Neglected Research and the Administration of Tdap During Pregnancy

On October 24 of last year (2012), the ACIP voted 14 to 1 in the recommendation of administering a pertussis booster (Adacel or Boostrix) during every pregnancy regardless of vaccination history, preferably after 20 weeks gestation.[*][*][*]
This over ruled the earlier suggestion of the administration of just one booster during the first pregnancy because antibody levels were found to wane substantially during the first year after vaccination. Hence, leading the ACIP to conclude a single dose of Tdap at one pregnancy would be insufficient to provide protection for subsequent pregnancies.[*]
In the post below, I will provide published literature as to why this particular approach is not well-founded on actual science or research. I will also provide some information on the relevant risks of pertussis during infancy, the safety concerns of administering Tdap during pregnancy and the modification of pertussis epidemiology due to the current vaccination program.
Problematic Ambitions in Administering Tdap During Pregnancy
The underlining goal in this particular vaccination strategy (according to the CDC) is twofold:[*]
Mainly (1) “reduce the burden of pertussis in infants by providing some protection until they are old enough to be vaccinated themselves” [*]
Secondly (2) “protect the mother from pertussis around the time of delivery, making her less likely to become infected and transmit pertussis to her infant.” [*]
Let us address these individually with published data…
Reducing the burden of pertussis in infants
The goal of reducing pertussis infection within the infant population via vaccination is ambitious and nothing new (Clinical Infectious Diseases 1990).[*][*][*] 
Decades of research examining newborn vaccination against pertussis has been amassed; none of which has been enough to implement a national recommendation from the ACIP…until now, with a twist.
The CDC now feels strongly that this particular new approach, vaccinating women late term during pregnancy, will provide the protection they are hoping for.
Unfortunately, relying on transplacental antibodies to provide protection against pertussis in infants is not based on published evidence.
In fact, the very board that recommended Tdap during pregnancy (ACIP) states the effectiveness of maternal anti-pertussis antibodies in preventing infant pertussis is not yet known (ACIP 2011, CDC 2011).[*][*]
This is one of two major concerns the ACIP voiced, acknowledging the complete “lack of evidence evaluating that transplacental maternal antibodies induced by Tdap in the protection of infants against pertussis” (Journal of Perinatology 2010).[*]
Even if data reflects an increase in infant antibodies to pertussis via maternal vaccination, because there is currently no correlate of protection in pertussis infection, it is uncertain whether this increase could be considered clinically protective (The Pediatric Infectious Disease Journal 2011).[*]
This is significant since the transfer of antibodies against pertussis to the offspring is influenced by various factors and determining a benchmark for correlation would aid in establishing if any protection is conferred. (Current known factors that influence transplacental antibodies: the age of women at delivery, mothers’ vaccination history, mothers’ immune response and ability to generate IgG immunoglobulins).[*- Tdap in risk groups 2012]
In fact, it is becoming more evident that the (aP) pertussis vaccines do not yield any correlation between antibody levels and protection against pertussis.[* source 17]
Currently, I am aware of two completed published studies (as mentioned by the CDC in 2011) providing data that evaluates antibody levels in newborns whose mothers received tdap during pregnancy, neither produce confirmation of protection against infection.[*][*][*]
What is certain is the evident “need for larger studies with longer follow-up to help understand the immunologic responses in pregnant women and the consequences on neonatal immunity” (Clinical Infectious Diseases 2013).[*]
Interference with Infant Immune Response to Primary DTaP Vaccination
(also known as blunting)
Data to consider, several studies have suggested that maternal pertussis antibodies can inhibit active pertussis-specific antibody production after administration of DTaP vaccine to infants of mothers vaccinated with Tdap during pregnancy, referred to as blunting (CDC 2011).[*] 
In fact, the ACIP states that this phenomenon known as blunting could result in an increase in pertussis susceptibility to children under 12 months (Journal of Perinatology 2010).[*] 
The ACIP assumes that maternal pertussis antibodies might reduce an infant's risk for  infection in the first few months of life, but neglects to apply actual data illustrating an increase in risk for disease after receipt of primary DTaP doses (CDC 2011).[*]
Instead, the ACIP applies data used in naturally acquired maternal pertussis-specific antibodies, stating that one study completed shows little or no interference between naturally acquired transplacental antibodies and the DTaP series (Clinical Infectious Diseases 2012).[*] 
No published literature is available yet for review examining vaccine-induced transplacental antibodies.
Based on data that has been completed, blunting does occur, we just don’t know to what degree and what the effects may be.
The theorized benefit of vaccinating pregnant mothers is a decline in risk for disease and death in infants aged <3 months, but the trade-off is a potential increase in the occurrence of pertussis in older infants (CDC 2011).[*]
According to the ACIP, the potential benefit of protection from maternal antibodies in newborns outweigh the potential risk for shifting disease burden to later in infancy (CDC 2011, The Pediatric Infectious Disease Journal 2011).[*][*]
Worth noting, two clinical trials are currently underway (one in Canada, the other in the USA) to evaluate the assess the immune response of infants receiving DTaP immunization at ages 2, 4, and 6 months whose mothers received Tdap during the third trimester of pregnancy (Vaccine 2012).[*][*- Tdap in risk groups 2012]
It is unfortunate (and, in my opinion, inappropriate) that this data was not completed prior to recommendation .
Evidence for Safety
Although in prelicensure evaluations, the safety of administering a booster dose of Tdap to pregnant women was not studied. The ACIP Pertussis Vaccines Work Group declares safety and expresses it as well established (CDC 2011).[*]

