Drug Safety

, Volume 36, Issue 6, pp 455–465 | Cite as

The PREGVAXGRIP Study: a Cohort Study to Assess Foetal and Neonatal Consequences of In Utero Exposure to Vaccination Against A(H1N1)v2009 Influenza

  • F. Chavant
  • I. Ingrand
  • A. P. Jonville-Bera
  • C. Plazanet
  • V. Gras-Champel
  • L. Lagarce
  • M. Zenut
  • A. Disson-Dautriche
  • S. Logerot
  • M. Auffret
  • A. Coubret-Dumas
  • M. L. Bruel
  • M. Boyer
  • M. A. Bos-Thompson
  • G. Veyrac
  • P. Carlier
  • M. N. Beyens
  • S. Lates
  • C. Damase-Michel
  • A. Castot
  • C. Kreft-Jaïs
  • M. C. Pérault-Pochat
Original Research Article

Abstract

Background

In October 2009, in the context of an A(H1N1)v2009 influenza pandemic, a vaccination campaign was launched in France, in which one of the priority groups was pregnant women, on account of the high risk of developing complications following infection by this virus.

Objective

The aim of this multicentric, prospective, observational study was to assess safety and pregnancy outcomes in a cohort of pregnant women when receiving the A(H1N1)v2009 influenza pandemic vaccine.

Methods

This was a prospective study that followed up pregnant women recruited mainly in vaccination centres and maternity departments. Following the expected delivery date, follow-up data were collected concerning the delivery, the infant, and, if appropriate, the reasons why the pregnancy did not reach its term.

Results

Between 1 November 2009 and 31 March 2010, 2,415 pregnant women were included at the time of vaccination; 97.6 % of women received a vaccine without adjuvant and 2.4 % received an adjuvanted vaccine. Ninety-two (3.9 %) women were vaccinated during the first trimester of pregnancy, 1,090 (46.5 %) during the second trimester, and 1,162 (49.6 %) during the third trimester. One hundred and thirty-three adverse events (5.5 % of women) were reported, of which 12 were unexpected or serious. There were 2,246 (93.0 %) known pregnancy outcomes with 12 spontaneous abortions (0.5 %), 6 stillbirths (0.3 %), and 4 therapeutic abortions (0.2 %). There were 65 neonates with congenital anomalies, among which 31 were major. But only one congenital malformation (1.4 %) was reported for the 92 women vaccinated in their first trimester. Of the women, 93.3 % were delivered full term and 6.7 % preterm. For 96 (4.2 %) neonates, a disorder was reported in the neonatal period and 130 (5.6 %) were transferred to the neonatology department.

Conclusions

This study suggests that exposure to the A(H1N1)v2009 pandemic influenza vaccine during pregnancy does not increase the risk of adverse pregnancy outcomes. However, because of the relatively small number of women exposed during the first trimester, other studies are needed to exclude an increased risk of malformation.

