetic fetopathy

Graves disease [4]

Hypothyroidism [5]

Obesity [6]

Phenylketonuria [7][8]

Substance use

Alcohol: fetal alcohol syndrome (embryo-fetal alcohol syndrome) [9]

Cigarette smoking [13][14]

Opioids

Cocaine [15]

Medications

The following drugs are no longer approved for clinical use. See “Pharmacotherapy during pregnancy“ for a comprehensive list of teratogenic drugs.

Diethylstilbestrol [16]

Thalidomide [17]

  • Previous use: a sedative that is used to treat nausea or vomiting in pregnant women (now administered in limited indications, e.g., multiple myeloma)
  • Effects: thalidomide embryopathy
    • Symmetrical amelia (complete absence of limbs)
    • Micromelia (“flipper limbs”)
    • Anotia (absence of the external ear)
    • Phocomelia: a teratogenic limb defect that is characterized by the absence of the proximal portion of a limb (hand or foot are directly attached to the shoulder or hip)

ThaLIMBdomine causes LIMB defects.

Physical agents

Radiation

Metal toxicity

Lead [19]

Mercury [21]

  • Etiology: methylmercury (can be found in contaminated seafood, esp. tilefish, swordfish, shark, and king mackerel)
  • Effects

Congenital cardiac defect associations

Condition Associated congenital cardiac defect
Maternal conditions
  • Transposition of great vessels
  • VSD
Infection
Substances/drugs
Hereditary conditions
  • 22q11 syndrome