Benefit of Early Initiation of Influenza Antiviral Treatment to Pregnant Women Hospitalized With Laboratory-Confirmed Influenza

The Journal of Infectious Diseases MAJOR ARTICLE Benefit of Early Initiation of Influenza Antiviral Treatment to Pregnant Women Hospitalized With LaboratoryConfirmed Influenza Ikwo K. Oboho,1,2,a Carrie Reed,2 Paul Gargiullo,2 Michelle Leon,2 Deborah Aragon,3 James Meek,4 Evan J. Anderson,5,6 Patricia Ryan,7 Ruth Lynfield,8 Craig Morin,8 Marisa Bargsten,9 Shelley M. Zansky,10 Brian Fowler,11 Ann Thomas,12 Mary Lou Lindegren,13 William Schaffner,13 Ilene Risk,14 Lyn Finelli,2,a and Sandra S. Chaves2 (See the editorial commentary by Tita and Andrews on pages 505–6.) Background. We describe the impact of early initiation of influenza antiviral treatment among pregnant women hospitalized with laboratory-confirmed influenza during the 2010–2014 influenza seasons. Methods. Severe influenza was defined as illness with ≥1 of the following: intensive care unit admission, need for mechanical ventilation, respiratory failure, pulmonary embolism, sepsis, or death. Within severity stratum, we used parametric survival analysis to compare length of stay by timing of antiviral treatment, adjusting for underlying conditions, influenza vaccination, and pregnancy trimester. Results. Among 865 pregnant women, the median age was 27 years (interquartile range [IQR], 23–31 years). Most (68%) were healthy, and 85% received antiviral treatment. Sixty-three women (7%) had severe influenza, and 4 died. Severity was associated with preterm delivery and fetal loss. Women with severe influenza were less likely to be vaccinated than those without severe influenza (14% vs 26%; P = .03). Among women treated with antivirals≤2 days versusthose treated >2 days from illness onset, the median length of staywas 2.2days (interquartile range [IQR],0.9–5.8days;n = 8)versus7.8days(IQR,3.0–20.6days;n = 7),respectively,forsevereinfluenza(P = .03)and2.4days(IQR,2.3–2.5days; n = 153) versus 3.1 days (IQR, 2.8–3.5 days; n = 62), respectively, for nonsevere influenza (P < .01). Conclusions. Earlyinitiationofinfluenzaantiviraltreatmenttopregnantwomenhospitalizedwithinfluenzamayreducethelengthofstay, especially among those with severe influenza. Influenza during pregnancy is associated with maternal and infant morbidity, and annual influenza vaccination is warranted. Keywords. influenza; pregnancy; influenza antiviral treatment; length of stay; early antiviral treatment. Pregnant women are at increased risk for seasonal and pandemic influenza-related complications [1–6]. During the 2009 influenza A(H1N1) pandemic, pregnant women represented 1% of the US population and yet accounted for 6% of hospitalizations and 5% of deaths associated with infection due to the pandemic strain (influenza A[H1N1]pdm09) [2]. Complications described during this period included intensive care unit (ICU) admission, respiratory failure, and preterm delivery [2–4, 7]. Since then, limited data have been published describing pregnant women with influenza [8–10]. Received 8 October 2015; accepted 24 December 2015; published online 3 February 2016. Presented in part: 2015 Epidemic Intelligence Service Conference, Atlanta, Georgia, April 2015; IDWeek 2014, Philadelphia, Pennsylvania, October 2014. Abstract 45298. a Present affiliations: Division of Global HIV/TB, Centers for Disease Control and Prevention, Atlanta, Georgia (I. K. O.) and Merck, West Point, Pennsylvania (L. F.). Correspondence: I. K. Oboho, Centers for Disease Control and Prevention, 1600 Clifton Rd, NE, Mailstop E-4, Atlanta, GA 30333 (). ® 2016;214:507–15 The Journal of Infectious Diseases Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US. DOI: 10.1093/infdis/jiw033 To reduce influenza-associated morbidity and mortality, the American College of Obstetrics and Gynecology and the Advisory Committee on Immunization Practices recommend annual influenza vaccination for pregnant women at any time during pregnancy [11–13]. However, current estimates of vaccination coverage among pregnant women are around 50% [14]. Considering the suboptimal influenza vaccine uptake in this group, antiviral medications are an important adjunct to managing treatment in pregnant women with suspected influenza [12]. The objectives of this study were to describe the epidemiology and clinical outcomes associated with hospitalizations for laboratory-confirmed influenza among pregnant women during recent influenza seasons in the United States and to assess the impact of early initiation of influenza antiviral treatment in this population. METHODS Setting and Population We used data from the Influenza Hospitalization Surveillance Network (FluSurv-NET). FluSurv-NET conducts population-based Early Influenza Treatment in Pregnancy • JID 2016:214 (15 August) • 507 1 Epidemic Intelligence Service, and 2Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia; 3Colorado Department of Public Health and Environment, Denver; 4Connecticut Emerging Infections Program, Yale School of Public Health, New Haven; 5Department of Medicine, Emory University School of Medicine, and 6Atlanta Veterans Affairs Medical Center, Georgia; 7 Maryland Department of Health and Mental Hygiene, Baltimore; 8Minnesota Department of Health, St. Paul; 9New Mexico Department of Health, Santa Fe; 10New York State Department of Health, Albany; 11Ohio Department of Health, Columbus; 12Emerging Infections Program, Oregon Public Health Division, Portland; 13Vanderbilt University School of Medicine, Nashville, Tennessee; and 14Salt Lake County Health Department, Salt Lake City, Utah surveillance in selected counties in California, Colorado, Connecticut, Georgia, Maryland, Michigan, Minnesota, New Mexico, New York, Ohio, Oregon, Rhode Island, Tennessee, and Utah. The network includes >240 hospitals covering approximately 27 million people (about 9% of the US population). Data collection was determined by the Centers for Disease Control and Prevention to be for routine public health surveillance purposes and thus was not subject to institutional review board (IRB) approval for human research protections. Participating sites submitted the study to their state and local IRBs for review as required. Data Collection and Definitions 508 • JID 2016:214 (15 August) • Oboho et al Statistical Analysis We used χ2 or Fisher exact tests to compare clinical characteristics among pregnant women and frequencies of outcomes and complications, by severity, for categorical variables. Kruskal–Wallis test was performed to assess differences in the distribution of nonnormally distributed continuous variables. When examining the impact of early initiation of antiviral treatment, we only included treated patients in our models, to avoid any potential treatment bias introduced by physicians’ inclination to treat more severe cases [16]. Assuming that treatment would need to be initiated for a full day before it could be beneficial, we exclude (...truncated)