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Thalidomide is a drug that was introduced on to the market on October 1, 1957 in West Germany. Thalidomide soon became a drug prescribed to pregnant women to combat symptoms associated with morning sickness.
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Thalidomide Structure |
When taken during the first trimester of pregnancy, Thalidomide prevented the proper growth of the foetus resulting in horrific birth defects in thousands of children around the world.
It was the linking of newborn abnormalities with the taking of thalidomide by an Australian clinician, William McBride, that identified it as a teratogenic agent causing a "thalidomide embryopathy".
Children were born with limb and other defects, mainly in first world countries, in the late 1950's and early 1960's and became known as "Thalidomide babies". (More? Musculoskeletal Abnormalities - Limb Reduction)
Not all species embryos are affected by the drug in the same way, with human and rabbit being most susceptible to the teratogenic effects. In addition, the effect on human development is also dependent upon the time and dose of the drug exposure, the "critical periods".
More recent research has shown a clinical revival for thalidomide in its use in non-pregnant women during cancer chemotherapy.
Page Links: Introduction | Some Recent Findings | Chemotherapy | References | Books | WWW Links | Glossary
Knobloch J, Rüther U. Shedding light on an old mystery: Thalidomide suppresses survival pathways to induce limb defects. Cell Cycle. 2008 Feb 14;7(9)
"Many hypotheses have been proposed to explain the molecular mechanism of thalidomide teratogenicity, in particular regarding to limb defects. Most experimental evidence in vivo has been provided for a model that suggests the generation of oxidative stress by thalidomide with subsequent down-regulation of Wnt and Akt survival pathways. ...We extend this model by presenting new data demonstrating an involvement of the transcription factors Tbx5 and Sall4 in thalidomide-induced molecular pathology."
Benegbi M. 45 years later...where do we stand? Can J Clin Pharmacol. 2007 Winter;14(1):e37-9.
Li PK, Pandit B, Sackett DL, Hu Z, Zink J, Zhi J, Freeman D, Robey RW, Werbovetz K, Lewis A, Li C. A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities. Mol Cancer Ther. 2006 Feb;5(2):450-6.
Reviews
McBride WG. Thalidomide embryopathy. Teratology. 1977 Aug;16(1):79-82.
Saunders EJ, Saunders JA. Drug therapy in pregnancy: the lessons of diethylstilbestrol, thalidomide, and bendectin. Health Care Women Int. 1990;11(4):423-32.
Stephens TD. Proposed mechanisms of action in thalidomide embryopathy. Teratology. 1988 Sep;38(3):229-39.
Newman CG The thalidomide syndrome: risks of exposure and spectrum of malformations. Clin Perinatol. 1986 Sep;13(3):555-73.
Fletcher I. Review of the treatment of thalidomide children with limb defeciency in Great Britain. Clin Orthop Relat Res. 1980 May;(148):18-25.
Articles
Benegbi M. 45 years later...where do we stand? Can J Clin Pharmacol. 2007 Winter;14(1):e37-9.
"The Thalidomide Victims Association of Canada (TVAC) was founded in 1988 and is the only organization in North America to work with and for Thalidomide victims. Our mission is to empower our members and to improve their quality of life through various programs and customized services. With the return of Thalidomide on the market, TVAC also took on the mandate of informing the public on the devastating effects of this medication and to promote awareness and caution when using any teratogenic products currently available".
McBride WG. Prescription drugs in the first trimester and congenital malformations. Aust N Z J Obstet Gynaecol. 1992 Nov;32(4):386.
Chuah B, Lim R, Boyer M, Ong AB, Wong SW, Kong HL, Millward M, Clarke S, Goh BC. Multi-centre phase II trial of Thalidomide in the treatment of unresectable hepatocellular carcinoma. Acta Oncol. 2007;46(2):234-8.
Li PK, Pandit B, Sackett DL, Hu Z, Zink J, Zhi J, Freeman D, Robey RW, Werbovetz K, Lewis A, Li C. A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities. Mol Cancer Ther. 2006 Feb;5(2):450-6.
Search Pubmed Now: Thalidomide[TITL] (2007: 2,672 Articles, 253 Reviews) | Drug use in pregnancy
A selection of recent general public information books on Thalidomide, available from various internet commercial suppliers (search using the book title). Please note that this listing does not reflect an endorsement of the book or its content and is provided for educational purposes only.
