Is first trimester exposure to the combination of antiretroviral therapy and folate antagonists a risk factor for congenital abnormalities?

Objectives: To assess use of antiretroviral therapy (ART) by HIV positive p regnant women in London since 1994 and the risk of congenital abnormalities associated with multidrug exposure during the first trimester of pregnancy . Methods: Retrospective multicentre study of medical, obstetric, and paediat ric notes of all mother-infant pairs, where the mother was known to be HIV infected before delivery, using a standardised proforma. Results: In this study of 195 mother-infant pairs, use of ART during any st age of pregnancy increased from 33.3% in 1994 to 92.5% in 1999 (p=0.01, tre nd). First trimester exposure increased from 0% in 1994 to 27.5% in 1999 (p =0.00045, trend). Congenital malformations were observed in nine infants (4 .6%). Compared with infants not exposed to ART or folate antagonists during the first trimester (n=148), exposure to both ART and folate antagonists d uring the first trimester (n=13) was associated with an increased risk of c ongenital abnormalities (4% v 23.1%; OR 7.10, 95% CI 1.5, 34.2). No malform ations were observed in the 34 children exposed to either ART or folate ant agonists alone during the first trimester. Conclusion: An increasing number of HIV infected women conceived while on A RT. Although there is no evidence of teratogenicity caused by ART if given alone during the first trimester, exposure to the combination of ART and fo late antagonists was associated with a significantly higher risk of congeni tal abnormalities in this cohort.