Pregnancy as a risk factor for severe influenza infection: an individual participant data meta-analysis

doi:10.1186/s12879-019-4318-3

Meta-Analysis

. 2019 Aug 2;19(1):683.

doi: 10.1186/s12879-019-4318-3.

Pregnancy as a risk factor for severe influenza infection: an individual participant data meta-analysis

Dominik Mertz^{1

2

3

4}, Calvin Ka-Fung Lo³, Lyubov Lytvyn², Justin R Ortiz⁵, Mark Loeb^{6

7

8}; FLURISK-INVESTIGATORS

Collaborators, Affiliations

Collaborators

FLURISK-INVESTIGATORS:
Li Wei Ang, Mehta Asmita Anlikumar, Isabelle Bonmarin, Victor Hugo Borja-Aburto, Heinz Burgmann, Jordi Carratalà, Gerardo Chowell, Catia Cilloniz, Jessica Cohen, Jeffery Cutter, Laurent Filleul, Shikha Garg, Steffen Geis, Melissa Helferty, Wan-Ting Huang, Seema Jain, Biljana Joves Sevic, Paul Kelly, Gabriela Kusznierz, Nicola Lehners, Luana Lenzi, Ivan T Ling, Robyn Mitchell, Siobhain A Mulrennan, Sergio A Nishioka, Robert Norton, Won Sup Oh, Pablo Orellano, Wolfgang Poeppl, Roberto Pontarolo, Odette Popovici, Alejandro Rodriquez, Bettina Schlehe, Paul Schnitzler, Bunyamin Sertogullarindan, Yuelong Shu, Geoffrey Taylor, Deborah L Thompson, Antoni Torres, Arianne B van Gageldonk-Lafeber, Diego Viasus, Quanyi Wang, Cuiling Xu

Affiliations

¹ Department of Medicine, McMaster University, Hamilton, ON, Canada.
² Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
³ Departments of Pathology and Molecular Medicine & Clinical Epidemiology and Biostatistics, McMaster University, MDCL 3203, 1200 Main St W, Hamilton, ON, L8N 3Z5, Canada.
⁴ Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada.
⁵ Initiative for Vaccine Research, World Health Organization, Geneva, Switzerland.
⁶ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada. loebm@mcmaster.ca.
⁷ Departments of Pathology and Molecular Medicine & Clinical Epidemiology and Biostatistics, McMaster University, MDCL 3203, 1200 Main St W, Hamilton, ON, L8N 3Z5, Canada. loebm@mcmaster.ca.
⁸ Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada. loebm@mcmaster.ca.

PMID: 31375073
PMCID: PMC6679491
DOI: 10.1186/s12879-019-4318-3

Meta-Analysis

Pregnancy as a risk factor for severe influenza infection: an individual participant data meta-analysis

Dominik Mertz et al. BMC Infect Dis. 2019.

. 2019 Aug 2;19(1):683.

doi: 10.1186/s12879-019-4318-3.

Authors

Dominik Mertz^{1

2

3

4}, Calvin Ka-Fung Lo³, Lyubov Lytvyn², Justin R Ortiz⁵, Mark Loeb^{6

7

8}; FLURISK-INVESTIGATORS

Collaborators

FLURISK-INVESTIGATORS:
Li Wei Ang, Mehta Asmita Anlikumar, Isabelle Bonmarin, Victor Hugo Borja-Aburto, Heinz Burgmann, Jordi Carratalà, Gerardo Chowell, Catia Cilloniz, Jessica Cohen, Jeffery Cutter, Laurent Filleul, Shikha Garg, Steffen Geis, Melissa Helferty, Wan-Ting Huang, Seema Jain, Biljana Joves Sevic, Paul Kelly, Gabriela Kusznierz, Nicola Lehners, Luana Lenzi, Ivan T Ling, Robyn Mitchell, Siobhain A Mulrennan, Sergio A Nishioka, Robert Norton, Won Sup Oh, Pablo Orellano, Wolfgang Poeppl, Roberto Pontarolo, Odette Popovici, Alejandro Rodriquez, Bettina Schlehe, Paul Schnitzler, Bunyamin Sertogullarindan, Yuelong Shu, Geoffrey Taylor, Deborah L Thompson, Antoni Torres, Arianne B van Gageldonk-Lafeber, Diego Viasus, Quanyi Wang, Cuiling Xu

