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

Eva M Jungmann¹, Danielle Mercey², Annemiek DeRuiter¹, Simon Edwards³, Sheila Donoghue⁴, Tamsin Booth⁵, Depeeka Mohan⁶, Hermione Lyall⁶ and Graham P Taylor⁷

¹ Department of Genitourinary Medicine, St Thomas's Hospital, London
² Department of Sexually Transmitted Diseases, Royal Free & University College Medical School, London
³ Department of Genitourinary Medicine, King's College Hospital, London
⁴ Department of Paediatrics, St George's Hospital, London
⁵ Department of Genitourinary Medicine, Chelsea & Westminster Hospital, London
⁶ Department of Paediatics, Imperial College, London
⁷ Department of Genitourinary Medicine, Imperial College, London

Correspondence to:
Dr Graham P Taylor, Department of Genitourinary Medicine and Communicable Diseases, Faculty of Medicine, Imperial College, Norfolk Place, London W2 1PG, UK g.p.taylor{at}ic.ac.uk

Objectives: To assess use of antiretroviral therapy (ART) by HIV positive pregnant 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 paediatric 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 stage of pregnancy increased from 33.3% in 1994 to 92.5% in 1999 (p=0.01, trend). 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 during the first trimester (n=13) was associated with an increased risk of congenital abnormalities (4% v 23.1%; OR 7.10, 95% CI 1.5, 34.2). No malformations were observed in the 34 children exposed to either ART or folate antagonists alone during the first trimester.

Conclusion: An increasing number of HIV infected women conceived while on ART. Although there is no evidence of teratogenicity caused by ART if given alone during the first trimester, exposure to the combination of ART and folate antagonists was associated with a significantly higher risk of congenital abnormalities in this cohort.

Key Words: antiretroviral therapy; folate antagonists; congenital abnormalities

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