TABLE 2—

International Screening for Drug Teratogenicity: The MADRE (Maternal Drug Exposure) Project of the International Clearinghouse for Birth Defects Surveillance and Research

Goal	Screen for potential teratogenicity of medications
Approach	Case-only study of cases of birth defects following reported exposure to maternal medication use during first trimester of pregnancy; all cases are malformed and all cases were exposed to some medication; analysis is through a modified case-affected control approach, stratified by registry
Current data	More than 15 000 cases of birth defects from 12 registries
Selected findings (antiseizure medications)	Confirmed classical associations: phenobarbital with oral clefts and heart defects; valproic acid with spina bifida, hypospadias, and heart defects; and carbamazepine and heart defects
	Testing associations suggested in literature: evaluated and confirmed the reported association between valproic acid and craniosynostosis
Evolution	Refine classification according to pathogenetic mechanisms; assess specific risks for multiple congenital anomalies; focus on selected major defects (heart defect subtypes, gastroschisis); increase registry participation