Affiliations

¹ Department of Medicine, McMaster University, Hamilton, ON, Canada.
² Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
³ Departments of Pathology and Molecular Medicine & Clinical Epidemiology and Biostatistics, McMaster University, MDCL 3203, 1200 Main St W, Hamilton, ON, L8N 3Z5, Canada.
⁴ Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada.
⁵ Initiative for Vaccine Research, World Health Organization, Geneva, Switzerland.
⁶ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada. loebm@mcmaster.ca.
⁷ Departments of Pathology and Molecular Medicine & Clinical Epidemiology and Biostatistics, McMaster University, MDCL 3203, 1200 Main St W, Hamilton, ON, L8N 3Z5, Canada. loebm@mcmaster.ca.
⁸ Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada. loebm@mcmaster.ca.

PMID: 31375073
PMCID: PMC6679491
DOI: 10.1186/s12879-019-4318-3

Abstract

Background: WHO identifies pregnant women to be at increased risk for severe outcomes from influenza virus infections and recommends that they be prioritized for influenza vaccination. The evidence supporting this, however, is inconsistent. Ecologic studies in particular suggest more severe outcomes from influenza infection during pregnancy than studies based on individual patient data. Individual studies however may be underpowered and, as reported in a previous systematic review, confounding factors could not be adjusted for. We therefore conducted an individual participant data meta-analysis to assess the risk for severe outcomes of influenza infection in pregnant women while adjusting for other prognostic factors.

Methods: We contacted authors of studies included in a recently published systematic review. We pooled the individual participant data of women of reproductive age and laboratory confirmation of influenza virus infection. We used a generalized linear mixed model and reported odds ratios (OR) and 95% confidence intervals (CI).

Results: A total of 33 datasets with data on 186,656 individuals were available, including 36,498 eligible women of reproductive age and known pregnancy status. In the multivariable model, pregnancy was associated with a 7 times higher risk of hospital admission (OR 6.80, 95%CI 6.02-7.68), among patients receiving medical care as in- or outpatients, pregnancy was associated with a lower risk of admission to intensive care units (ICU; OR 0.57, 95%CI 0.48-0.69), and was not significantly associated with death (OR 1.00, 95%CI 0.75-1.34).

Conclusions: Our study found a higher risk of influenza associated hospitalization among pregnant women as compared to non-pregnant women. We did not find a higher mortality rate or higher likelihood of ICU admission among pregnant women who sought medical care. However, this study did not address whether a true community based cohort of pregnant women is at higher risk of influenza associated complications.

Keywords: Influenza; Meta-analysis; Pregnancy; Severity; Vaccine.

PubMed Disclaimer

Conflict of interest statement

ML has received funding and in-kind research support from influenza vaccine manufacturers (Sanofi and Seqirus). DM is a member of the editorial board of BMC Infectious Diseases.