References

  1. 1.
    French Advisory Council for Public Health. Guidance on health priority setting for the use of pandemic vaccines against A(H1N1) 2009 influenza virus. 2009 (cited 2009). Available from: http://www.hcsp.fr/docspdf/avisrapports/hcspa20090907_H1N1.pdf.
  2. 2.
    Bone A, Guthmann JP, Nicolau J, Levy-Bruhl D. Population and risk group uptake of H1N1 influenza vaccine in mainland France 2009–2010: results of a national vaccination campaign. Vaccine. 2010;28(51):8157–61.PubMedCrossRefGoogle Scholar
  3. 3.
    Jamieson DJ, Honein MA, Rasmussen SA, Williams JL, Swerdlow DL, Biggerstaff MS, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet. 2009;374(9688):451–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Siston AM, Rasmussen SA, Honein MA, Fry AM, Seib K, Callaghan WM, et al. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA. 2010;303(15):1517–25.PubMedCrossRefGoogle Scholar
  5. 5.
    Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol. 1998;148(11):1094–102.PubMedCrossRefGoogle Scholar
  6. 6.
    Dodds L, McNeil SA, Fell DB, Allen VM, Coombs A, Scott J, et al. 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.PubMedGoogle Scholar
  7. 7.
    Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April–June 2009. N Engl J Med. 2009;361(20):1935–44.PubMedCrossRefGoogle Scholar
  8. 8.
    Mosby LG, Rasmussen SA, Jamieson DJ. 2009 Pandemic influenza A (H1N1) in pregnancy: a systematic review of the literature. Am J Obstet Gynecol. 2011;205:10–8.Google Scholar
  9. 9.
    Dubar G, Azria E, Tesniere A, Dupont H, Le Ray C, Baugnon T, et al. French experience of 2009 A/H1N1v influenza in pregnant women. PLoS One. 2010;5(10).Google Scholar
  10. 10.
    Hewagama S, Walker SP, Stuart RL, Gordon C, Johnson PD, Friedman ND, et al. 2009 H1N1 influenza A and pregnancy outcomes in Victoria, Australia. Clin Infect Dis. 2010;50(5):686–90.PubMedCrossRefGoogle Scholar
  11. 11.
    Creanga AA, Johnson TF, Graitcer SB, Hartman LK, Al-Samarrai T, Schwarz AG, et al. Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women. Obstet Gynecol. 2010;115(4):717–26.PubMedCrossRefGoogle Scholar
  12. 12.
    The ANZIC Influenza Investigators and Australian Maternity Outcomes Surveillance System. Critical illness due to 2009 A/H1N1 influenza in pregnant and postpartum women: population based cohort study. BMJ. 2010;340:c1279.Google Scholar
  13. 13.
    Tamma PD, Ault KA, del Rio C, Steinhoff MC, Halsey NA, Omer SB. Safety of influenza vaccination during pregnancy. Am J Obstet Gynecol. 2009;201(6):547–52.PubMedCrossRefGoogle Scholar
  14. 14.
    Perthus I, Amar E, De Vigan C, Doray B, Francannet C. Registries of congenital malformations in France: situation in 2008. BEH. 2008;28–29:246–8.Google Scholar
  15. 15.
    Vendittelli F, Riviere O, Crenn-Hebert C, Claris O, Tessier V, Pinquier D, et al. Audipog perinatal network. Part 1: principal perinatal health indicators, 2004–2005. Gynecol Obstet Fertil. 2008;36(11):1091–100.PubMedCrossRefGoogle Scholar
  16. 16.
    Caillet C, Durrieu G, Jacquet A, Faucher A, Ouaret S, Perrault-Pochat MC, et al. Safety surveillance of influenza A(H1N1)v monovalent vaccines during the 2009–2010 mass vaccination campaign in France. Eur J Clin Pharmacol. 2011;67(6):649–51.PubMedCrossRefGoogle Scholar
  17. 17.
    Hwang SM, Choe KW, Cho SH, Yoon SJ, Park DE, Kang JS, et al. The adverse events of influenza A (H1N1) vaccination and its risk factors in healthcare personnel in 18 military healthcare units in Korea. Jpn J Infect Dis. 2011;64(3):183–9.PubMedGoogle Scholar
  18. 18.
    Vellozzi C, Burwen DR, Dobardzic A, Ball R, Walton K, Haber P. Safety of trivalent inactivated influenza vaccines in adults: background for pandemic influenza vaccine safety monitoring. Vaccine. 2009;27(15):2114–20.PubMedCrossRefGoogle Scholar
  19. 19.
    Fiore AE, Uyeki TM, Broder K, Finelli L, Euler GL, Singleton JA, et al. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Recomm Rep. 2010;59(RR-8):1–62.Google Scholar
  20. 20.
    Wilcox AJ. Surveillance of pregnancy loss in human populations. Am J Ind Med. 1983;4(1–2):285–91.PubMedCrossRefGoogle Scholar
  21. 21.
    Zinaman MJ, Clegg ED, Brown CC, O’Connor J, Selevan SG. Estimates of human fertility and pregnancy loss. Fertil Steril. 1996;65(3):503–9.PubMedGoogle Scholar
  22. 22.
