Vaccine/Toxoid
PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk
BREASTFEEDING RECOMMENDATION: Compatible
PREGNANCY SUMMARY
Although no reports describing the use of tetanus toxoid/reduced diphtheria toxoid/acellular pertussis vaccine adsorbed (Tdap) or diphtheria/tetanus toxoids/acellular pertussis vaccine adsorbed (DTaP) in human pregnancy have been located, one report did describe the inadvertent administration of acellular pertussis vaccine without toxoids in early gestation. Diphtheria/tetanus toxoids are recommended in pregnancy under certain conditions (see Diphtheria/Tetanus Toxoids [Adult]) and whole cell pertussis vaccine (no longer available) has been used in late pregnancy. Studies in which Tdap is given in the 2nd and 3rd trimesters have been proposed to determine if higher titers of pertussis antibodies can be obtained in the newborn (1–4). Currently, if tetanus or diphtheria protection is needed during pregnancy, the CDC and the American College of Obstetricians and Gynecologists (ACOG) recommend that Tdap be considered in the 2nd or 3rd trimesters, or earlier if protection is needed urgently (5–7). Tdap should only be given once during a lifetime.
Pertussis antibodies are known to cross the placenta and could potentially provide infants greater protection until they reach the age for active immunization. The American Academy of Pediatrics has recommended that pregnant adolescents should be given the same consideration for immunization as nonpregnant adolescents, and that the vaccine should be given before 36 weeks’ gestation (4). However, the CDC concluded that it was not clear if the increased titers of pertussis antibodies would be adequate to protect the infant from pertussis, nor was it known if the increased titers would interfere with later active immunization of the infant (6). If Tdap is used in pregnancy, health care professionals are encouraged to call the toll-free number 877-311-8972 for information about patient enrollment in the Organization of Teratology Information Specialists (OTIS) Pertussis Vaccines study.
FETAL RISK SUMMARY
Acellular pertussis vaccine is available in five formulations: Tdap (for adolescents/adults) (Adacel, Boostrix); and DTaP (for infants/children) (Daptacel, Infanrix, Tripedia). Pertussis vaccine is a combination, noninfectious product containing the two toxoids and inactivated pertussis vaccine (8–12) (see also Tetanus/Diphtheria Toxoids [Adult]). Compared with DTaP, Tdap has reduced diphtheria toxoid. All five of the vaccines are given as an IM injection. The acellular vaccine replaced the whole cell vaccine in 1997 (13). In addition to the two toxoids, the vaccines contain three pertussis antigens (inactivated pertussis toxin [PT], formaldehyde-treated filamentous hemagglutinin [FHA], and pertactin) adsorbed onto aluminum hydroxide. The pertussis antigens are isolated from Bordetella pertussis, the cause of whopping cough. The adolescent/adult formulations are indicated for active booster immunization to prevent tetanus, diphtheria, and pertussis as a single dose in persons 10–18 years of age (Boostrix) and 11–64 years of age (Adacel) (8,9). The infant/children products are indicated for the active immunization of infants and children 6 weeks to 7 years of age (before the seventh birthday) (10–12). The information presented here applies to all of the formulations.
Reproduction studies have been conducted in rats and rabbits. DTaP (Infanrix) was given IM to rats prior to gestation and Tdap (Boostrix) was administered IM during organogenesis (days 6, 8, and 11) and later in pregnancy (day 15) (8). Each dose of Boostrix was about 45 times the human dose based on body weight (HD). No adverse effects were observed on pregnancy, lactation, or embryo–fetal or preweaning development, and there was no evidence of teratogenic effects. Studies have not been conducted for carcinogenicity, mutagenicity, or effects on fertility (8).
In rabbits, Adacel was administered IM twice before conception, during organogenesis (day 6), and later in pregnancy (day 29). Each dose was 17 times the HD. No adverse effects were observed on pregnancy, parturition, lactation, embryo–fetal or preweaning development, and there was no evidence of teratogenic effects (9).
A 1986 review on the epidemiology of pertussis cited a 1943 reference in which pertussis vaccine was given to 29 women during the sixth and seventh month of pregnancy (14). High protective antibody titers were found in mothers and their newborns. Because of the date, the product used was probably the whole cell pertussis vaccine (14).
