Background:  Because animal studies have indicated an association between first trimester pregnancy exposure to certain ART drugs and central nervous system birth defects, the ongoing Antiretroviral Pregnancy Registry (APR) critically reviews all central nervous system defects.

Methods:  APR is a prospective exposure-registration cohort study designed to detect a potential increase in the risk of birth defects. Clinicians voluntarily register pregnant women with prenatal exposures to ART and provide birth outcomes. Birth defect prevalence is compared to CDC’s population-based surveillance system. While the primary analysis is based on prospective data, APR complements its analyses by comprehensive review of other data sources (e.g., clinical trials, epidemiological studies, and retrospective data).

Results:  From 1989 through July 2005, APR has monitored 5169 live births exposed to ART. Among 1980 first trimester exposures, there were 59 birth defects (3.0%, 95%CI 2.3 to 3.8). This overall rate is not significantly different from CDC’s rate of 3.1 per 100 live births (95%CI 3.1 to 3.2). After first trimester exposures, 4 cases of central nervous system defects were detected among 1980 live births (0.20 of 100 live births, 95%CI 0.004 to 0.40). Among those with later exposure, 5 had central nervous system defects among 3189 live births (0.16 of 100 live births, 95%CI 0.02 to 0.29). According to national data, about 1 in 235 live births have central nervous system or eye defects. In APR, central nervous system defects after first trimester exposure included holoprosencephaly, brain growth retardation, and 2 with hydrocephalus; and ,after later exposures, Dandy Walker, lipomeningocele, caudal thalamic notch cyst, and 2 with hydrocephalus. None were exposed to efavirenz. Among retrospective cases, there were 4 myelomeningocele (neural tube) defects, 3 with efavirenz exposure, and a Dandy Walker defect with efavirenz exposure as reported in the product label (Sustiva® BMS, 8 of 2004). There were no central nervous system defects in other supplemental studies reviewed.

Conclusions:  Within the detection power of the sample to date, APR data demonstrate no teratogenicity overall. There does not appear to be an increased risk of central nervous system defects in the prospective analysis. In the supplemental data, there do not appear to be any patterns other than the already identified efavirenz signal. Prospective reports of ART exposures are critically important to determine teratogenic potential (which can be made by calling 800-258-4263) and may avoid reporting bias inherent in other forms of data collection.