    Saraiya M, Berg CJ, Shulman H, Green CA, Atrash HK. Estimates of the annual number of clinically recognized pregnancies in the United States, 1981–1991. Am J Epidemiol. 1999;149(11):1025–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Goldhaber MK, Fireman BH. Re: “Estimates of the annual number of clinically recognized pregnancies in the United States, 1981–1991”. Am J Epidemiol. 2000;152(3):287–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Nybo AA, Wohlfahrt J, Christens P, Olsen J, Melbye M. Is maternal age an independent risk factor for fetal loss? West J Med. 2000;173(5):331.PubMedCrossRefGoogle Scholar
  25. 25.
    Lacroix I, Damase-Michel C, Kreft-Jais C, Castot A, Montastruc JL. 2009 H1N1 influenza vaccines in pregnant women: the French Pharmacovigilance survey. Vaccine. 2011;29(7):1357–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Dlugacz Y, Fleischer A, Carney MT, Copperman N, Ahmed I, Ross Z, et al. 2009 H1N1 vaccination by pregnant women during the 2009–10 H1N1 influenza pandemic. Am J Obstet Gynecol. 2012;206(4):339 e1–8.Google Scholar
  27. 27.
    Tavares F, Nazareth I, Monegal JS, 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;29:6358–65.Google Scholar
  28. 28.
    Pasternak B, Svanstrom H, Molgaard-Nielsen D, Krause TG, Emborg HD, Melbye M, et al. Vaccination against pandemic A/H1N1 2009 influenza in pregnancy and risk of fetal death: cohort study in Denmark. BMJ. 2012;344:e2794.PubMedCrossRefGoogle Scholar
  29. 29.
    Pasternak B, Svanstrom H, Molgaard-Nielsen D, Krause TG, Emborg HD, Melbye M, et al. Risk of adverse fetal outcomes following administration of a pandemic influenza A(H1N1) vaccine during pregnancy. JAMA. 2012;308(2):165–74.PubMedCrossRefGoogle Scholar
  30. 30.
    Fell DB, Sprague AE, Liu N, Yasseen AS 3rd, Wen SW, Smith G, et al. H1N1 influenza vaccination during pregnancy and fetal and neonatal outcomes. Am J Public Health. 2012;102(6):e33–40.PubMedCrossRefGoogle Scholar
  31. 31.
    Lin TH, Lin SY, Lin CH, Lin RI, Lin HC, Chiu TH, et al. AdimFlu-S((R)) influenza A (H1N1) vaccine during pregnancy: the Taiwanese Pharmacovigilance Survey. Vaccine. 2012;30(16):2671–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Moro PL, Tepper NK, Grohskopf LA, Vellozzi C, Broder K. Safety of seasonal influenza and influenza A (H1N1) 2009 monovalent vaccines in pregnancy. Expert Rev Vaccine. 2012;11(8):911–21.CrossRefGoogle Scholar
  33. 33.
    Oppermann M, Fritzsche J, Weber-Schoendorfer C, Keller-Stanislawski B, Allignol A, Meister R, et al. A(H1N1)v2009: a controlled observational prospective cohort study on vaccine safety in pregnancy. Vaccine. 2012;30(30):4445–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • F. Chavant
    • 1
  • I. Ingrand
    • 1
  • A. P. Jonville-Bera
    • 2
  • C. Plazanet
    • 1
  • V. Gras-Champel
    • 3
  • L. Lagarce
    • 4
  • M. Zenut
    • 5
  • A. Disson-Dautriche
    • 6
  • S. Logerot
    • 7
  • M. Auffret
    • 8
  • A. Coubret-Dumas
    • 9
  • M. L. Bruel
    • 10
  • M. Boyer
    • 11
  • M. A. Bos-Thompson
    • 12
  • G. Veyrac
    • 13
  • P. Carlier
    • 14
  • M. N. Beyens
    • 15
  • S. Lates
    • 16
  • C. Damase-Michel
    • 17
  • A. Castot
    • 18
  • C. Kreft-Jaïs
    • 18
  • M. C. Pérault-Pochat
    • 1
  1. 1.Service de Pharmacologie clinique, Centre Régional de PharmacoVigilance et de Renseignement sur les MédicamentsCHU de PoitiersPoitiersFrance
  2. 2.Centre Régional de PharmacoVigilanceCHU de ToursToursFrance
  3. 3.Centre Régional de PharmacoVigilanceCHU d’AmiensAmiensFrance
  4. 4.Centre Régional de PharmacoVigilanceCHU d’AngersAngersFrance
  5. 5.Centre Régional de PharmacoVigilanceCHU de Clermont-FerrandClermont-FerrandFrance
  6. 6.Centre Régional de PharmacoVigilanceCHU de DijonDijonFrance
  7. 7.Centre Régional de PharmacoVigilanceCHU de GrenobleGrenobleFrance
  8. 8.Centre Régional de PharmacoVigilanceCHU de LilleLilleFrance
  9. 9.Centre Régional de PharmacoVigilanceCHU de LimogesLimogesFrance
  10. 10.Centre Régional de PharmacoVigilanceCHU de LyonLyonFrance
  11. 11.Centre Régional de PharmacoVigilanceCHU de MarseilleMarseilleFrance
  12. 12.Centre Régional de PharmacoVigilanceCHU de MontpellierMontpellierFrance
  13. 13.Centre Régional de PharmacoVigilanceCHU de NantesNantesFrance
  14. 14.Centre Régional de PharmacoVigilanceCHU de Paris Fernand-WidalParisFrance
  15. 15.Centre Régional de PharmacoVigilanceCHU de Saint-EtienneSaint-EtienneFrance
  16. 16.Centre Régional de PharmacoVigilanceCHU de StrasbourgStrasbourgFrance
  17. 17.Centre Régional de PharmacoVigilanceCHU de ToulouseToulouseFrance
  18. 18.AFSSAPSSaint Denis CedexFrance

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