Tdap vaccination during pregnancy

A 32-year-old G2P1001 is seen for her first prenatal visit at 7 weeks’ gestation. This patient is certain she had a tetanus booster 8 years ago, following an injury; she also believes she had a whooping cough vaccine after the delivery of her first child 3 years ago. She is uncertain about being vaccinated again, but would like information about the evidence supporting Tdap vaccination during pregnancy.

Q: Why is pertussis (whooping cough) of particular concern in the context of pregnancy?

A: Pertussis, caused by the bacterium Bordetella pertussis, usually starts with cold-like symptoms, with mild cough or fever. After 1 to 2 weeks, severe coughing can begin. Unlike the common cold, pertussis is typically associated with paroxysmal coughing that may continue for weeks. Diagnosis is through evaluation of symptoms, physical examination and, ultimately, by obtaining a nasopharyngeal swab for isolation of B. pertussis. In 2012, more than 48,000 cases of pertussis were reported in the United States and worldwide; there are 30 million–50 million cases every year.

The potential complications in infants with pertussis include apnea (67%), pneumonia (23%), encephalopathy (0.4%), and death (1%), secondary to refractory pulmonary hypertension. The majority of pertussis cases reported in the United States, specifically hospitalizations and deaths related to this infection, occur in infants aged <3 months,¹ who are below the age limit for pertussis vaccination under current national guidelines (the first dose of the childhood vaccine series is given at age 2 months).

Because vaccination against pertussis is not an option for infants younger than age 2 months, other strategies have evolved to prevent pertussis in them. Identification of newborns begins with informing pregnant women that their newborns will be vulnerable to pertussis, and discussing strategies to prevent what could be a catastrophic infection. Since 2004, an average annual rate of approximately 3000 infant pertussis cases per year, with more than 19 deaths per year, has been reported to the National Notifiable Diseases Surveillance System, with significant outbreaks initially reported in California and Washington State.²

Adapted from National Center for Health Statistics. Health, United States, 2012: With Special Feature on Emergency Care. Hyattsville, MD. 2013.

Q: What strategies have evolved to protect vulnerable newborns against pertussis?

A: Vaccination against pertussis in family members and other caregivers of newborns is one strategy to provide protection in this vulnerable period. This approach derives from studies demonstrating that the majority of newborns who contract pertussis acquire the disease from immediate family members, including their mothers.³ This strategy, known as “cocooning,” was initiated in 2006 by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), and consisted of a recommendation to administer the combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) to all women in the immediate postpartum period and all other unvaccinated family members and caregivers.⁴ Tdap is an inactivated vaccine: The pertussis antigen component is purified from the B. pertussis bacterium and then inactivated. There are no live bacteria in the vaccine, and it cannot cause pertussis in a vaccinated child or adult.

This practice, however, has been difficult to implement widely. Although moderate success was achieved in vaccinating postpartum mothers, programs have reported limited success in vaccinating fathers or other family members.⁵ More importantly, cocooning strategies leave infants entirely dependent for protection upon the willingness of adults around them to be vaccinated; they have no endogenous protective antibodies against pertussis until they begin their own vaccine series at age 2 months.

Q: Why is vaccination of pregnant women against pertussis now a primary strategy against infection in newborns? Is the vaccine safe during pregnancy?

A: Concerns about the limited effectiveness of a cocooning strategy for pertussis vaccination led to consideration of maternal immunization against pertussis during pregnancy. This approach allows transplacental passage of maternal antibodies to the fetus, providing neonatal coverage until the infancy vaccine series against pertussis can begin. Studies have provided evidence supporting the presence of efficient transplacental transfer of pertussis antibodies.^6,7 In addition, cord blood from newborns whose mothers received Tdap during pregnancy had higher concentrations of pertussis antibodies compared to samples from infants born to unvaccinated mothers.^6,7 The half-life of maternally transferred pertussis antibodies is reported to be approximately 6 weeks.⁸ While the most effective level of maternal antipertussis antibodies in preventing infant pertussis has not yet been definitively established, it is likely that these specific antibodies confer protection and modify the severity of pertussis in infants.⁹ Such an effect would be directly comparable to the demonstrated protective effect of maternally derived anti-influenza antibodies in preventing influenza-specific illness in infants born to women vaccinated during pregnancy.¹⁰

Because boosted pertussis antibody levels appear to peak after several weeks, followed by a decline over several months,^11,12 ACIP concluded in its 2011 recommendations that unvaccinated pregnant women should preferably receive Tdap in the third or late second trimesters to optimize coverage both for them and for their newborns (subsequently revised in 2013 to recommend vaccination to all women).² ACIP also stated that if Tdap vaccination could not be accomplished during pregnancy, postpartum vaccination was still appropriate-although for the reasons outlined above, suboptimal-for newborn protection overall.

Data regarding the safety of administering Tdap to pregnant women are available from both vaccine registry information and from small studies.^2,7,13 ACIP concluded that available data do not suggest any higher frequency or specific pattern of adverse events in pregnant women attributable to the vaccine. Both tetanus and diphtheria toxoids (Td) and tetanus toxoid vaccines have been used extensively worldwide in pregnant women to prevent neonatal tetanus, with no increase in teratogenic effects above background population risks.^14,15 From a safety perspective, ACIP concluded, however, that administration of Tdap after 20 weeks’ gestation would minimize the risk of any low-frequency adverse events and minimize any spurious and potentially confrontational associations that could be construed as causative with administration earlier in pregnancy.² There is no evidence, either demonstrated or theoretical, of adverse fetal outcomes from vaccinating pregnant women using inactivated antigenic agents.

