Background: Although use of efficacious interventions, including antiretrovirals (ARVs), has dramatically reduced the rate of mother-to-child transmission of human immunodeficiency virus, the safety of in utero ARV exposure remains of concern.
Methods: Data regarding 1112 infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group protocol P1025 born between 2002 and 2007 were analyzed for this study. Congenital anomalies were classified based on the Metropolitan Atlanta Congenital Defects Program guidelines. Associations between congenital anomalies and timing of first in utero exposure to ARVs were evaluated by logistic regression analysis.
Results: Congenital anomalies were identified and confirmed in 61 of the 1112 infants, resulting in a prevalence of 5.49/100 live births (95% confidence interval, 4.22–6.99). Among the 80 anomalies identified, the organ systems involved included cardiovascular (n = 33), musculoskeletal (n = 15), renal (n = 9), genitourinary (n = 6), craniofacial (n = 4), and central nervous system (n = 2). First trimester exposure to efavirenz was associated with a significantly increased risk of congenital anomalies (odds ratio, 2.84; 95% confidence interval, 1.13–7.16). No significant associations were observed between exposure to other individual ARVs or classes of ARVs started at any time during pregnancy and infant congenital anomalies.
Conclusions: The observed rate of congenital anomalies in this cohort is higher than previously reported for the general population, but it is consistent with rates observed in other recent studies of children born to human immunodeficiency virus–infected women. Cardiovascular anomalies occurred most frequently. With the exception of a known teratogen (efavirenz), no statistically significant associations between in utero exposure to ARVs and congenital anomalies were identified.
From the *Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN; †Department of Epidemiology, Boston University School of Public Health, Boston, MA; ‡Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; §Henry M. Jackson Foundation for the Advancement of Military Medicine, Prevention Sciences Program, Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; ¶Department of Pediatrics, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, PA; ‖Division of Pediatric Infectious Disease and Immunology, University of Miami Miller School of Medicine, Miami, FL; **Department of Biostatistics, Harvard School of Public Health, Boston, MA; and ††Pediatric, Adolescent, and Maternal AIDS (PAMA) Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
Accepted for publication September 2, 2011.
Jeffrey T. Talbot is currently at Mercer University School of Medicine, Macon, GA.
The authors received funding support for the research on which this article is based from the National Institutes of Health (NIH). Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) (grant U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) (grant AI068632). This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement number 5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and number 1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-HD-9-001/HHSN267200800001C). The authors have no other funding or conflicts of interest to disclose.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Address for correspondence: Katherine M. Knapp, MD, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 600, Memphis, TN 38105–3678. E-mail: email@example.com.
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