**8. Immunization in pregnancy**

high vaccine coverage; this disadvantage has been reduced but not eliminated by using booster doses of reduced antigenic vaccine (ap) [31–33]. The duration of protection, however,

The introduction of pertussis vaccines, especially acellular ones, has certainly resulted in a strong containment of the incidence of disease, as a result of a gradual increase in vaccine coverage in

However, the illusion of having found a suitable tool to solve a relevant public health problem such as pertussis was short-lived. Since the early 2000s, a rise in pertussis incidence has been observed in several geographic areas, even where high vaccine coverage has been achieved for a long time [35]. This scenario underlines the need to identify a vaccine strategy that prevents the circulation of infection in all age groups and that, above all, helps to prevent illness

For several years, the cocoon strategy, which foresees the protection of infants in the first months of life through vaccination of the mother in postpartum and of the family contacts as potential sources of infection, has been considered a promising strategy of vaccination [2].

The rationale of this approach is related to fact that the source of infection for the newborn is represented by parents (5–55% of cases), grandparents (6–8%), and siblings (up to 20%) [36, 37].

However, it is necessary to consider that the maximum immunological response to vaccination does not occur within 14 days after the administration of a booster dose and, for this reason,

Anyway, the cocooning was recommended in the early 2000s in some developed countries and

This strategy has not been completely successful for several reasons [41]: the poor effectiveness, due to the large number of subjects to be vaccinated in order to prevent a single case of pertussis; the inadequate acceptance by family and close contacts of the newborn, especially if there is no pertussis epidemic ongoing (which leads to a perceived low risk); the difficulty in reaching all potential candidates for vaccination, especially if large families are involved; the

A study conducted in Italy has calculated the number needed to vaccinate (NNV) within the cocoon strategy, that is, the number of people to be vaccinated in order to prevent one hospitalization due to pertussis in 1 year in children <12 months old. The NNV was very high, ranging

The difficulties in implementing the cocoon strategy, its related high costs, and the not completely satisfactory results achieved, lead to the design of a new approach, which is currently

postpartum immunization does not allow to immediately protect the mother [38].

high economic resources needed to implement such a program in all newborns.

between 5404 and 9289, depending on the considered variables [42].

considered the main strategy: woman's vaccination during pregnancy.

tends to decrease, regardless of the administration of whole or acellular vaccine [34].

in infants who have the highest risk of severe and even deadly complications.

most Western countries.

68 Pertussis - Disease, Control and Challenges

**7. Cocoon strategy**

since 2005 by ACIP [39, 40].

Vaccination of pregnant women with dTpa vaccine is nowadays considered the best strategy for the protection of <2 months of age infants, which are a high-risk cohort being too young to be vaccinated.

However, vaccination during pregnancy has been considered for a long time a negligible option because of the difficulty to assess its effectiveness and safety.

The rationale for vaccination in pregnancy with a single dose of dTap is to provide protection against pertussis to the baby in his first months of life through the transplacental passage of maternal antibodies. One of the concerns firstly considered was the possible interference of maternal antibodies on the child's ability to mount an adequate immune response to pediatric DTaP or to other conjugated vaccines containing tetanus or diphtheria toxoids. Other concerns were related to the lack of data on safety and potential teratogenicity. However, now it is well known that there are no potentially serious adverse events in either the mother or the fetus following vaccination during pregnancy [43, 44]. One of the issues for the development of recommendations addressed to immunization of women during pregnancy and lactation is the lack of studies to make evidence-based decisions. Most of the available data on vaccine safety are derived from passive surveillance records. According to the CDC, the risk of a fetus following mother's vaccination during pregnancy is only theoretical. However, when considering vaccination, it is important to distinguish between live and inactivated vaccines. In particular, there is no theoretical reason to suspect that inactivated, bacterial or toxoid vaccines (pertussis one included), are associated with an increased risk of adverse events when given during pregnancy or lactation [45].

