Objective
We sought to determine whether tetanus–diphtheria–pertussis vaccination (Tdap) in pregnancy provides newborns antibodies against pertussis when compared to mothers who did not receive Tdap.
Study Design
Paired maternal and umbilical cord blood samples were collected at the time of delivery and the serum stored at –86°C. For each paired sample of maternal and cord blood, the medical chart and vaccine history was reviewed to determine whether Tdap was received or not.
Results
Newborns born from mothers who received Tdap during pregnancy had significantly higher concentrations of diphtheria antitoxin ( P < .001), tetanus antitoxin ( P = .004), and antibodies to pertussis toxin ( P < .001), filamentous hemagglutinin ( P = .002), pertactin ( P < .001), and fimbriae 2/3 ( P < .001) when compared to newborns from mothers who did not receive Tdap. There was a significant increase in the odds that newborns from mothers who received Tdap during pregnancy have antibodies that may provide protection against diphtheria ( P = .0141), pertussis toxin ( P < .0001), and fimbriae 2/3 ( P = .0146).
Conclusion
Administering Tdap during pregnancy increases antibody titers against diphtheria and pertussis antigens. Maternal Tdap may prevent neonatal pertussis infection.
Pertussis (whooping cough) is a respiratory tract infection caused by Bordetella pertussis . The disease is most severe in young infants, who have the highest hospitalization and complication rates. Almost all deaths associated with confirmed pertussis infection occur in infants ≤6 months of age, most too young to have received their primary series of tetanus toxoid (TT), diphtheria toxoid (DT), and acellular pertussis antigens vaccine.
The annual incidence of pertussis in the United States has increased 3-fold since 1980, even though immunization rates for young children have been 80%. During 1997 through 2000 in the United States, the highest pertussis attack rate (55.5 cases per 100,000 population) occurred in infants <1 year of age, which is in contrast to the attack rate of 0.8-5.5 cases per 100,000 population in other age groups. In 2000, each of the 17 pertussis-related deaths reported to the Centers for Disease Control and Prevention occurred in US-born infants who contracted pertussis at ≤4 months of age.
In 2005, the Food and Drug Administration licensed the tetanus, reduced diphtheria, and acellular pertussis antigens vaccine (Tdap) for persons 11-64 years of age and in 2006, the Advisory Committee for Immunization Practices (ACIP) recommended Tdap for routine use in adolescents and adults. ACIP recommended the vaccine could be used in pregnancy, but preferred postpartum maternal administration in an effort to immunize the persons who were surrounding the infant.
This report provides the results of active Tdap immunization to 52 pregnant women who were compared to 52 pregnant women who did not receive Tdap during pregnancy. Paired maternal serum and umbilical cord serum were collected for each group. TT and DT antibodies and antibodies to the pertussis antigens pertactin (PRN), pertussis toxin (PT), filamentous hemagglutinin (FHA), and fimbriae (FIM) 2/3 were measured.
Materials and Methods
Our subjects were pregnant women attending the University of Louisville Obstetrical Clinic from October 2008 through December 2009. Institutional approval was obtained for use of discarded maternal and umbilical cord blood samples. All patients were encouraged to receive Tdap during the second trimester of pregnancy. However, the exact timing of the administration of Tdap could not be determined as some patients received Tdap prior to pregnancy and some received Tdap at referring clinics. Routinely collected maternal blood and umbilical cord blood samples were retained, centrifuged to separate the serum, and the serum was frozen at –86°C until analyzed. The medical chart was used as a source for the vaccine history as to whether the patient received Tdap or did not receive Tdap.
Laboratory methods
Vaccine
The Tdap used in this study was manufactured by Sanofi Pasteur (Swiftwater, PA) and contained the following toxoid and antigen concentrations: DT, 2 Lf U; TT, 5 Lf U; PT, 2.5 μg; FHA, 5.0 μg; PRN, 3.0 μg; and FIM, 2/3 5 μg.
