This chapter should be cited as follows:
Maertens K, Leuridan E, Glob. libr. women's med.,
ISSN: 1756-2228; DOI 10.3843/GLOWM.419423
The Continuous Textbook of Women’s Medicine Series – Obstetrics Module
Volume 17
Maternal immunization
Volume Editors:
Professor Asma Khalil, The Royal College of Obstetricians and Gynaecologists, London, UK; Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George’s University Hospitals NHS Foundation Trust, London, UK
Professor Flor M Munoz, Baylor College of Medicine, TX, USA
Professor Ajoke Sobanjo-ter Meulen, University of Washington, Seattle, WA, USA
Chapter
Pertussis
First published: May 2023
Study Assessment Option
By completing 4 multiple-choice questions (randomly selected) after studying this chapter readers can qualify for Continuing Professional Development awards from FIGO plus a Study Completion Certificate from GLOWM
See end of chapter for details
INTRODUCTION
Neonates are most susceptible to severe pertussis-related morbidity and mortality. Despite high global vaccination coverage of pertussis-containing vaccines, pertussis incidence has increased, particularly in documented high-income countries. This increasing incidence does not only affect young infants, but also older age categories who are, however, less affected by clinical consequences of pertussis disease.
During the past decade, immunization of pregnant women with acellular pertussis (aP)-containing vaccines has been implemented in a number of countries worldwide to reduce the burden of pertussis disease in young infants and thus to protect them during the early, vulnerable first months of life. Vaccination against pertussis in pregnancy induces pertussis-specific antibodies in the mother, which are transferred across the placenta or via breastmilk towards the neonate, until protection by infant vaccination is provided. A large body of evidence has been generated in the last decade that support the safety, immunogenicity, and effectiveness of pertussis vaccination during pregnancy and that endorse the implementation of this vaccination strategy on a broad scale.
PERTUSSIS EPIDEMIOLOGY AND CLINICAL DISEASE BURDEN
The epidemiology of pertussis has a cyclical nature, peaking every 3–5 years and the disease is endemic in all countries worldwide. Despite the availability of successful universal pertussis vaccination programs, the disease remains an important public health problem and is nowadays still one of the most common vaccine-preventable diseases in the world.1 In recent years, some countries have experienced an increase in the incidence of pertussis.2,3 The reasons for this resurgence are likely multifactorial, including an increase in disease awareness due to strengthening of surveillance systems, an increase in overall laboratory capacity and testing and an enhanced sensitivity of the PCR diagnostic methods, waning immunity both after natural infection and vaccination, the switch from whole cell pertussis (wP) to acellular pertussis (aP)-containing vaccines in many high-income countries resulting in a shift from a T-Helper-1 (Th1) and Th17 driven immune response to a Th2 driven immune response, pathogen adaptation with changes in the antigenic and genotypic characteristics of circulating Bordetella pertussis strains resulting in the emergence of Pertactin (Prn)-deficient strains, particularly in countries using aP-containing vaccines, and additional factors such as variable vaccine uptake and inadequate booster vaccination coverage.4 However, the relative contribution of each of these individual factors is not entirely clear.
The majority of data on the burden of pertussis disease still come from high-income countries. Therefore, assessing the global burden of pertussis is more challenging as comprehensive and reliable data from low- and middle-income countries (LMIC) are often lacking. Global figures from the World Health Organization (WHO) for 2018 projected 169,240 pertussis cases,5 which is likely a serious underestimation of the true burden of the disease. A WHO modeling study including data from 2014 was used to estimate global pertussis cases and deaths. This modeling study estimated that there were 24.1 million pertussis cases and 160,700 deaths from pertussis in children younger than 5 years in 2014, with the African region contributing the largest proportions.6
Pertussis disease occurs at all ages. Yet, the incidence, clinical presentation and potential complications of the disease vary across different age groups as outlined in Table 1.
1
Clinical presentation and complications of pertussis per age group (adapted from Pink book CDC: https://www.cdc.gov/vaccines/pubs/pinkbook/index.html).
Pertussis clinical features | Pertussis among children, adolescents, and adults | Pertussis complications in children |
Incubation period 7–10 days (range 4–21 days) Insidious onset, similar to the common cold with non-specific cough Fever usually minimal throughout course of illness Catarrhal stage: 1–2 weeks Paroxysmal cough stage: 1–6 weeks Convalescence stage: weeks to months | Presentation in infants may be with cough and apnoea The typical "whoop" is often absent Disease in older children and adults is often milder than in infants and young children Infection may be asymptomatic, or may present as classic pertussis Persons with mild disease may transmit the infection Older persons often source of infection for children | Secondary bacterial pneumonia – most common Neurologic complications – seizures, encephalopathy, more common among infants Otitis media Anorexia Dehydration Pneumothorax Epistaxis Subdural hematomas Hernias Rectal prolapse |
The highest incidence of pertussis disease can be found in infants below 6 months of age, too young to be completely protected by the currently available infant vaccines and vaccination schedules and most vulnerable to severe pertussis-related disease and mortality. The clinical spectrum of pertussis disease in infants alters from trivial to severe illness with life-threatening complications, sometimes resulting in death.7
Pertussis also occurs in older children, adolescents, and adults who frequently serve as an important source of infection for infants.8 Serologic surveys indicate that pertussis is more common than generally appreciated with a discrepancy in the number of individuals with elevated antibody titers to pertussis antigens compared to the actual reported pertussis incidence.9,10,11 Some of these serologic surveys included pregnant women who had not been recently vaccinated documenting low levels of pertussis-specific antibodies in pregnant women and the lack of transplacental transported antibodies to their infants to protect them from disease.12,13,14