Thalidomide Kid (Paperback) by Kate, Rigby (Author)
Thalidomide - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References (Paperback) by ICON Health Publications (Author)
Internet supplier link: Amazon
Alcohol "Fetal Alcohol Syndrome"
Infection
cytomegalovirus
Trauma
These links require online access to Merck Manuals on Women's Health Issues. http://www.merck.com/mrkshared/mmanual_home2/sec22/sec22.jsp
Risk Factors Present Before Pregnancy
Risk Factors That Develop During Pregnancy
Diseases that complicate Pregnancy
Problems Affecting the Fetus or Newborn
Mitral Valve Prolapse
High Blood Pressure
Anemias
Kidney Disease
Infectious Disease
Diabetes
Thyroid
Liver
Asthma
Systemic Lupus Erythematosus
Rheumatoid Arthritis
Myasthenia Gravis
Idiopathic Thrombocytopenic Purpura
>Surgery During Pregnancy
Relate to lifestyle, environment and nutrition. Some examples of this form of abnormality are the impact of excess alcohol on neural development (Fetal alcohol syndrome), viral infection (rubella) at a critical stage of development, inadequate dietry folate intake (neural tube defects), effects of prescription drugs (Thalidomide- limb development) and even maternal endocrine function (thyroid development).
In addition to these obvious maternally-derived abnormalities, there is growing evidence that the interuterine environment has a strong influence on later postnatal health. This theory is based on the early statistical analysis of disease/longevity in babies with low birth weights in England by Barker, and has been called the "Barker Hypothesis". (More? Barker Hypothesis)
Sudden Infant Death Syndrome (SIDS)
Malnutrition
Infection
Trauma
see also Normal Childhood Development
These developmental abnormalities usually involve only small DNA mutations affecting individual or a few genes, two exceptions are the major chromosomal abnormalities usualy trisomy; trisomy 21 (Down syndrome) and trisomy 18 (Edwards syndrome) (also trisomy 9, 13, 15). Note that the occurance of chromosomal abnormalities also increases with increasing maternal age. There are many pamphlets providing information about prenatal diagnosis (see NSW State Health Publication Checking your baby's health before birth).
Each section of the notes covering early development and specific systems contain references to specific abnormalities (on Page 2 of each notes section). The best source for Australian statistical data is the Australian Institute of Health and Welfare National Perinatal Statistics Unit, UNSW which publishes "Congenital Malformations Australia" every 2 years. Be aware that some congenital abnormalities, by their nature, affect multiple systems. In the USA, the Center for Disease Control (CDC) keeps and publishes relevant statistical information. A very difficult issue in abnormal development are the many different Ethical implications.
This current page is a link to Normal and Abnormal Development and Population Data.
You should look at normal development. Development Notes
Alternatively, go on to look at Systematic Development of organs and tissues.
For those wanting to see dynamic processes of development (and have a reasonably quick connection) then the Movies pages are good for watching changes occur.
The study of human development has relied extensively on studying the process in other model animals. For those wanting to see the process of development in other species then the other embryos pages are a good start.
Home Page
Embryo stages
Fetal Dev
Dev Notes 1
Dev Notes 2
System Notes
Acknowledgements
Abnormal Development
Australian Statistics
Abnormalities by Systems
Prenatal Diagnosis
Fetal Origins Hypothesis
Intrauterine Growth Retardation
Twinning
Genetic Abnormalities
Down Syndrome
Edwards Syndrome
Maternal Factors
Neural Tube Defects
Fetal Alcohol Syndrome
Smoking
Chemical
Drugs
Thalidomide
Radiation
Heavy Metal
Iodine Deficiency
Viral Infection
Rubella
Parvovirus
Varicella
Databases
NINDS Factsheets
Movies
Audio
Class Notes
Serial Images
K12 Students
Abnormal Development
Embryology in the News
Histology
Site Map
School of Med Sci
UNSW Medicine
University of NSW
UNSW Cell Biology
NCBI Books
New 2010 Site
Enjoyed this site? Visit the New 2010 Site!
This was the landmark association of a prescription drug with teratogenic effects on human development. As a consequence this tragedy significant changes to drug testing and pregnancy advice occurred.
More recently, the valuable therapeutic effects of this drug (and its analogues) in cancer has led to a revival of its use in non-pregnany woment.
This Syndrome is 100% preventable.
The page links to internal resources coving specific topics and also uses the online Merck Manuals, which cover this topic with some excellent short summaries.
Please email Dr Mark Hill if you wish to make a comment about this current project.
