Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study

Laura K Walsh, Jessy Donelle, Linda Dodds, Steven Hawken, Kumanan Wilson, Eric I Benchimol, Pranesh Chakraborty, Astrid Guttmann, Jeffrey C Kwong, Noni E MacDonald, Justin R Ortiz, Ann E Sprague, Karina A Top, Mark C Walker, Shi Wu Wen, Deshayne B Fell, Laura K Walsh, Jessy Donelle, Linda Dodds, Steven Hawken, Kumanan Wilson, Eric I Benchimol, Pranesh Chakraborty, Astrid Guttmann, Jeffrey C Kwong, Noni E MacDonald, Justin R Ortiz, Ann E Sprague, Karina A Top, Mark C Walker, Shi Wu Wen, Deshayne B Fell

Abstract

Objective: To determine whether any association exists between exposure to 2009 pandemic H1N1 (pH1N1) influenza vaccination during pregnancy and negative health outcomes in early childhood.

Design: Retrospective cohort study.

Setting: Population based birth registry linked with health administrative databases in the province of Ontario, Canada.

Participants: All live births from November 2009 through October 2010 (n=104 249) were included, and children were followed until 5 years of age to ascertain study outcomes.

Main outcome measures: Rates of immune related (infectious diseases, asthma), non-immune related (neoplasms, sensory disorders), and non-specific morbidity outcomes (urgent or inpatient health services use, pediatric complex chronic conditions) were evaluated from birth to 5 years of age; under-5 childhood mortality was also assessed. Propensity score weighting was used to adjust hazard ratios, incidence rate ratios, and risk ratios for potential confounding.

Results: Of 104 249 live births, 31 295 (30%) were exposed to pH1N1 influenza vaccination in utero. No significant associations were found with upper or lower respiratory infections, otitis media, any infectious diseases, neoplasms, sensory disorders, urgent and inpatient health services use, pediatric complex chronic conditions, or mortality. A weak association was observed between prenatal pH1N1 vaccination and increased risk of asthma (adjusted hazard ratio 1.05, 95% confidence interval 1.02 to 1.09) and decreased rates of gastrointestinal infections (adjusted incidence rate ratio 0.94, 0.91 to 0.98). These results were unchanged in sensitivity analyses accounting for any potential differential healthcare seeking behavior or access between exposure groups.

Conclusions: No associations were observed between exposure to pH1N1 influenza vaccine during pregnancy and most five year pediatric health outcomes. Residual confounding may explain the small associations observed with increased asthma and reduced gastrointestinal infections. These outcomes should be assessed in future studies.

Conflict of interest statement

Competing interests: All authors have completed and submitted the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support for the work as described above; KAT has received grants from GlaxoSmithKline and personal fees and non-financial support from Pfizer, both of which were unrelated to the submitted work; no other relationships or activities that could appear to have influenced the submitted work.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Fig 1
Fig 1
Flow diagram of study. *Information on maternal 2009 pandemic H1N1 influenza vaccination was collected between 2 November 2009 and 31 October 2010. †Invalid birth date (n=21), duplicate record (n=31), invalid linkage (n=209), women who were not continuously eligible to receive healthcare in Ontario during pregnancy or infant not eligible at birth for provincial healthcare (n=13 426)

