Abstract
Data from previous seasonal epidemics and pandemics have confirmed that pregnant women are at increased risk for severe influenza virus infection. Complications including fetal loss, higher rates of hospitalization and maternal death are most notable during the late gestational period. Antiviral therapy and influenza vaccination are recommended in pregnant women as both are effective and safe. This review discusses the epidemiology, pathophysiology, treatment and prevention of influenza virus infection in pregnancy, with a focus on recent developments.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1 . Influenza occurring in pregnant women: a statistical study of thirteen hundred and fifty cases. JAMA 72(14), 978–980 (1919).
- 2 . 1918 pandemic influenza and pneumonia in a large civil hospital. IMJ Ill Med. J. 150(6), 612–616 (1976).
- 3 . Deaths from Asian influenza associated with pregnancy. Am. J. Obstet. Gynecol. 78, 1172–1175 (1959).
- 4 . Influenza vaccination in pregnancy: current evidence and selected national policies. Lancet Infect. Dis. 8(1), 44–52 (2008).
- 5 . Observations on excess mortality associated with epidemic influenza. JAMA 176, 776–782 (1961).
- 6 2009 H1N1 influenza A and pregnancy outcomes in Victoria, Australia. Clin. Infect. Dis. 50(5), 686–690 (2010).
- 7 Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis. PLoS Med. 8(7), e1001053 (2011).
- 8 Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 303(15), 1517–1525 (2010).
- 9 , California Pandemic (H1N1) Working Group. Severe 2009 H1N1 influenza in pregnant and postpartum women in California. N. Engl. J. Med. 362(1), 27–35 (2010).
- 10 Maternal morbidity and perinatal outcomes among pregnant women with respiratory hospitalizations during influenza season. Am. J. Obstet. Gynecol. 189(6), 1705–1712 (2003).
- 11 ANZIC Influenza Investigators, Critical Care Services and 2009 H1N1 Influenza in Australia and New Zealand. N. Engl. J. Med. 361(20), 1925–1934 (2009).
- 12 ANZIC Influenza Investigators and Australasian Maternity Outcomes Surveillance System. Critical illness due to 2009 A/H1N1 influenza in pregnant and postpartum women: population based cohort study. BMJ 340, c1279–c1279 (2010).
- 13 Pandemic (H1N1) 2009 in pregnant Japanese women in Hokkaido. J. Obstet. Gynaecol. Res. 38(1), 130–136 (2012).
- 14 H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet. 374(9688), 451–458 (2009).
- 15 Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women. Obstet. Gynecol. 115(4), 717–726 (2010).
- 16 . Pregnancy-related mortality resulting from influenza in the United States During the 2009–2010 pandemic. Obstet. Gynecol. 126(3), 486–490 (2015).
- 17 Avian influenza virus in pregnancy. Rev. Med. Virol. 26(4), 268–284 (2016).
- 18 Death of woman with peripartum influenza B virus infection and necrotizing pneumonia. Emerging Infect. Dis. 20(7), 1258–1260 (2014).
- 19 Viral pneumonitis is increased in obese patients during the first wave of pandemic A(H1N1) 2009 virus. PLoS ONE 8(2), e55631 (2013).
- 20 . Respiratory physiology in pregnancy. Clin. Chest Med. 13(4), 555–565 (1992).
- 21 . Pneumonia in pregnancy. Obstet. Gynecol. Clin. North Am. 28(3), 553–569 (2001).
- 22 . Physiologic changes in pregnancy and their impact on critical care. Crit. Care Med. 33(Suppl. 10), S256–S258 (2005).
- 23 . Pneumonia in pregnancy. Crit. Care Med. 33(10 Suppl), S390–S397 (2005).
- 24 . Hemodynamic changes in pregnancy. Semin. Perinatol. 24(1), 11–14 (2000).
- 25 . Emerging infections and pregnancy. Emerg. Infect. Dis. 12(11), 1638–1643 (2006).
- 26 . Immunological relationship between the mother and the fetus. Int. Rev. Immunol. 21(6), 471–495 (2002).
- 27 . Autoimmune disorders and pregnancy. Semin. Perinatol. 15(3), 238–250 (1991).
- 28 Pregnancy and systemic lupus erythematosus: review of clinical features and outcome of 51 pregnancies at a single institution. Clin. Rev. Allergy Immunol. 38(2–3), 302–306 (2010).
- 29 . Immunology at the maternal–fetal interface: lessons for T cell tolerance and suppression. Annu. Rev. Immunol. 18(1), 367–391 (2000).
- 30 Pregnancy does not attenuate the antibody or plasmablast response to inactivated influenza vaccine. J. Infect. Dis. 212(6), 861–870 (2015). •• Valuable work adding to our understanding of immunology of pregnancy.
- 31 Pregnant women infected with pandemic H1N1pdm2009 influenza virus displayed overproduction of peripheral blood CD69+ lymphocytes and increased levels of serum cytokines. PLoS ONE 9(9), e107900 (2014).
