Immunisation against influenza during pregnancy

Since the A/H1N1 2009 influenza pandemic, universal immunisation of pregnant women against seasonal flu has been recommended in many areas of the world.1 2 3 Despite experience with immunisation against seasonal flu in pregnancy over many years, uptake of influenza vaccine in pregnancy during the 2009 A/H1N1 2009 pandemic was low and immunisation rates among pregnant women generally remain low.4 5 One commonly cited reason for this is concern among women and clinical staff about the safety of the vaccine during pregnancy.6

In a linked research paper (doi:10.1136/bmj.e2794), Pasternak and colleagues present findings from an important new Danish national cohort study of women vaccinated against influenza A/H1N1 2009.7 The study suggests that women who are immunised in pregnancy have a lower risk of fetal loss than non-immunised women. The study provides reassuring information for people who are worried about the safety of the vaccine and evidence of the benefits of vaccination, which were previously only hypothesised. This is particularly important because the influenza vaccination season has just started in the southern hemisphere, where the A/California/7/2009 strain is included in the current vaccine. After a World Health Organization consultation, it has also been recommended that an A/California/7/2009 (H1N1) pdm09-like virus be included in vaccines for use during the 2012-13 northern hemisphere influenza season.

Voluntary reporting systems have also yielded reassuring information about the safety of influenza vaccines during pregnancy.8 9 Several aspects of the safety of influenza vaccines in pregnancy have been questioned.

Live vaccines are generally not recommended because they carry a theoretical risk to the fetus. The A/H1N1 2009 and seasonal influenza vaccines are, however, inactivated so do not pose this risk.

The presence of thiomersal, which is used as a preservative, has also triggered concerns. However, although trace amounts of thiomersal may be present in some vaccines, early exposure in utero or infancy has not been associated with deficits in neuropsychological functioning in children.10

Lastly, the safety of adjuvants, which are included in vaccines to improve the immune response, has been questioned. Again, experience with adjuvanted seasonal influenza vaccines in pregnancy suggests there are no safety concerns. The present study, which included more than 7000 women treated with an adjuvanted vaccine (including squalene, DL-α-tocopherol, and polysorbate 80) provides further evidence to support the conclusion that adjuvants are safe in pregnancy.7

Studies of influenza A/H1N1 2009 rapidly found that infected pregnant women were at particularly high risk of severe illness.11 Subsequently, once cohorts of infected women had been followed through pregnancy, the results suggested that women were also at risk of poor perinatal outcomes.12 Previous studies had suggested that infection with seasonal flu was associated with increased risks in pregnancy, although the risks were not as high as with A/H1N1 2009. Prevention of infection through immunisation is likely to reduce these risks, and the new study suggests that immunisation against A/H1N1 2009 is associated with a decreased risk of stillbirth.7 However, this observational study cannot establish causality. The causes of stillbirth are multifactorial, and although the researchers accounted for confounding by the presence of medical comorbidities they did not adjust for obstetric complications so residual confounding is possible.

The current study has other limitations. The study excluded women of fewer than seven weeks’ gestation and included only a small number of women who were immunised in the first trimester of pregnancy. The lack of an association between spontaneous abortion and immunisation could therefore be due to the small number of women immunised in early pregnancy. Further research that deals with this question as well as other outcomes, such as congenital anomalies, in the context of longer term safety monitoring is therefore important.

Pasternak and colleagues’ study provides even clearer evidence that the benefits of immunisation against influenza outweigh the risks for pregnant women. However, in this national cohort, only 13% of pregnant women were immunised.7 In the 2010-11 influenza season in the United Kingdom, between a third and a half of eligible pregnant women were immunised.4 A study in one Australian centre showed an increase in immunisation rates from 30% to 40% in pregnant women after the introduction of a staff and patient educational campaign.6 Although women who were not vaccinated most commonly cited concern about fetal risk as the reason for non-vaccination, the second most common reason was that medical and midwifery staff had not suggested immunisation.6 The authors of the Australian study speculated that immunisation rates could have been as high as 78% if immunisation had been offered as part of hospital based antenatal care.

It is clear from other studies that women who are offered influenza vaccination by their healthcare professional are more likely to be immunised and to have positive attitudes towards vaccine safety and effectiveness.5 It is the duty of all professionals who care for pregnant women to be aware of these findings on the safety of influenza vaccine in pregnancy, and to ensure that pregnant women receive an offer of vaccination that includes accurate evidence based information on risk. Further consideration should be given to the availability of immunisation services within hospital based care settings.