Last updated: December 6, 2022

Summarytoggle arrow icon

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.

Overviewtoggle arrow icon

  • 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
Overview of mechanisms of teratogenesis
Phase 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
  • The physical effects of teratogens are widely varied (see individual conditions for specific manifestations).
    • VACTERL association [1]
      • Vertebral, anal, cardiac, tracheoesophageal fistula, renal, and limb abnormalities
      • Due to a defect during the development of embryonic mesoderm
    • Limb deformities
      • Syndactyly: fusion of two or more fingers or toes (most common congenital malformation of the limbs)
      • Polymelia/polydactyly: supernumerary limbs, fingers, or toes
      • Oligodactyly, adactyly: absence of one or more of the fingers or toes
      • Ectromelia: collective term for hypoplasia and/or aplasia of one or more long bones, resulting in limb deformity
      • Peromelia/perodactyly: amputation-like stump of a limb, finger, or toe

Maternal conditionstoggle arrow icon

Diabetes mellitus (pregestational diabetes mellitus or gestational diabetes mellitus) [2]

Obesity [3]

Graves disease [4]


Phenylketonuria (maternal PKU) [5][6]

Substance use during pregnancytoggle arrow icon

Alcohol: fetal alcohol syndrome (embryo-fetal alcohol syndrome) [7]


Mechanism of teratogenesis

Clinical findings

Cigarette smoking during pregnancy [12][13]


Cocaine [15]

Medicationstoggle arrow icon

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)

ThaLIMBdomide causes LIMB defects.

Physical agentstoggle arrow icon

Radiation exposure during pregnancy

Metal toxicitytoggle arrow icon

Lead [19]

Mercury [21]

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

Conditions associated with congenital cardiac defectstoggle arrow icon

Overview of conditions associated with congenital cardiac defects
Condition Associated congenital cardiac defect
Maternal conditions
  • Transposition of great vessels
  • VSD
Hereditary conditions

Referencestoggle arrow icon

  1. Guidelines for Diagnostic Imaging During Pregnancy and Lactation. Updated: October 1, 2017. Accessed: January 29, 2019.
  2. Wattendorf DJ, Muenke M. Fetal alcohol spectrum disorders. Am Fam Physician. 2005; 72 (2): p.279-285.
  3. Fetal Alcohol Syndrome Among Children Aged 7–9 Years — Arizona, Colorado, and New York, 2010. Updated: January 30, 2015. Accessed: October 8, 2020.
  4. Abdelrahman A, Conn R. Eye abnormalities in fetal alcohol syndrome. Ulster Med J. 2009; 78 (3): p.164-165.
  5. Ronen GM, Andrews WL. Holoprosencephaly as a possible embryonic alcohol effect. Am J Med Genet. 1991; 40 (2): p.151-154.doi: 10.1002/ajmg.1320400206 . | Open in Read by QxMD
  6. Weiss K, Kruszka PS, Levey E, Muenke M. Holoprosencephaly from conception to adulthood. American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 2018; 178 (2): p.122-127.doi: 10.1002/ajmg.c.31624 . | Open in Read by QxMD
  7. Khoury MJ, Gomez-Farias M, Mulinare J. Does maternal cigarette smoking during pregnancy cause cleft lip and palate in offspring?. Am J Dis Child. 1989; 143 (3): p.333-337.
  8. Bruin JE, Gerstein HC, Holloway AC. Long-term consequences of fetal and neonatal nicotine exposure: A critical review. Tox Sci. 2010; 116 (2): p.364-374.doi: 10.1093/toxsci/kfq103 . | Open in Read by QxMD
  9. Kocherlakota P. Neonatal Abstinence Syndrome. Pediatrics. 2014; 134 (2): p.e547-e561.doi: 10.1542/peds.2013-3524 . | Open in Read by QxMD
  10. Forray A. Substance use during pregnancy. F1000Research. 2016; 5: p.887.doi: 10.12688/f1000research.7645.1 . | Open in Read by QxMD
  11. Laronda MM, Unno K, Butler LM, Kurita T. The development of cervical and vaginal adenosis as a result of diethylstilbestrol exposure in utero. Differentiation. 2012; 84 (3): p.252-260.doi: 10.1016/j.diff.2012.05.004 . | Open in Read by QxMD
  12. Vargesson N. Thalidomide-induced teratogenesis: History and mechanisms. Birth Defects Res C Embryo Today. 2015; 105 (2): p.140-156.doi: 10.1002/bdrc.21096 . | Open in Read by QxMD
  13. Eriksson UJ, Håkan Borg LA, Cederberg J, et al. Pathogenesis of diabetes-induced congenital malformations. Ups J Med Sci. 2000; 105 (2): p.53-84.doi: 10.1517/03009734000000055 . | Open in Read by QxMD
  14. Stothard KJ, Tennant PWG, Bell R, Rankin J. Maternal Overweight and Obesity and the Risk of Congenital Anomalies. JAMA. 2009; 301 (6): p.636.doi: 10.1001/jama.2009.113 . | Open in Read by QxMD
  15. Moleti M, Di Mauro M, Sturniolo G, Russo M, Vermiglio F. Hyperthyroidism in the pregnant woman: Maternal and fetal aspects. Journal of Clinical & Translational Endocrinology. 2019; 16: p.100190.doi: 10.1016/j.jcte.2019.100190 . | Open in Read by QxMD
  16. Chen H. Atlas of Genetic Diagnosis and Counseling. Humana Press ; 2006
  17. Enns et al.. Maternal Phenylketonuria. Pediatrics. 2008; 122 (2): p.445-449.doi: 10.1542/peds.2008-1485 . | Open in Read by QxMD
  18. Santos J, Nogueira R, Pinto R, Cerveira I, Pereira S. First trimester diagnosis of VACTERL association. Clin Pract. 2013; 3 (1): p.e5.doi: 10.4081/cp.2013.e5 . | Open in Read by QxMD
  19. Lead Screening During Pregnancy and Lactation. Updated: August 1, 2012. Accessed: January 19, 2018.
  20. Siebel S, Solomon BD. Mitochondrial factors and VACTERL association-related congenital malformations. Mol Syndromol. 2013; 4 (1-2): p.63-73.doi: 10.1159/000346301 . | Open in Read by QxMD
  21. Gilbert-Barness E. Teratogenic causes of malformations. Ann Clin Lab Sci. 2010; 40 (2): p.99-114.

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