Diphtheria, Tetanus, and Pertussis Vaccines

Number: 0653

Policy

1. Aetna considers diphtheria, tetanus toxoid, and whole-cell or acellular pertussis vaccines medically necessary preventive services according to the recommendations of the Advisory Committee on Immunization Practices (ACIP).

2. Aetna considers combination vaccination with diphtheria-tetanus-acellular pertussis (DTaP), inactivated polio, and hepatitis B (Pediarix^®, GlaxoSmithKline) an acceptable medically necessary alternative to these individual vaccines for the doses that are generally administered at 2 months, 4 months, and 6 months of age.

   Aetna considers combination vaccination with diphtheria-tetanus-whole-cell pertussis (DTP) and Haemophilis influenzae type b (Hib) (TriHIBit^™, Sanofi Pasteur, Inc.) an acceptable medically necessary alternative to these individual vaccines for the fourth dose of the childhood vaccination series, which is generally administered at 15-18 months of age.

   Aetna considers combination vaccination with diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus and Haemophilus influenzae type b (Pentacel^®, Sanofi Pasteur, Inc.) an acceptable medically necessary alternative to these individual vaccines in children 6 weeks through 4 years of age (prior to 5 years of age) for administration as a 4-dose series at 2 months, 4 months, 6 months, and 15 - 18 months of age.

   Aetna considers combination vaccination with diphtheria, tetanus, pertussis, and poliomyelitis (KinrixTM, GlaxoSmithKline) medically necessary as the fifth dose in the DTaP vaccine series and the fourth dose in the inactivated poliovirus vaccine (IPV) series in children 4 through 6 years of age whose previous DTaP vaccine doses have been with Infanrix^® and/or Pediarix^® for the first three doses and Infanrix^® for the fourth dose.

3. Aetna considers Boostrix (GlaxoSmithKline), a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) a medically necessary preventive service for active booster immunization against tetanus, diphtheria, and pertussis as a single dose in individuals 10 through 64 years of age.

4. Aetna considers Adacel (Sanofi Pasteur, Inc.), a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap), a medically necessary preventive service for active booster immunization against tetanus, diphtheria, and pertussis as a single dose in individuals 11 through 64 years of age.  Adacel may be used as an alternative to tetanus and diphtheria toxoids (Td) booster immunization for individuals in this age group.

5. Aetna considers the Tdap vaccine a medically necessary preventive service for immunization against tetanus, diphtheria, and pertussis as a single dose in all individuals 65 years of age and older and in pregnant women regardless of prior vaccination history, or in women immediately postpartum if not administered during pregnancy. Aetna considers the Tdap vaccine a medically necessary preventive service for immunization against tetanus, diptheria, and pertussis as a single dose in children 7 through 10 years of age with incomplete or unknown pertussis vaccine history.

6. Aetna considers immunization with DTaP, DTP, tetanus toxoid (TT), or Td medically necessary for treatment of contaminated wounds.

7. Aetna considers preservative-free tetanus and diphtheria toxoids (Td) (DECAVAC, Sanofi Pasteur, Inc.) an acceptable alternative to standard Td for medically necessary indications.

Background

The routine diphtheria, tetanus, and pertussis vaccination schedule for children aged less than 7 years comprises five doses of vaccine containing diphtheria, tetanus, and pertussis antigens. Three (primary) doses should be administered during the first year of life, generally at ages 2, 4, and 6 months. To maintain adequate immunity during preschool years, U.S. Advisory Committee on Immunization Practices (ACIP) recommends the fourth (first booster) dose for children aged 15 to 18 months.  ACIP recommends the fifth (second booster) dose for children aged 4-6 years to confer continued protection against disease during the early years of schooling. 

Fewer side effects have been reported with the diphtheria-tetanus-acellular pertussis (DTaP) vaccines than with diphtheria-tetanus-whole-cell pertussis vaccines (DTP), thus DTaP vaccines are recommended by ACIP for all five doses in the vaccination schedule.

In March, 2006, the Center for Disease Control and Prevention's ACIP provided provisional recommendations for the use of DTaP vaccine for adolescents (Broder, et al., 2006; AAP, 2006):

• Adolescents aged 11 to 18 years should receive a single dose of Tdap instead of tetanus and diphtheria toxoids vaccine for booster immunization against tetanus, diphtheria, and pertussis if they have completed the recommended childhood diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP)/diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) vaccination series and have not received Td or Tdap.
• Those adolescents aged 11 to 18 years who received Td, but not Tdap, should receive a single dose of Tdap to confer protection against pertussis, provided they have completed the recommended childhood DTP/DTaP vaccination series. Vaccine providers should administer Tdap and tetravalent meningococcal conjugate vaccine to adolescents aged 11 to 18 years during the same visit, assuming that both vaccines are indicated and available.

