Exposure to Fetotoxic Agents

Many variations occur in the complex process of human development. Although population heterogeneity is based on such events, some deviations from the usual developmental process result in aberrations of normal structure and function. These adverse alterations have been scrutinized in an effort to determine their cause. The clinician investigating the effects of exposure to fetotoxic agents must consider whether the patient is known to have reproductive risks, whether there has been exposure to fetotoxic agents during pregnancy, and whether structural or functional abnormalities are likely to develop in the fetus.

Many harmful agents are responsible for altering the biologic process of human development (eg, radiation, viruses, medications, and drugs). Aberrations that result from fetal exposure to harmful agents is especially tragic because such exposure is often preventable. However, even the most careful investigation will fail to reveal the cause in the majority of developmental handicaps.

Approximately 3-5% of newborns in the United States have abnormalities at birth that are serious enough to require some form of treatment. Moreover, full recognition of malformations, anomalies, or defects may take years. Thus, estimates that as much as 10% of the total population suffer from some structural or functional developmental disability do not appear unreasonable.

Evaluation

The timing of exposure is crucial, as fetal organs or structures are most vulnerable to adverse influences during organogenesis.

Table 14-4 lists some of the potential adverse effects related to the timing of fetotoxic exposure. The route of exposure, the length of time that the exposure occurred, and the total dose received during exposure may also influence the outcome of the pregnancy.

Evaluation of studies of potential toxic exposures is difficult owing to the large number of possible fetotoxic agents and interactive effects of certain agents, the retrospective nature of most studies, the difficulty evaluating damage, the presence or absence of influences that may alter the effects of an agent, and the presence or absence of certain genotypes that might alter an individual’s susceptibility. Therefore, specific criteria to recognize teratogens in humans have been defined (

Table 14-5). The known mechanisms of abnormal development are summarized in

Table 14-6, which also outlines a working hypothesis of the pathogenesis, common pathways, and final manifestations of abnormal development.

Counseling of the parents should include review of the exposure history and discussion of the particular agent involved, as well as possible sequelae. In some cases, intervention may be possible. In other cases, if an abnormal pregnancy is found, the parents may elect to abort an affected fetus. Effective counseling should provide the best information available to assist the parents in what is always a very difficult decision.

The FDA standards for drug labeling with regard to teratogenicity are listed in

Table 14-7.

References

American College of Obstetricians and Gynecologists: ACOG Technical Bulletin No. 212. Early pregnancy loss. September 1995.

American College of Obstetricians and Gynecologists: ACOG Practice Bulletin No 3. Medical management of tubal pregnancy. December 1998.

Centers for Disease Control and Prevention: Current Trends Ectopic Pregnancy - United States, 1990-1992. MMWR 1995;44:46.

Pisarska MD, Carson SA, Buster JE: Ectopic pregnancy. Lancet 1998;351:1115.

Regan L: Prospective study of spontaneous abortion. In: Beard RW, Sharp F (editors). Early Pregnancy Loss: Mechanisms and Treatment. Roy Coll Obstet Gynaecol, 1988.

Tulandi T: New protocols for ectopic pregnancy. Contemp Ob Gyn 1999;44:42.

Yao M, Tulandi T: Current status of surgical and nonsurgical management of ectopic pregnancy. Fertil Steril 1997;67:421.

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Revision date: July 3, 2011
Last revised: by David A. Scott, M.D.