Antiretroviral therapy during the first trimester was associated with birth defects, but the benefits of preventing mother-to-child HIV transmission should be weighed carefully against the risk of infection, according to researchers.

The French Perinatal Cohort study involved 13,124 live births from 1994 to 2010 and included mother-child pairs across 90 health care centers in the Paris area, in which mothers were HIV positive. Children were followed until age 2 years. Of these, 42% were exposed to ART during the first trimester.

Jeanne Sibiude, MD, of the Public Hospital System of Paris, and of the Population Health Research Center of Epidemiology in France, and colleagues assessed birth defects in the study population using the European Surveillance of Congenital Anomalies (EUROCAT) and Metropolitan Atlanta Congenital Defects Program (MACDP) classifications.

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According to EUROCAT classification results, birth defect prevalence was 4.4% (95% CI: 4%–4.7%). After adjusting for maternal age, geographical origin, IV drug-use and type of maternity center, researchers observed significant associations between exposure to zidovudine during the first trimester and congenital heart defects (adjusted OR=2.2; 95% CI: 1.3–3.7; P=0.003).

The use of didanosine (Videx/Videx EC, Bristol-Myers Squibb) and indinavir (Crixivan, Merck) were associated with head and neck defects (adjusted OR=3.4; 95% CI: 1.1–10.4; P=0.04 and adjusted OR=3.8; 95% CI: 1.1–13.8; P=0.04, respectively).

Exposure to efavirenz during the first trimester was associated with neurological defects (adjusted OR=3.0; 95% CI: 1.1-8.5; P=0.04). This association should be “interpreted with caution,” according to the researchers.

Sibiude and colleagues noted that study limitations included the absence of data on termination of pregnancy, stillbirths, tobacco and alcohol intake and concomitant medication.

They called for further research to elucidate the mechanism behind in utero ART and heart defects, but added “whatever the impact that some ARV drugs may have on birth defects, it is surpassed by the major role of ART in the successful prevention of mother-to-child transmission of HIV.”

In an accompanying editorial, Lynne M. Mofenson, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the NIH, and D. Heather Watts, MD, of the Office of the Global AIDS Coordinator of the US Department of State, pointed out that systematic research into the association between birth defects and antiretroviral drug exposure is limited.

Despite the fact that the greatest HIV burden comes from resource-limited countries, in which multiple factors that increase birth defect risk are already at play, data on the topic comes from mostly high-resource countries, they added.

“While the Sibiude study raises some important questions, given the enormous benefits of maternal antiretroviral drugs, the unclear clinical significance of the heart defects and the lack of a specific pattern of CNS defects with efavirenz, no change in prescribing practices is indicated, but continued surveillance is critical,” they wrote.


  1. Sibiude J. PLoS ONE. 2014;doi:10.1371/journal.pmed.1001635.
  2. Mofenson LM. PLoS ONE. 2014;doi:10.1371/journal.pmed.1001636.

Disclosure: The study was sponsored and funded by the French National Agency for Research on AIDS and Viral Hepatitis.