References

    1. Rothberg MB, Haessler SD, Brown RB. Complications of viral influenza. Am J Med 2008;121:258-64. 10.1016/j.amjmed.2007.10.040
    1. Centers for Disease Control Influenza. In: Atkinson W, Wolfe S, Hamborsky J, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed Public Health Foundation, 2012.
    1. Steinhoff MC. Epidemiology and prevention of influenza. In: Nelson K, Masters Williams C, eds. Infectious Disease Epidemiology. Theory and Practice. 2nd ed Jones and Bartlett Publishers, 2007: 577-600.
    1. Mertz D, Kim TH, Johnstone J, et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ 2013;347:f5061. 10.1136/bmj.f5061
    1. Siston AM, Rasmussen SA, Honein MA, et al. Pandemic H1N1 Influenza in Pregnancy Working Group Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 2010;303:1517-25. 10.1001/jama.2010.479
    1. Harris J. Influenza occurring in pregnant women. J Am Med Assoc 1919;72:978-80 10.1001/jama.1919.02610140008002.
    1. Freeman DW, Barno A. Deaths from Asian influenza associated with pregnancy. Am J Obstet Gynecol 1959;78:1172-5. 10.1016/0002-9378(59)90570-8
    1. Low DE, McGeer A. Pandemic (H1N1) 2009: assessing the response. CMAJ 2010;182:1874-8. 10.1503/cmaj.100900
    1. Jamieson DJ, Honein MA, Rasmussen SA, et al. Novel Influenza A (H1N1) Pregnancy Working Group H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009;374:451-8. 10.1016/S0140-6736(09)61304-0
    1. Kumar A, Zarychanski R, Pinto R, et al. Canadian Critical Care Trials Group H1N1 Collaborative Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 2009;302:1872-9. 10.1001/jama.2009.1496
    1. Dodds L, McNeil SA, Fell DB, et al. Impact of influenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women. CMAJ 2007;176:463-8. 10.1503/cmaj.061435
    1. Schanzer DL, Langley JM, Tam TWS. Influenza-attributed hospitalization rates among pregnant women in Canada 1994-2000. J Obstet Gynaecol Can 2007;29:622-9. 10.1016/S1701-2163(16)32559-2
    1. Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998;148:1094-102. 10.1093/oxfordjournals.aje.a009587
    1. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2017-18 Influenza Season. MMWR Recomm Rep 2017;66:1-20. 10.15585/mmwr.rr6602a1
    1. American College of Obstetricians and Gynecologists ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol 2018;131:e214-7. 10.1097/AOG.0000000000002662
    1. National Advisory Committee on Immunization (NACI). Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine for 2018-2019. 2018. .
    1. Castillo E, Poliquin V. No. 357-Immunization in Pregnancy. J Obstet Gynaecol Can 2018;40:478-89. 10.1016/j.jogc.2017.11.010
    1. Skowronski DM, De Serres G. Is routine influenza immunization warranted in early pregnancy? Vaccine 2009;27:4754-70. 10.1016/j.vaccine.2009.03.079
    1. Mak TK, Mangtani P, Leese J, Watson JM, Pfeifer D. Influenza vaccination in pregnancy: current evidence and selected national policies. Lancet Infect Dis 2008;8:44-52. 10.1016/S1473-3099(07)70311-0
    1. Ortiz JR, Perut M, Dumolard L, et al. A global review of national influenza immunization policies: Analysis of the 2014 WHO/UNICEF Joint Reporting Form on immunization. Vaccine 2016;34:5400-5. 10.1016/j.vaccine.2016.07.045
    1. Madhi SA, Cutland CL, Kuwanda L, et al. Maternal Flu Trial (Matflu) Team Influenza vaccination of pregnant women and protection of their infants. N Engl J Med 2014;371:918-31. 10.1056/NEJMoa1401480
    1. Tapia MD, Sow SO, Tamboura B, et al. Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer-blind, randomised phase 4 trial. Lancet Infect Dis 2016;16:1026-35. 10.1016/S1473-3099(16)30054-8