Symptoms of pertussis infections in this older age group tend to be less severe than in infants but are often associated with a persistent cough. Occasionally pertussis can even be asymptomatic. Only limited data are available on the impact of pertussis on pregnant women. A small US study showed comparable pertussis incidence in pregnant compared to non-pregnant women, but found a higher hospitalization rate and a higher likelihood of symptoms in pregnant compared to non-pregnant women.15 On the other hand, a study by Murphy et al. observed no increased morbidity and mortality, abnormal fetal development or adverse pregnancy outcomes after pertussis infection in pregnancy and comparable clinical symptoms and pertussis incidence between pregnant and non-pregnant women.16
PERTUSSIS VACCINES
Globally, two general types of pertussis vaccines are currently in use.17 The wP-containing vaccines are suspensions of the inactivated whole Bordetella pertussis organism combined with other antigens. These wP vaccines are only licensed for use in young children, with booster doses administered to adolescents and adults being all aP based vaccines. The pertussis components in the aP containing vaccines include one or more highly purified pertussis antigens. All contain pertussis toxin (PT), and in different combinations, they also contain filamentous hemagglutinin (FHA), pertactin (PRN) or fimbriae (FIM) in addition to other non-pertussis antigens.18
In most parts of the world, the first-generation, wP-containing vaccines are still used, whereas most high-income countries have gradually switched to the second-generation aP-containing vaccines due to the improved reactogenicity profile of the aP-containing vaccines. However, it has become apparent that immunity induced by the aP-containing vaccines wanes significantly faster than that induced by wP-containing vaccines. Therefore, the WHO currently recommends that countries using wP-containing vaccines for their primary immunization schedule should continue to do so, since these vaccines appear to provide longer lasting protection.18 Currently, there is no serological correlate of protection known for pertussis, but higher antibody titers against PT and to a lesser extent to PRN, have been associated with better protection against pertussis disease.19
There are several aP-containing vaccines available that may be used in adolescents and adults, and are thus included in national-level recommendations for use in pregnancy.
Adacel© (marketed in Europe as Covaxis© or Triaxis©) is a five-component aP-containing vaccine. It contains PT (2.5 μg), FHA (5 μg), PRN (3 μg), FIM type 2 and 3 (5 μg), tetanus toxoid (5 Lf [limit of flocculation], diphtheria toxoid (2 Lf) and adjuvant (0.33 mg aluminum). Adacel© is licensed for use in most countries for persons of 4 years or older. Combined with inactivated polio vaccine (IPV), the product is marketed as Repevax©.20 Boostrix© is a three-component aP containing vaccine. It contains PT (8 μg), FHA (8 μg), PRN (2.5 μg), tetanus toxoid (5 Lf) and diphtheria toxoid (2.5 Lf) and adjuvant (<0.39 mg aluminum). Boostrix© is licensed in most countries for persons 4 years of age or older. It is also available combined with IPV as Boostrix-IPV©.21
CURRENT EVIDENCE FOR THE USE OF PERTUSSIS VACCINES IN PREGNANT WOMEN
As a result of the resurgence of pertussis disease, with young infants disproportionately affected by severe morbidity and mortality, national advisory bodies [e.g., USA (2011),22 UK (2012),23 Belgium (2013)24 and others] started to recommend immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine for all pregnant women, at every pregnancy.25 In the meanwhile, pertussis vaccination during pregnancy is already implemented in a variety of other countries worldwide including Argentina,26 Australia,27 Canada,28 Italy,29 Mexico,30 The Netherlands,31 and Portugal32 amongst others.
The vaccination strategy offers passive protection to infants from birth until the start of their primary immunization series in the first months of life, thereby closing the neonatal susceptibility gap for pertussis infection.
Safety of pertussis vaccination during pregnancy
The first large prospective safety study on Tdap vaccination during pregnancy was published soon after the implementation of the strategy in the United Kingdom. In that report, safety data from 20,074 pregnant women vaccinated with Tdap during pregnancy were compared to a historical control group of unvaccinated women. These data showed no increased risk for adverse pregnancy and neonatal outcomes following Tdap vaccination during pregnancy.33 Also in the US, shortly after the implementation of the strategy, data from 123,494 singleton pregnancies monitored for adverse reactions following Tdap vaccination during pregnancy were published. No association between Tdap vaccination during pregnancy and increased risk for preterm birth, small for gestational age or hypertensive disorders during pregnancy was found. Only a small increased relative risk for chorioamnionitis at delivery was noted.34
As more evidence on the safety of Tdap vaccination during pregnancy became available over the years, these data were summarized in a systematic review including data from a total of 1.4 million pregnant women, of which 199,846 women had received a pertussis-component-containing vaccine during pregnancy. In that review, no increased risk for all prespecified safety outcomes was found, with the exception of a slightly increased relative risk for postvaccination fever and chorioamnionitis at delivery.35 The increased risk of fever was only significant in one large US cohort study that included 438,487 live births and estimated that an additional six cases of fever per 100,000 vaccinated pregnant women occurred as compared to unvaccinated pregnant women.36 However, in another study, pregnant women experienced fever after Tdap vaccination at a similar or even lower frequency compared to non-pregnant women.37 Overall, six studies showed a small increase in the relative risk of chorioamnionitis after Tdap vaccination during pregnancy.34,37,38,39,40,41 This increase was only significant in three studies that all used the “presence of respective ICD-9 codes” in electronic patient data as the definition of chorioamnionitis.34,39,41 Whether there is a causal relationship between chorioamnionitis and Tdap vaccination during pregnancy is still controversial because an increased risk for preterm birth or sepsis in infants from Tdap vaccinated women would be expected as a consequence of the increased risk for chorioamnionitis. However, in all studies reporting the association, the rate of preterm birth was even lower in infants from Tdap vaccinated women compared to infants from unvaccinated women. In addition, in some studies, the risk for admission to the neonatal intensive care unit was also lower in infants from Tdap-vaccinated women compared to infants born to unvaccinated women. To further rule out the possible relationship between Tdap vaccination during pregnancy and maternal and neonatal safety outcomes, future studies should apply standardized definitions of safety outcomes as suggested by the Global Alignment on Immunization Safety Assessment in Pregnancy Consortium.42
