First Trimester Exposure to Antiretroviral Therapy and Risk of Birth Defects

More than 3 million human immunodeficiency virus (HIV)-infected women worldwide give birth each year [1], and an increasing number conceive while receiving antiretroviral (ARV) treatment for their own infection or to prevent mother-to-child transmission (MTCT). Yet, the fetal safety of many of the currently approved ARV medications for use in non-pregnant adult populations is largely unknown. ARVs are associated with numerous toxicities in both adults and children [2, 3], and therefore it seems biologically plausible that they would also be toxic to the developing fetus. Until recently, data on the potential teratogenic effect of ARVs had mainly been obtained from animal studies [4], case reports [5, 6], and surveillance data [7]. Nowadays, we do have the results provided by several cohort studies [8–15], but the evidence to date is still limited by differences in the definition and ascertainment of cases across the studies and variations in the selection of control groups. Moreover, some of the studies included a selective sample of relatively healthy participants. Thus, there is a compelling need to have further safety data for the use of ARVs during pregnancy, particularly for disadvantaged populations often neglected by volunteered based research. Large health care utilization databases are an efficient resource for conducting population-based studies with valid reference groups [16–18]. We therefore used data from the Tennessee Medicaid Program (TennCare), linked to vital records and supplemented by in-depth medical chart reviews, to assess the risk of birth defects after in utero exposure to ARVs among infants born to HIV-infected women enrolled in TennCare between 1994 and 2009. Key elements of the database have been validated and these data have been used to conduct several epidemiologic studies of medications in pregnancy [19–22].