    1. Tsatsaris V, Capitant C, Schmitz T, et al. Inserm C09-33 PREFLUVAC (Immunogenicity and Safety of an Inactivated Nonadjuvanted A[H1N1v] Influenza Vaccine in Pregnant Women) Study Group Maternal immune response and neonatal seroprotection from a single dose of a monovalent nonadjuvanted 2009 influenza A(H1N1) vaccine: a single-group trial. Ann Intern Med 2011;155:733-41. 10.7326/0003-4819-155-11-201112060-00005
    1. Zuccotti G, Pogliani L, Pariani E, Amendola A, Zanetti A. Transplacental antibody transfer following maternal immunization with a pandemic 2009 influenza A(H1N1) MF59-adjuvanted vaccine. JAMA 2010;304:2360-1. 10.1001/jama.2010.1729
    1. Zaman K, Roy E, Arifeen SE, et al. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med 2008;359:1555-64. 10.1056/NEJMoa0708630
    1. Steinhoff MC, Katz J, Englund JA, et al. Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial. Lancet Infect Dis 2017;17:981-9. 10.1016/S1473-3099(17)30252-9
    1. Nair H, Brooks WA, Katz M, et al. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet 2011;378:1917-30. 10.1016/S0140-6736(11)61051-9
    1. Poehling KA, Edwards KM, Griffin MR, et al. The burden of influenza in young children, 2004-2009. Pediatrics 2013;131:207-16. 10.1542/peds.2012-1255
    1. Bhat N, Wright JG, Broder KR, et al. Influenza Special Investigations Team Influenza-associated deaths among children in the United States, 2003-2004. N Engl J Med 2005;353:2559-67. 10.1056/NEJMoa051721
    1. Fiore AE, Uyeki TM, Broder K, et al. Centers for Disease Control and Prevention (CDC) Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Recomm Rep 2010;59(RR-8):1-62.
    1. Omer SB. Maternal Immunization. N Engl J Med 2017;376:2497. 10.1056/NEJMra1509044
    1. Legge A, Dodds L, MacDonald NE, Scott J, McNeil S. Rates and determinants of seasonal influenza vaccination in pregnancy and association with neonatal outcomes. CMAJ 2014;186:E157-64. 10.1503/cmaj.130499
    1. Ding H, Black CL, Ball S, et al. Influenza vaccination coverage among pregnant women - United States, 2016-17 influenza season. MMWR Morb Mortal Wkly Rep 2017;66:1016-22. 10.15585/mmwr.mm6638a2
    1. Yuen CY, Tarrant M. Determinants of uptake of influenza vaccination among pregnant women - a systematic review. Vaccine 2014;32:4602-13. 10.1016/j.vaccine.2014.06.067
    1. Chamberlain AT, Seib K, Ault KA, et al. Factors associated with intention to receive influenza and tetanus, diphtheria, and acellular pertussis (Tdap) vaccines during pregnancy: a focus on vaccine hesitancy and perceptions of disease severity and vaccine safety. PLoS Curr 2015;7:ecurrents.outbreaks.d37b61bceebae5a7a06d40a301cfa819. 10.1371/currents.outbreaks.d37b61bceebae5a7a06d40a301cfa819
    1. Wilson RJ, Paterson P, Jarrett C, Larson HJ. Understanding factors influencing vaccination acceptance during pregnancy globally: A literature review. Vaccine 2015;33:6420-9. 10.1016/j.vaccine.2015.08.046
    1. MacDougall DM, Halperin SA. Improving rates of maternal immunization: Challenges and opportunities. Hum Vaccin Immunother 2016;12:857-65. 10.1080/21645515.2015.1101524
    1. Moro PL, Broder K, Zheteyeva Y, et al. Adverse events following administration to pregnant women of influenza A (H1N1) 2009 monovalent vaccine reported to the Vaccine Adverse Event Reporting System. Am J Obstet Gynecol 2011;205:473. 10.1016/j.ajog.2011.06.047
    1. Moro PL, Tepper NK, Grohskopf LA, Vellozzi C, Broder K. Safety of seasonal influenza and influenza A (H1N1) 2009 monovalent vaccines in pregnancy. Expert Rev Vaccines 2012;11:911-21. 10.1586/erv.12.72
    1. Keller-Stanislawski B, Englund JA, Kang G, et al. Safety of immunization during pregnancy: a review of the evidence of selected inactivated and live attenuated vaccines. Vaccine 2014;32:7057-64. 10.1016/j.vaccine.2014.09.052
    1. Fell DB, Platt RW, Lanes A, et al. Fetal death and preterm birth associated with maternal influenza vaccination: systematic review. BJOG 2015;122:17-26. 10.1111/1471-0528.12977