What does ‘well established’ mean exactly….
The data that is used to established safety which resulted in the ACIP’s recommendation was collected from:

Vaccine Adverse Event Reporting System (VAERS)

Sanofi Pasteur pregnancy registry

GlaxoSmithKline pregnancy registry
The ACIP asserts that no data collected suggests any elevated frequency or unusual patterns of adverse events in pregnant women who received Tdap (CDC 2011, Can Fam Physician. 2013).[*][*]
It is worth noting, all three are passive surveillance programs which have several limitations which include: unverified reports, underreporting, inconsistent data quality and absence of an unvaccinated control group (Drug Safety 2008).[*] 
Data Evaluated From VAERS:

-Only 130 reports met safety research criteria (AJOG 2012).   [*] 

-The data was collected before Tdap was routinely recommended in pregnancy (AJOG 2012). [*]

-Only 3% of women were administered the vaccine in the recommended third trimester (77% in the first trimester, 19% second trimester, 3% third trimester) (AJOG 2012). [*] 

The most frequent pregnancy-specific adverse event was spontaneous abortion occurring in 16% of reports (AJOG 2012). [*] 
GlaxoSmithKline Registry:

From GSK pregnancy registry: “The safety of Boostrix (tdap) during pregnancy has not been established, and no adequate human studies have been performed. [*]

None of these products, except RETROVIR® (zidovudine, AZT) after the first trimester, is approved for use during pregnancy.”[*] 
Sanofi Pasteur Registry:

From the Sanofi Pasteur pregnancy registry: “This is a company-run, passive, pregnancy surveillance system designed to collect and analyze the outcome of vaccination.” [*]

“There are no adequate and well-controlled studies of Adacel in pregnant women and data are limited. Sanofi Pasteur does not recommend the use of Adacel vaccine in any manner other than that described in the package insert.”[*][*][*]
From a safety perspective, ACIP adds that administration of Tdap after 20 weeks' gestation is preferred in the hope to minimize the risk for any low-frequency adverse event and the possibility that any spurious association might appear causative.[*]
Risk of pertussis infection

In all honesty, when it comes down to it – expecting mothers are going to make the decision to get the Tdap booster if the perceived benefits outweigh any risk.
One could read 30 peer reviewed publication arguing for (and against) Tdap during pregnancy, but it always comes down to perceived risk.
To estimate risk and the potential impact of Tdap administered during pregnancy, let us evaluate the data and statistics from 2010-2011.
Using the National Notifiable Diseases Surveillance System during 2000–2011, the annual mean of pertussis cases in infants aged <12 months was 2,746 cases - with deaths equaling to 18.[*]
Using the 2010 birth rate (4,007,000 live births) and this data, we can determine the following risk assessment for 2010:[*]

