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Influenza vaccination in pregnancy (query bank)

Published: 19/01/2015

Question

What is the evidence for both benefit and harm for pregnant women receiving influenza vaccination?

Answer

A Cochrane review of vaccines for preventing influenza in healthy adults (Demicheli) retrieved 23 reports of the effectiveness and safety of vaccine administration in pregnant women (about 1.6 million mother-child couples). The main results are summarised as:

"The effects of influenza vaccine administration in pregnant women and their newborns has been investigated in a RCT (Zaman 2008) in which 23 valent pneumococcal vaccine was administered to the control group. For this reason, the RCT was excluded from the review and the evidence for effectiveness and efficacy is based only on observational studies (case-control and cohort studies).

The effectiveness of vaccination with seasonal inactivated parenteral vaccine during pregnancy for preventing ILI [influenza-like illness]in newborns was not statistically significant. The evidence comes from two cohort studies using either HR or RR adjusted estimates. However, it seems that vaccination has a modest effect against ILI in pregnant women (NNV 92, 95% CI 63 to 201) and against laboratory-confirmed influenza in newborns from vaccinated women (NNV 27, 95% CI 18 to 185)."

(Evidence level III)

A Cochrane review of the impact of influenza vaccinations in pregnancy for improving maternal, neonatal and infant health outcomes (Salam) is currently in preparation.

A systematic review on the effectiveness and safety of influenza vaccination during pregnancy for pregnant women, their fetus and infant up to six months of age (McMillan) concluded that:

"Influenza vaccine administered during pregnancy is effective and provides a similar reduction in influenza-like illness as it does for a healthy adult population. Despite this, there is no evidence on the effectiveness of the influenza vaccine at reducing severe illness or hospitalization in pregnant women. Infants of pregnant women vaccinated during their second or third trimester can expect to have reduced rates of influenza and influenza-related hospitalization, for their first six months of life.

Influenza vaccination during pregnancy had no association with adverse outcomes for the fetus including premature birth, small for gestational age, congenital malformation, spontaneous abortion [miscarriage] and fetal death."

Other systematic reviews have addressed specific adverse effects:

  • A systematic review of fetal death and preterm birth associated with maternal influenza vaccination (Fell) included one randomised clinical trial and 26 observational studies. Meta-analyses were not considered appropriate because of high clinical and statistical heterogeneity. Most studies reported no association between fetal death or preterm birth and influenza vaccination during pregnancy. Although several reported risk reductions, results may be biased by methodological shortcomings of observational studies of influenza vaccine effectiveness.
  • Bratton et al identified studies that assessed outcomes of stillbirth or miscarriage after administration of influenza vaccine during pregnancy. Women in the influenza vaccine group had a lower likelihood of stillbirth (relative risk [RR], 0.73; 95% confidence interval [CI], .55-.96); this association was similar when restricted to the H1N1pdm09 vaccine (RR, 0.69; 95% CI, .53-.90). The pooled estimate for miscarriage was not significant (RR, 0.91; 95% CI, .68-1.22).

The following recent overviews of influenza vaccination in pregnancy were identified:

  • Public Health England. Influenza vaccination in pregnancy: information for healthcare professionals. Jan 2015.
    This single page summary addresses the following questions, and cites 8 references:
    • Is the vaccine safe for mother and baby?
    • What are the risks of flu immunisation in pregnancy?
    • How effective is the vaccine?
    • What can I do as a healthcare professional?
  • UK Teratology Information Service. Use of seasonal influenza vaccines in pregnancy. June 2014
    "Data on seasonal and pandemic influenza infection suggest that pregnant women, especially those with pre-existing medical conditions and those in the later stages of pregnancy, are at increased risk of complications and are more likely to experience adverse fetal outcomes such as miscarriage or stillbirth. Data regarding the risk of congenital malformation following maternal influenza infection during pregnancy are conflicting. Some studies have reported an association, but a causal link to maternal fever rather than a direct effect of the influenza virus on the fetus has been proposed.
    The current evidence does not suggest that exposure to inactivated influenza vaccines in pregnancy is associated with an increased risk of adverse fetal effects, although data regarding first trimester exposure are relatively limited and the formulations of the vaccines studied vary". 
  • Canadian Paediatric Society. The benefits of influenza vaccine in pregnancy for the fetus and the infant younger than six months of age, Nov 2014
    "Influenza is a serious problem for infants <6 months of age, whose hospitalization rates for influenza and associated illness are comparable with rates in the elderly. Because influenza vaccines are not effective in this age group, the optimal evidence-based strategy is to administer trivalent inactivated influenza vaccines during pregnancy. Immunizing with trivalent inactivated influenza vaccines in the second and third trimester is well studied and safe, not only providing protection for the pregnant woman and her infant <6 months of age, but also for the fetus by decreasing the risk for low birth weight". 

(Evidence level IV)

References:

  • Bratton KN, Wardle MT, Orenstein WA, Omer SB. Maternal Influenza Immunization and Birth Outcomes of Stillbirth and Spontaneous Abortion: A Systematic Review and Meta-analysis. Clin Infect Dis. 2014 Nov 18. pii: ciu915. [Epub ahead of print] Abstract
  • Canadian Paediatric Society. The benefits of influenza vaccine in pregnancy for the fetus and the infant younger than six months of age. Practice Point. Paediatr Child Health 2014;19(9):e121-22
  • Demicheli V, Jefferson T, Al-Ansary LA, Ferroni E, Rivetti A, Di Pietrantonj C. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD001269. DOI: 10.1002/14651858.CD001269.pub5.
  • Fell D, Platt R, Lanes A, Wilson K, Kaufman J, Basso O, Buckeridge D. Fetal death and preterm birth associated with maternal influenza vaccination: systematic review. BJOG. 2015 Jan;122(1):17-26. Abstract. Full text available to Fellows and Members.
  • McMillan M, Kralik D, Porritt K, Marshall H. Influenza Vaccination During Pregnancy: A Systematic Review Of Effectiveness And Adverse Events. The JBI Database of Systematic Reviews and Implementation Reports; Vol 12, No 6 (2014). Abstract.
  • Public Health England. Influenza vaccination in pregnancy: information for healthcare professionals. Jan 2015.
  • Salam RA, Das JK, Bhutta ZA. Impact of haemophilus influenza type B (Hib) and viral influenza vaccinations in pregnancy for improving maternal, neonatal and infant health outcomes (Protocol). Cochrane Database of Systematic Reviews 2012, Issue 7. Art. No.: CD009982. DOI: 10.1002/14651858.CD009982. Abstract. Full text available to RCOG Fellows, Members and Trainees.
  • UK Teratology Information Service. Use of seasonal influenza vaccines in pregnancy. Full monograph (available to health care professionals only) or summary (freely available). June 2014

Search date: January 2015

Classification of evidence levels

Ia Evidence obtained from meta-analysis of randomised controlled trials.

Ib Evidence obtained from at least one randomised controlled trial.

IIa Evidence obtained from at least one well-designed controlled study without randomisation.

IIb Evidence obtained from at least one other type of well-designed quasi-experimental study.

III Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case studies.

IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities.

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