Recently, a Canadian study looked at the long-term safety of exposure to Tdap vaccination during pregnancy. Of 625,643 live births, 12,045 were exposed to Tdap in utero and followed for up to 6 years of age. No significant increased risks of adverse childhood outcomes after prenatal Tdap exposure were observed. Children born from women vaccinated against Tdap in pregnancy even had a lower risk of upper respiratory tract and gastrointestinal infections and a lower chance of needing urgent and inpatient health services.43
Since vaccination against pertussis is recommended in every pregnancy regardless of previous vaccination status and the time that elapsed since the last pregnancy, Sukumaran et al. studied the possible adverse outcomes of repeat Tdap vaccines during subsequent pregnancies. Using the Vaccine Safety Datalink network in the United States including data from 29,155 pregnant women, no increased risk of large local reactions, premature delivery, small for gestational age, or other adverse events following immunization were found when repeated booster doses were administered in intervals of at least 2 years.44,45
Immunogenicity of pertussis vaccination during pregnancy
Upon Tdap vaccination of pregnant women, vigorous antibody responses against all vaccine included antigens are induced. Yet, the persistence of these Tdap-specific antibodies is relatively short with already significant waning of antibody levels 1 year after vaccination. However, antibody levels 1 year after vaccination were still significantly higher than antibody levels in women not vaccinated with Tdap during pregnancy. These data illustrate that Tdap vaccination during pregnancy possibly does not provide optimal protection to the newborn during subsequent pregnancies46,47 and that vaccination in every pregnancy is needed, regardless of the interval between subsequent pregnancies.
Limited data on the comparison of immune responses to Tdap between pregnant and non-pregnant women are available. Two relatively small studies reported similar antibody responses between pregnant and non-pregnant women.46,48 However, one of the two studies reported lower T-cell responses to pertussis antigens in pregnant as compared to non-pregnant women.46 On the other hand, a third study involving a larger sample size observed lower antibody responses to PT and FHA in pregnant as compared to non-pregnant women.49 Therefore, data on possible differences in immune responses between pregnant and non-pregnant women are still inconclusive and further research is needed. Certainly because still no clear correlate of protection for pertussis is available.
To date, studies on the immunogenicity of Tdap vaccination in pregnant women were solely performed on women primed with wP-containing vaccines in infancy. However, women exclusively primed with aP-containing vaccines are slowly entering childbearing age. A US study50 found that type of pertussis vaccine a woman received during childhood significantly impacted maternal responses to vaccination during pregnancy, efficiency of transplacental transfer of antibodies, and infant antibody levels at birth. Infants born to aP-primed women had an anti-PT GMC that was less than half that of those born to wP-primed women. Anti-FHA GMCs as well as the efficiency of transplacental anti-PT transfer were significantly lower in infants born to aP-primed women compared with wP-primed women. These data suggest that infants born to aP-primed women may be more vulnerable to pertussis prior to their primary DTaP series. However, the exact clinical implications of these findings are unknown.
Tdap vaccination mainly induces IgG1 antibodies,51,52 which are actively transported across the placenta to the newborn resulting in higher antibody levels in the term neonate than in the mother.47,48,53,54,55 A reduction in this transplacental transport is seen in the case of a premature delivery. Yet, preterm infants born to women vaccinated with Tdap during pregnancy have significantly higher cord blood antibody levels compared to preterm infants born to unvaccinated women showing that despite the reduction in transplacental transport, there is still an acceptable level of transport of maternal antibodies from mother to infant in case of preterm delivery.56 Therefore, it is meaningful to vaccinate pregnant women against pertussis, even when a preterm delivery is threatening, since preterm infants do benefit from Tdap vaccination during pregnancy and especially because preterm infants are more vulnerable for pertussis-related complications.57,58,59
The vaccine-induced pertussis-specific maternal antibodies transported from mother to infant across the placenta offer protection to the newborn until the infant primary vaccination is started. However, high concentrations of maternal antibodies present at the moment of the infants’ immunization can have a suppressive effect on the infants’ immune response to their own vaccination.
To date, most studies looking at blunting were performed in high-income countries, where aP-containing vaccines are used for infant immunization. In these studies, data are conflicting regarding the antigen-specific antibodies affected, the degree, quantity and duration of such modifications in infant immune responses.47,48,54,56,60,61,62,63,64 Therefore, an individual-participant data meta-analysis of ten studies investigating infants’ antibody responses to routine immunization after Tdap vaccination during pregnancy was performed showing blunting for all vaccines including pertussis antigens after primary immunization with aP-containing vaccines in infants born to women vaccinated with Tdap during pregnancy. This blunting even persisted for some antigens beyond booster immunization in the first or second year of life.
Few data on possible modification of infant immune responses after Tdap vaccination during pregnancy are available for wP-containing vaccines, the vaccines most exclusively used in low-middle income countries (LMICs). In a study conducted in Thailand, infants born to women vaccinated against Tdap in pregnancy and vaccinated with wP-containing vaccines for their infant vaccination showed significantly lower pertussis-specific antibody levels after the completion of their primary immunization schedule compared to infants vaccinated with aP-containing vaccines.55 These results might provide clues that more interference is present if infants are vaccinated with wP compared to aP-containing vaccines. Therefore, it is important to investigate whether these data are confirmed in larger studies and whether the increase in interference is clinically significant in LMICs.
