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Clinical Trial
. 2014 May 7;311(17):1760-9.
doi: 10.1001/jama.2014.3633.

Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: a randomized clinical trial

Flor M Munoz  1 , Nanette H Bond  2 , Maurizio Maccato  3 , Phillip Pinell  3 , Hunter A Hammill  4 , Geeta K Swamy  5 , Emmanuel B Walter  6 , Lisa A Jackson  7 , Janet A Englund  8 , Morven S Edwards  9 , C Mary Healy  9 , Carey R Petrie  10 , Jennifer Ferreira  10 , Johannes B Goll  10 , Carol J Baker  1
Affiliations
Clinical Trial

Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: a randomized clinical trial

Flor M Munoz et al. JAMA. .

Erratum in

  • Data Errors in Table.
    [No authors listed] [No authors listed] JAMA. 2017 Jan 24;317(4):442. doi: 10.1001/jama.2016.20705. JAMA. 2017. PMID: 28118432 No abstract available.
  • Notice of Data Errors.
    Baker CJ. Baker CJ. JAMA. 2017 Jan 24;317(4):441-442. doi: 10.1001/jama.2016.19244. JAMA. 2017. PMID: 28118445 No abstract available.

Abstract

Importance: Maternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine could prevent infant pertussis.

Objective: To evaluate the safety and immunogenicity of Tdap immunization during pregnancy and its effect on infant responses to diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine.

Design, setting, and participants: Phase 1-2, randomized, double-blind, placebo-controlled, clinical trial conducted from 2008 to 2012. Forty-eight pregnant women aged 18 to 45 years received Tdap (n = 33) or placebo (n = 15) at 30 to 32 weeks' gestation, with crossover immunization postpartum.

Interventions: Tdap vaccination at 30 to 32 weeks' gestation or postpartum.

Main outcomes and measures: Primary outcomes were maternal and infant adverse events, pertussis illness, and infant growth and development until age 13 months. Secondary outcomes were antibody concentrations in pregnant women before and 4 weeks after Tdap immunization or placebo, at delivery and 2 months' postpartum, and in infants at birth, at 2 months, and after the third and fourth doses of DTaP.

Results: No Tdap-associated serious adverse events occurred in women or infants. Injection site reactions after Tdap immunization were reported in 26 (78.8% [95% CI, 61.1%-91.0%]) and 12 (80% [95% CI, 51.9%-95.7%]) pregnant and postpartum women, respectively (P > .99). Systemic symptoms were reported in 12 (36.4% [ 95% CI, 20.4%-54.9%]) and 11 (73.3% [95% CI, 44.9%-92.2%]) pregnant and postpartum women, respectively (P = .03). Growth and development were similar in both infant groups. No cases of pertussis occurred. Significantly higher concentrations of pertussis antibodies were measured at delivery in women who received Tdap during pregnancy vs postpartum (eg, pertussis toxin antibodies: 51.0 EU/mL [95% CI, 37.1-70.1] and 9.1 EU/mL [95% CI, 4.6-17.8], respectively; P < .001) and in their infants at birth (68.8 EU/mL [95% CI, 52.1-90.8] and 14.0 EU/mL [95% CI, 7.3-26.9], respectively; P < .001) and at age 2 months (20.6 EU/mL [95% CI, 14.4-29.6] and 5.3 EU/mL [95% CI, 3.0-9.4], respectively; P < .001). Antibody responses in infants born to women receiving Tdap during pregnancy were not different following the fourth dose of DTaP.

Conclusions and relevance: This preliminary assessment did not find an increased risk of adverse events among women who received Tdap vaccine during pregnancy or their infants. For secondary outcomes, maternal immunization with Tdap resulted in high concentrations of pertussis antibodies in infants during the first 2 months of life and did not substantially alter infant responses to DTaP. Further research is needed to provide definitive evidence of the safety and efficacy of Tdap immunization during pregnancy.

Trial registration: clinicaltrials.gov Identifier: NCT00707148.

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Conflict of interest statement

Conflict of Interest:

No conflict of interest related to this study was reported by the following authors: Bond, Maccato, Pinell, Hammill, Jackson, C. R. Petrie, J. Ferreira and J. Goll performed this work supported by NIAID-DMID contract (Clinical Research in Infectious Disease (CRID), HHSN272200800013C).

F. Munoz has served as a speaker for Sanofi Pasteur and as consultant for Novartis, GlaxoSmithKline (GSK), and Novavax. She has also conducted clinical trials sponsored by Hoffmann-LaRoche, GlaxoSmithKline Biologicals, and Gilead Sciences.

G. Swamy reports receiving consulting and lecturing fees as well as grant support for vaccine-related studies from GSK, as well as for advisory boards, lectures, and the development of educational presentations. She has received grant funding from GSK specific to influenza vaccine and HPV infection.

E. Walter has served as a consultant and advisor for Merck and as a speaker for Sanofi Pasteur. He has conducted clinical trials sponsored by GSK, Merck, Novartis, and Pfizer.

J. Englund has received research support from Novartis, Gilead, Chimerix, and Roche. She was a consultant for GSK in 2012–2013 and served on a GSK DSMB on 2012–13, she also received travel expenses from Abbvie (part of Abbot) in 2013.

M. Edwards serves as consultant for and has received grants from Novartis Vaccines.

C. Healy has conducted trials with grants from Sanofi Pasteur and Novartis, and serves as advisor for Novartis Vaccines..

C. Baker serves as consultant and advisory board member to Novartis Vaccines, and advisory board member for Pfizer Inc.

Figures

Figure 1
Figure 1. Parts A–B
A. Flow diagram for pregnant women study participants. B. Flow diagram for non-pregnant women study participants.
Figure 1
Figure 1. Parts A–B
A. Flow diagram for pregnant women study participants. B. Flow diagram for non-pregnant women study participants.
See this image and copyright information in PMC

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