Broadening Indications for Maternal Influenza Vaccination

The primary indication for influenza vaccination of pregnant women is to decrease the risk of serious complications during pregnancy [1]. The case fatality rates for pregnant women during the influenza pandemics of 1918 and 1957 ranged from 20% to 50% in various reports [2]. As a consequence, pregnancy— with or without comorbidities—was considered a high-risk condition by the Surgeon General’s Advisory Committee. A large collaborative perinatal project sponsored by the National Institute for Neurological and Communicative Disorders and Stroke from 1959 to 1965 enrolled over 50 000 pregnant women and their offspring who were intensively followed for all events prior to and after delivery found that influenza vaccine administered to 2291 women during pregnancy had no untoward effects [3, 4]. From this study, it can be estimated that about 2 million women received influenza vaccine during pregnancy between 1959 and 1965. Despite the evidence of safety, influenza vaccine was no longer recommended for pregnant women without chronic underlying conditions after 1966 because ‘‘influenza-associated excess mortality among pregnant women has not been documented except in the pandemics.’’ [5]. Reports of influenzarelated deaths continued to occur, and the sensitivity of the data derived from death certificates was questioned [6, 7]. In the early 1990s, investigators looked at risk of influenza-associated hospitalizations during pregnancy and found significant excess occurrence of pneumonia that increased as the pregnancy progressed. This led to reconsideration of the indication for influenza vaccination during pregnancy. In 1995, influenza vaccine was encouraged for all pregnant women who would be in the third trimester during an influenza season [8]. Two years later, all pregnant women in the second or third trimester during an influenza season were recommended to receive influenza vaccine [9]. The recommendation was extended in 2004 to include all pregnant women and women who will become pregnant during the influenza season [10]. It is logical to assume that vaccineinduced maternal immunoglobin G (IgG) antibodies transmitted to the fetus would provide protection for the infant during the first months of life [11]. Protection against all febrile acute respiratory illness and laboratory-confirmed illness was demonstrated in a controlled trial in Bangladesh by Zaman et al. in 2008 [12]. Subsequently, several reports showed reduced influenza-related hospitalizations of infants born to vaccinated women [13–15]. However, the potential benefit of pregnancy vaccination goes beyond prevention of acute respiratory illness in early infancy. An added observation of the Zaman et al. study in Bangladesh was that the infants born to influenzavaccinated women had significantly higher birth weights than those born to women who received the pneumococcal vaccine. In addition, a cohort analysis of Georgia surveillance data showed reduced likelihood of prematurity associated with maternal influenza vaccination [16]. This observation was confirmed by a 13-year retrospective study in Nova Scotia[17], and a prospective study in Rhode Island of women infected with the 2009 pandemic influenza A (H1N1) virus [18]. Coupled with observations of fetal distress occurring with maternal febrile illness leading to premature labor and emergency cesarean section, this provides a broader view of the potential fetal harm resulting from influenza during pregnancy [6]. The report by Bloom-Feshbach et al [19] in this issue of The Journal of Infectious Diseases provides further evidence of the risk of maternal influenza for the fetus. Significant reductions in live births were observed in the United States and Scandinavian countries after the most intense wave of the 1918 pandemic with the nadir of births 6.1 to 6.8 months after the respective peaks of influenza-related mortality. The authors concluded that the observed drop in birth rates was consistent with the concept that infection with the pandemic influenza virus caused first-trimester miscarriages in approximately 10% of pregnant women. The average decline in Received 20 June 2011; accepted 20 June 2011. Correspondence: W. P. Glezen, MD, MVM Department, One Baylor Plaza, MS:BCM-280, Houston, TX, 77030 (wglezen@bcm.edu). The Journal of Infectious Diseases 2011;204:1151–3 The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com 0022-1899 (print)/1537-6613 (online)/2011/2048-0001$14.00 DOI: 10.1093/infdis/jir513