The ACIP also provided provisional recommendations for the use of the Tdap vaccine for adults.  The following provisional recommendations for a single dose of Tdap apply to adults 19 years of age and older who have not previously received Tdap (Broder, et al., 2006; AAP, 2006, ACIP, 2011):

• Adults should receive a single dose of Tdap to replace a single dose of Td for booster immunization against tetanus, diphtheria, and pertussis.
• Adults who have or who anticipate having close contact with an infant less than 12 months of age (e.g., parents, grandparents, childcare providers, and healthcare workers) should receive a single dose of Tdap.
• Health-care personnel who work in hospitals or ambulatory care settings and have direct patient contact should receive a single dose of Tdap as soon as feasible if they have not previously received Tdap.
• Tdap may be given regardless of interval since receipt of the last dose of tetanus or diphtheria toxoid-containing vaccine to protect against pertussis.

In January, 2011, the American Academy of Pediatrics Committee on Infectious Diseases and the ACIP provided the following recommendations for the use of Tdap vaccine in children and adults:

• Removal of a minimum interval between receipt of a tetanus or diphtheria toxoid containing vaccine and Tdap when Tdap is otherwise indicated.
• Administration of a single dose of Tdap to children 7 through 10 years of age with incomplete or unknown pertussis vaccine history.
• Administration of a single dose of Tdap to individuals 65 years of age or older who have or anticipate having close contact with an infant younger than 12 months of age (e.g., grandparents, child care providers, health care workers).
• Administration of a single dose of Tdap in place of Td to any individual 65 years of age or older who has not previously received Tdap.

The ACIP Pertussis Vaccine Working Group (2010) recommended pertussis protection for individuals 65 years of age and older who have or who anticipate having close contact with an infant age less than12 months of age (e.g., grandparents, child care providers, health care workers).  Neither of the two Tdap vaccines approved for use in the U.S. is licensed for adults 65 years of age and older, but research indicates that the vaccines are safe for individuals in this age group and would help reduce transmission of pertussis to infants. Both manufacturers are pursuing licensure with the FDA for this age group.

Four vaccines containing DTaP are licensed for use as the complete five-dose series in the United States: ACEL-IMUNE^® (Lederle Laboratories), Tripedia^® (Sanofi Pasteur, Inc.), Infanrix^® (GlaxoSmithKline), and DAPTACEL^® (Sanofi Pasteur, Inc.).  Certiva^TM  (Abbott Laboratories) and Pentacel^® (Sanofi Pasteur, Inc.), two other DTaP licensed vaccines, are approved for use for the first four doses of the five-dose series. The dose of all six vaccines - ACEL-IMUNE, Tripedia, Infanrix, DAPTACEL, Certiva, and Pentacel - is 0.5 ml, administered intramuscularly. As of Spring 2011, Tripedia will no longer be manufactured.

According to established guidelines, diphtheria, tetanus, and whole-cell pertussis combined with Haemophilus influenzae type b (Hib) vaccine (diphtheria, tetanus, and pertussis-Haemophilus influenzae type b vaccine) (TriHIBit) is an acceptable alternative to diphtheria, tetanus and acellular pertussis and Haemophilus influenzae type b vaccine administered at separate sites as boosters following any Hib vaccine.  However, according to the ACIP, this DTaP/Hib combination products should not be used for the primary immunization in infants at 2, 4, or 6 months of age.

According to established guidelines, for the first three doses of DTaP, a hepatitis B – inactivated polio - DTaP combination vaccine (Pediarix) is an acceptable alternative to DTaP, hepatitis B and inactivated polio vaccines administered at separate sites.

For an unimmunized person aged 7 years or older, ACIP recommends that tetanus and adult-strength diphtheria toxoids (Td) be administered with a subsequent dose 1-2 months later and a third dose 6-12 months after the second dose. 