A 2003 article reviewed the current prevalence of pertussis in the United States including its morbidity and mortality in different age groups (13). The author also discussed a 1990 serologic study conducted in her institution in which the placental transfer of maternal antibodies to pertussis was evaluated (the mothers had not received a pertussis vaccine during pregnancy) (15). Antibodies to PT in cord sera were 2.9 times higher than those in maternal sera, suggesting active transport to the embryo–fetus. In contrast, cord sera titers of antibodies to FHA and agglutinin did not differ significantly from maternal sera. Because cord blood concentrations of anti-pertussis immunoglobulin G (IgG) were nearly comparable to maternal titers, the author concluded that maternal immunization would be effective in providing infants with protection until they reached the age for active immunization (13).
A 1999 study evaluated the safety and efficacy of an acellular pertussis vaccine, which did not contain diphtheria or tetanus toxoids, in healthy men and women 18 years of age or older (16). Although pregnant women were excluded, 2 of the 200 female subjects conceived. The first woman conceived about 8 days after immunization. A spontaneous abortion occurred on gestational day 34. The second woman became pregnant within 0–4 weeks of immunization. She underwent an elective abortion at about 1 month of gestation. The investigators concluded that neither outcome was related to the vaccine (16).
BREASTFEEDING SUMMARY
No reports describing the administration of any of the four formulations of pertussis vaccine during human lactation have been located. Tdap should present no risk to a nursing infant because antibodies to pertussis, tetanus, and diphtheria should be present in both the mother and the infant. Moreover, DTaP is indicated for infants and children 6 weeks through 6 years of age (before seventh birthday). The CDC and ACOG recommend Tdap in breastfeeding women who have not received the vaccine previously or 2 years or more have elapsed since the most recent Td administration (5,6).
References
1.McIntyre P. Vaccines for other neonatal infections. Expert Rev Vaccines 2004;3:375–8.
2.Van Rie A, Wendelboe AM, Englund JA. Role of maternal pertussis antibodies in infants. Pediatr Infect Dis J 2005;24(Suppl):S62–5.
3.Forsyth K, Tan T, von Konig CHW, Caro JJ, Plotkin S. Potential strategies to reduce the burden of pertussis. Pediatr Infect Dis J 2005;(Suppl):S69–74.
4.Committee on Infectious Diseases. American Academy of Pediatrics. Prevention of pertussis among adolescents: recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. Pediatrics 2006;117:965–78.
5.American College of Obstetricians and Gynecologists. Update on immunization and pregnancy: tetanus, diphtheria, and pertussis vaccination. Committee Opinion, No. 438, August 2009.
6.Advisory Committee on Immunization Practices (ACIP). Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants. MMWR 2008;57(RR4):1–51. Available at http://www.cdc.gov/mmwr/PDF/rr/n5704.pdf. Accessed December 28, 2009.
7.CDC. Guidelines for Vaccinating Pregnant Women. Available at http://www.cdc.gov/vaccines/pubs/preg-guide.htm. Accessed May 16, 2010.
8.Product information. Boostrix. GlaxoSmithKline, 2007.
9.Product information. Adacel. Sanofi Pasteur, 2007.
10.Product information. Infanrix. GlaxoSmithKline, 2007.
11.Product information. Daptacel. Sanofi Pasteur, 2007.
12.Product information. Tripedia. Sanofi Pasteur, 2007.
13.Edwards KM. Pertussis: an important target for maternal immunization. Vaccine 2003;21:3483–6.
14.Muller AS, Leeuwenburg J, Pratt DS. Pertussis: epidemiology and control. Bull World Health Organ 1986;64:321–31.
15.Van Savage J, Decker MD, Edwards KM, Sell SH, Karzon DT. Natural history of pertussis antibody in the infant and effect on vaccine response. J Infect Dis 1990;161:487–92.
16.Rothstein EP, Pennridge Pediatric Associates, Anderson EL, Decker MD, Poland GA, Reisinger KS, Blatter MM, Jacobson RM, Mink CM, Gennevois D, Izu AE, Sinangil F, Langenberg AGM. An acellular pertussis vaccine in healthy adults: safety and immunogenicity. Vaccine 1999;17:2999–3006.