Review
Influenza vaccination in pregnancy: current evidence and selected national policies

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Summary

In several countries, pregnant women are recommended seasonal influenza vaccination and identified as a priority group for vaccination in the event of a pandemic. We review the evidence for the risks of influenza and the risks and benefits of seasonal influenza vaccination in pregnancy. Data on influenza vaccine safety in pregnancy are inadequate, but the few published studies report no serious side-effects in women or their infants, including no indication of harm from vaccination in the first trimester. National policies differ widely, mainly because of the limited data available, particularly on vaccination in the first trimester. The evidence of excess morbidity during seasonal influenza supports vaccinating healthy pregnant women in the second or third trimester and those with comorbidities in any trimester. The evidence of excess mortality in two previous influenza pandemics supports vaccinating in any trimester during a pandemic.

Introduction

Certain population groups are known to be at higher risk of morbidity and mortality from influenza infection. Pregnancy is considered to be one of the conditions conferring increased risk; however, several countries, including the UK and Germany, do not routinely vaccinate in pregnancy,1, 2 whereas others, such as the USA and Canada, recommend vaccinating healthy pregnant women regardless of trimester.3, 4 In Australia, the vaccine is offered to healthy pregnant women in any trimester who will be in the second or third trimester during the influenza season.5 WHO's current position paper recommends that all pregnant women should be immunised during the influenza season.6 There has been no indication that inactivated vaccines given during pregnancy harm the fetus; however, safety data are limited.

Information on the burden of disease from seasonal influenza in healthy pregnant women is also limited. This is by contrast with the possible burden that may occur in an influenza pandemic, which is of international concern.7 The 2005 UK Health Departments' Influenza Pandemic Contingency Plan8 identified pregnant women in the third trimester as a provisional priority group for immunisation, recognising that morbidity and mortality patterns from a new pandemic strain cannot be predicted.

We examine the risks from both seasonal and pandemic influenza infection together with the benefits and risks of inactivated vaccine to the mother and fetus. The UK Yellow Card data (the UK's passive reporting system on adverse events associated with medicines), current WHO recommendations, and the policies of selected countries are also reviewed. All references to influenza vaccines in this Review refer to inactivated vaccines only. “Comorbidity” is used to describe medical conditions that are associated with increased risk of influenza-related complications.

Section snippets

Risk of seasonal influenza in pregnant women

Women are commonly exposed to influenza (figure) during pregnancy. 11% of 1659 women in the 1993–94 influenza season in the UK had a four-fold rise in antibody titres indicative of new influenza infections.9 Following the 1989–90 severe influenza season in the UK, a one in 15 random sample of records of all fatal cases was compared with a “regular” season in 1985–86.10 Using these methods, eight deaths in pregnant women were counted in the severe season and two in the regular season, suggesting

The benefits and risks of influenza vaccination in pregnancy

The potential benefits of protecting against the increased risk from influenza in pregnancy need to be balanced against any actual or theoretical concerns of vaccination during pregnancy.

UK data: Yellow Card reporting 1994–2004

For this Review, the Post Licensing Division of the UK Medicines and Healthcare products Regulatory Agency (MHRA) searched the Yellow Card database from June 1, 1994 to June 22, 2004. A causal link between influenza vaccination and adverse events cannot be formed from these case reports and, as with other passive reporting schemes, inherent limitations in these systems include lack of information on the denominator, under-reporting, and incomplete information on confounders. Among 1366 reports

Recommendations from WHO and selected countries

In 2004 and 2006, the GACVS recommended that authorities reconsider their national policies and review the risk-benefit of influenza vaccination in pregnancy, “given the high risk to the mother—and thus to the fetus—of the disease itself and the likely small risk to mother and fetus of the inactivated influenza vaccine”.58, 59 The 2005 WHO position paper contains a stronger statement that “influenza vaccination in pregnancy is considered safe and is recommended for all pregnant women during the

Discussion

In two previous influenza pandemics (1918–19 and 1957–58), pregnant women were at higher risk of morbidity and mortality from influenza-related complications compared with non-pandemic years. In seasonal influenza, pregnant women are at increased risk of influenza-related hospital admission compared with non-pregnant or postpartum women during influenza-exposed periods and occasionally increased mortality in a severe season. This risk rises with increasing length of gestation, and even more

Conclusions

There is evidence to support seasonal influenza vaccination in pregnancy in two groups: healthy pregnant women in the second or third trimester and pregnant women with comorbidities in any trimester. There is also good evidence that pregnant women are more vulnerable during pandemic influenza. Further evaluation of the assumed benefits from maternal immunisation is needed. It is encouraging that the first randomised effectiveness trial of maternal influenza immunisation in the third trimester

Search strategy and selection criteria

Data for this Review were identified by searches of the PubMed database without date restriction up to August, 2007, for relevant articles in English, with the following medical subject headings: (1)“influenza, human” OR “influenza A virus”, (2) “influenza vaccine”, (3) “pregnancy”, “pregnancy trimesters”, OR “pregnancy outcome”, OR “pregnancy maintenance”, OR “pregnancy complications”, alone and in combination with major topic subheadings: “administration and dosage”, “adverse effects”,

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