    1. McMillan M, Porritt K, Kralik D, Costi L, Marshall H. Influenza vaccination during pregnancy: a systematic review of fetal death, spontaneous abortion, and congenital malformation safety outcomes. Vaccine 2015;33:2108-17. 10.1016/j.vaccine.2015.02.068
    1. 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 2015;60:e11-9. 10.1093/cid/ciu915
    1. Hviid A, Svanström H, Mølgaard-Nielsen D, Lambach P. Association between pandemic influenza A(H1N1) vaccination in pregnancy and early childhood morbidity in offspring. JAMA Pediatr 2017;171:239-48. 10.1001/jamapediatrics.2016.4023
    1. van der Maas N, Dijs-Elsinga J, Kemmeren J, van Lier A, Knol M, de Melker H. Safety of vaccination against influenza A (H1N1) during pregnancy in the Netherlands: results on pregnancy outcomes and infant’s health: cross-sectional linkage study. BJOG 2016;123:709-17. 10.1111/1471-0528.13329
    1. Zerbo O, Qian Y, Yoshida C, Fireman BH, Klein NP, Croen LA. Association between influenza infection and vaccination during pregnancy and risk of autism spectrum disorder. JAMA Pediatr 2017;171:e163609. 10.1001/jamapediatrics.2016.3609
    1. Heinonen O, Slone D, Shapiro S. Immunizing agents. In: Kaufman D, ed. Birth Defects and Drugs in Pregnancy. Publishing Sciences Group, 1977: 314-21.
    1. Fell DB, Wilson K, Ducharme R, et al. Infant respiratory outcomes associated with prenatal exposure to maternal 2009 A/H1N1 influenza vaccination. PLoS One 2016;11:e0160342. 10.1371/journal.pone.0160342
    1. Ludvigsson JF, Ström P, Lundholm C, et al. Maternal vaccination against H1N1 influenza and offspring mortality: population based cohort study and sibling design. BMJ 2015;351:h5585. 10.1136/bmj.h5585
    1. Ortiz JR, Neuzil KM, Ahonkhai VI, et al. Translating vaccine policy into action: a report from the Bill & Melinda Gates Foundation Consultation on the prevention of maternal and early infant influenza in resource-limited settings. Vaccine 2012;30:7134-40. 10.1016/j.vaccine.2012.09.034
    1. Fell DB, Bhutta ZA, Hutcheon JA, et al. Report of the WHO technical consultation on the effect of maternal influenza and influenza vaccination on the developing fetus: Montreal, Canada, September 30-October 1, 2015. Vaccine 2017;35:2279-87. 10.1016/j.vaccine.2017.03.056
    1. Harris T, Wong K, Stanford L, Fediurek J, Crowcroft N, Deeks S. Did narcolepsy occur following administration of AS03-adjuvanted A(H1N1) pandemic vaccine in Ontario, Canada? A review of post-marketing safety surveillance data. Euro Surveill 2014;19:20900. 10.2807/1560-7917.ES2014.19.36.20900
    1. Skowronski DM, Janjua NZ, De Serres G, et al. Effectiveness of AS03 adjuvanted pandemic H1N1 vaccine: case-control evaluation based on sentinel surveillance system in Canada, autumn 2009. BMJ 2011;342:c7297. 10.1136/bmj.c7297
    1. Kochhar S, Bauwens J, Bonhoeffer J, GAIA Project Participants. Electronic address: Safety assessment of immunization in pregnancy. Vaccine 2017;35(48 Pt A):6469-71. 10.1016/j.vaccine.2017.09.033
    1. Bonhoeffer J, Kochhar S, Hirschfeld S, et al. GAIA project participants Global alignment of immunization safety assessment in pregnancy - The GAIA project. Vaccine 2016;34:5993-7. 10.1016/j.vaccine.2016.07.006
    1. Munoz FM, Eckert LO, Katz MA, et al. Key terms for the assessment of the safety of vaccines in pregnancy: Results of a global consultative process to initiate harmonization of adverse event definitions. Vaccine 2015;33:6441-52. 10.1016/j.vaccine.2015.07.112
    1. MacGillivray DM, Kollmann TR. The role of environmental factors in modulating immune responses in early life. Front Immunol 2014;5:434. 10.3389/fimmu.2014.00434
    1. Chen T, Liu H-X, Yan H-Y, Wu D-M, Ping J. Developmental origins of inflammatory and immune diseases. Mol Hum Reprod 2016;22:858-65. 10.1093/molehr/gaw036