- 32 . Preparing for the next pandemic. N. Engl. J. Med. 352(18), 1839–1842 (2005).
- 33 Association between severe pandemic 2009 influenza A (H1N1) virus infection and immunoglobulin G(2) subclass deficiency. Clin. Infect. Dis. 50(5), 672–678 (2010).
- 34 The lower serum immunoglobulin G2 level in severe cases than in mild cases of pandemic H1N1 2009 influenza is associated with cytokine dysregulation. Clin. Vaccine Immunol. 18(2), 305–310 (2011).
- 35 Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study. BJOG 107(10), 1282–1289 (2000).
- 36 Risk of fetal death after pandemic influenza virus infection or vaccination. N. Engl. J. Med. 368(4), 333–340 (2013).
- 37 . 2009 pandemic influenza A (H1N1) in pregnancy: a systematic review of the literature. Am. J. Obstet. Gynecol. 205(1), 10–18 (2011).
- 38 Centers for Disease Control and Prevention (CDC). Maternal and infant outcomes among severely ill pregnant and postpartum women with 2009 pandemic influenza A (H1N1) – United States, April 2009-August 2010. MMWR Morb Mortal Wkly Rep. 60(35), 1193–1196 (2011).
- 39 Effect of respiratory hospitalization during pregnancy on infant outcomes. Am. J. Obstet. Gynecol. 204(Suppl. 1), S54–S57 (2011).
- 40 . Influenza and congenital anomalies: a systematic review and meta-analysis. Hum. Reprod. 29(4), 809–823 (2014).
- 41 . Maternal hyperthermia and the risk for neural tube defects in offspring: systematic review and meta-analysis. Epidemiology 16(2), 216–219 (2005).
- 42 . Review: hyperthermia and fever during pregnancy. Birth Defects Res. A Clin. Mol. Teratol. 76(7), 507–516 (2006).
- 43 . Pregnancy outcome and clinical status of gilts following experimental infection by H1N2, H3N2 and H1N1pdm09 influenza A viruses during the last month of gestation. Arch. Virol. 160(10), 2415–2425 (2015).
- 44 . The influence of experimental infection of gilts with swine H1N2 influenza A virus during the second month of gestation on the course of pregnancy, reproduction parameters and clinical status. BMC Vet. Res. 10(1), 123 (2014).
- 45 . Maternal influenza infection is likely to alter fetal brain development indirectly: the virus is not detected in the fetus. Int. J. Dev. Neurosci. 23(2–3), 299–305 (2005).
- 46 Influenza transmission in the mother–infant dyad leads to severe disease, mammary gland infection, and pathogenesis by regulating host responses. PLoS Pathog. 11(10), e1005173 (2015).
- 47 Pregnancy-related immune adaptation promotes the emergence of highly virulent H1N1 influenza virus strains in allogenically pregnant mice. Cell Host Microbe. 21(3), 321–333 (2017).
- 48 . Pregnancy as a risk factor for severe outcomes from influenza virus infection: a systematic review and meta-analysis of observational studies. Vaccine. 35(4), 521–528 (2017). •• Meta-analysis showing no increase in mortality or severe outcomes in pregnant women with influenza which contrasts other data and highlights need for further good quality studies.
- 49 Extracorporeal membrane oxygenation in pregnancy. J. Card. Surg. 30(10), 781–786 (2015).
- 50 . Clinical management of pandemic 2009 influenza A(H1N1) infection. Chest 137(4), 916–925 (2010).
- 51 Impact of influenza in the post-pandemic phase: clinical features in hospitalized patients with influenza A (H1N1) pdm09 and H3N2 viruses, during 2013 in Santa Fe, Argentina. J Med. Virol. 89(7), 1186–1191 (2017).
- 52 Intensive care unit surveillance of influenza infection in France: the 2009/10 pandemic and the three subsequent seasons. Euro Surveill. 20(46), 30066 (2015).
- 53 Relative incidence and individual-level severity of seasonal influenza A H3N2 compared with 2009 pandemic H1N1. BMC Infect Dis. 17(1), 337 (2017).
- 54 Antiviral agents for the treatment and chemoprophylaxis of influenza – recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep. 60(1), 1–24 (2011).
- 55 . Continuing challenges in influenza. Ann. NY Acad. Sci. 1323(1), 115–139 (2014).
- 56 . The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews. PLoS ONE 8(4), e60348 (2013).
- 57 . Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 348, g2545–g2545 (2014).
- 58 . Advances in antivirals for non-influenza respiratory virus infections. Influenza Other Respir. Viruses 7(Suppl. 3), 36–43 (2013).
- 59 Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir. Med. 2(5), 395–404 (2014).
- 60 . Outcomes of infants exposed to oseltamivir or zanamivir in utero during pandemic (H1N1) 2009. Am. J. Obstet. Gynecol. 209(2), 130.e1–130.e9 (2013).
- 61 Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia. J. Infect. Dis. 206(2), 148–157 (2012).
