Maternal immunization with tetanus toxoid and reduced diphtheria toxoid acellular pertussis (Tdap) vaccine could prevent infant pertussis. The effect of vaccine-induced maternal antibodies on infant responses to diphtheria and tetanus toxoids acellular pertussis (DTaP) immunization is unknown.
To evaluate the safety and immunogenicity of Tdap immunization during pregnancy and its effect on infant responses to DTaP.
Design, Setting and Participants
Phase I, randomized, double-masked, placebo-controlled clinical trial conducted in private (Houston) and academic (Durham, Seattle) obstetric practices from 2008 to 2012. Forty eight healthy 18–45 year-old pregnant women received Tdap (n=33) or placebo (n=15) at 30–32 weeks’ gestation with cross-over Tdap immunization postpartum.
Tdap vaccination at 30–32 weeks’ gestation or post-partum.
Primary: Maternal and infant adverse events, pertussis illness and infant growth and development (Bayley-III screening test) until 13 months of age. Secondary: 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, 2 months, and after the third (7 months) and fourth (13 months) doses of DTaP.
All participants delivered healthy newborns. No Tdap-associated serious adverse events occurred in women or infants. Injection site reactions after Tdap immunization were reported in 78.8% (95% CI: 61.1%, 91.0%) and 80% (CI: 51.9%, 95.7%) pregnant and postpartum women, respectively. Injection site pain was the predominant symptom. Systemic symptoms were reported in 36.4% (CI: 20.4%, 54.9%) and 73.3% (CI: 44.9%, 92.2%) pregnant and postpartum women, respectively. Malaise and myalgia were most common. 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 and in their infants at birth and at age 2 months when compared to infants of women immunized postpartum. Antibody responses in infants of Tdap recipients during pregnancy were modestly lower after 3 DTaP doses, but not different following the fourth dose.
Conclusions and Relevance
This preliminary safety assessment did not find an increased risk of adverse events among women who received Tdap vaccine at 30–32 weeks’ gestation or their infants. 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 vaccination during pregnancy.
ClinicalTrials.gov, study identifier: NCT00707148. URL: http://www.clinicaltrials.gov