Background:  The safety of in utero exposure to antiretrovirals (ARV) remains of concern. The objective of this study was to estimate the prevalence of congenital anomalies among infants in IMPAACT P1025, a prospective cohort study in the US, and to evaluate possible associations with in utero exposure to ARV.

Methods:  The study population comprised all infants enrolled in P1025 who were born between 2002 and 2007. All infants identified by the clinical sites as having congenital anomalies were reviewed for this analysis (reviewers blinded to ARV exposure history). Congenital anomalies were classified as per the Antiretroviral Pregnancy Registry. Odds ratios (OR) and 95% confidence intervals (95%CI) of the association between identified congenital anomalies and timing of first in utero exposure (classified as first or second/third trimester exposure vs none) to ARV (individual drugs and ARV classes) were estimated by logistic regression analysis.

Results:  Of 1306 infants enrolled in P1025 by October 26, 2007, 1112 met inclusion criteria for this analysis. Of these 1112 infants, 61 had confirmed congenital anomalies, resulting in a congenital anomaly rate of 5.49/100 live births (95%CI 4.22 to 6.99). Organ systems involved were:  cardiovascular (n = 33), genitourinary (n = 7), renal (n = 8), musculoskeletal (n = 15, including accessory digits of hand or foot, n = 7), craniofacial (n = 3), central nervous system (n = 3). First trimester exposure to efavirenz was associated with a significantly increased risk of congenital anomalies (OR 2.89, 95%CI 1.15 to 7.25). Exposure to other individual ARV or classes of ARV, starting either in first or second/third trimester, was not significantly associated with an increased risk of anomalies. Race, maternal age, and substance use during pregnancy (tobacco, alcohol, and other drugs) were not significantly associated with an increased risk of congenital anomalies.

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Conclusions:  The observed rate of congenital anomalies in this cohort is higher than previously reported for the general population in 2008 (2.76/100 live births; Metropolitan Area Congenital Defects Program) and for populations of HIV-infected women and their children (Antiretroviral Pregnancy Registry, 2.9/100 live births; Women and Infant Transmission Study, 3.56/100 live births). Cardiovascular anomalies occurred most frequently. With the exception of a known teratogen (efavirenz), no statistically significant associations between in utero exposure to ARV and congenital anomalies were identified.