[tri-med] FYI - Environmental Causes of Human Congenital Malformations: The Pediatrician's Role in Dealing With These Complex Clinical Problems Caused by a Multiplicity of Environmental and Genetic Factors 

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PEDIATRICS Vol. 113 No. 4 April 2004, pp. 957-968


http://pediatrics.aappublications.org/cgi/content/abstract/113/4/S1/957
Environmental Causes of Human Congenital Malformations: The Pediatrician's Role 
in Dealing With These Complex Clinical Problems Caused by a Multiplicity of 
Environmental and Genetic Factors 
ABSTRACT 

There have been amazing advances in embryology, teratology, reproductive 
biology, genetics, and epidemiology in the past 50 years that have provided 
scientists and clinicians with a better perspective on the causes of congenital 
malformations. We still cannot provide the families of children with 
malformations a definitive diagnosis and cause in every instance. The purpose 
of this article is to inform pediatricians about environmental drugs, 
chemicals, and physical agents that have been documented to produce congenital 
malformations and reproductive effects and to indicate that the multitude of 
teratogenic agents account for only a small proportion of malformations. The 
most common known cause is genetic, but the largest group, unfortunately, is 
unknown. There are a number of important clinical rules that are important for 
clinicians to use when determining the cause of their patient's congenital 
malformations: 

  1.. No teratogenic agent should be described qualitatively as a teratogen, 
because a teratogenic exposure includes not only the agent but also the dose 
and the time in pregnancy when the exposure has to occur. 

  2.. Even agents that have been demonstrated to result in malformations cannot 
produce every type of malformation. Known teratogens may be presumptively 
implicated by the spectrum of malformations that they produce. It is easier to 
exclude an agent as a cause of birth defects than to conclude definitively that 
it was responsible for birth defects, because of the existence of genocopies of 
some teratogenic syndromes. 

  3.. When evaluating the risk of exposures, the dose is a crucial component in 
determining the risk. Teratogenic agents follow a toxicologic dose-response 
curve. This means that each teratogen has a threshold dose below which there is 
no risk of teratogenesis, no matter when in pregnancy the exposure occurred. 

  4.. The evaluation of a child with congenital malformations cannot be 
performed adequately unless it is approached with the same scholarship and 
intensity as the evaluation of any other complicated medical problem. 

  5.. Each physician must recognize the consequences of providing erroneous 
reproductive risks to pregnant women who are exposed to drugs and chemicals 
during pregnancy or alleging that a child's malformations are attributable to 
an environmental agent without performing a complete and scholarly evaluation. 

  6.. Unfortunately, clinical teratology and clinical genetics is not 
emphasized in medical school and residency education programs, but 
pediatricians have a multitude of educational aids to assist them in their 
evaluations, which includes consultations with clinical teratologists and 
geneticists, the medical literature, and the OMIM web site. 


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