Secondary prevention of tetanus is accomplished after an acute injury through appropriate wound cleansing and debridement and the administration of Td and human tetanus immune globulin (TIG), when indicated.   ACIP recommends that Td or DPT be administered intramuscularly to patients with tetanus-prone wounds (i.e., those older than 6 hours, deep (greater than 1 cm), grossly contaminated, exposed to saliva or feces, stellate, ischemic or infected (including abscesses), as well as avulsions, punctures, or crush injuries) if they are younger than 7 years and if it has been more than 5 years since their last dose of tetanus.   ACIP also recommends that TIG be administered if patients previously have received fewer than 3 doses of tetanus toxoid and for patients aged 60 years or older. In adults without tetanus-prone wounds, ACIP recommends that Td be administered to patients who previously have received fewer than 3 doses of tetanus toxoid or if it has been more than 10 years since their last dose.

DECAVAC (Sanofi Pasteur, Inc.) is a preservative free formulation of tetanus and diphtheria toxoids (Td).  It has been approved by the U.S. Food and Drug Administration (FDA) for active immunization of persons 7 years of age or older for prevention of tetanus and diphtheria.  DECAVAC is supplied as preservative-free prefilled syringes, and according to the manufacturer, contains only trace amounts of thimerosal (mercury derivative) from the manufacturing process. 

Boostrix (Tdap) (GlaxoSmithKline) is a combination tetanus toxoid (T), reduced diphtheria toxoid (d) and acellular pertussis vaccine (ap), and has been approved by the FDA as a booster immunization against pertussis in combination with tetanus and diphtheria for individuals 10 through 64 years of age.   Pertussis is generally less severe in adolescents than in infants, but it is thought that adolescents might transmit the disease to susceptible infants and other family members (FDA, 2005).  In the last 20 years, rates of pertussis infection have been increasing in very young infants who have not received all their immunizations and in adolescents and adults (FDA, 2005).  Boostrix has the same components as DTaP vaccine for infants and young children, but in reduced quantities. Boostrix is indicated for use as a single booster dose to adolescents 10 to 18 years of age.  Clinical studies submitted for FDA approval demonstrated that the immune response to the pertussis component of Boostrix in adolescents was adequate compared to the immune response to three doses of DTaP vaccine in infants in a previous study.  The immune response to the T and d components of Boostrix was found to be comparable to standard Td vaccine.  The durability of the immune response to Boostrix is not known.

Adacel^TM (Tdap) (Sanofi Pasteur, Inc.), is a combination tetanus toxoid (T), reduced diphtheria toxoid (d) and acellular pertussis vaccine (ap), and has been approved by the FDA as a booster immunization against pertussis in combination with tetanus and diphtheria as a single dose in persons 11 through 64 years of age.  Adacel contains the same components as DAPTACEL, a DTaP vaccine indicated for infants and children manufactured by Sanofi Pasteur; however, the diphtheria toxoid and one of the pertussis components are in reduced quantities.  Clinical studies submitted for FDA approval compared the antibody responses of adolescents and adults who received it with the antibody responses of infants who had received Daptacel.  The antibody responses of the adolescents and adults who received a single dose of Adacel were at least as good as those observed in the infants following three doses of Daptacel.  For diphtheria and tetanus, the antibody responses following Adacel were comparable to those following immunization with a U.S. licensed Td vaccine.

Among adolescent recipients of Adacel, injection site pain and low grade fever were observed more frequently than among those who received Td vaccine.  Rates of adverse reactions were similar in adults receiving Adacel vaccine or receiving Td vaccine.  The durability of the immune response to Adacel is not known.

Pentacel (Sanofi Pasteur, Inc.) received FDA approval for immunization against diphtheria, tetanus, pertussis (whooping cough), poliomyelitis (polio) and Haemophilus influenzae type b (Hib).  It is the first DTaP-based combination vaccine for use in infants in the United States that includes both polio and Hib vaccine components.

The FDA approval of Pentacel was based on the results of multi-center clinical studies conducted in the United States and Canada that involved more than 5,000 children who received at least one dose of Pentacel. The safety of Pentacel was compared both to separately administered Daptacel, IPOL and ActHIB vaccines and to other single-entity vaccine formulations.  Pentacel is approved for use in children 6 weeks through 4 years of age (prior to 5 years of age).

Pentacel is approved for administration as a four - dose series at 2, 4 and 6, and 15-18 months of age.  The first dose may be given as early as six weeks of age.  Four doses of Pentacel constitute a primary immunization course against pertussis.  Three doses of Pentacel constitute a primary immunization course against diphtheria, tetanus, Haemophilis influenzae type b invasive disease, and poliomyelitis; the fourth dose constitutes a booster vaccination against diphtheria, tetanus, Haemophilis influenzae type b invasive disease, and poliomyelitis.

If a decision is made to withhold pertussis vaccine, vaccination against diphtheria, tetanus, poliomyelitis and invasive disease due to Haemophilis influenzae type b should be provided.