Without Vaccination:

Risk pertussis infection under 12 months = 0.007%

Risk of death = 0.000004%


With Vaccination:

Risk of pertussis infection under 12 months = 0.005%

Risk of death = 0.000002%
Not to make light of pertussis infection, but more people died of being struck by lightning (count = 29)  then babies dying of pertussis infection in 2010.[*]
Yet, I’m pretty sure mothers perceive the risk of pertussis as more glaring then being struck by lightning.

Changing epidemiology due to vaccination and the increased risk to infants
Everyone is quick to  proclaim the benefits of herd immunity when vaccinating, yet not so many are so swift as to declare its faults (such as protecting some while placing others at greater risk).
The implementation of a vaccine against pertussis infection, with decreasing natural boosting,  has changed the epidemiology of infection to the disease.[*]
The resurgence of pertussis in the post-vaccination era has been widely documented. In fact, it is the chief reason for the ACIP recommendation in vaccinating pregnant mothers. 

The overall incidence of pertussis has been increasing steadily
 since 2007 and has now surpassed peak rates observed
 during 2004-2005. source

Yet, a shift of cases from school-age children to adolescents, adults and children under 1 year of age has been described in the last decade. As a consequence, pertussis circulating in these new populations is considered  being the source of infection for infants and newborns (The Pediatric Infectious Disease Journal 2011, BMC Infectious Diseases 2013). [*][*]
One study that examined the increase of pertussis in California between 2006 and 2011, demonstrated decaying protection against pertussis during 5 years after a child’s fifth dose of the Tdap booster. The authors state this waning might be one of the causes of reported increased infection in adolescents which increases the risk of transmission to infants (Can Fam Physician 2013).[*]

source here - CDC
The solution for a severely limited booster vaccine? Cocooning.
Unfortunately, this strategy of cocooning (vaccinating pregnant women immediately postpartum and all other close contacts of infants with Tdap) to reduce the risk for transmission of pertussis to infants is an insufficient strategy (CDC 2011).[*]
The ACIP recognizes this as well as the CDC(CDC 2011).[*]
The solution for this latest failing strategy and inadequate vaccine? Simply, vaccinate during pregnancy. 


Which to choose
If you still regard the risk of pertussis infection to outweigh any known and unknown risks of vaccinating during pregnancy, then consider this: Please request the Adacel vaccine.
The Adacel vaccine contains antigens that intend to elicit antibodies against fimbriae (types 2 and 3) which play a critical role in the attachment of the bacteria to the respiratory cells (which would, in theory, make a mother less likely to transmit the disease to her child).[*][*][*]
Boostrix contains mainly antigens that intend to modify and lessen symptoms of disease, which would make a mother more likely to become an asymptomatic carrier of the disease, which places her child more at risk.[* sources 3-8]
Information on Tdap boosters:

Boostrix contains: pertussis antigens (inactivated pertussis toxin [PT] 361 and formaldehyde-treated filamentous hemagglutinin [FHA] and pertactin). also  - contains aluminum hydroxide as adjuvant (not more than 0.39 mg aluminum by assay), 4.5 mg of sodium chloride, ≤100 mcg of residual formaldehyde, and 387 ≤100 mcg of polysorbate 80 (Tween 80).

Adacel contains: 2.5 mcg detoxified pertussis toxin (PT), 5 mcg filamentous hemagglutinin  (FHA), 3 mcg pertactin (PRN), 5 mcg fimbriae types 2 and 3 (FIM). Also dose includes 1.5 mg aluminum phosphate (0.33 mg aluminum) as the adjuvant, ≤5 mcg residual formaldehyde.
I would also encourage you to read more about pertussis infection here: CDC Pinkbook Pertussis.

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The Perfect Storm - How the increase in pertussis vaccine usage is causing an 'epidemic'