Influenza Vaccine Given to Pregnant Women Reduces Hospitalization Due to Influenza in Their Infants

Influenza is the leading cause of vaccine-preventable death in the United States [1], responsible for 200,000 hospitalizations and 36,000 deaths per year [2]. The highest burden of disease is among infants, pregnant women, elderly persons, and people with certain chronic medical conditions. In children, the highest incidence of hospitalization attributable to influenza is among infants aged <1 year, with those aged <6 months at highest risk [3]. Rates of hospitalization of healthy infants for influenza are similar to those of high-risk adults, and rates are even higher among infants with underlying chronic medical problems, particularly respiratory conditions [3]. Inactivated influenza vaccine is recommended by the Centers for Disease Control and Prevention (CDC) for all pregnant women and children, except for infants aged <6 months (for whom the vaccine is poorly immunogenic) and for persons with a serious allergy to egg protein [4, 5]. Strategies for protecting these groups have included only washing hands, avoiding contact with persons infected with influenza, and vaccinating close contacts [4], but the effectiveness of these strategies is unknown. One potential approach to protecting young infants against influenza infection is to vaccinate their mothers during pregnancy [6, 7]. Both animal and human studies support the possibility of protecting the offspring against influenza by immunization of the mother. Antibodies (immunoglobulin G) cross the placenta via active transport from the mother to the fetus, particularly in the final weeks of pregnancy [8–11]. Additional antibodies (immunoglobulin A) are transferred from the mother to the infant via breastmilk [12]. One study showed that an infant's concentration of influenza antibodies at birth correlated with that of the mother. Although the study failed to find a protective effect, infants with higher concentrations of influenza antibodies had delayed onset and decreased severity of influenza infection [13]. The same protection could be achieved via influenza vaccination of pregnant women [13–16]. Another study showed influenza vaccination during pregnancy resulted in influenza-specific antibody concentrations in the infants at birth that were higher than those in their mothers, suggesting active transport from mother to infant [14]. The presence of maternally derived antibodies in infancy does not inhibit development of natural immunity later in life from vaccination or natural infection [16, 17]. Two previous studies of hospitalized infants have compared rates of influenza-like illness or medically attended acute respiratory infections between infants whose mothers had received influenza vaccine during pregnancy and infants whose mothers had not received this vaccine; however, neither study found a protective effect [18, 19]. Recently, a clinical trial evaluated women who received inactivated influenza vaccine during their third trimester of pregnancy in Bangladesh, where influenza circulates year-round, and followed up their infants for up to 24 weeks after birth. Researchers in that study found a 63% decrease in the number of laboratory-confirmed influenza infections in those infants, compared with infants of women in a control group who received a conjugate pneumococcal vaccine during pregnancy. However, the study did not assess the vaccine's effectiveness for either hospitalization or severity of illness in the infants [20]. We conducted a matched case-control study of infants at Yale—New Haven Children's Hospital, a large urban hospital in the northeastern United States, to assess the effectiveness of influenza vaccine given to pregnant women in decreasing the number of hospitalizations for laboratory-documented influenza among their infants.