Cohort study on transplacental antibody transfer to fetal growth-restricted infants of tdap-vaccinated pregnant women, study protocol

BACKGROUND: Pertussis is endemic with epidemic peaks affecting all age groups and is a severe disease in infants too young to be vaccinated. Maternal tetanus-diphtheria-acellular-pertussis (Tdap)-vaccination has an estimated vaccine effectiveness against pertussis disease of approximately 90% for infants up to 2 months, thus shortening the vulnerable period. Maternal vaccination protects through transplacental transfer of maternal antibodies via an active receptor-mediated process. This process may be impaired in fetuses with fetal growth restriction (FGR), primarily caused by placental insufficiency. In the Netherlands, term infants from mothers Tdap-vaccinated during pregnancy receive diphtheria, tetanus, and pertussis, inactivated poliovirus, Haemophilus influenzae type b, and hepatitis B (DTaP-IPV-Hib-HepB) vaccinations at age 3-5-12 months. Infants born preterm or from unvaccinated mothers are recommended to receive an extra dose at 2 months-of-age. For term FGR infants from vaccinated mothers this 3-5-12 month schedule may be suboptimal due to compromised placental function, including transplacental transfer of maternal antibodies. Consequently, protection from maternal vaccination up to their first vaccination may be less optimal compared to term infants who are appropriate for gestational age (AGA) or small for gestational age (SGA). AIM: This study investigates whether following maternal Tdap vaccination, concentrations of passively acquired maternal IgG antibodies against Tdap vaccine antigens in 2-month-old FGR infants are at least as high as in 2-month-old term AGA- and SGA infants. METHOD: This is a prospective, observational cohort study involving Tdap-vaccinated pregnant women carrying a fetus with signs of SGA or FGR. Blood samples will be collected from mothers (finger-stick) and their infants (umbilical cord) at birth, and at 2 months (heel-stick), to measure Tdap-specific IgG antibody concentrations. Additionally, questionnaire data on general health will be gathered at three different time points. Results will be compared with historical studies investigating transfer of maternal antibodies after Tdap vaccination during pregnancy in AGA preterms and terms. DISCUSSION: By comparing the concentrations of IgG antibodies against Tdap vaccine antigens among FGR, SGA, AGA preterms and terms, we will contribute to insights into the necessity of optimizing the immunization schedule for FGR infants.