Adjuvanted vaccines in pregnancy: no evidence for effect of the adjuvanted H1N1/09 vaccination on occurrence of preeclampsia or intra-uterine growth restriction § Alies Coenders a , Nienke K. Koopmans a , Kim Broekhuijsen b , Henk Groen c , Janna M.A. Karstenberg-Kramer d , Kim van Goor d , Mariette Groenewout a , Aren J. van Loon b , Marijke M. Faas d , Maria G. van Pampus e, * a University of Groningen, University Medical Center Groningen, Department of Obstetrics and Gynecology, Groningen, The Netherlands b Martini Hospital Groningen, Department of Obstetrics and Gynecology, Groningen, The Netherlands c University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands d University of Groningen, University Medical Center Groningen, Department of Pathology and Medical biology, Section Medical biology, Groningen, The Netherlands e Onze Lieve Vrouwe Gasthuis, Department of Obstetrics and Gynecology, PO Box 95500, 1090 HM Amsterdam, The Netherlands Introduction At the beginning of 2009 the first cases of a new Influenza A virus were identified and described [1]. This H1N1/09 influenza, informally called swine flu, continued to spread and quickly became a pandemic. Several countries decided to provide vaccines for high-risk groups. Some of these vaccines contained adjuvants which stimulate the immune response, thereby reducing the amount of vaccine needed per person [2]. Pregnant women, especially those in the second and third trimester, were among the high-risk groups for developing complications of infection with H1N1/09 [3]. Therefore, the Dutch government advised vaccina- tion of pregnant women after the first trimester [4]. The Focetria European Journal of Obstetrics & Gynecology and Reproductive Biology 187 (2015) 14–19 A R T I C L E I N F O Article history: Received 16 October 2014 Accepted 13 January 2015 Keywords: H1N1/09 Adjuvant Vaccination Preeclampsia Intra-uterine growth restriction. A B S T R A C T Objective: During the H1N1/09 pandemic, pregnant women in the Netherlands were vaccinated with an adjuvanted vaccine. During pregnancy, the maternal immune system changes to enable placental development and growth and acceptance of the semi-allogeneic fetus. As an adjuvant is a pro- inflammatory substance, it may interfere with these immunological changes, resulting in poor placentation or placental growth, which may result in preeclampsia (PE) and fetal intra-uterine growth restriction (IUGR). This study investigated a possible association between adjuvanted H1N1/09 vaccination and the development of PE and/or IUGR. Study Design: Case-control study. Cases were Dutch women with PE and/or IUGR occurring during H1N1/09 vaccination program. Controls had uncomplicated pregnancies during the same period. Maternal characteristics, pregnancy and neonatal outcomes were collected from medical files. Participants were contacted by telephone to enquire about vaccination. Data were analyzed using t- tests, Chi-square tests or Fisher’s exact tests. Multivariate analysis was conducted to control for confounders. Results: We included 254 cases and 247 controls. Of the cases, 90 (35.4%) were vaccinated, compared to 87 (35.2%) of the controls (OR:1.009, 95% CI:0.70–1.46, p:0.961). The majority (73.5%) had been vaccinated in second and third trimester. In multivariate analysis, there were no confounders influencing these results. Exploratory subgroup analysis did not show an association between vaccination status in subgroups of women with either PE or IUGR. Conclusion: Our study showed no association between adjuvanted H1N1/09 vaccination and PE and/or IUGR. ß 2015 Elsevier Ireland Ltd. All rights reserved. § This study was conducted in Groningen, The Netherlands. * Corresponding author: Tel.: +31205999111, 1114 (tracer number). E-mail addresses: m.g.vanpampus@olvg.nl, marielle.van.pampus@gmail.com (M.G. van Pampus). Contents lists available at ScienceDirect European Journal of Obstetrics & Gynecology and Reproductive Biology jou r nal h o mep ag e: w ww .elsevier .co m /loc ate/ejo g rb http://dx.doi.org/10.1016/j.ejogrb.2015.01.011 0301-2115/ß 2015 Elsevier Ireland Ltd. All rights reserved.