Associations between influenza vaccination during pregnancy and outcomes related to maternal influenza disease, infant anthropometry/nutritional status, and cost-effectiveness in Nepal

Abstract

Globally, influenza causes 3-5 million severe illnesses and 290,000-650,000 deaths each year. Pregnant individuals and infants are at increased risk of influenza-associated morbidity and mortality, making maternal vaccination a high priority to protect pregnant/postpartum individuals and their infants via maternal antibodies. Although influenza mortality rates are estimated to be higher in low- and middle-income countries (LMICs), empiric data on the influenza disease burden are limited. In addition, the impact of maternal influenza vaccination on infant anthropometry and nutritional status has not been evaluated while accounting for bias related to missing anthropometric measurements due to fetal or infant death. Best practices for implementing maternal immunization programs have also not been established including the potential cost-effectiveness of a maternal influenza vaccine policy by administration trimester. To date, four randomized-controlled trials in LMICs have reported on influenza vaccine efficacy among mother-infant dyads, but data on the influenza disease burden and potential benefits of vaccination beyond prevention of infection are limited in LMICs compared to high-income country (HIC) contexts. In the following dissertation aims, we address these gaps by leveraging data collected between 2011-2014 as part of a maternal influenza vaccine randomized-controlled trial in Sarlahi District, Nepal (NCT01034254) among pregnant participants (15-40 years) and their infants who were followed through 6 months postpartum. Among pregnant/postpartum participants, we assessed the impact of maternal influenza vaccination on maternal influenza disease severity (Chapter 2). Among singleton pregnancies, we characterized the effect of maternal influenza vaccination on infant anthropometry and nutritional status measured at birth while accounting for outcomes truncated by death (Chapter 3). In Chapter 4, we used a decision tree to project costs and health outcomes and to estimate the cost-utility of national maternal influenza vaccine policies in Nepal recommending vaccination in the second or third trimester compared to maintaining the standard of care of no vaccine policy. Overall, our results highlight that maternal influenza vaccination may reduce the risk of moderate influenza illness among pregnant/postpartum individuals as well as moderate-to-severe undernutrition among infants, especially when vaccine and circulating strains are well-matched. However, additional studies are needed to confirm these protective effects. Additionally, the cost-effectiveness analysis illustrated that while third trimester vaccination in Nepal was the most cost-effective intervention, both second and third trimester vaccination were cost-effective under the willingness-to-pay threshold. This dissertation provides important contributions to the evidence base that could inform vaccine policy decision-making and facilitate increased access to maternal influenza vaccines in LMICs.