Sensitivity, specificity, and positive predictive value of multiple malformations in isotretinoin embryopathy surveillance.

Isotretinoin causes serious birth defects in about 25% of babies exposed in the first trimester of pregnancy. Despite warnings about the drug's teratogenicity, cases of isotretinoin embryopathy continue to occur; more than 80 such cases have been reported since 1982. The true magnitude of the problem is unknown, however, and case estimates range to more than 1,000. The need for isotretinoin embryopathy (IE) surveillance is therefore great. Sixty-one known cases were evaluated to determine the sensitivity (proportion of cases with a given defect pattern) of various defect combinations. Using data from the Metropolitan Atlanta Congenital Defects Program for the period before isotretinoin was available, we evaluated the specificity (proportion of malformed infants without exposure who do not have the pattern of defects) for the various defect combinations. Ear malformations (microtia, anotia, absence or stricture of auditory canal, missing pinnae) have an associated sensitivity of 70.5% and a specificity of 99.5%. Ear defects combined with central nervous system (CNS) defects (microcephalus, hydrocephalus, reduction deformities of the brain) and cardiovascular (CVS) defects (conotruncal defects, aortic arch abnormalities) have an associated sensitivity of 19.7% and a specificity of 100.0%. The case definition of ear defects combined with either CNS or CVS defects maximizes both specificity (99.9%) and sensitivity (45.9%). The investigators are now evaluating the feasibility of using this pattern of defects to monitor for IE within a national monitoring program.