Vaccines against pertussis that are currently used in pregnancy also contain tetanus toxoid (TT) and diphtheria toxoid (DT), so there is a theoretical potential interference with infant vaccines containing tetanus and diphtheria components. However, studies evaluating this aspect showed mixed and inconsistent results. Both for tetanus and diphtheria, some studies showed lower whereas others showed equal or even higher antibody levels after completion of the primary immunization in infants born to Tdap-vaccinated women compared to infants from unvaccinated women. For both diseases, this reduction in antibody levels had no impact on the clinical protection as the percentage of infant with seroprotective antibody levels was comparable between infants from Tdap vaccinated compared to unvaccinated women.47,48,54,60,61,62,63,68
Another important aspect of potential modification of infants’ immune responses is that some vaccines given during infancy are conjugated to TT or DT as a carrier protein, and thus a modification of the immune response to these vaccinations occur. After primary immunization with Haemophilus influenzae type b (Hib)-containing vaccine, Hib anti-polyribosylribitol phosphate levels were higher in infants born to women vaccinated with Tdap during pregnancy compared with infants of unvaccinated women, both after vaccination with aP- and wP-containing infant vaccines.63,68,69 However, no impact on clinical protection against Hib was observed.68 After primary immunization with meningococcal C-containing vaccines, anti-meningococcus C antibody levels did not differ between infants born to Tdap-vaccinated women versus unvaccinated pregnant women.69 However, Tdap immunization during pregnancy was associated with lower anti-pneumococcal capsular polysaccharide levels after immunization with pneumococcal conjugate vaccine (PCV)-13, a vaccine that is conjugated to CRM197, though this was not associated with lower seroprotection rates for most serotypes.63,70 In contrast to interference to PCV-13, no interference has been observed to nine of ten pneumococcal serotypes that are conjugated to protein D (as part of PCV-10) in infants born to Tdap-vaccinated women and vaccinated with PCV-10.71
Breastfeeding might provide additional protection against pertussis to the lactating infant via the transfer of vaccine-induced pertussis-specific antibodies in breast milk.72 Pertussis-specific secretory IgA and to a smaller extent IgG antibodies were detected in breastmilk of women vaccinated against pertussis during pregnancy, both after term and preterm delivery, with the highest antibody levels present in colostrum and then gradually declining until 12 weeks postpartum.73,74,75 However, whether these elevated pertussis-specific antibody levels in breastmilk could potentially contribute to protection against pertussis disease has not yet been demonstrated.
Effectiveness of pertussis vaccination during pregnancy
The effectiveness of Tdap vaccination during pregnancy for the prevention of pertussis in newborns has been well studied. In a systematic review, data from 855,546 mother–infant pairs from the United Kingdom, Spain, Australia, and United States were summarized.35 In all studies considering laboratory-confirmed pertussis infection, vaccine effectiveness was high, ranging from 69% to 91% for the prevention of pertussis infection in infants below 3 months of age,66,67,76,77,78,79,80 from 91% to 94% for the prevention of pertussis-related hospitalization,78,80 and 95% for the prevention of pertussis-related deaths.66 In a study by Becker-Dreps et al., slightly lower vaccine effectiveness rates were reported, probably because of the inclusion of clinically suspected cases on top of laboratory-confirmed cases in the analysis.81 Since prematurity is an important risk factor for pertussis-related complications, Tdap vaccination during pregnancy also needs to protect this vulnerable group. In the US, vaccination against pertussis in pregnancy was associated with a 91% vaccine effectiveness in preventing pertussis in preterm born infants below 6 months of age.82
Optimal timing of pertussis vaccination during pregnancy
The optimal timing of vaccination against pertussis in pregnancy is the time window in pregnancy where administration of an aP-containing vaccine is associated with (1) the highest transfer of pertussis-specific antibodies across the placenta to the fetus, (2) the highest vaccine effectiveness in young infants, and (3) the least inhibition of the infants’ immune response to their own vaccines. This optimal time window is still under debate, which is reflected in the varying national recommendations on pertussis vaccination during pregnancy. In general, Tdap vaccination during pregnancy is recommended in most countries for all pregnant women during every pregnancy in the late second or early third trimester of pregnancy.
When looking at the impact of timing on transfer of pertussis-specific antibodies across the placenta to the fetus and thus the impact of timing on the presence of pertussis-specific antibodies in cord blood, a study conducted in Thailand showed that vaccination with Tdap earlier in pregnancy was associated with higher pertussis-specific antibody levels in cord blood.55 Also, three other studies83,84,85 found that Tdap vaccination in the early third trimester of pregnancy resulted in higher pertussis-specific antibody levels in cord blood compared to vaccination in the late third trimester of pregnancy. Besides antibody levels, also the avidity of cord blood anti-PT IgG antibodies was higher when women were vaccinated in the early third trimester compared to late third trimester of pregnancy.86 In addition, a Swiss study demonstrated higher anti-PT and anti-FHA IgG levels in cord blood of women vaccinated between 13 and 25 weeks' gestational age compared to women vaccinated after 25 weeks' gestational age.87 This observation was also confirmed in preterm born infants.88 Given the discrepancy in studies on the optimal timing of Tdap vaccination during pregnancy and to further elucidate the optimal timepoint for vaccination in pregnancy to afford maximal protection to newborns, a recent multi-country analysis aimed to model the impact of timing of vaccination during pregnancy on infant antibody titers at birth. This analysis showed that term born infants on average achieve the highest antibody levels at birth if women were vaccinated at 31 weeks' gestational age. When this analysis considered both term and preterm infants, they showed that an interval of at least 7.5 weeks between vaccination and delivery was needed to achieve the highest cord blood antibody levels.89
Recently, some studies have tried to look at the effect of timing of pertussis vaccination during pregnancy on vaccine effectiveness, but results have been inconclusive so far probably because most studies were not powered to measure differences in vaccine effectiveness based on timing of vaccination during pregnancy.
