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

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.

Figure 1.. Pertussis Toxin Antibody Concentrations at Birth of Infants of Tdap-Immunized and Tdap-Unimmunized Mothers

Each box indicates the interquartile range (IQR) of pertussis toxin antibody concentration, with the bottom and top corresponding to the 25th and 75th percentiles; bold line inside the box indicates the median; solid triangle indicates the geometric mean concentration; whiskers indicate minimum and maximum values. Dashed line indicates the lower limit of quantitation. The lower and upper limits of quantitation were 15 and 480 IU/mL, respectively. Per accepted practice, values less than the lower limit of quantitation (n = 45 for immunized, n = 199 for unimmunized) were halved and those greater than the upper limit of quantitation were doubled (n = 2 for immunized, n = 0 for unimmunized). Tdap indicates tetanus, diphtheria, and acellular pertussis.

Figure 2.. Pertussis Toxin Antibody Concentrations at Birth of Infants of Tdap-Immunized Mothers (n = 312) by Week of Immunization

Each box indicates the interquartile range (IQR) of pertussis toxin antibody concentration, with the bottom and top corresponding to the 25th and 75th percentiles; bold line inside the box indicates the median; solid triangle indicates the geometric mean concentration; whiskers indicate minimum and maximum values. Individual data points are shown for weeks with small numbers of patients (weeks 27, 35, 36). Dashed line indicates the lower limit of quantitation. The lower and upper limits of quantitation were 15 and 480 IU/mL, respectively. Per accepted practice, values less than the lower limit of quantitation were halved (n = 1 at week 27, n = 3 at week 28, n = 4 at week 29, n = 8 at week 30, n = 5 at week 31, n = 8 at week 32, n = 7 at week 33, n = 6 at week 34, n = 2 at week 35, n = 1 at week 36) and those greater than the upper limit of quantitation were doubled (n = 1 at week 28, n = 1 at week 31). Tdap indicates tetanus, diphtheria, and acellular pertussis.