The Pregnancy and Influenza Project: design of an observational case-cohort study to evaluate influenza burden and vaccine effectiveness among pregnant women and their infants Mark Thompson, PhD; Jennifer Williams, MSN, MPH, FNP-BC; Allison Naleway, PhD; De-Kun Li, MD, PhD; Susan Chu, PhD; Sam Bozeman, MPH; Holly A. Hill, MD, PhD; Janet Cragan, MD; David K. Shay, MD, MPH; on behalf of the Pregnancy and Influenza Project Workgroup T he 2009 influenza A(H1N1) pan- demic demonstrated that research is sorely needed to better understand how influenza affects pregnant women and their infants. Robust data are also needed on the effectiveness of maternal influenza vaccination in preventing ma- ternal illness as well as subsequent infant illness. The Centers for Disease Control and Prevention (CDC) has funded a pro- spective study that seeks to enroll ap- proximately 5000 pregnant women to follow up throughout the 2010 through 2011 influenza season to identify 300- 500 women with influenza virus infec- tion. Here we provide an overview of the objectives, design, and rationale for the Pregnancy and Influenza Project (PIP), which will be conducted with members of Kaiser Permanente in 2 metropolitan areas in the United States. Study objectives PIP has 5 major objectives. The first is to assess the burden of influenza in a group of prospectively enrolled pregnant women. Although pregnant women were especially vulnerable to severe illness during the re- cent influenza A(H1N1) pandemic 1 and at least 2 prior pandemics, 2 fewer data are available concerning the risk of influenza complications among pregnant women with seasonal influenza, particularly labo- ratory-confirmed influenza infections. 3 Therefore, our first objective is to assess the incidence of laboratory-confirmed symp- tomatic influenza infection among preg- nant women at all stages of pregnancy and 1 month postpartum and to evaluate the severity of illness episodes. Results from prior research on medi- cally attended clinical illness have been in- consistent, although there is some indica- tion that susceptibility to infection and the risk of severe complications is greatest in the third trimester. 4,5 PIP will distinguish between episodes of influenza vs noninflu- enza febrile acute respiratory illness (ARI) by testing women reporting ARI symp- toms with well-validated, sensitive, and specific real-time reverse transcription polymerase chain reaction (rRT-PCR) as- says. The severity of influenza illness will be characterized by collecting data on clin- ical symptoms, subjective severity, illness duration, functional impairment, and whether or not medical care was sought. Specific goals for better understanding the burden of influenza among pregnant women are outlined in Table 1. Informa- From the Influenza Division (Drs Thompson and Shay), National Center on Birth Defects and Developmental Disabilities (Ms Williams and Dr Cragan), and Global Immunizations Division (Dr Chu), Centers for Disease Control and Prevention, Atlanta, GA; Abt Associates Inc, Cambridge, MA (Mr Bozeman); RTI International, Research Triangle Park, NC (Dr Hill); Kaiser Permanente Center for Health Research, Portland, OR (Dr Naleway); and Division of Research, Kaiser Foundation Research Institute, Oakland, CA (Dr Li). Received Dec. 16, 2010; accepted Jan. 5, 2011. Reprints: David K. Shay, MD, MPH, Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Rd. N.E., Mailstop A-20, Atlanta, GA 30333. dks4@cdc.gov. Supported by the Centers for Disease Control and Prevention (Contract 200-2010-F-33132 to Abt Associates Inc). Conflict of Interest: none. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention, Abt Associates Inc, Kaiser Permanente Center for Health Research, or Kaiser Permanente Northern California Division of Research. Publication of this article was supported by the Centers for Disease Control and Prevention and the Association of Maternal and Child Health Programs. 0002-9378/$36.00 © 2011 Published by Mosby, Inc. doi: 10.1016/j.ajog.2011.01.006 The US Centers for Disease Control and Prevention is conducting an observational study of 300-500 women infected with influenza during pregnancy. Women are being recruited from members of the Kaiser Permanente health plan in 2 metropolitan areas before and during the 2010 through 2011 influenza season either following routine prenatal care visits or presentation with an acute respiratory infection. All enrolled mothers and their infants will be followed up through 1 month after delivery. Infants of mothers who had influenza during pregnancy and 1000 infants of mothers who were not diagnosed with influenza during pregnancy will be followed up for an additional 5 months. The Pregnancy and Influenza Project is focused on better understanding the burden of influenza during and after pregnancy and estimating the effectiveness of maternal influenza vaccination against influenza among women and their infants confirmed by real-time reverse transcription polymerase chain reaction assays. Key words: infant, influenza, influenza vaccine, pregnancy, vaccine effectiveness www. AJOG.org Supplement to JUNE 2011 American Journal of Obstetrics & Gynecology S69