Vaccination Against Pandemic A/H1N1 2009 Influenza in Pregnancy and Risk of Fetal Death: Cohort Study in Denmark

Overview

Journal BMJ

Specialty General Medicine

Date 2012 May 4

PMID 22551713

Citations 47

Authors

Bjorn Pasternak

Henrik Svanstrom

Ditte Molgaard-Nielsen

Tyra G Krause

Hanne-Dorthe Emborg

Mads Melbye

Anders Hviid

Affiliations

Soon will be listed here.

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.

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References

Walter D, Bohmer M, An der Heiden M, Reiter S, Krause G, Wichmann O . Monitoring pandemic influenza A(H1N1) vaccination coverage in Germany 2009/10 - results from thirteen consecutive cross-sectional surveys. Vaccine. 2011; 29(23):4008-12. DOI: 10.1016/j.vaccine.2011.03.069. View

Huang W, Chen W, Teng H, Huang W, Huang Y, Hsu C . Adverse events following pandemic A (H1N1) 2009 monovalent vaccines in pregnant women--Taiwan, November 2009-August 2010. PLoS One. 2011; 6(8):e23049. PMC: 3151285. DOI: 10.1371/journal.pone.0023049. View

Andersen T, Madsen M, Jorgensen J, Mellemkjoer L, Olsen J . The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull. 1999; 46(3):263-8. View

Schneeweiss S . Sensitivity analysis and external adjustment for unmeasured confounders in epidemiologic database studies of therapeutics. Pharmacoepidemiol Drug Saf. 2006; 15(5):291-303. DOI: 10.1002/pds.1200. View

Moro P, Broder K, Zheteyeva Y, Revzina N, Tepper N, Kissin D . Adverse events following administration to pregnant women of influenza A (H1N1) 2009 monovalent vaccine reported to the Vaccine Adverse Event Reporting System. Am J Obstet Gynecol. 2011; 205(5):473.e1-9. PMC: 6602056. DOI: 10.1016/j.ajog.2011.06.047. View

Pierce M, Kurinczuk J, Spark P, Brocklehurst P, Knight M . Perinatal outcomes after maternal 2009/H1N1 infection: national cohort study. BMJ. 2011; 342:d3214. PMC: 3114455. DOI: 10.1136/bmj.d3214. View

Knudsen L, Olsen J . The Danish Medical Birth Registry. Dan Med Bull. 1998; 45(3):320-3. View

Lohse S, Farkas D, Lohse N, Skouby S, Nielsen F, Lash T . Validation of spontaneous abortion diagnoses in the Danish National Registry of Patients. Clin Epidemiol. 2010; 2:247-50. PMC: 2998814. DOI: 10.2147/CLEP.S13815. View

. Influenza vaccination coverage among pregnant women - 29 States and New York City, 2009-10 season. MMWR Morb Mortal Wkly Rep. 2012; 61(7):113-8. View

10.

Sturmer T, Rothman K, Avorn J, Glynn R . Treatment effects in the presence of unmeasured confounding: dealing with observations in the tails of the propensity score distribution--a simulation study. Am J Epidemiol. 2010; 172(7):843-54. PMC: 3025652. DOI: 10.1093/aje/kwq198. View

11.

Lacroix I, Damase-Michel C, Kreft-Jais C, Castot A, Montastruc J . 2009 H1N1 influenza vaccines in pregnant women: the French Pharmacovigilance survey. Vaccine. 2010; 29(7):1357-8. DOI: 10.1016/j.vaccine.2010.12.011. View

12.

Wallach Kildemoes H, Sorensen H, Hallas J . The Danish National Prescription Registry. Scand J Public Health. 2011; 39(7 Suppl):38-41. DOI: 10.1177/1403494810394717. View

13.

Pedersen C, Gotzsche H, Moller J, Mortensen P . The Danish Civil Registration System. A cohort of eight million persons. Dan Med Bull. 2006; 53(4):441-9. View

14.

Jorgensen F . [Ultrasonography of pregnant women in Denmark 1999-2000. Description of the development since 1980-1990]. Ugeskr Laeger. 2003; 165(46):4409-15. View

15.

Flenady V, Koopmans L, Middleton P, Froen J, Smith G, Gibbons K . Major risk factors for stillbirth in high-income countries: a systematic review and meta-analysis. Lancet. 2011; 377(9774):1331-40. DOI: 10.1016/S0140-6736(10)62233-7. View

16.

Tavares F, Nazareth I, Monegal J, Kolte I, Verstraeten T, Bauchau V . Pregnancy and safety outcomes in women vaccinated with an AS03-adjuvanted split virion H1N1 (2009) pandemic influenza vaccine during pregnancy: a prospective cohort study. Vaccine. 2011; 29(37):6358-65. DOI: 10.1016/j.vaccine.2011.04.114. View

17.

Nybo Andersen A, Vastrup P, Wohlfahrt J, Andersen P, Olsen J, Melbye M . Fever in pregnancy and risk of fetal death: a cohort study. Lancet. 2002; 360(9345):1552-6. DOI: 10.1016/S0140-6736(02)11518-2. View

18.

Mak T, Mangtani P, Leese J, Watson J, Pfeifer D . Influenza vaccination in pregnancy: current evidence and selected national policies. Lancet Infect Dis. 2007; 8(1):44-52. DOI: 10.1016/S1473-3099(07)70311-0. View

19.

Molbak K, Widgren K, Jensen K, Ethelberg S, Andersen P, Christiansen A . Burden of illness of the 2009 pandemic of influenza A (H1N1) in Denmark. Vaccine. 2011; 29 Suppl 2:B63-9. DOI: 10.1016/j.vaccine.2011.03.064. View

20.

Dodds L, McNeil S, Fell D, Allen V, Coombs A, Scott J . Impact of influenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women. CMAJ. 2007; 176(4):463-8. PMC: 1800555. DOI: 10.1503/cmaj.061435. View