The Impact of Timing of Pertussis Vaccination During Pregnancy on Infant Antibody Levels at Birth: A Multi-Country Analysis

Abstract

Background: Pertussis vaccination during pregnancy is an effective strategy at reducing pertussis-related morbidity and mortality in infancy and is recommended across several countries. However, the optimal timepoint for vaccination in pregnancy to afford maximal protection to newborns is yet to be elucidated. This multi-country analysis aimed to model the impact of timing of vaccination during pregnancy on infant antibody titers at birth.

Methods: A multi-country analysis on a cohort of mother-infant pairs (n=698) vaccinated between 19.6-37.1 weeks gestation was conducted. Data taken from four parent studies on pertussis vaccination during pregnancy were modelled using natural cubic splines and linear mixed models to study the association of both gestational age at vaccination and the interval between vaccination and delivery with pertussis-specific cord blood antibody levels after pertussis vaccination during pregnancy.

Results: Term born infants on average achieve the highest antibody levels at birth if women are vaccinated before 31 weeks' gestation. When considering both term and preterm deliveries, an interval of at least 7.5 weeks between vaccination and delivery is required to achieve the highest cord blood antibody levels. The models show that vaccinating earlier than these timeframes will also provide the infant with equally high antibody levels at birth.

Conclusions: Vaccinating in the second and early third trimester results in the highest antibody levels at birth. Vaccinating earlier within this window is needed to provide equal benefits to both term and preterm born infants.

Keywords: Tdap; multi-country analysis; pregnancy; timing; vaccination.

Figure 1

Boxplots comparing cord blood antibody titers across study groups for anti-PT (left), anti-FHA (centre) and anti-PRN antibodies (right), reported in IU/mL (BE1, VN1, TL1) or EU/mL (BE2, BE3). Geometric Mean Concentrations (GMCs) are represented by dashed horizontal lines. BE1, Belgium 1; VN1, Vietnam 1; TL1, Thailand 1; BE2, Belgium 2; BE3, Belgium 3; PT, Pertussis Toxin; FHA, Filamentous Hemagglutinin; PRN, Pertactin.

Figure 2

Observed GMCs (points) and model estimates (solid line) with 95% confidence intervals (shaded area) for antibody titers across covariates. Note, results of the LMMs are presented as graphical representations, keeping stated covariates constant to visualise the effect of timing of maternal vaccination on cord antibody titers. (A) Model 1: GMC estimates for cord anti-PT titers at delivery by GAV across country with covariates: weight = mean birth weight, BA-EDD = 0 days. (B) Model 2: GMC estimates for cord anti-PT titers at delivery by interval between GAV and GAD across country with covariates: weight = mean birth weight. (C) Model 3: GMC estimates for cord anti-FHA titers at delivery by GAV across study groups with covariates: weight = mean birth weight, vaccine = Boostrix^®. (D) Model 4: GMC estimates for cord anti-FHA titers at delivery by interval between GAV and GAD across study groups with covariates: weight = mean birth weight. (E) Model 5: GMC estimates for cord anti-PRN titers at delivery by GAV across country with covariates: weight = mean birth weight, age = mean age of mother at birth. (F) Model 6: GMC estimates for cord anti-PRN titers at delivery by interval between GAV and GAD across country with covariates: weight = mean birth weight, age = mean age of mother at birth, being term born. BA-EDD = number of days delivered before/after the due date, GAD = gestational age at delivery, GAV = gestational age at vaccination, GMC = geometric mean concentration, BE1 = Belgium 1, VN1 = Vietnam 1, TL1 = Thailand 1, BE2 = Belgium 2, BE3 = Belgium 3, PT = Pertussis Toxin, FHA = Filamentous Haemmaglutinin, PRN = Pertactin, LMMs = linear mixed models.