Two tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines were licensed in 2005 for use in adults and adolescents in the United States: Adacel (sanofi pasteur) and Boostrix (GlaxoSmith-Kline). Both vaccines are licensed for single-dose use as protection against pertussis and to replace the next dose of tetanus and diphtheria toxoids (Td) vaccine. However, the available evidence does not address the safety of Tdap in pregnant women, and it does not indicate whether Tdapinduced transplacental maternal antibodies provide newborns with early protection against pertussis or interfere with their immune response to routine vaccinations. Until more evidence is available, the Advisory Committee on Immunization Practices (ACIP) for the Centers for Disease Control and Prevention recommends that physicians weigh the theoretic risks and benefits before administering Tdap to pregnant women.

Pertussis

Pertussis is highly infectious, with rates of up to 90 percent in exposed nonimmune household contacts. Untreated patients remain infectious for six weeks or longer. Parents with pertussis are the source of Bordetella pertussis infection in at least 25 percent of cases in newborns. The risk of complications and death is highest in infants six months and younger, and remains elevated until one or two doses of diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine have been given.

Vaccination with Tdap may prevent transmission of B. pertussis to infants. Ideally, women of childbearing age should receive Tdap before conception. It has not been proven safe for use in pregnant women and is not recommended. If a pregnant patient has not been vaccinated, she will receive some protection against pertussis by ensuring that children in her household are up to date with recommended doses of DTaP, and that adults and adolescents in the household have received a dose of Tdap. Physicians should monitor these patients for exposure to pertussis and other respiratory illnesses, and antimicrobials can be given for postexposure prophylaxis, if necessary.

A macrolide antibiotic (erythromycin, azithromycin [Zithromax], or clarithromycin [Biaxin]) is preferred for postexposure prophylaxis and treatment of pertussis. Antimicrobials generally do not affect the severity or course of illness after paroxysmal cough has begun, but they can eliminate B. pertussis and stop transmission to newborns. A macrolide should be given to women with pertussis that is acquired late in pregnancy, to their household contacts, and to their infants. Early recognition of pertussis is necessary to ensure the effectiveness of this approach.

Infants younger than one month who receive erythromycin are at increased risk of infantile hypertrophic pyloric stenosis. For this reason, and because azithromycin is associated with fewer adverse effects than erythromycin, azithromycin is the preferred antimicrobial for prophylaxis of newborns exposed to pertussis.

Tetanus

Obstetric tetanus is defined as tetanus during pregnancy or within six weeks after termination of a pregnancy. It occurs after contamination of wounds or abrasions, or after nonsterile deliveries or abortions. Obstetric tetanus has the highest mortality rate when the incubation period is short and respiratory complications are present. Cases can be complicated by gram-negative sepsis.

Neonatal tetanus is associated with contamination of the umbilical stump. Onset occurs during the first month of life, and symptoms (e.g., increasing irritability, difficulty feeding) commonly begin at three to 14 days of life.

Ensuring maternal and neonatal tetanus protection as part of prenatal care is a priority for women who are due for a booster dose of Td. For women who did not receive a dose of Tdap before pregnancy, administering Td during pregnancy and Tdap in the postpartum period could increase the risk or severity of an adverse reaction. In these women, deferring the Td booster during pregnancy and substituting Tdap in the immediate postpartum period may be considered.

Prevention of obstetric and neonatal tetanus depends on antitoxin being present at delivery. Administration of two doses of tetanus toxoid at least four to six weeks before delivery stimulates antitoxin that protects the mother and crosses the placenta, thereby protecting the newborn against tetanus when the risk is highest. Pregnant women who receive a booster dose of tetanus toxoid have a measurable immune response within five days, with a peak response in less than two weeks. Placental transport of antitoxin is efficient; cord blood levels generally are similar to maternal levels. After the neonatal period, infants are at little risk of tetanus until they become mobile, typically at an age when sustained protection has been induced by three doses of DTaP.

Treatment is directed at neutralizing unbound toxin via administration of human tetanus immune globulin, removing the source of infection through debridement, and the use of an antimicrobial. Control of rigidity and spasms, and of respiratory and autonomic dysfunction and their complications, requires careful and sustained attention that is best provided in intensive-care settings with subspecialty consultation.

Diphtheria

Respiratory diphtheria can occur during any trimester of pregnancy, at term, or in the postpartum period. The mortality rate of obstetric respiratory diphtheria is estimated at 50 percent without infusion of diphtheria antitoxin, even with tracheostomy or intubation. It is accompanied by fetal loss or premature birth in approximately one third of survivors. Postpartum women with respiratory diphtheria can transmit Corynebacterium diphtheriae to their newborns.

Protection against respiratory diphtheria is predominantly from immunoglobulin G antibody to diphtheria toxin induced after infection with toxin-producing C. diphtheriae or after vaccination with diphtheria toxoid. Maternal antitoxin is transferred to the fetus; trans-placental maternal antitoxin provides newborns with protection against diphtheria if the mother is immune. Consumption of breast milk does not affect the infant response to diphtheria toxoid–containing vaccines, and ingestion of colostrum from an immune mother does not increase the concentration of diphtheria antitoxin in infant sera.

Early treatment with serum diphtheria antitoxin improves survival and pregnancy outcomes, although complications may require prolonged supportive care. Antibiotics are given to limit transmission and to prevent continued production of diphtheria toxin. Because respiratory diphtheria does not always confer protection against future illness, patients should complete active immunization with diphtheria toxoid after recovery.

Vaccination

Administering Tdap during routine wellness visits to women and girls of childbearing age is the most effective strategy to ensure that women are protected against pertussis, tetanus, and diphtheria, and it minimizes any theoretic effect of vaccination on infant immune response if the woman becomes pregnant. Because Tdap contains only toxoids and purified bacterial components, women who receive Tdap do not need to wait after vaccination to become pregnant.

ACIP recommends administration of Tdap in the immediate postpartum period, before discharge from the hospital or birthing center. Pregnant women who have not received Tdap and who have indications for tetanus or diphtheria booster protection should receive Td during pregnancy. However, most women can substitute Tdap in the immediate postpartum period for Td during pregnancy if they have received past tetanus toxoid-containing vaccinations. When the history of tetanus toxoid vaccination is uncertain, physicians can determine the concentration of tetanus antitoxin to ensure protective levels (at least 1.0 IU per mL, as determined by enzyme-linked immunosorbent assay).

Because diphtheria is rare in the United States, serologic screening for diphtheria antitoxin typically is not necessary. However, if a pregnant woman plans to travel to an area in which diphtheria is endemic, protection can be improved by administration of a booster dose of Td during pregnancy or a dose of Tdap in the postpartum period.