An observational study from the US showed that vaccination in the third trimester between 27 and 36 weeks' gestational age, the recommended vaccination timeframe in the US, was more protective in the prevention of laboratory-confirmed pertussis in term born infants below 8 and below 12 weeks of age compared to vaccination outside this timeframe. A further analysis within the same study unfortunately did not reach a definite conclusion on whether vaccination early in the third trimester, between 27 and 31 weeks' gestational age, was associated with higher protection than vaccination later in the third trimester, between 32 and 36 weeks' gestational age, likely due to the small number of pertussis cases in each category.90
In addition, another study from the US reported that infants below 18 months of age and whose mother received the pertussis vaccine before 27 weeks' gestational age did not have reductions in pertussis rates compared with infants from unvaccinated women.81 A study from Spain reported that the vaccine effectiveness of vaccination against pertussis in pregnancy was 88% in the prevention of laboratory-confirmed pertussis in infants below 2 months of age. No difference in vaccine effectiveness was found between infants from mothers vaccinated between 26 and 31 weeks' gestational age versus infants from mothers vaccinated after 32 weeks' gestational age.91
Given the fact that results regarding the optimal timing of vaccination during pregnancy are still inconclusive and some aspects of the optimal timing are not yet studies, more research on the optimal timing of Tdap vaccination during pregnancy and the impact of this timing on immunogenicity in both women and infant, transfer of vaccine-induced antibodies across the placenta and via breastfeeding and vaccine effectiveness is certainly needed.
PRACTICE RECOMMENDATIONS
- Vaccination of pregnant women with an acellular pertussis (aP)-containing vaccine is recommended for all pregnant women during every pregnancy in a lot of countries worldwide.
- Recommendations vary across countries in view of timing on when to vaccinate during pregnancy. However, in most countries, vaccination in the late second or early third trimester of pregnancy is recommended.
CONFLICTS OF INTEREST
The author(s) of this chapter declare that they have no interests that conflict with the contents of the chapter.
Feedback
Publishers’ note: We are constantly trying to update and enhance chapters in this Series. So if you have any constructive comments about this chapter please provide them to us by selecting the "Your Feedback" link in the left-hand column.
REFERENCES
Hartzell JD, Blaylock JM. Whooping cough in 2014 and beyond: an update and review. Chest 2014;146(1):205–14. | |
Plotkin SA. The pertussis problem. Clin Infect Dis 2014;58(6):830–3. | |
Tan T, Dalby T, Forsyth K, et al. Pertussis Across the Globe: Recent Epidemiologic Trends From 2000 to 2013. Pediatr Infect Dis J 2015;34(9):e222–32. | |
Esposito S, Stefanelli P, Fry NK, et al. Pertussis Prevention: Reasons for Resurgence, and Differences in the Current Acellular Pertussis Vaccines. Front Immunol 2019;10:1344. | |
World Health Organization. Pertussis reported cases and incidence. 2022 [Available from: https://immunizationdata.who.int/pages/incidence/pertussis.html] | |
Yeung KHT, Duclos P, Nelson EAS, et al. An update of the global burden of pertussis in children younger than 5 years: a modelling study. Lancet Infect Dis 2017;17(9):974–80. | |
Cherry JD. Pertussis in Young Infants Throughout the World. Clin Infect Dis 2016;63(suppl 4):S119-s22. | |
Craig R, Kunkel E, Crowcroft NS, et al. Asymptomatic Infection and Transmission of Pertussis in Households: A Systematic Review. Clin Infect Dis 2020;70(1):152–61. | |
Wehlin L, Ljungman M, Kühlmann-Berenzon S, et al. Pertussis seroprevalence among adults of reproductive age (20–39 years) in fourteen European countries. Apmis 2021;129(9):556–65. | |
Scott S, van der Sande M, Faye-Joof T, et al. Seroprevalence of pertussis in the Gambia: evidence for continued circulation of bordetella pertussis despite high vaccination rates. Pediatr Infect Dis J 2015;34(4):333–8. | |
Chlibek R, Smetana J, Sosovickova R, et al. Seroepidemiology of whooping cough in the Czech Republic: estimates of incidence of infection in adults. Public Health 2017;150:77–83. | |
Wanlapakorn N, Thongmee T, Vichaiwattana P, et al. Antibodies to Bordetella pertussis antigens in maternal and cord blood pairs: a Thai cohort study. PeerJ 2017;5:e4043. | |
Türkoğlu E, Sönmez C, Özer E, et al. Low pertussis antibody levels in maternal and umbilical cord blood samples in Turkey. Turk J Pediatr 2016;58(6):573–8. | |
Healy CM, Munoz FM, Rench MA, et al. Prevalence of pertussis antibodies in maternal delivery, cord, and infant serum. J Infect Dis 2004;190(2):335–40. | |
Skoff TH, Faulkner AE, Liang JL, et al. Pertussis Infections Among Pregnant Women in the United States, 2012–2017. Clin Infect Dis 2021;73(11):e3836-e41. | |
Murphy TV, Slade BA, Broder KR, et al. Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008;57(Rr-4):1–51. | |
Edwards K, Decker M. Pertussis vaccines. Plotkin’s vaccines. 72018. p. 711–61. | |
World Health Organization. Pertussis vaccines: WHO position paper – September 2015. Wkly Epidemiol Rec 2015;90(35):433–58. | |
Plotkin SA. Complex correlates of protection after vaccination. Clin Infect Dis 2013;56(10):1458–65. | |
Sanofi Pasteur Limited Company. Summary of Product Characteristics. Adacel. 2011. | |
GlaxoSmithKline Inc. Summary of Product Characteristics. Boostrix. 2008. | |
The American College of Obstetricians and Gynecologists. Update on Immunization and Pregnancy: Tetanus, Diphtheria, and Pertussis Vaccination 2017. [Available from: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/09/update-on-immunization-and-pregnancy-tetanus-diphtheria-and-pertussis-vaccination] | |
Public Health England. The Green Book. Chapter 11: The UK Immunisation schedule 2022. [Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1060682/Greenbook-chapter-11-11Mar22.pdf] | |
Hoge Gezondheidsraad. Immunisatie tijdens de zwangerschap: Belgische richtlijnen 2020. [Available from: https://www.health.belgium.be/sites/default/files/uploads/fields/fpshealth_theme_file/20201106_hgr-8754_immunisatie_tijdens_de_zwangerschap_vweb.pdf] | |
Abu-Raya B, Maertens K, Edwards KM, et al. Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement. Front Immunol 2020;11:1282. | |
Direccion de Control de Enfermedades Immunoprevenibles Ministerio de Salud de la Nacion Argentina. Calendario Nacional de Vacunación. Información sobre vacunas y el calendario de vacunación. 2021 [Available from: https://www.argentina.gob.ar/salud/vacunas] | |
Australian Government. Department of Health and Aged Care. Immunisation for pregnancy. 2022 [Available from: https://www.health.gov.au/health-topics/immunisation/when-to-get-vaccinated/immunisation-for-pregnancy] | |
Public Health Agency of Canada. Update on Immunization in pregnancy with Tetanus Toxoid, Reduced Diphtheria Toxoid, Reduced Acellular Pertussis (Tdap) Vaccine. 2018 [Available from: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/healthy-living/update-immunization-pregnancy-tdap-vaccine/update-immunization-pregnancy-tdap-vaccine-eng.pdf. | |
Ministero della Salute. Direzione Generale della Prevenzione Sanitaria. Ufficio 5 Prevenzione delle Malattie Transmissibili e Profilassi Internazionale. Vaccinazioni raccomandate per le donne in età fertile e in gravidanza. 2019 [Available from: https://www.trovanorme.salute.gov.it/norme/renderNormsanPdf?anno=2019&codLeg=71540&parte=1&serie=null] | |
Gobierno de México. Vacuna Tdpa protege contra tétanos, difteria y pertussis acelular. 2015 [Available from: https://www.gob.mx/salud/articulos/vacuna-tdpa-protege-contra-tetanos-difteria-y-pertussis-acelular] | |
Rijksinstituut voor Volksgezondheid en Milieu. Ministerie van Volksgezondheid WeS. Waarom de 22 wekenprik? [Available from: https://rijksvaccinatieprogramma.nl/22wekenprik/waarom-22-wekenprik] | |
República Portuguesa. Programa Nacional de Vacinação 2020. 2020. | |
Donegan K, King B, Bryan P. Safety of pertussis vaccination in pregnant women in UK: observational study. BMJ 2014;349:g4219. | |
Kharbanda EO, Vazquez-Benitez G, Lipkind HS, et al. Evaluation of the association of maternal pertussis vaccination with obstetric events and birth outcomes. JAMA 2014;312(18):1897–904. | |
Vygen-Bonnet S, Hellenbrand W, Garbe E, et al. Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review. BMC Infect Dis 2020;20(1):136. | |
Kharbanda EO, Vazquez-Benitez G, Lipkind HS, et al. Maternal Tdap vaccination: Coverage and acute safety outcomes in the vaccine safety datalink, 2007–2013. Vaccine 2016;34(7):968–73. | |
Layton JB, Butler AM, Li D, et al. Prenatal Tdap immunization and risk of maternal and newborn adverse events. Vaccine 2017;35(33):4072–8. | |
Berenson AB, Hirth JM, Rahman M, et al. Maternal and infant outcomes among women vaccinated against pertussis during pregnancy. Hum Vaccin Immunother 2016;12(8):1965–71. | |
DeSilva M, Vazquez-Benitez G, Nordin JD, et al. Maternal Tdap vaccination and risk of infant morbidity. Vaccine 2017;35(29):3655–60. | |
Griffin JB, Yu L, Watson D, et al. Pertussis Immunisation in Pregnancy Safety (PIPS) Study: A retrospective cohort study of safety outcomes in pregnant women vaccinated with Tdap vaccine. Vaccine 2018;36(34):5173–9. | |
Morgan JL, Baggari SR, McIntire DD, et al. Pregnancy outcomes after antepartum tetanus, diphtheria, and acellular pertussis vaccination. Obstet Gynecol 2015;125(6):1433–8. | |
Eckert LO, Jones CE, Kachikis A, et al. Obstetrics risk Assessment: Evaluation of selection criteria for vaccine research studies in pregnant women. Vaccine 2020;38(29):4542–7. | |
Laverty M, Crowcroft N, Bolotin S, et al. Health Outcomes in Young Children Following Pertussis Vaccination During Pregnancy. Pediatrics 2021;147(5). | |
Sukumaran L, McCarthy NL, Kharbanda EO, et al. Association of Tdap Vaccination With Acute Events and Adverse Birth Outcomes Among Pregnant Women With Prior Tetanus-Containing Immunizations. JAMA 2015;314(15):1581–7. | |
Sukumaran L, Omer SB. Repeat Tdap Vaccination and Adverse Birth Outcomes–Reply. JAMA 2016;315(12):1286. | |
Huygen K, Caboré RN, Maertens K, et al. Humoral and cell mediated immune responses to a pertussis containing vaccine in pregnant and nonpregnant women. Vaccine 2015;33(33):4117–23. | |
Halperin SA, Langley JM, Ye L, et al. A Randomized Controlled Trial of the Safety and Immunogenicity of Tetanus, Diphtheria, and Acellular Pertussis Vaccine Immunization During Pregnancy and Subsequent Infant Immune Response. Clin Infect Dis 2018;67(7):1063–71. | |
Munoz FM, Bond NH, Maccato M, et al. Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: a randomized clinical trial. JAMA 2014;311(17):1760–9. | |
Fortner KB, Swamy GK, Broder KR, et al. Reactogenicity and immunogenicity of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant and nonpregnant women. Vaccine 2018;36(42):6354–60. | |
Havers FP, Skoff TH, Rench MA, et al. Maternal Tdap Vaccination during Pregnancy: Impact on Infant Anti-pertussis Antibody Concentrations by Maternal Pertussis Priming Series. Clin Infect Dis. 2022. | |
Giammanco A, Taormina S, Chiarini A, et al. Analogous IgG subclass response to pertussis toxin in vaccinated children, healthy or affected by whooping cough. Vaccine 2003;21(17–18):1924–31. | |
Hendrikx LH, Schure RM, Oztürk K, et al. Different IgG-subclass distributions after whole-cell and acellular pertussis infant primary vaccinations in healthy and pertussis infected children. Vaccine 2011;29(40):6874–80. | |
Post AL, Li SH, Berry M, et al. Efficiency of placental transfer of vaccine-elicited antibodies relative to prenatal Tdap vaccination status. Vaccine 2020;38(31):4869–76. | |
Maertens K, Caboré RN, Huygen K, et al. Pertussis vaccination during pregnancy in Belgium: Results of a prospective controlled cohort study. Vaccine 2016;34(1):142–50. | |
Wanlapakorn N, Maertens K, Chaithongwongwatthana S, et al. Assessing the reactogenicity of Tdap vaccine administered during pregnancy and antibodies to Bordetella pertussis antigens in maternal and cord sera of Thai women. Vaccine 2018;36(11):1453–9. | |
Maertens K, Orije MRP, Herzog SA, et al. Pertussis Immunization During Pregnancy: Assessment of the Role of Maternal Antibodies on Immune Responses in Term and Preterm-Born Infants. Clin Infect Dis 2022;74(2):189–98. | |
van der Maas NAT, Sanders EAM, Versteegh FGA, et al. Pertussis hospitalizations among term and preterm infants: clinical course and vaccine effectiveness. BMC Infect Dis 2019;19(1):919. | |
Winter K, Harriman K. Risk Markers for Pertussis Among Infants <4 Months of Age: Understanding the Hispanic Disparity. Pediatr Infect Dis J 2018;37(2):126–31. | |
Abu-Raya B, Bettinger JA, Vanderkooi OG, et al. Burden of Children Hospitalized With Pertussis in Canada in the Acellular Pertussis Vaccine Era, 1999–2015. J Pediatric Infect Dis Soc 2020;9(2):118–27. | |
Hoang HT, Leuridan E, Maertens K, et al. Pertussis vaccination during pregnancy in Vietnam: Results of a randomized controlled trial Pertussis vaccination during pregnancy. Vaccine 2016;34(1):151–9. | |
Maertens K, Hoang TT, Nguyen TD, et al. The Effect of Maternal Pertussis Immunization on Infant Vaccine Responses to a Booster Pertussis-Containing Vaccine in Vietnam. Clin Infect Dis 2016;63(suppl 4):S197-s204. | |
Maertens K, Caboré RN, Huygen K, et al. Pertussis vaccination during pregnancy in Belgium: Follow-up of infants until 1 month after the fourth infant pertussis vaccination at 15 months of age. Vaccine 2016;34(31):3613–9. | |
Ladhani SN, Andrews NJ, Southern J, et al. Antibody responses after primary immunization in infants born to women receiving a pertussis-containing vaccine during pregnancy: single arm observational study with a historical comparator. Clin Infect Dis 2015;61(11):1637–44. | |
Rice TF, Diavatopoulos DA, Smits GP, et al. Antibody responses to Bordetella pertussis and other childhood vaccines in infants born to mothers who received pertussis vaccine in pregnancy – a prospective, observational cohort study from the United Kingdom. Clin Exp Immunol 2019;197(1):1–10. | |
Abu-Raya B, Maertens K, Munoz FM, et al. The Effect of Tetanus-Diphtheria-Acellular-Pertussis Immunization During Pregnancy on Infant Antibody Responses: Individual-Participant Data Meta-Analysis. Front Immunol 2021;12:689394. | |
Amirthalingam G, Campbell H, Ribeiro S, et al. Sustained Effectiveness of the Maternal Pertussis Immunization Program in England 3 Years Following Introduction. Clin Infect Dis 2016;63(suppl 4):S236-s43. | |
Baxter R, Bartlett J, Fireman B, et al. Effectiveness of Vaccination During Pregnancy to Prevent Infant Pertussis. Pediatrics 2017;139(5). | |
Wanlapakorn N, Maertens K, Thongmee T, et al. Levels of antibodies specific to diphtheria toxoid, tetanus toxoid, and Haemophilus influenzae type b in healthy children born to Tdap-vaccinated mothers. Vaccine 2020;38(44):6914–21. | |
Zimmermann P, Perrett KP, Messina NL, et al. The Effect of Maternal Immunisation During Pregnancy on Infant Vaccine Responses. EClinicalMedicine 2019;13:21–30. | |
Maertens K, Burbidge P, Van Damme P, et al. Pneumococcal Immune Response in Infants Whose Mothers Received Tetanus, Diphtheria and Acellular Pertussis Vaccination During Pregnancy. Pediatr Infect Dis J 2017;36(12):1186–92. | |
Barug D, Berbers GAM, van Houten MA, et al. Infant antibody levels following 10-valent pneumococcal-protein D conjugate and DTaP-Hib vaccinations in the first year of life after maternal Tdap vaccination: An open-label, parallel, randomised controlled trial. Vaccine 2020;38(29):4632–9. | |
Maertens K, De Schutter S, Braeckman T, et al. Breastfeeding after maternal immunisation during pregnancy: providing immunological protection to the newborn: a review. Vaccine 2014;32(16):1786–92. | |
De Schutter S, Maertens K, Baerts L, et al. Quantification of vaccine-induced antipertussis toxin secretory IgA antibodies in breast milk: comparison of different vaccination strategies in women. Pediatr Infect Dis J 2015;34(6):e149–52. | |
Orije MRP, Larivière Y, Herzog SA, et al. Breast Milk Antibody Levels in Tdap-Vaccinated Women After Preterm Delivery. Clin Infect Dis 2021;73(6):e1305-e13. | |
Abu Raya B, Srugo I, Kessel A, et al. The induction of breast milk pertussis specific antibodies following gestational tetanus-diphtheria-acellular pertussis vaccination. Vaccine 2014;32(43):5632–7. | |
Amirthalingam G, Andrews N, Campbell H, et al. Effectiveness of maternal pertussis vaccination in England: an observational study. Lancet 2014;384(9953):1521–8. | |
Dabrera G, Amirthalingam G, Andrews N, et al. A case-control study to estimate the effectiveness of maternal pertussis vaccination in protecting newborn infants in England and Wales, 2012–2013. Clin Infect Dis 2015;60(3):333–7. | |
Skoff TH, Blain AE, Watt J, et al. Impact of the US Maternal Tetanus, Diphtheria, and Acellular Pertussis Vaccination Program on Preventing Pertussis in Infants <2 Months of Age: A Case-Control Evaluation. Clin Infect Dis 2017;65(12):1977–83. | |
Bellido-Blasco J, Guiral-Rodrigo S, Míguez-Santiyán A, et al. A case-control study to assess the effectiveness of pertussis vaccination during pregnancy on newborns, Valencian community, Spain, 1 March 2015 to 29 February 2016. Euro Surveill 2017;22(22). | |
Saul N, Wang K, Bag S, et al. Effectiveness of maternal pertussis vaccination in preventing infection and disease in infants: The NSW Public Health Network case-control study. Vaccine 2018;36(14):1887–92. | |
Becker-Dreps S, Butler AM, McGrath LJ, et al. Effectiveness of Prenatal Tetanus, Diphtheria, Acellular Pertussis Vaccination in the Prevention of Infant Pertussis in the U.S. Am J Prev Med 2018;55(2):159–66. | |
Mott K, Huybrechts KF, Glynn RJ, et al. Tetanus, Diphtheria, Acellular Pertussis Vaccination During Pregnancy and Risk of Pertussis in the Newborn in Publicly and Privately Insured Mother-infant Pairs in the United States. Pediatr Infect Dis J 2021;40(7):681–7. | |
Abu Raya B, Srugo I, Kessel A, et al. The effect of timing of maternal tetanus, diphtheria, and acellular pertussis (Tdap) immunization during pregnancy on newborn pertussis antibody levels – a prospective study. Vaccine 2014;32(44):5787–93. | |
Naidu MA, Muljadi R, Davies-Tuck ML, et al. The optimal gestation for pertussis vaccination during pregnancy: a prospective cohort study. Am J Obstet Gynecol 2016;215(2):237.e1–6. | |
Healy CM, Rench MA, Swaim LS, et al. Association Between Third-Trimester Tdap Immunization and Neonatal Pertussis Antibody Concentration. JAMA 2018;320(14):1464–70. | |
Abu-Raya B, Giles ML, Kollmann TR, et al. The Effect of Timing of Tetanus-Diphtheria-Acellular Pertussis Vaccine Administration in Pregnancy on the Avidity of Pertussis Antibodies. Front Immunol 2019;10:2423. | |
Eberhardt CS, Blanchard-Rohner G, Lemaître B, et al. Maternal Immunization Earlier in Pregnancy Maximizes Antibody Transfer and Expected Infant Seropositivity Against Pertussis. Clin Infect Dis 2016;62(7):829–36. | |
Eberhardt CS, Blanchard-Rohner G, Lemaître B, et al. Pertussis Antibody Transfer to Preterm Neonates After Second- Versus Third-Trimester Maternal Immunization. Clin Infect Dis 2017;64(8):1129–32. | |
Gomme J, Wanlapakorn N, Ha HTT, et al. The Impact of Timing of Pertussis Vaccination During Pregnancy on Infant Antibody Levels at Birth: A Multi-Country Analysis. Front Immunol 2022;13:913922. | |
Winter K, Cherry JD, Harriman K. Effectiveness of Prenatal Tetanus, Diphtheria, and Acellular Pertussis Vaccination on Pertussis Severity in Infants. Clin Infect Dis 2017;64(1):9–14. | |
Godoy P, García-Cenoz M, Rius C, et al. Effectiveness of maternal pertussis vaccination in protecting newborn: A matched case-control study. J Infect 2021;83(5):554–8. |
Online Study Assessment Option
All readers who are qualified doctors or allied medical professionals can now automatically receive 2 Continuing Professional Development credits from FIGO plus a Study Completion Certificate from GLOWM for successfully answering 4 multiple choice questions (randomly selected) based on the study of this chapter.
Medical students can receive the Study Completion Certificate only.
(To find out more about FIGO’s Continuing Professional Development awards programme CLICK HERE)