Teratogenic mechanisms of medical drugs.
BACKGROUND Although prescription drug use is common during pregnancy, the human teratogenic risks are undetermined for more than 90% of drug treatments approved in the USA during the past decades. A particular birth defect may have its origins through multiple mechanisms and possible exposures, including medications. A specific pathogenic process may result in different outcomes depending upon factors such as embryonic age at which a drug is administered, duration and dose of exposure and genetic susceptibility. This review focuses on the teratogenic mechanisms associated with a number of medications. METHODS We used three methods to identify the teratogenic mechanisms of medications: the MEDLINE and EMBASE databases, two recent books on teratogenic agents and a list of drugs classified as U.S. Food and Drug Administration class D or X. Mechanisms were included only if they are associated with major structural birth defects and medications that are used relatively frequently by women of reproductive age. RESULTS We identified six teratogenic mechanisms associated with medication use: folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption and specific receptor- or enzyme-mediated teratogenesis. Many medications classified as class X are associated with at least one of these mechanisms. CONCLUSIONS Identifying teratogenic mechanisms may not only be relevant for etiologic and post-marketing research, but may also have implications for drug development and prescribing behavior for women of reproductive age, especially since combinations of seemingly unrelated prescription and over the counter medications may utilize similar teratogenic mechanisms with a resultant increased risk of birth defects.
van Gelder
Marleen M H J
MM
Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, The Netherlands. m.vangelder@ebh.umcn.nl
van Rooij
Iris A L M
IA
Miller
Richard K
RK
Zielhuis
Gerhard A
GA
de Jong-van den Berg
Lolkje T W
LT
Roeleveld
Nel
N
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D052244:Endocrine Disruptors / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000009:adverse effects; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000098:blood supply / Q000187:drug effects*; D005492:Folic Acid / Q000378:metabolism; D005493:Folic Acid Antagonists / Q000009:adverse effects; D006801:Humans; D051379:Mice; D009432:Neural Crest / Q000002:abnormalities / Q000187:drug effects; D018384:Oxidative Stress; D021041:Placental Circulation / Q000187:drug effects; D011247:Pregnancy; D055553:Prescription Drugs / Q000009:adverse effects*; D051381:Rats
D052244:Endocrine Disruptors; D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D055553:Prescription Drugs; D005492:Folic Acid