Children who have completed a 4 - dose series with Pentacel should receive a fifth dose of DTaP vaccine at 4-6 years of age.  Because the pertussis antigens in Daptacel vaccine are the same as those in Pentacel (although with different amounts of detoxified PT and FHA), these children should receive Daptacel as their fifth dose of DTaP.  However, data are not available to evaluate the safety of Daptacel following four previous doses of Pentacel.

KIinrix (GlaxoSmithKline) received FDA approval for active immunization against diphtheria, tetanus, pertussis, and poliomyelitis as the fifth dose in the DTaP vaccine series and the fourth dose in the IPV series in children 4 through 6 years of age whose previous DTaP vaccine doses have been with Infanrix and/or Pediarix for the first three doses and Infanrix for the fourth dose.

Clinical studies of Kinrix demonstrated that Kinrix offers similar protection to the separately administered DTaP and IPV vaccines, with a comparable safety profile. These results were confirmed in the pivotal Phase III trial of Kinrix, which was a randomized, controlled study conducted in the U.S. in which 3,156 children 4 to 6 years of age were vaccinated with Kinrix.  All children studied had previously received 4 doses of DTaP (Infanrix) and 3 doses of IPV (IPOL).  All children in the study also received the second dose of U.S.-licensed measles, mumps and rubella (MMR) vaccine (M-M-RII) at the same time.

The ACIP, American Academy of Family Physicians (AAFP) and the American Academy of Pediatrics (AAP) prefer combination vaccines because they offer a way to reduce the constraints associated with the administration of separate vaccines.  Using combination vaccines may help avoid missed opportunities to protect children through vaccination during their vulnerable early months.  Additionally, a reduction in the overall number of shots given during one office or clinic visit is preferred by many immunization providers, parents and children.  Other potential advantages of combination vaccines include reducing the cost of stocking and administering vaccines, as well as fewer office visits, which can save parents time and money.

The ACIP recommends routine administration of Tdap vaccine to postpartum women prior to hospital discharge. The vaccine may be administered regardless of whether the mother is breastfeeding.

Gall (2008) stated that the active immunization of pregnant women during pregnancy to protect them from disease and protect their neonate with passive antibodies is a biologic fact. Fortunately, many infectious diseases occur infrequently due to excellent pediatric vaccine programs. However, most adults and many physicians are unaware of the risks of not administering vaccines especially to pregnant women. Influenza vaccine (trivalent inactivated influenza vaccine) is recommended by ACIP for pregnant women in any trimester of pregnancy and TdaP vaccine is recommended by the ACIP to be given before pregnancy, during pregnancy, or in the immediate post-partum period. Only 2 % of the adult population in the United States are protected against pertussis and it is estimated that only 25 % of pregnant women receive influenza vaccine during the influenza season.

The ACIP recommends that women’s health care providers should implement a maternal Tdap vaccination program for women who have not previously received Tdap (Neale, 2011).  Health care providers should administer Tdap preferably during the third or late second trimester (after 20 weeks gestation). Alternatively, Tdap should be administered immediately postpartum. If a tetanus and diphtheria booster vaccination is indicated during pregnancy for a woman who has not previously received Tdap (such as wound management, more than 10 years since last Td), then healthcare providers should administer Tdap preferably during the third or late second trimester (after 20 weeks gestation). For pregnant women with unknown or incomplete tetanus vaccination, to ensure protection against maternal and neonatal tetanus, those who never have been vaccinated against tetanus should receive three vaccinations containing tetanus and reduced diphtheria toxoids during pregnancy. The recommended schedule is 0, 4 weeks, and 6-12 months. The ACIP recommends that Tdap should replace the first dose of Td, preferably during the third or late second trimester of pregnancy (after 20 weeks gestation). The ACIP previously recommended that Tdap be given immediately postpartum (Murphy, et al., 2008). By shifting the maternal Tdap dose from the immediate postpartum period -- which was recommended by ACIP in 2008 -- to the late stages of pregnancy (after 20 weeks gestation), protection against pertussis is provided directly to the mother and indirectly to the fetus through transplacental antibodies (Neale, 2011). Thus, when the baby is born, it will already have some protection before starting the DTaP series.

On February 22, 2012, ACIP voted to expand its recommendation for Tdap vaccine.   Cognizant of the fact that among seniors the disease may be underdiagnosed due to absent of the characteristic "whoop", and taking into consideration the rebound that pertussis has made in the United States during the last 30 years, ACIP is now recommending routine administration to individuals aged 65 and older.. It should also be noted that the number of reported cases peaked in 2010 at 27,550, with roughly 700 involving seniors, according to the CDC (Lowes, 2012).

