Safety experience of influenza vaccination in pregnant women in the US over a 20-year period

ECDC comment

Since the experience of the 2009 pandemic and observed higher rates of severe disease due to A(H1N1) in pregnant vs. non-pregnant women in some series in the pandemic  [1] a number of European countries (though not all) have started to recommend seasonal influenza immunisation for their pregnant women

Safety experience of influenza vaccination in pregnant women in the US over a 20-year period  Adverse events in pregnant women following administration of trivalent inactivated influenza vaccine and live attenuated influenza vaccine in the Vaccine Adverse Event Reporting System, 1990-2009Moro PL .Broder K, Zheteyeva Y,  Walton K, Rohan P, Sutherland A,  Guh  A et al. (2010)American Journal of Obstetrics and Gynaecology 2010. 203

Since the experience of the 2009 pandemic and observed higher rates of severe disease due to A(H1N1) in pregnant vs. non-pregnant women in some series in the pandemic  [1] a number of European countries (though not all) have started to recommend seasonal influenza immunisation for their pregnant women.  The United States authorities have recommended such routine immunisation of pregnant women in their second and third trimester since 1997 and throughout pregnancy since 2004. Though only a minority of American  pregnant women follow this advice (12-24% in the 2005-8 period) [2] it still represents a major collective experience that European countries can draw upon. 

This report is of 20 years experience in the United States (US) using the routine passive Vaccine Adverse Event Reporting System (VAERS) jointly owned by the US Centers for Disease Control and Prevention and its regulatory Food and Drug Administration.  The period of study for seasonal trivalent inactivated influenza vaccines (TIV) was over the period 1990 to 2009 while the period for Live Attenuated Influenza Vaccine (LAIV) (not yet licensed for use across Europe) during the period July 2003 through to mid-2009. LAIV vaccine is not recommended for use in pregnant women in the US but was used accidentally in women before it was appreciated they were pregnant. The authors analysed information concerning : state of residence, maternal date of birth, maternal age, gestational age, time between vaccination and onset of adverse event, major symptoms, seriousness, laboratory data, concomitant vaccinations, illness at the time of vaccination, and pre-existing medical conditions.(3) The authors calculated rates of reported Adverse Events Following Immunisation (AEFIs) using denominators from the estimated number of pregnant women immunized with seasonal influenza vaccine.[2,3]  They found a total of 148 reports after TIV vaccination and 27 reports after LAIV vaccination were identified. Twenty TIV (13.5%) and 1 LAIV (4%) reports were classified as serious. No specific AEFI’s were reported in 30 TIV (20.3%) and 16 LAIV (59%) reports and there were no specific congenital malformations. The most common pregnancy-specific AEFI was spontaneous abortion in the following proportion: 17 after TIV (11.5%) and 3 after LAIV (11%). The estimated reporting rate of spontaneous abortion was 1.9 per million pregnant women vaccinated with a maximum of 5.5 per million in any one season (2008-9). This compared with considerably higher rates of spontaneous miscarriage of 10.4% in women under 25 years in the USA rising to 22.4% of all pregnancies in those aged 35 years and above.[3] There no consistent reports of any specific abnormality associated with immunisation. The authors conclude that no unusual patterns of pregnancy complications or foetal outcomes were observed in the VAERS reports of pregnant women after the administration of either TIV or LAIV vaccines.

ECDC Comment (29 October 2010):

This study is reassuring but has to be considered critically, as the authors do themselves drawing on a number of useful references. While this study found no evidence of an excess of adverse events following immunisation of pregnant women against influenza, it would be premature to conclude as yet that there is no additional risk at all from such vaccination. As a passive reporting system it is vulnerable to under-reporting of AEFIs and that is suggested by the implausibly low incidence of spontaneous abortion and congenital malformations reported. However there is strong evidence of advantages to the mother and child from maternal immunisation.[4] What is needed is further study with linked databases or comprehensive follow-up of cohorts of women.[5] Some such studies are underway for study of the 2009 pandemic infection and vaccine in Europe.   

  1. 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 Aug 8;374(9688):451-8.
  2. Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Recomm Rep. 2010 August 6th   / 59(rr08);1-62 . http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5908a1.htms_cid=rr5908a1_e
  3. Moro PL .Broder K, Zheteyeva Y,  Walton K, Rohan P, Sutherland A,  Guh  A et al.   Adverse events in pregnant women following administration of trivalent inactivated influenza vaccine and live attenuated influenza vaccine in the Vaccine Adverse Event Reporting System, 1990-2009 American Journal of Obstetrics and Gynaecology 2010. 203
  4. Zaman K, Roy E, Arifee KS  et al  Effectiveness of Maternal Influenza Immunization in Mothers and Infants The New England Journal of Medicine 2008 359. Sep 17. 
  5. Verstraeten T, DeStefano F, Chen RT, Miller E. Vaccine safety surveillance using large linked databases: opportunities, hazards and proposed guidelines Expert Rev Vaccines. 2003 Feb;2(1):21-9.