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: 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.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.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.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.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.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.