As of 2008 [46], the Advisory Committee on Immunization Practices (ACIP) recommended that pregnant women not previously vaccinated with dTap should receive a dose in the immediate postpartum period prior to hospital discharge; could receive dTap even a 2-year interval after a previous dose of dT vaccine; should receive dT during pregnancy as protection against tetanus and diphtheria when indicated; could postpone dT vaccine during pregnancy and replace it with dTap vaccine in the immediate postpartum period, if sufficient protection against tetanus and diphtheria was already available. In conclusion, although there were no contraindications for the administration of dTap vaccine during pregnancy, healthcare professionals had to evaluate risks and benefits before deciding to administer dTap to a pregnant woman.

Subsequently, an analysis was performed comparing immunization in pregnancy to postpartum vaccination in terms of impact, effectiveness, and costs [47]. Vaccination during pregnancy turned out to allow to prevent more cases of disease, hospitalization, and death than the postpartum approach for two reasons: first, because protection is achieved for both the mother and the child at birth; second, because vaccination, when performed during the third trimester of gestation, optimizes the transplacental transfer of maternal antibodies to the fetus, ensuring protection for the newborn during his first months of life.

Based on this evidence, ACIP [48] recommended in 2011 the use of dTpa to all pregnant women who had not previously received the vaccine. The vaccine has to be administered between the end of the second and the beginning of the third trimester, preferably after the 20th week. If the vaccine has not been given during pregnancy, one dose of dTap should be given immediately after delivery. In 2012, the recommendation was extended to all women at each new pregnancy, regardless of their previous vaccination status [48].

in the immediate postpartum, before discharge from the hospital, for mothers who have not

Pertussis Immunization in Pregnancy: A Review http://dx.doi.org/10.5772/intechopen.72085 71

In Canada, the National Advisory Committee on Immunization (NACI) recommends that all women who have not received a dose of dTpa vaccine after 26 weeks of pregnancy should be encouraged to undergo vaccination. In particular circumstances, such as in an epidemic situation, all women over the 26th gestation week may be offered dTap regardless of their previous

Since 2013, in New Zealand, vaccination is recommended for every new pregnancy between the 28th and 38th week of gestation [58]. In Australia, the guidelines in the latest edition of "The Australian Immunization Handbook" recommend a booster dose for all women in the third

In Europe, following the 2012 epidemic, the United Kingdom launched an immunization program for pregnant women offering vaccination between the 16th and 32nd week of gestation [60]. Belgium (week 24–32), Ireland (week 27–36), Czech Republic (week 28–36) [61], and Italy

Although the impact of pertussis has been considerably reduced since the introduction of vaccination programs in the 1950s, the disease continues to be a public health issue, especially in

The spread of *B. pertussis* in the cohort of infants is facilitated by the circulation of the pathogen among older age groups (where cases are often atypical and misdiagnosed) that easily become sources of infection for unvaccinated children. The shift of the disease to the older age groups is related to waning immunity occurring after both natural infection and immunization.

It is therefore necessary to implement vaccination strategies taking into account the most vulnerable groups. On one hand, it is recommended to administer booster doses with dTpa vaccine every 10 years to maintain effective immune protection in previously vaccinated population. On the other hand, it is necessary to adopt a preventive strategy addressed to younger babies, already starting immunization in the prenatal age. Women's vaccination in the third trimester of pregnancy appears to be an effective tool as it allows, through the transplacental passage of specific antibodies, newborn's protection in the first few months of life,

For a more complete protection of the infant, it would be desirable to simultaneously promote the cocoon strategy, immunizing all members of the family and those who will be in close contact with the newborn, to avoid the transmission of the bacterium by these subjects.

Given the new epidemiological situation and on the basis of the scientific evidence, vaccination in the third trimester of pregnancy is currently recommended in several countries such as

the United States, Canada, Australia and other European countries (UK, Italy, etc.).

received dTap in pregnancy or for those with an unknown vaccination status [48].

trimester of each pregnancy (preferably between the 28th and the 32nd week) [59].

(after the 28th week) [62] recommend vaccination in pregnancy.

at least until he reaches the right age to start immunization.

immunological condition [57].

**9. Conclusions**

children in their first months of life.

This indication was based on the results of some studies which showed that the production of protective antibodies after vaccination is maximum in the first month and is much lower even after less than 1 year; after 1 year, the antibody protection provided by the mother is no longer sufficient to protect the baby in his first months of life, unless vaccination is made during pregnancy. It has been confirmed that dTap administration should preferably take place during the second trimester of gestation, especially between the 27th and 36th week [49, 50], although a study conducted by Abu Raya et al. has shown that avidity of IgG antibodies against *Bordetella pertussis* is greater if vaccination is performed between the 27th and 30th week of gestation [51, 52].

Recently, an observational perspective study [53] has been conducted in Switzerland to evaluate the best time for maternal vaccination in order to adequately protect preterm infants who, among newborns, are a group even more susceptible and at risk. Antibody levels, expressed as geometric mean titers, were evaluated in preterm children born from two cohorts of women vaccinated with dTap, one in the second and one in the third trimester. The results showed a significantly higher level of antibodies in infants born from mothers vaccinated in the second compared to those vaccinated in the third trimester. One possible explanation is that immunization during the second trimester allows a longer transfer time and a higher accumulation of antibodies in newborns This is the first study showing the benefits of maternal immunization in the second trimester for preterm infants. Noteworthy, these interesting results have to be validated as it is well known that the placental transfer of antibodies is greatly effective during the last trimester of pregnancy.

There is no evidence of adverse effects on the fetus after maternal vaccination with inactivated or toxoid vaccines, and coadministration of dTap and flu vaccines is allowed, and it is safe in pregnancy and can optimize the immune response [54, 55].

A study conducted in New Zealand evaluated the safety of dTap vaccine administered during pregnancy; a cohort of 403 newborns was followed for 6–12 months after birth (84% of whom completed a 12-months follow-up), monitoring over time the onset of possible adverse effects related to vaccination. Several parameters such as gestational age at birth, growth parameters, evidence of congenital abnormalities, immunization status, timeliness of immunization, and possible appearance of pertussis infection after birth were considered. The study showed that there were no significant differences in birth weight, gestational age at birth, congenital anomalies or altered growth parameters, comparing newborns from immunized or unvaccinated mothers. No cases of pertussis occurred in the cohort studied, in spite of the high rates of disease in the community and there were no adverse events related to vaccination. Therefore, these data can be added to the growing pool of evidence that dTap vaccine administration during pregnancy is an adequate and safe strategy to reduce the impact of pertussis in infants [56].

In the United States, the CDC recommends a dose of dTap at each pregnancy, between the 27th and 36th week of gestation (preferably between 28th and 32th). dTap vaccine is also recommended in the immediate postpartum, before discharge from the hospital, for mothers who have not received dTap in pregnancy or for those with an unknown vaccination status [48].

In Canada, the National Advisory Committee on Immunization (NACI) recommends that all women who have not received a dose of dTpa vaccine after 26 weeks of pregnancy should be encouraged to undergo vaccination. In particular circumstances, such as in an epidemic situation, all women over the 26th gestation week may be offered dTap regardless of their previous immunological condition [57].

Since 2013, in New Zealand, vaccination is recommended for every new pregnancy between the 28th and 38th week of gestation [58]. In Australia, the guidelines in the latest edition of "The Australian Immunization Handbook" recommend a booster dose for all women in the third trimester of each pregnancy (preferably between the 28th and the 32nd week) [59].

In Europe, following the 2012 epidemic, the United Kingdom launched an immunization program for pregnant women offering vaccination between the 16th and 32nd week of gestation [60]. Belgium (week 24–32), Ireland (week 27–36), Czech Republic (week 28–36) [61], and Italy (after the 28th week) [62] recommend vaccination in pregnancy.
