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

Educational Objective
To understand the strategy of immunization during pregnancy to protect young infants from pertussis.
1 Credit CME
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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Article Information

Corresponding Author: C. Mary Healy, MD, Infectious Disease Section, Department of Pediatrics, Baylor College of Medicine, 1102 Bates St, Ste 1120, Houston, TX 77030 (chealy@bcm.edu).

Accepted for Publication: September 10, 2018.

Author Contributions: Dr Healy had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Healy, Rench, Baker.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Healy, Smith.

Critical revision of the manuscript for important intellectual content: Healy, Rench, Swaim, Sangi-Haghpeykar, Mathis, Martin, Baker.

Statistical analysis: Healy, Smith, Sangi-Haghpeykar, Mathis.

Obtained funding: Healy.

Administrative, technical, or material support: Healy, Rench, Swaim, Martin, Baker.

Supervision: Healy, Baker.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Healy reported receiving research grants from Sanofi Pasteur and Novartis Vaccines and serving on advisory boards for Novartis Vaccines, Pfizer Inc, and Novavax Inc. Dr Baker reported serving on scientific advisory boards for Seqirus Inc and as a consultant for Pfizer Inc. No other authors reported disclosures.

Funding/Support: This article was made possible by award CDC-CI10-101203PPHF12 from the Centers for Disease Control and Prevention (CDC), through the Houston Department of Health and Human Services (HDHHS).

Role of the Funder/Sponsor: The sponsor was involved in the design of the study, performance of laboratory assays, interpretation of the data, and critical review of the manuscript. The sponsor had no role in collection, management, or statistical analysis of the data and did not have the right to prevent publication of the study.

Additional Contributions: We thank Lucia Pawloski, PhD (research biologist, Pertussis and Diphtheria Laboratory, CDC), and Maria Lucia Tondella, PhD (team lead, Pertussis and Diphtheria Laboratory, CDC), for their assistance in performing the study. We thank Robin Schroeder (administrative coordinator, Baylor College of Medicine) for her assistance in manuscript preparation. Drs Pawloski and Tondella received no compensation for their role in the study. Baylor College of Medicine received salary support for Ms Schroeder for her role in the study.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC or HDHHS.

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