The risks related to influenza infection in pregnant women have been recognised for a long time.1 The pandemic of the virus A/H1N1 in the 2009-2010 season was no exception: pregnant women were at greater risk of contracting a severe form of A/H1N1 influenza than the general population, and those who contracted the infection had a higher frequency of adverse pregnancy outcomes than those who did not contract the virus.2,3 Although the safety data are limited, pregnant women were included in the priority categories in the vaccination programmes against A/H1N1. This focus has made available a lot of data for retrospective assessments of the safety of the vaccine, which are now available.
The European Medicines Agency (EMA) coordinated the monitoring of the vaccine's safety in Europe, because, given the urgency of vaccination, when it was put on the market there was no clinical data on the use of the vaccine. In Italy, concern spread throughout the population about the risks of the vaccine and adjuvants contained in it, and the phenomenon also affected the category of pregnant women. To assess the foetal and neonatal consequences associated with administering the vaccine A/H1N1 during pregnancy, an observational cohort study was conducted4 between 1 October 2009 and 30 September 2010 on women residing in Lombardy, aged between 12 and 55 years, who had given birth between the 23th and the 45th week of pregnancy. The study was coordinated by the National Centre for Epidemiology at the Istituto Superiore di Sanità (National Institute of Health), in collaboration with the Prevention Office, the Epidemiology Office and the Pharmacovigilance Centre of the Lombardy Region.
The women vaccinated (exposed) were compared with women eligible for vaccination but not vaccinated (not exposed) in order to assess the consequences of exposure to the vaccine. The following mother parameters were analysed: type of birth, access to the ICU, pre-eclampsia/eclampsia and death (during or post-partum) and gestational diabetes. The following fetal and neonatal consequences were evaluated: perinatal death, premature delivery, access to neonatal resuscitation and neonatal intensive care and congenital malformations. There were 86,171 eligible pregnant women, of which 6,246 had been vaccinated. Of these, 3,615 (57.9%) had received the vaccination in the third trimester of gestation and 2,557 (40.9%) in the second trimester. There was no difference between the women exposed and not exposed to the vaccination in terms of the selected outcomes, with the exception of a limited increase in the prevalence of gestational diabetes (adjusted odds ratio: 1.26, 95% confidence interval from 1.04 to 1.53) and pre-eclampsia/eclampsia (adjusted odds ratio: 1.19, 95% confidence interval from 1.02 to 1.39) in the women vaccinated compared to those not vaccinated. The foetal and neonatal consequences were similar in the two groups of women. Congenital malformations were detected in the group of exposed women, but the figure was not statistically significant.
This study provides important information about the safety of the H1N1 vaccine during pregnancy which, compared to the past, support greater confidence in vaccination campaigns involving pregnant women. However, it is important to carry out a meta-analysis of all the available studies to confirm the safety of the vaccine given the possibility of new pandemics. Certainly there is a need for continued research into vaccination during pregnancy to shed light on current uncertainties, such as safety of adjuvants in the vaccine or the consequences of vaccination in the first trimester of pregnancy (not evaluated in this analysis).
Observational studies and "real time" surveillance play a central role in monitoring the safety of vaccines during pregnancy, but it would be desirable to increase cooperation at the international level to align the research methods and tools for data collection in order to reduce the heterogeneity between the observational studies and be able to be of benefit to future meta-analysis of aggregate data of different studies or individual figures.5
Section Monitoring Averse Reactions to Medicines, Pisa University Hospital, FV Centre Tuscany
- Infl Other Resp Viruses 2013;7:1033-9.
- Brit Med J 2011;342:d3214. CDI
- Lancet 2009;374:451-8. CDI
- Brit Med J 2014;348:g3361. CDI
- Brit Med J 2014;348:g3500. CDI