Figures

**Fig. 1**
Flow chart Legend: IPD Individual patient data

See this image and copyright information in PMC

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References

1. Siston AM, Rasmussen SA, Honein MA, Fry AM, Seib K, Callaghan WM, et al. Pandemic 2009 influenza a(H1N1) virus illness among pregnant women in the United States. JAMA. 2010;303(15):1517–1525. doi: 10.1001/jama.2010.479. - DOI - PMC - PubMed
1. Creanga AA, Johnson TF, Graitcer SB, Hartman LK, Al-Samarrai T, Schwarz AG, et al. Severity of 2009 pandemic influenza a (H1N1) virus infection in pregnant women. Obstet Gynecol. 2010;115(4):717–726. doi: 10.1097/AOG.0b013e3181d57947. - DOI - PubMed
1. Vaccines against influenza WHO position paper - November 2012. Releve epidemiologique hebdomadaire 2012;87(47):461–476. - PubMed
1. Mertz D, Kim TH, Johnstone J, Lam PP, Science M, Kuster SP, et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ. 2013;347:f5061. doi: 10.1136/bmj.f5061. - DOI - PMC - PubMed
1. Mertz D, Geraci J, Winkup J, Gessner BD, Ortiz JR, Loeb M. Pregnancy as a risk factor for severe outcomes from influenza virus infection: a systematic review and meta-analysis of observational studies. Vaccine. 2017;35(4):521–528. doi: 10.1016/j.vaccine.2016.12.012. - DOI - PMC - PubMed

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[1] Siston AM, Rasmussen SA, Honein MA, Fry AM, Seib K, Callaghan WM, et al. Pandemic 2009 influenza a(H1N1) virus illness among pregnant women in the United States. JAMA. 2010;303(15):1517–1525. doi: 10.1001/jama.2010.479. - DOI - PMC - PubMed

[2] Siston AM, Rasmussen SA, Honein MA, Fry AM, Seib K, Callaghan WM, et al. Pandemic 2009 influenza a(H1N1) virus illness among pregnant women in the United States. JAMA. 2010;303(15):1517–1525. doi: 10.1001/jama.2010.479. - DOI - PMC - PubMed

[3] Creanga AA, Johnson TF, Graitcer SB, Hartman LK, Al-Samarrai T, Schwarz AG, et al. Severity of 2009 pandemic influenza a (H1N1) virus infection in pregnant women. Obstet Gynecol. 2010;115(4):717–726. doi: 10.1097/AOG.0b013e3181d57947. - DOI - PubMed

[4] Creanga AA, Johnson TF, Graitcer SB, Hartman LK, Al-Samarrai T, Schwarz AG, et al. Severity of 2009 pandemic influenza a (H1N1) virus infection in pregnant women. Obstet Gynecol. 2010;115(4):717–726. doi: 10.1097/AOG.0b013e3181d57947. - DOI - PubMed

[5] Vaccines against influenza WHO position paper - November 2012. Releve epidemiologique hebdomadaire 2012;87(47):461–476. - PubMed

[6] Vaccines against influenza WHO position paper - November 2012. Releve epidemiologique hebdomadaire 2012;87(47):461–476. - PubMed

[7] Mertz D, Kim TH, Johnstone J, Lam PP, Science M, Kuster SP, et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ. 2013;347:f5061. doi: 10.1136/bmj.f5061. - DOI - PMC - PubMed

[8] Mertz D, Kim TH, Johnstone J, Lam PP, Science M, Kuster SP, et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ. 2013;347:f5061. doi: 10.1136/bmj.f5061. - DOI - PMC - PubMed

[9] Mertz D, Geraci J, Winkup J, Gessner BD, Ortiz JR, Loeb M. Pregnancy as a risk factor for severe outcomes from influenza virus infection: a systematic review and meta-analysis of observational studies. Vaccine. 2017;35(4):521–528. doi: 10.1016/j.vaccine.2016.12.012. - DOI - PMC - PubMed

[10] Mertz D, Geraci J, Winkup J, Gessner BD, Ortiz JR, Loeb M. Pregnancy as a risk factor for severe outcomes from influenza virus infection: a systematic review and meta-analysis of observational studies. Vaccine. 2017;35(4):521–528. doi: 10.1016/j.vaccine.2016.12.012. - DOI - PMC - PubMed

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Pregnancy as a risk factor for severe influenza infection: an individual participant data meta-analysis

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Pregnancy as a risk factor for severe influenza infection: an individual participant data meta-analysis

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