Safety of oseltamivir during pregnancy: a comparative study using the EFEMERIS database A-B Beau, a C Hurault-Delarue, a T Vial, b J-L Montastruc, a C Damase-Michel, a I Lacroix a a Service de Pharmacologie Me´dicale, CHU Toulouse, Universite´ de Toulouse, INSERM 1027, Toulouse, France b Centre Re´gional de PharmacoVigilance, Hospices Civils de Lyon, Lyon, France Correspondence: A-B Beau, Service de Pharmacologie Me´dicale, Faculte´ de Me´decine, 37 Alle´es Jules-Guesde, 31000 Toulouse, France. Email beau.a@chu-toulouse.fr Accepted 26 November 2013. Published Online 11 February 2014. Objective To compare pregnancy outcome between women exposed and unexposed to oseltamivir during pregnancy. Design A comparative observational cohort study of women exposed to oseltamivir during pregnancy. Setting A French prescription database (EFEMERIS) that includes data for pregnant women was used. EFEMERIS records prescribed and dispensed reimbursed drugs during pregnancy and pregnancy outcomes in Haute-Garonne, South West France. Population Women who delivered from 1 July 2004 to 31 December 2010. Methods The study compared exposed and unexposed pregnant women. Two women unexposed to oseltamivir were individually matched, by maternal age, month, and year of delivery, with one women exposed to oseltamivir. Multivariable conditional logistic regression and multivariable Cox proportional hazards regression were used to evaluate associations between each outcome and exposure to oseltamivir during pregnancy. Main outcome measures Pregnancy loss for any cause, preterm delivery, low birthweight, neonatal pathology, and congenital malformation. Results A cohort of 337 (0.58% of women included in EFEMERIS) women exposed to oseltamivir were compared with 674 unexposed women. The risk for pregnancy loss (HR 1.52; 95 % CI 0.80–2.91), for preterm birth (adjusted OR 0.64; 95% CI 0.31–1.27), and for neonatal pathology (adjusted OR 0.62; 95% CI 0.23–1.54) did not differ between exposed and unexposed groups. When exposure during organogenesis was considered, one case of congenital anomaly (2.0%) among 49 exposed women and one case (1.0%) among 99 unexposed women were observed (crude OR 2.00; 95% CI 0.13–32.00). Conclusions There was no significant association between adverse pregnancy outcomes and exposure to oseltamivir during pregnancy. Keywords Adverse pregnancy outcomes, EFEMERIS, influenza A (H1N1), oseltamivir, pregnancy. Please cite this paper as: Beau A-B, Hurault-Delarue C, Vial T, Montastruc J-L, Damase-Michel C, Lacroix I. Safety of oseltamivir during pregnancy: a comparative study using the EFEMERIS database. BJOG 2014;121:895–900. Introduction Pregnant women are at increased risk for severe illness, hospitalisation, and complications as a result of influenza, especially during the second and third trimesters. An increased risk for miscarriage, stillbirth, and preterm birth has also been reported in pregnant women with influenza infection. 1–5 Oseltamivir (Tamiflu; F. Hoffman-La Roche Ltd., Basel, Switzerland) and zanamivir (Relenza; GlaxoSmithKline Inc., Ontario, Canada) are neuraminidase inhibitors recom- mended for the treatment and prophylaxis of influenza types A and B. 6,7 They have been used to treat influenza since 2006, and their use has increased with the spread of the influenza A (H1N1) pandemic in 2009. Data suggest a moderate benefit: treatment with antivirals, if taken within 48 hours of the onset of symptoms, reduced the duration of the illness by ~1 day only. 7–9 Even if there are limited safety data, it was assumed that the moderate maternal benefit justified their use during pregnancy. Current French health authority guidelines recommend the use of neur- aminidase inhibitors for the treatment and prophylaxis of influenza in women at any time of pregnancy. Recently, a few studies have investigated the potential adverse effects of the use of neuraminidase inhibitors during pregnancy on the fetus. 10–14 These studies found no 895 ª 2014 Royal College of Obstetricians and Gynaecologists DOI: 10.1111/1471-0528.12617 www.bjog.org Maternal medicine