Safety of Immunization during Pregnancy A review of the ...

1 Safety of Immunization during Pregnancy Safety of Immunization during Pregnancy A review of the evidenceGlobal Advisory Committee on Vaccine Safety World Health Organization 2014 All rights reserved. Publications of the World Health Organization are available on the WHO website ( ) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: Requests for permission to reproduce or translate WHO publications whether for sale or for non-commercial distribution should be addressed to WHO Press through the WHO website ( ).)

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4 Layout coordinator: WHO/GRAD esign and layout: Jean-Claude FattierSafety of Immunization during Pregnancy Safety of Immunization during Pregnancy A review of the evidenceGlobal Advisory Committee on Vaccine Safety ContentsAcknowledgements ..61 Introduction ..72 Methodology ..83 Vaccines reviewed ..9 Inactivated vaccines ..9 Non-adjuvanted inactivated trivalent seasonal and monovalent pandemic influenza vaccines ..9 Adjuvanted influenza vaccines ..11 Meningococcal vaccines ..12 Tetanus toxoid vaccines.

5 13 Live attenuated vaccines ..15 Rubella mono and combined live attenuated vaccines ..15 Oral poliovirus vaccines ..17 Yellow fever vaccines ..184 Obstacles to accurate assessment of risk ..21 Summary and overall recommendations ..21 References ..246 Global Advisory Committee on Vaccine Safety AcknowledgementsWe would like to acknowledge the contribution to this review received from the subgroup on Safety of vaccines during Pregnancy and lactation of the Global Advisory Committee on Vaccine Safety (GACVS).

6 The subgroup was composed of six GACVS members: Brigitte Keller-Stanislawski, Hanna Nohynek, Robert Pless, Gargandeep Kang, Melinda Wharton, Punam Mangtani, and supported by Kathy Neuzil (PATH) and Janet Englund (University of Washington, Seattle Children s Hospital) as independent experts. Philipp Lambach and Patrick Zuber provided WHO secretarial support. 7 Safety of Immunization during Pregnancy A review of the evidence1. IntroductIonVaccine-preventable infectious diseases are responsible for significant maternal, neonatal, and young infant morbidity and mortality.

7 Changes in the immune response in pregnant women which are thought to occur in order to allow the woman to tolerate the semi-allogeneic foetus may interfere with the development of the specific immune response to pathogens. These immunological changes may alter the susceptibility of the woman and the foetus to certain infectious diseases (1) and increase the risk of more serious outcomes. The immature adaptive immune systems of neonates and premature infants make them particularly vulnerable to morbidity and mortality due to of pregnant women can protect them directly against vaccine-preventable infections, and in so doing potentially protect the foetus.

8 It can also directly protect the foetus and infant via specific antibodies transferred from the mother during the its meeting in November 2011, the Strategic Advisory Group of Experts (SAGE) of WHO asked the Global Advisory Committee on Vaccine Safety (GACVS) to provide support to a review of evidence on the Safety of vaccinations in pregnant and lactating women. This request related to uncertainties about the Safety of vaccination whether intended or inadvertent of pregnant women during mass vaccination campaigns.

9 Such evidence would be particularly important in situations where manufacturers do not recommend the vaccination of pregnant women on solely precautionary grounds. However, evidence related to this issue is limited, as pre-licensing clinical trials of vaccines do not usually include pregnant and lactating women. Reports available also provide limited post-licensing data, as once again, pregnant women are usually not included in clinical trials. This in turn has limited the ability to make evidence-based decisions and provide optimal guidance on the use of vaccines in this population.

10 8 Global Advisory Committee on Vaccine Safety 2. methodologyThis report presents an overview of the relevant literature on the Safety of vaccination of pregnant women. In addition to reviewing the published literature, GACVS contacted regulatory authorities and pharmaceutical companies to obtain results of ongoing surveillance programmes for pertussis-containing and meningococcal vaccines in pregnant women. The cut-off point for the literature review was May 2013. The availability and amount of data were assessed, as well as their overall quality in terms of consistency, strengths, and weaknesses.