Maternal Pertussis Immunization and Immunoglobulin G Levels in Early- to Late-Term and Preterm Infants

Abstract

Importance: Maternal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination protects newborns against severe pertussis. Data on transplacental antibody transfer on Tdap vaccination before 24 weeks' gestation remain scarce and are particularly relevant for preterm infants to increase the time interval for maternal antibody transfer.

Objective: To assess noninferiority of anti-pertussis toxin (anti-PT) immunoglobulin G (IgG) antibody levels at age 2 months in early- to late-term infants following Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 30 0/7 and 33 0/7 weeks' gestation and compared with preterm infants.

Design, setting, and participants: This prospective, multicenter cohort study included pregnant women aged 18 years or older in birthing centers and hospitals in the Netherlands between August 2019 and November 2021 who received Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation. Women with imminent premature birth were recruited if they had received maternal Tdap vaccination between 20 and 24 weeks' gestation. Blood samples were collected from mothers at delivery, from the umbilical cord, and from infants at age 2 months. Data from infants' blood samples at age 2 months were compared with a reference cohort (recruited between January 2014 and February 2016) of early- to late-term infants of the same age whose mothers had received Tdap vaccination between 30 0/7 and 33 0/7 weeks' gestation.

Exposure: Maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation or 30 0/7 and 33 0/7 weeks' gestation.

Main outcomes and measures: The primary outcome was the geometric mean concentration (GMC) of anti-PT IgG antibodies in early- to late-term infants (≥37 0/7 weeks' gestation) at age 2 months, comparing maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' vs 30 0/7 and 33 0/7 weeks' gestation (reference cohort). Anti-PT GMC in 2-month-old infants born preterm (<35 0/7 weeks' gestation) compared with early- to late-term infants after maternal Tdap vaccination between 20 and 24 weeks' gestation was a secondary outcome.

Results: In total, 221 women who delivered 239 offspring were enrolled in the study; 66 early- to late-term infants (median gestational age [GA], 40.6 weeks [IQR, 39.8-41.0 weeks]; 38 [57.6%] male) and 73 preterm infants (median GA, 32.1 weeks [IQR, 29.5-33.0 weeks]; 42 [54.5%] female) had blood samples collected at 2 months of age. Anti-PT GMC was 14.7 IU/mL (95% CI, 10.6-20.4 IU/mL) in early- to late-term infants following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 27.3 IU/mL (95% CI, 20.1-37.1 IU/mL) in 55 infants in the reference group (median GA, 40.3 [IQR, 39.1-41.0]; 33 [60.0%] female). The mean anti-PT GMC in preterm infants in the study group was 11.2 IU/mL (95% CI, 8.1-15.3 IU/mL) (P = .23 compared with early- to late-term infants).

Conclusions and relevance: In this cohort study, 2-month-old preterm and early- to late-term infants showed significantly lower anti-PT antibody levels following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 30 0/7 and 33 0/7 weeks' gestation; preterm and early- to late-term infants had similar anti-PT antibody levels, but both groups showed significantly lower antibody levels compared with the reference group. Epidemiological research should investigate whether maternal Tdap vaccination before 24 weeks' gestation provides sufficient protection against clinical pertussis, particularly in preterm infants, as long as no correlate of protection is available.

Figure 1.. Flowchart of Study Procedures

Term includes early- to late-term births (≥37 0/7 weeks’ gestation). GA indicates gestation; Tdap, tetanus, diphtheria, and acellular pertussis. ^aIncluding 14 pairs of twins and 2 sets of triplets, among whom 1 sample was not collected due to perinatal death. ^bTwo infants had a sample obtained at 2 months but no umbilical cord blood sample. ^cFour infants had a sample obtained at 2 months but no umbilical cord blood sample. ^dSeventy-three infants from 60 mothers had a blood sample obtained at 2 months of age.

Figure 2.. Individual Immunoglobulin G (IgG) Antibody Concentrations and Geometric Mean Concentrations (GMCs) After Second- vs Third-Trimester Tetanus, Diphtheria, and Pertussis Vaccination in Early- and Full-Term Mother-Infant Pairs at Different Time Points

Horizontal lines represent GMCs and vertical bars, 95% CIs. DT indicates diphtheria toxoid; FHA, filamentous hemagglutinin; GA, gestation; Prn, pertactin; PT, pertussis toxin; TT, tetanus toxoid. ^aP < .05. ^bP < .01. ^cP < .001.

Figure 3.. Individual Immunoglobulin G (IgG) Antibody Concentrations and Geometric Mean Concentrations (GMCs) After Second-Trimester Tetanus, Diphtheria, and Pertussis Vaccination in Early- and Full-Term vs Preterm Mother-Infant Pairs at Different Time Points

All women were vaccinated between 20 0/7 and 24 0/7 weeks’ gestation (GA). Horizontal lines represent GMCs and vertical bars, 95% CIs. DT indicates diphtheria toxoid; FHA, filamentous hemagglutinin; Prn, pertactin; PT, pertussis toxin; TT, tetanus toxoid. ^aP < .05. ^bP < .01. ^cP < .001.