Antibody quantitation
DT, TT, PT, FHA, PRN, and FIM antibody levels were measured as previously described. Briefly, antigen (a gift from Sanofi Pasteur) was absorbed onto polystyrene microtiter plates. Sera, assayed at dilutions ranging from 1:50 to 1:6400, was added to the coated plates. Bound antibodies were detected using a goat antihuman IgG alkaline phosphate-labeled antibody followed by nitrophenyl phosphate substrate. The absorbance readings were measured and quantitated against an international reference sera with known quantities of the respective antibodies to provide a specific antibody concentration in the sera tested, using a spectrophotometer capable of reading microtiter plates (spectramax 3400 PC; Molecular Devices, Sunnyvale, CA). The definition of a protective level for each of the antigens was as follows: DT, >0.10 IU/mL; TT, >0.10 IU/mL; PT, 5 enzyme-linked immunosorbent assay U {ELU]/mL; FHA, 3 ELU/mL; PRN, 5 ELU/mL; and FIM 2/3, 5 ELU/mL.
Statistical methods
The primary analysis used analysis of variance to examine whether newborns from mothers who received Tdap during pregnancy had higher concentrations of antibodies to DT, TT, PT, FHA, PRN, or FIM compared to newborns from mothers who did not receive Tdap during pregnancy. Antibody levels below the limit of detection were assigned the lower limit of detection value for that antigen. In a secondary analyses, Pearson correlation coefficients were calculated to explore the correlation between a mother’s and her newborn’s antibody level.
Exploratory analysis
The correlate of immunity for the 4 pertussis antibodies is not established, but data indicate that multicomponent vaccines have increased efficacy. This indicates the level of individual antibodies associated with a protective effect against the individual developing the disease has not been determined, but the sum of all antibodies contribute to efficacy. Increased levels of IgG antibody to FIM, PRN, and PT have been associated with disease prevention. The defined protective levels were created by the detectable level of the diagnostic test. That is, if an individual’s antibody was at or above the detectable level for the antibody, the individual was defined as having protection. This practice is consistently used in the literature, for tetanus and diphtheria and hepatitis B. Zaman et al studied maternal immunization with inactivated influenza vaccine and showed significant benefit to the mother and a 63% reduction in proven influenza illness in infants up to 6 months of age.
We assumed that the sum of >1 pertussis antibody would contribute to an increased protective effect. This assumption allowed us to pursue an exploratory analysis of the concept that increased antibody levels above a detectable level may indicate greater protection. We used multilogistic regression to test the odds that a newborn was protected from each of the potential pathogens. For the model, when an antibody level was less than the predefined protective level, the protection was coded as a 0 (representing no protection). Lastly, we used linear regression techniques to test if a newborn’s antibody level could be predicted from group affiliation (Tdap or no Tdap).
Results
There were no adverse reactions to the vaccine.
The current study collected serological data from 104 pregnant women and their newborns (total n = 208 samples). Half (n = 52) of the pregnant women received the Tdap during the antepartum period, while the other half (n = 52) of pregnant women did not receive Tdap.
As seen in Table 1 , newborns born from mothers who received Tdap during pregnancy had significantly higher concentrations of anti-DT (0.571 vs 1.970, P < .001), anti-TT (4.237 vs 9.015, P = .004), anti-PT (11.010 vs 28.220, P < .0001), anti-FHA (26.830 vs 104.15, P = .002), anti-PRN (24.700 vs 333.01, P < .001), and anti-FIM 2/3 (82.830 vs 1198.99, P < .001) when compared to newborns born from mothers who did not receive Tdap during pregnancy. Also, there was a significant correlation between a mother’s antibody level and their newborn’s antibody level ( Table 2 ).
| Outcome Antibodies | Mother did not receive Tdap, mean (SEM) n = 52 | Mother received Tdap, mean (SEM) n = 52 | P value a |
|---|---|---|---|
| Diphtheria | 0.571 (0.157) | 1.970 (0.291) | < .001 |
| Tetanus | 4.237 (1.381) | 9.015 (0.981) | .004 |
| PT | 11.010 (1.796) | 28.220 (2.768) | < .001 |
| FHA | 26.830 (4.022) | 104.15 (21.664) | .002 |
| PRN | 24.700 (5.765) | 333.01 (56.435) | < .001 |
| FIM 2/3 | 82.83 (14.585) | 1198.99 (189.937) | < .001 |
| Antibody | Pearson correlation coefficient ( P value) |
|---|---|
| Diphtheria | 0.345 (< .0001 a ) |
| Tetanus | 0.204 (< .001 a ) |
| PT | 0.158 (.055) |
| FHA | 0.165 (.045 a ) |
| PRN | 0.965 (< .001 a ) |
| FIM 2/3 | 0.293 (< .001 a ) |
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