- 62 Antiviral resistance during the 2009 influenza A H1N1 pandemic: public health, laboratory, and clinical perspectives. Lancet Infect. Dis. 12(3), 240–248 (2012).
- 63 A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan, November to December 2013. Euro Surveill. 19(1), pii:0666 (2014).
- 64 . Determinants of uptake of influenza vaccination among pregnant women – a systematic review. Vaccine 32(36), 4602–4613 (2014).
- 65 The Australian Immunisation Handbook (10th Edition). www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook/10-home.
- 66 . Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices, United States, 2015–16 influenza season. MMWR Morb. Mortal. Wkly. Rep. 64(30), 818–825 (2015).
- 67 . The rationale for quadrivalent influenza vaccines. Hum. Vaccin. Immunother. 8(1), 81–88 (2012).
- 68 . Increased prevalence of influenza B/Victoria lineage viruses during early stages of the 2015 influenza season in New South Wales, Australia: implications for vaccination and planning. Euro Surveill. 20(31), pii:21201 (2015).
- 69 . Seasonal influenza vaccine policy, use and effectiveness in the tropics and subtropics - a systematic literature review. Influenza Other Respir. Viruses. 10(4), 254–267 (2016). •• Valuable paper highlighting large number of countries without National Influenza Immunization Guidelines.
- 70 Effectiveness of seasonal trivalent influenza vaccine for preventing influenza virus illness among pregnant women: a population-based case-control study during the 2010–2011 and 2011–2012 influenza seasons. Clin. Infect. Dis. 58(4), 449–457 (2014).
- 71 . Effectiveness of seasonal trivalent influenza vaccination against hospital-attended acute respiratory infections in pregnant women: a retrospective cohort study. Vaccine 34(32), 3649–3656 (2016).
- 72 Effectiveness of maternal influenza immunization in mothers and infants. N. Engl. J. Med. 359(15), 1555–1564 (2008). •• One of the only randomized-controlled trials available and showed significant benefit of maternal vaccination for infants <6 months old in whom vaccination is contraindicated.
- 73 Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer-blind, randomised Phase IV trial. Lancet Infect. Dis. 16(9), 1026–1035 (2016).
- 74 Year-round influenza immunisation during pregnancy in Nepal: a Phase IV, randomised, placebo-controlled trial. Lancet Infect. Dis. 17(9), 981–989 (2017).
- 75 . Influenza vaccine given to pregnant women reduces hospitalization due to influenza in their infants. Clin. Infect. Dis. 51(12), 1355–1361 (2010).
- 76 Influenza vaccination coverage among pregnant women – United States, 2014–15 influenza season. MMWR Morb Mortal Wkly Rep. 64(36), 1000–1005 (2015).
- 77 Public Health England. Surveillance of influenza and other respiratory viruses in the United Kingdom: Winter 2014–2015. www.gov.uk/government/uploads_attachment_data/file429617/Annualreport_March2015_ver4.pdf.
- 78 Influenza vaccination during pregnancy: a qualitative study of the knowledge, attitudes, beliefs, and practices of general practitioners in central and south-western Sydney. BMC Fam. Pract. 15(1), 102 (2014).
- 79 . Perinatal survival and health after maternal influenza A(H1N1)pdm09 vaccination: a cohort study of pregnancies stratified by trimester of vaccination. Vaccine 33(38), 4850–4857 (2015).
- 80 Birth outcomes for Australian mother–infant pairs who received an influenza vaccine during pregnancy, 2012–2014: The FluMum Study. Vaccine 35(10), 1403–1409 (2017).
- 81 Risk of adverse fetal outcomes following administration of a pandemic influenza A(H1N1) vaccine during pregnancy. JAMA 308(2), 165–174 (2012).
- 82 No association between influenza vaccination during pregnancy and adverse birth outcomes. Vaccine 35(24), 3186–3190 (2017). • Important paper highlighting the safety of maternal influenza vaccination.
- 83 Safety of influenza vaccination during pregnancy: a review of subsequent maternal obstetric events and findings from two recent cohort studies. Vaccine 32(26), 3122–3127 (2014).
- 84 Seasonal trivalent influenza vaccination during pregnancy and the incidence of stillbirth: population-based retrospective cohort study. Clin. Infect. Dis. 62(10), 1221–1227 (2016).
- 85 Fetal death and preterm birth associated with maternal influenza vaccination: systematic review. BJOG 122(1), 17–26 (2015).
- 86 Effect of influenza vaccination in the first trimester of pregnancy. Obstet. Gynecol. 120(3), 532–537 (2012).
- 87 Maternal vaccination against H1N1 influenza and offspring mortality: population based cohort study and sibling design. BMJ 351, h5585 (2015).
- 88 Influenza vaccination of pregnant women and protection of their infants. N. Engl. J. Med. 371(10), 918–931 (2014).
- 89 . Immunogenicity and clinical efficacy of influenza vaccination in pregnancy. Front. Immunol. 6, 289 (2015).