Monitoring for congenital malformations.

Abstract

Many countries instituted birth defects monitoring systems in the wake of the thalidomide tragedy. Having these systems in place will shorten the time before an alarm is signaled, should a teratogen of the potency of thalidomide be introduced. However, with stronger laws and regulations for testing drugs for adverse reproductive outcomes, a tragedy on the scale of thalidomide from ingestion of prescribed drugs by pregnant women is unlikely. Prospective parents could be exposed at the critical times to new physical, infectious, or nondrug chemical agents teratogenically as potent as thalidomide. (Teratogenic agents whose widespread use antedates monitoring will not cause rate changes or clusters detectable by monitoring.) What seems more likely is that the introduction of "weakly" teratogenic agents, or the inadvertent use of new drugs that are teratogenic, like isotretinoin, will be responsible for increases in birth defects. In neither of these situations are large numbers of cases likely to accumulate in short periods of time, particularly in the relatively small catchment areas (fewer than 50 to 100,000 births per year) of many monitoring programs. In addition to having to cope with this problem of rare outcomes, many monitoring systems have not been able to obtain complete ascertainment of CMs, at least not from single, rapidly reporting sources. Two remedies to these inadequacies are possible: Expand the catchment area. All births in the US, for instance, could be monitored if information on specific CMs was included on birth certificates, which were then transmitted to a central agency that could analyse the data rapidly. Alternatively, if different monitoring systems had comparable methods of ascertainment and diagnostic classifications, their data could be pooled with greater reliability than is currently possible. CMs in newborns are only one indicator of teratogenicity. At least 20% of all conceptions end in spontaneous abortions. A much higher proportion of abortuses have chromosome abnormalities, congenital malformations, or both, than newborns. The time necessary for such outcomes to manifest after the introduction of a new teratogen could be considerably shorter than the time before significant increases of CMs occurred in liveborns and stillborns. Monitoring the spontaneous abortion rate or chromosomal and other abnormalities in abortuses would be an important adjunct to monitoring newborns. However, since some teratogens may only cause CMs in newborns, the current approach to monitoring should not be abandoned. Moreover, the problems of ascertainment encountered in monitoring newborns are greater still in monitoring abortuses.(ABSTRACT TRUNCATED AT 400 WORDS)