In October, 2012, ACIP updated their recommendations to state that providers of prenatal care implement a Tdap immunization program for all pregnant women.  The recommendation specifies that health-care personnel should administer a dose of Tdap during each pregnancy irrespective of the patient’s prior history of receiving Tdap and that if not administered during pregnancy, Tdap should be administered immediately postpartum (CDC, 2012).

The ACIP recommendation noted that by receiving Tdap during pregnancy, maternal pertussis antibodies transfer to the newborn, likely providing protection against pertussis in early life, before the baby starts getting DTaP vaccines and that Tdap will also protect the mother at time of delivery, making her less likely to transmit pertussis to her infant. If not vaccinated during pregnancy, Tdap should be given immediately postpartum, before leaving the hospital or birthing center. ACIP further report that the U.S. remains on track to have the most reported pertussis cases since 1959, with more than 32,000 cases already reported along with 16 deaths, the majority of which are in infants. ACIP further delineated special circumstances for vaccination. First, "in pregnant women due for tetanus booster, if a tetanus and diphtheria booster vaccination is indicated during pregnancy (i.e., >10 years since previous Td), then Tdap should be administered. Optimal timing is between 27 and 36 weeks gestation to maximize the maternal antibody response and passive antibody transfer to the infant...As part of standard wound management to prevent tetanus, a tetanus toxoid–containing vaccine might be recommended for wound management in a pregnant woman if ≥5 years have elapsed since the previous Td booster. If a Td booster is recommended for a pregnant woman, health-care providers should administer Tdap...To ensure protection against maternal and neonatal tetanus, pregnant women who never have been vaccinated against tetanus should receive three vaccinations containing tetanus and reduced diphtheria toxoids. The recommended schedule is 0, 4 weeks, and 6 through 12 months. Tdap should replace 1 dose of Td, preferably between 27 and 36 weeks gestation to maximize the maternal antibody response and passive antibody transfer to the infant" (CDC, 2012).

Terranella et al (2013) stated that infants less than 2 months of age are at highest risk of pertussis morbidity and mortality.  Until recently, the ACIP recommended protecting young infants by "cocooning" or vaccination of post-partum mothers and other close contacts with tetanus toxoid, reduced Tdap booster vaccine.  The ACIP recommends pregnancy vaccination as a preferred and safe alternative to post-partum vaccination.  The ACIP cocooning recommendation has not changed.  These investigators used a cohort model reflecting U.S. 2009 births and the diphtheria-tetanus-acellular pertussis schedule to simulate a decision and cost-effectiveness analysis of Tdap vaccination during pregnancy compared with post-partum vaccination with or without vaccination of other close contacts (i.e., cocooning).  They analyzed infant pertussis cases, hospitalizations, and deaths, as well as direct disease, indirect, and public health costs for infants in the 1st year of life.  All costs were updated to 2011 U.S. dollars.  Pregnancy vaccination could reduce annual infant pertussis incidence by more than post-partum vaccination, reducing cases by 33 % versus 20 %, hospitalizations by 38 % versus 19 %, and deaths by 49 % versus 16 %.  Additional cocooning doses in a father and 1 grandparent could avert an additional 16 % of cases but at higher cost.  The cost per quality-adjusted life-year saved for pregnancy vaccination was substantially less than post-partum vaccination ($414,523 versus $1,172,825).  The authors concluded that Tdap vaccination during pregnancy could avert more infant cases and deaths at lower cost than post-partum vaccination, even when post-partum vaccination is combined with additional cocooning doses.  Pregnancy dose vaccination is the preferred alternative to post-partum vaccination for preventing infant pertussis.