Q: How and why have pertussis vaccine recommendations for pregnancy changed?

A: The most recent ACIP/CDC recommendations were issued in February 2013,¹⁶ and were developed after careful consideration of newer data related to efficacy and durability of the current pertussis (Tdap) vaccine. In reviewing nationally reported data for pertussis cases in 2012, the CDC was concerned that infection and death rates had surpassed the most recent peak year of 2010: For 2012, 41,880 pertussis cases and 14 deaths in infants aged <12 months were reported (Figure 1).¹⁶ In addition, since the 2011 ACIP vaccine recommendations were issued, vaccination rates with Tdap among pregnant women have been low. One survey of pregnant women from August 2011 to April 2012 estimated that only 2.6% of women had received Tdap during their most recent pregnancy.¹⁷ Furthermore, antipertussis antibodies available for passive transfer have been shown to be even shorter-lived than previously thought, with substantial decay of levels after 1 year.¹⁸ Therefore, newer data strongly suggest that Tdap vaccination in one pregnancy would not provide high-enough antibody levels to persist and protect newborns delivered in subsequent pregnancies,¹⁹ although maternal cellular immunity would be expected to be more durable.

As a result of these concerns and the Committee’s ongoing review of emerging peer-reviewed and reported data regarding Tdap vaccination efficacy related to pregnancy, revised recommendations for use of Tdap in pregnant women were released by the ACIP and CDC in February 2013. The strongly preferred approach of administration of Tdap during, rather than after, a pregnancy was maintained in the recommendations. It is now recommended, however, that a woman receive Tdap during each of her pregnancies, to maximize passive immunity and protection for all of her newborns. The new recommendations further narrow the optimal timing of Tdap administration during pregnancy. Vaccination is suggested during the third trimester, ideally close to 30 weeks’ gestation (preferably during weeks 27–36), when active transport of IgG antibodies becomes most efficient.²⁰ Vaccination later in the third trimester may not allow the minimum of 2 weeks that is required to mount a maximal antibody response to the vaccine antigens.²¹ With this window of vaccine timing, the highest achievable concentration of maternal antibodies can be transferred to the fetus before birth. These newly revised recommendations have been endorsed by the American College of Obstetricians and Gynecologists in a recently published Committee Opinion.²²

Q: Is it safe to give repeated doses of Tdap?

A: Published data on administration of 2 doses of Tdap and on multiple doses of a tetanus-toxoid-containing vaccine show that receipt of a second dose of Tdap at a 5- or 10-year interval in healthy nonpregnant adolescents and adults was well tolerated; injection-site pain was the most commonly reported adverse event.^23,24 Although 94% of subjects reported at least one injection-site event such as erythema, swelling, and pain, these rates were not significantly higher after a second dose compared to the first vaccine dose, and only 4%–5% of recipients reported grade 3/3 pain.

A theoretical risk exists for more severe local reactions in pregnant women who receive Tdap vaccine during multiple closely spaced pregnancies.¹⁶ These can include the Arthus reaction, a type III hypersensitivity reaction that manifests as local vasculitis due to deposition of IgG-based immune complexes in dermal blood vessels. The risk of this adverse effect may be increased with higher levels of preexisting antibody.²⁵ Because most of the data evaluating this risk are historical and relate to vaccines with much higher levels of tetanus toxoid than in current preparations, ²⁶ the already-low risk of these types of adverse effects is felt to be significantly lower today than previously reported.

Q: Are there special situations to be considered for using Tdap during pregnancy?

1.     Pregnant women due for a tetanus booster. If Td booster vaccination would be considered during pregnancy, Tdap should be used, optimally at 27–36 weeks’ gestation.

2.     Wound management during pregnancy. If a tetanus-toxoid-containing vaccine is being given for wound management during pregnancy (if ≥5 years since previous Td booster), Tdap should be given.

Summary

1.     Tdap vaccination is both safe and recommended for all pregnant women during every pregnancy, regardless of the timing of their last Tdap immunization.

2.     Pregnant women should ideally receive the Tdap vaccine at 27–36 weeks’ gestation.

Dr. Silverman is an associate at the Center for Fetal Medicine and Women’s Ultrasound in Los Angeles and is a Clinical Professor in the Department of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California, Los Angeles.

This opinion was developed by the Publications Committee of the Society for Maternal-Fetal Medicine with the assistance of Neil Silverman, MD, and was approved by the Executive Committee of the Society. Neither Dr. Silverman nor any member of the Publications Committee (see the list of 2014 members at www.smfm.org) has a conflict of interest to disclose with regard to the content of this article.

Disclaimer: The practice of medicine continues to evolve and individual circumstances will vary. Clinical practice also may vary. This opinion reflects information available at the time of acceptance for publication and is not designed nor intended to establish an exclusive standard of perinatal care. This publication is not expected to reflect the opinions of all members of the Society for Maternal-Fetal Medicine.

www.Contemporaryobgyn.net/Tdap-pregnancy.pdf

References

1. The Centers for Disease Control and Prevention. Pertussis (Whooping Cough). www.cdc.gov/pertussis/about/index.html. Accessed March 13, 2014.

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3. The Centers for Disease Control and Prevention. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) in pregnant women and persons who have or anticipate having close contact with an infant aged < 12 months-Advisory Committee on Immunization Practices, 2011. MMWR. 2011;60:1424–1426.

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