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Original Investigation
October 9, 2018

Association Between Third-Trimester Tdap Immunization and Neonatal Pertussis Antibody Concentration

Author Affiliations
  • 1Infectious Disease Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas
  • 2Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas
  • 3Department of Statistics, Baylor College of Medicine, Houston, Texas
  • 4Pertussis and Diphtheria Laboratory, Centers for Disease Control and Prevention, Atlanta, Georgia
  • 5Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas
  • 6Now with Department of Pediatrics, The University of Texas Health Science Center at Houston
JAMA. 2018;320(14):1464-1470. doi:10.1001/jama.2018.14298
Key Points

Question  Does maternal immunization with Tdap vaccine during the third trimester of pregnancy yield high concentrations of pertussis antibodies at birth? Is there an optimal gestational age for immunization?

Findings  In this prospective cohort study of 626 pregnancies, neonates whose mothers received Tdap immunization in the third trimester compared with those whose mothers received no Tdap vaccine during pregnancy had a geometric mean concentration of pertussis toxin antibodies in cord blood of 47.3 IU/mL vs 12.9 IU/mL, a difference that was statistically significant. Concentrations of cord blood antibodies were highest when immunization occurred at 27 to 30 weeks and declined thereafter.

Meaning  Maternal immunization with Tdap vaccine during the third trimester was associated with higher pertussis toxin antibody concentrations in neonates than no maternal immunization; immunization early in the third trimester was associated with the highest concentrations.

Abstract

Importance  Immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in the United States during weeks 27 through 36 of pregnancy to prevent life-threatening infant pertussis. The optimal gestation for immunization to maximize concentrations of neonatal pertussis toxin antibodies is unknown.

Objective  To determine pertussis toxin antibody concentrations in cord blood from neonates born to women immunized and unimmunized with Tdap vaccine in pregnancy and optimal gestational age for immunization to maximize concentrations of neonatal antibodies.

Design, Setting, and Participants  Prospective, observational, cohort study of term neonates in Houston, Texas (December 2013-March 2014).

Exposures  Tdap immunization during weeks 27 through 36 of pregnancy or no Tdap immunization.

Main Outcomes and Measures  Primary outcome was geometric mean concentrations (GMCs) of pertussis toxin antibodies in cord blood of Tdap-exposed and Tdap-unexposed neonates and proportions of Tdap-exposed and Tdap-unexposed neonates with pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher, cutoffs representing quantifiable antibodies or levels that may be protective until the infant immunization series begins. Secondary outcome was the optimal gestation for immunization to achieve maximum pertussis toxin antibodies.

Results  Six hundred twenty-six pregnancies (mean maternal age, 29.7 years; 41% white, 27% Hispanic, 26% black, 5% Asian, 1% other; mean gestation, 39.4 weeks) were included. Three hundred twelve women received Tdap vaccine at a mean gestation of 31.2 weeks (range, 27.3-36.4); 314 were unimmunized. GMC of neonatal cord pertussis toxin antibodies from the Tdap-exposed group was 47.3 IU/mL (95% CI, 42.1-53.2) compared with 12.9 IU/mL (95% CI, 11.7-14.3) in the Tdap-unexposed group, for a GMC ratio of 3.6 (95% CI, 3.1-4.2; P < .001). More Tdap-exposed than Tdap-unexposed neonates had pertussis toxin antibody concentrations of 15 IU/mL or higher (86% vs 37%; difference, 49% [95% CI, 42%-55%]), 30 IU/mL or higher (72% vs 17%; difference, 55% [95% CI, 49%-61%]), and 40 IU/mL or higher (59% vs 12%; difference, 47% [95% CI, 41%-54%]); P < .001 for each analysis. GMCs of pertussis toxin antibodies were highest when Tdap vaccine was administered during weeks 27 through 30 and declined thereafter, reaching a peak at week 30 (57.3 IU/mL [95% CI, 44.0-74.6]).

Conclusions and Relevance  Immunization with Tdap vaccine during the third trimester of pregnancy, compared with no immunization, was associated with higher neonatal concentrations of pertussis toxin antibodies. Immunization early in the third trimester was associated with the highest concentrations.

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