    1. Barker DJP, Thornburg KL. The obstetric origins of health for a lifetime. Clin Obstet Gynecol 2013;56:511-9. 10.1097/GRF.0b013e31829cb9ca
    1. Ray JG, Vermeulen MJ, Bharatha A, Montanera WJ, Park AL. Association between MRI exposure during pregnancy and fetal and childhood outcomes. JAMA 2016;316:952-61. 10.1001/jama.2016.12126
    1. Gershon AS, Wang C, Guan J, Vasilevska-Ristovska J, Cicutto L, To T. Identifying patients with physician-diagnosed asthma in health administrative databases. Can Respir J 2009;16:183-8. 10.1155/2009/963098
    1. Radhakrishnan DK, Dell SD, Guttmann A, Shariff SZ, Liu K, To T. Trends in the age of diagnosis of childhood asthma. J Allergy Clin Immunol 2014;134:1057-62.e5. 10.1016/j.jaci.2014.05.012
    1. Feudtner C, Feinstein JA, Zhong W, Hall M, Dai D. Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation. BMC Pediatr 2014;14:199. 10.1186/1471-2431-14-199
    1. Austin PC. Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research. Commun Stat Simul Comput 2009;38:1228-34 10.1080/03610910902859574.
    1. Cole SR, Hernán MA. Constructing inverse probability weights for marginal structural models. Am J Epidemiol 2008;168:656-64. 10.1093/aje/kwn164
    1. Lipsitch M, Tchetgen Tchetgen E, Cohen T. Negative controls: a tool for detecting confounding and bias in observational studies. Epidemiology 2010;21:383-8. 10.1097/EDE.0b013e3181d61eeb
    1. Wilson SE, Chung H, Schwartz KL, et al. Rotavirus vaccine coverage and factors associated with uptake using linked data: Ontario, Canada. PLoS One 2018;13:e0192809. 10.1371/journal.pone.0192809
    1. Brookhart MA, Wyss R, Layton JB, Stürmer T. Propensity score methods for confounding control in nonexperimental research. Circ Cardiovasc Qual Outcomes 2013;6:604-11. 10.1161/CIRCOUTCOMES.113.000359
    1. Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med 2015;34:3661-79. 10.1002/sim.6607
    1. Schneeweiss S, Rassen JA, Glynn RJ, Avorn J, Mogun H, Brookhart MA. High-dimensional propensity score adjustment in studies of treatment effects using health care claims data. Epidemiology 2009;20:512-22. 10.1097/EDE.0b013e3181a663cc
    1. Top KA, Arkell C, Scott H, et al. Effect of package insert language on health-care providers’ perceptions of influenza vaccination safety during pregnancy. Lancet Glob Health 2016;4:e690-1. 10.1016/S2214-109X(16)30182-6
    1. Munoz FM, Greisinger AJ, Wehmanen OA, et al. Safety of influenza vaccination during pregnancy. Am J Obstet Gynecol 2005;192:1098-106. 10.1016/j.ajog.2004.12.019
    1. Benowitz I, Esposito DB, Gracey KD, Shapiro ED, Vázquez M. Influenza vaccine given to pregnant women reduces hospitalization due to influenza in their infants. Clin Infect Dis 2010;51:1355-61. 10.1086/657309
    1. Eick AA, Uyeki TM, Klimov A, et al. Maternal influenza vaccination and effect on influenza virus infection in young infants. Arch Pediatr Adolesc Med 2011;165:104-11. 10.1001/archpediatrics.2010.192
    1. Poehling KA, Szilagyi PG, Staat MA, et al. New Vaccine Surveillance Network Impact of maternal immunization on influenza hospitalizations in infants. Am J Obstet Gynecol 2011;204(Suppl 1):S141-8. 10.1016/j.ajog.2011.02.042
    1. Black SB, Shinefield HR, France EK, Fireman BH, Platt ST, Shay D, Vaccine Safety Datalink Workgroup Effectiveness of influenza vaccine during pregnancy in preventing hospitalizations and outpatient visits for respiratory illness in pregnant women and their infants. Am J Perinatol 2004;21:333-9. 10.1055/s-2004-831888
    1. Shakib JH, Korgenski K, Presson AP, et al. Influenza in infants born to women vaccinated during pregnancy. Pediatrics 2016;137:e20152360. 10.1542/peds.2015-2360.
    1. Sukumaran L, McCarthy NL, Kharbanda EO, et al. Infant hospitalizations and mortality after maternal vaccination. Pediatrics 2018;141:e20173310. 10.1542/peds.2017-3310

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit