PURPOSE OF THE STUDY.
The use of effective, fully suppressive antiretroviral (ARV) therapy during pregnancy dramatically lowers mother-to-child transmission of HIV. Currently, nucleoside reverse transcriptase inhibitors form the foundation of ARV combination therapy for pregnant women; however, these drugs have potential negative consequences for the developing fetus. This study examined the prevalence of congenital anomalies in infants who were exposed in utero to ARV drugs.
International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) protocol P1025 is a prospective, observational study of infants born to HIV-infected mothers. The current study population included 1112 singleton infants enrolled in P1025 for whom the congenital anomalies case-report form had been completed.
Affected infants were identified through computerized screening of the case-report form. These cases were then reviewed and classified by a panel of clinicians who were not aware of the mother’s ARV exposure during pregnancy.
Eighty congenital anomalies were identified in 1112 infants, resulting in a congenital anomaly rate of 5.49 per 100 births and included: cardiovascular (33), musculoskeletal (15), renal (9), genitourinary (6), craniofacial (4), and central nervous system (2) events. The only specific ARV drug association was with efavirenz, a known teratogen.
ARV use during pregnancy has been associated with increased risks for prematurity and mitochondrial toxicity. A number of studies (reviewed in the current report) have documented that the congenital anomaly prevalence rate in infants born to HIV-infected mothers is significantly higher than for the general US population (∼3 per 100 live births). Cardiovascular anomalies were most frequent, and except for efavirenz, no significant association between in utero exposure and congenital anomalies was identified.
As with all medical interventions, the use of ARV therapy for prevention of mother-to-child transmission of HIV is not risk free. The increase in congenital anomalies seen in this and other cohorts of children exposed to ARV drugs in utero is significant. Although the severity and long-term impact of these findings on the overall outcome and quality of life of affected infants were not described, it is unlikely that these would justify alteration in the approach to prevention of perinatal HIV disease.
- Copyright © 2012 by the American Academy of Pediatrics