Healy et al (2013) noted that Tdap recommendations assume that pertussis-specific antibodies in women immunized pre-conception, during, or after previous pregnancies persist at sufficient levels to protect newborn infants.  These investigators measured pertussis-specific immunoglobulin G (IgG) by IgG-specific enzyme-linked immunosorbent assay (ELISA) in maternal-umbilical cord serum pairs where mothers received Tdap during the prior 2 years.  Geometric mean concentrations (GMCs) of pertussis antibodies and cord-maternal GMC ratios were calculated.  A total of 105 mothers (mean age of 25.3 years [range of 15.3 to 38.4 years]; mean gestation of 39 weeks [range of 37 to 43 weeks]) immunized with Tdap vaccine a mean of 13.7 months (range of 2.3 to 23.9 months) previously were included; 72 (69 %) had received Tdap post-partum, 31 at a routine healthcare visit and 2 as contacts of another newborn.  There was no difference in GMCs for pertussis-specific IgG in maternal delivery or infant cord sera for women immunized before (n = 86) or during (n = 19) early pregnancy.  Placental transport of antibodies was 121 % to 186 % from mothers immunized before and during pregnancy, respectively.  Estimated GMC of IgG to pertussis toxin was less than 5 ELISA units (EU)/ml at infant age 2 months (start of infant immunization series).  More infants of mothers immunized during pregnancy had pertussis toxin levels estimated to be higher than the lower limit of quantitation of the assay (4 EU/ml) through age 2 months (52 % versus 38 %; p = 0.34).  The authors concluded that infants of mothers immunized pre-conception or in early pregnancy have insufficient pertussis-specific antibodies to protect against infection.  Maternal immunization during the 3rd trimester, immunization of other infant contacts, and re-immunization during subsequent pregnancies may be necessary.

In a retrospective cohort study, Shakib et al (2013) evaluated pregnancy and birth outcomes in infants born to women who did or did not receive Tdap vaccine during pregnancy.  Pregnant women 12 to 45 years of age who received Tdap at Intermountain Healthcare facilities and their infants were identified and compared with mother-infant pairs without documented Tdap from May 2005 through August 2009.  Primary measures included pregnancy outcomes and infant health outcomes at birth through 12 months.  From 162,448 pregnancies these investigators identified 138 women (0.08 %) with documented Tdap administration during pregnancy (cases); 552 pregnant women without documented Tdap were randomly selected as controls.  Of 138 immunized women, 63 % received Tdap in the 1st trimester and 37 % after.  Tdap was given most commonly as wound prophylaxis.  The incidence of spontaneous or elective abortion was no greater in Tdap cases than in controls.  There were no significant differences in preterm delivery, gestational age, or birth weight between groups.  One or more congenital anomaly was identified in 3.7 % (95 % confidence interval [CI]: 1.2 % to 8.5 %) of case infants and 4.4 % (95 % CI: 2.7 % to 6.5 %) of control infants (p = 0.749).  In infants born to women receiving Tdap during pregnancy, 3.6 % (0.8 % to 10.2 %) had International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses consistent with complex chronic conditions within 12 months compared with 10.4 % (95 % CI: 7.2 % to 14.4 %) of infants of controls (p = 0.054).  The authors concluded that documented Tdap administration during pregnancy was uncommon and occurred most often in the 1st trimester as prophylaxis following trauma.  No increase in adverse outcomes was identified in infants born to women receiving Tdap compared with infants of controls.

In a phase I/II, randomized, double-blind, placebo-controlled, clinical trial, Munoz et al (2014) evaluated the safety and immunogenicity of Tdap immunization during pregnancy and its effect on infant responses to DTaP vaccine.  A total of 48 pregnant women aged 18 to 45 years received Tdap (n = 33) or placebo (n = 15) at 30 to 32 weeks' gestation, with cross-over immunization post-partum.  Tdap vaccination was carried out at 30 to 32 weeks' gestation or post-partum.  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' post-partum, and in infants at birth, at 2 months, and after the 3rd and 4th doses of DTaP.  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 % to 91.0 %]) and 12 (80 % [95 % CI: 51.9 % to 95.7 %]) pregnant and post-partum women, respectively (p > 0.99).  Systemic symptoms were reported in 12 (36.4 % [95 % CI: 20.4 % to 54.9 %]) and 11 (73.3 % [95 % CI: 44.9 % to 92.2 %]) pregnant and post-partum women, respectively (p = 0.03).  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 versus post-partum (e.g., pertussis toxin antibodies: 51.0 EU/ml [95 % CI: 37.1 to 70.1] and 9.1 EU/ml [95 % CI: 4.6 to 17.8], respectively; p < 0.001) and in their infants at birth (68.8 EU/ml [95 % CI: 52.1 to 90.8] and 14.0 EU/ml [95 % CI: 7.3 to 26.9], respectively; p < 0.001) and at age 2 months (20.6 EU/ml [95 % CI: 14.4 to 29.6] and 5.3 EU/ml [95 % CI: 3.0 to 9.4], respectively; p < 0.001).  Antibody responses in infants born to women receiving Tdap during pregnancy were not different following the 4th dose of DTaP.  The authors concluded that 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.

The above policy is based on the following references: