Study Protocol of the PIMPI-project, a Cohort Study on Acceptance, Tolerability and Immunogenicity of Second Trimester Maternal Pertussis Immunization in Relation to Term and Preterm Infants

Abstract Background Maternal immunization confers passive immunity to the fetus by transplacental antibody transfer. Infants may be better protected against pertussis if the mother received a diphtheriae, tetanus and acellular pertussis (Tdap) vaccination in the second trimester of pregnancy compared to the third trimester. This study evaluates IgG antibody concentrations in term and preterm infants at birth and 2 months after birth after maternal Tdap-vaccination between 200 and 240 w of gestation vs third trimester Tdap-vaccination. Further aims are assessing the determinants that underlie acceptance of second trimester maternal Tdap-vaccination as well as the tolerability of vaccination. Methods This prospective cohort study consists of two parts. In the acceptance part, pregnant women complete a questionnaire on determinants that underlie acceptance of a second trimester Tdap-vaccination, which is offered subsequently between 200 and 240 w of gestation. Vaccinated women complete an additional questionnaire on vaccination tolerability. Vaccinated women may also participate in the immunogenicity part, in which blood is drawn from mother at delivery and from infant at birth and 2 months after birth. Women are also eligible for the immunogenicity part if they received a Tdap-vaccination between 200 and 240 w of gestation via the national immunization program and get hospitalized for an imminent preterm delivery. Blood sampling continues until 60 term and 60 preterm mother-infant-pairs have been included. Pertussis-specific IgG antibody concentrations are determined in serum using a fluorescent bead-based multiplex immunoassay. For term infants, non-inferiority in IgG antibody concentrations against pertussis toxin (anti-PT) will be assessed referred to a historical control group in which mothers were Tdap-vaccinated between 300 and 320 w of gestation. For preterm infants, non-inferiority of anti-PT IgG concentrations is referred to as 85% of infants having ≥ 20 international units/mL at 2 months after birth. Discussion This study investigates acceptance, tolerability and immunogenicity regarding maternal Tdap-immunization between 200 and 240 w of gestation. Its results provide insight into the effects of second trimester Tdap-vaccination on IgG antibody concentrations in term and preterm infants before primary infant vaccinations. Results on acceptance and tolerability guide antenatal care providers in communication with pregnant women and maintain the safety of second trimester Tdap-vaccination. Trial registration: EU Clinical Trials Register, 2018-002976-41, retrospectively registered 24 July 2019, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-002976-41.