Impact of Timing of Influenza Vaccination in Pregnancy on Transplacental Antibody Transfer, Influenza Incidence, and Birth Outcomes: A Randomized Trial in Rural Nepal

This placebo-controlled randomized trial in rural Nepal found that maternal influenza vaccination in either the second or third trimester of pregnancy provided similar birth outcomes and protection from influenza in infancy. Abstract Background Maternal influenza vaccination protects mothers and their infants in low resource settings, but little is known about whether the protection varies by gestational age at vaccination. Methods Women of childbearing age in rural southern Nepal were surveilled for pregnancy, consented and randomized to receive maternal influenza vaccination or placebo, with randomization stratified on gestational age (17-25 or 26-34 weeks). Enrollment occurred in 2 annual cohorts, and vaccinations occurred from April 2011 through September 2013. Results In sum, 3693 women consented and enrolled, resulting in 3646 live births. Although cord blood antibody titers and the rise in maternal titers were generally greater when women were vaccinated later in pregnancy, this was not statistically significant. The incidence risk ratio (IRR) for maternal influenza in pregnancy through 6 months postpartum was 0.62 (95% confidence interval [CI]: 0.35, 1.10) for those vaccinated 17-25 weeks gestation and 0.89 (95% CI: 0.39, 2.00) for those 26-34 weeks. Infant influenza IRRs were 0.73 (95% CI: 0.51, 1.05) for those whose mothers were vaccinated earlier in gestation, and 0.63 (95% CI: 0.37, 1.08) for those later. Relative risks (RR) for low birthweight were 0.83 (95% CI: 0.71, 0.98) and 0.90 (95% CI: 0.72, 1.12) for 17-25 and 26-34 weeks gestation at vaccination, respectively. IRRs did not differ for small-for-gestational age or preterm. No RRs were statistically different by timing of vaccine receipt. Conclusions Vaccine efficacy did not vary by gestational age at vaccination, making maternal influenza immunization programs easier to implement where women present for care late in pregnancy. Clinical Trials Registration NCT01034254