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Influenza A/H1N1 MF59 adjuvanted vaccine in pregnant women and adverse perinatal outcomes: multicentre study

BMJ 2013; 346 doi: (Published 04 February 2013) Cite this as: BMJ 2013;346:f393
  1. F Rubinstein, director of epidemiology and academic affairs123,
  2. P Micone, associate investigator4,
  3. A Bonotti, associate investigator1,
  4. V Wainer, associate investigator4,
  5. A Schwarcz, associate investigator4,
  6. F Augustovski, director of health technology assessment and economic evaluations123,
  7. A Pichon Riviere, executive director and director of health technology assessment and economic evaluations12,
  8. A Karolinski, general coordinator and head of education and research4
  9. on behalf of “EVA” Study Research Group (Estudio “Embarazo y Vacuna Antigripal”)
  1. 1Institute for Clinical Effectiveness and Health Policy, Emilio Ravignani 2024, Buenos Aires, Argentina
  2. 2School of Public Health, University of Buenos Aires, Buenos Aires, Argentina
  3. 3Division of Family and Community Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
  4. 4Centro de Investigación en Salud Poblacional (CISAP), Population Health Research Center, Hospital Durand, Buenos Aires, Argentina
  1. Correspondence to: F Rubinstein frubinstein{at}
  • Accepted 2 January 2013


Objective To assess the risk of adverse perinatal events of vaccination of pregnant women with an MF59 adjuvanted vaccine.

Design Cross sectional multicentre study.

Setting 49 public hospitals in major cities in Argentina, from September 2010 to May 2011.

Participants 30 448 mothers (7293 vaccinated) and their 30 769 newborns.

Main outcome measure Primary composite outcome of low birth weight, preterm delivery, or fetal or early neonatal death up to seven days postpartum.

Results Vaccinated women had a lower risk of the primary composite outcome (7.0% (n=513) v 9.3% (n=2160); adjusted odds ratio 0.80, 95% confidence interval 0.72 to 0.89). The propensity score analysis showed similar results. Adjusted odds ratios for vaccinated women were 0.74 (0.65 to 0.83) for low birth weight, 0.79 (0.69 to 0.90) for preterm delivery, and 0.68 (0.42 to 1.06) for perinatal mortality. These findings were consistent in further subgroup analysis. No significant differences in maternal outcomes were found.

Conclusion This large study using primary data collection found that MF59 adjuvanted A/H1N1 influenza vaccine did not result in an increased risk of adverse perinatal events and suggested a lower risk among vaccinated women. These findings should contribute to inform stakeholders and decision makers on the prescription of vaccination against influenza A/H1N1 in pregnant women.


  • Contributors: FR and AK conceived the project, designed the study and formulated the methods, conducted the project and were project leaders, analysed and interpreted the data, wrote the first draft of the manuscript, and provided background knowledge to the data analysis and interpretation. PM coordinated the project, helped to supervise enrolment, analysed and interpreted the data, assisted in the writing and editing of the manuscript, did the literature search, and reviewed all abstracts and full text articles. AB and VW supervised enrolment, coordinated field work, interpreted the data analysis, and assisted in the writing and editing of the manuscript. AS helped to design the study and formulate the methods, interpreted the data, and assisted in the writing and editing of the manuscript. FA and APR participated in the design of the study and in the analysis and interpretation of the data and assisted in the writing and editing of the manuscript. FR is the guarantor.

  • Funding: This study was funded by an independent research grant from Novartis Argentina SA (Internal Protocol No V111_17TP. 2010). The investigators designed and conducted the study; performed the analysis and interpretation of the data; and are responsible for the results, conclusions, and recommendations.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: this study was funded by Novartis Argentina SA and conducted under an independent research grant to the Institute for Clinical Effectiveness and Health Policy; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The study protocol was approved by the institutional review boards of the Italian Hospital and all participating hospitals. All patients gave written informed consent.

  • Data sharing: Further information is available on request from the corresponding author at frubinstein{at} Consent for data sharing was not obtained from the participants, but the presented data are anonymised and risk of identification is low.

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