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Vaccination against pandemic A/H1N1 2009 influenza in pregnancy and risk of fetal death: cohort study in Denmark

BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e2794 (Published 02 May 2012) Cite this as: BMJ 2012;344:e2794
  1. Björn Pasternak, registrar and postdoctoral fellow12,
  2. Henrik Svanström, statistician1,
  3. Ditte Mølgaard-Nielsen, researcher1,
  4. Tyra G Krause, consultant3,
  5. Hanne-Dorthe Emborg, epidemiologist3,
  6. Mads Melbye, professor1,
  7. Anders Hviid, senior investigator1
  1. 1Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen, Denmark
  2. 2Department of Clinical Sciences, Infectious Diseases Unit, Lund University, Malmö, Sweden
  3. 3Department of Infectious Disease Epidemiology, Statens Serum Institut, Copenhagen, Denmark
  1. Correspondence to: B Pasternak bjp{at}ssi.dk
  • Accepted 22 March 2012

Abstract

Objective To investigate whether an adjuvanted pandemic A/H1N1 2009 influenza vaccine in pregnancy was associated with an increased risk of fetal death.

Design Nationwide register based cohort study.

Setting Denmark.

Participants All clinically recognised singleton pregnancies that ended between November 2009 and September 2010. Individual level data on exposure to an inactivated AS03 pandemic A/H1N1 2009 influenza vaccine (Pandemrix) and potential confounders were linked to the study cohort using a unique person identifier.

Main outcome measures The primary outcome measure was risk of fetal death (spontaneous abortion and stillbirth combined) in H1N1 vaccinated compared with unvaccinated pregnancies, adjusting for propensity scores. Secondary outcome measures were spontaneous abortion (between seven and 22 weeks’ gestation) and stillbirth (after 22 completed weeks’ gestation).

Results The cohort comprised 54 585 pregnancies; 7062 (12.9%) women were vaccinated against pandemic A/H1N1 2009 influenza during pregnancy. Overall, 1818 fetal deaths occurred (1678 spontaneous abortions and 140 stillbirths). Exposure to the H1N1 vaccine was not associated with an increased risk of fetal death (adjusted hazard ratio 0.79, 95% confidence interval 0.53 to 1.16), or the secondary outcomes of spontaneous abortion (1.11, 0.71 to 1.73) and stillbirth (0.44, 0.20 to 0.94). Estimates for fetal death were similar in pregnant women with (0.82, 0.44 to 1.53) and without comorbidities (0.77, 0.47 to 1.25).

Conclusion This large cohort study found no evidence of an increased risk of fetal death associated with exposure to an adjuvanted pandemic A/H1N1 2009 influenza vaccine during pregnancy.

Footnotes

  • Contributors: All authors contributed to the conception and design of the study, the analysis and interpretation of the study results, and critical revision of the manuscript. BP and AH drafted the manuscript. HS conducted the statistical analyses. HS, TGK, HDE, and AH acquired the data. AH and MM supervised the study. AH is the guarantor. All authors approved the final version of the manuscript for submission.

  • Funding: This study was funded by the Danish Medical Research Council (postdoctoral grant No 11-115854 to BP) and Lund University (ALF; fellowship grant to BP). The funding bodies had no role in the study design; the collection, analysis, and interpretation of the data; the writing of the article; and the decision to submit it for publication. All authors are independent from the funding agencies.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: BP had support from the Danish Medical Research Council and Lund University for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the Danish Data Protection Agency. Ethical approval is not required for register based research in Denmark.

  • Data sharing: No additional data available.

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