Protecting newborns against pertussis: the value of vaccinating during pregnancy

Abstract

Resurgence of pertussis has recently been reported in several countries with long-standing pertussis immunization and high vaccination coverage. This situation requires consideration of alternative immunization strategies to protect newborns. In the absence of a vaccine that confers long-lasting immunity, maternal vaccination for pertussis during pregnancy seems to be a safe, immunogenic, effective and accepted strategy to protect infants during the first weeks of life. The existing scientific evidence provides the grounds for pregnant women and healthcare workers to make informed decisions regarding this measure as well as for countries with high pertussis-related infant morbidity and mortality that should consider implementation. Furthermore, this could be a promising strategy to address other vaccine-preventable diseases of pregnancy and the neonatal period.

Keywords:

• child health
• coverage
• maternal immunization
• neonatal pertussis
• pregnancy
• vaccination
• whooping cough

Pertussis is currently a major cause of infant morbidity and mortality worldwide and an emerging public health concern. A resurgence of pertussis cases has recently been reported in several countries with long-standing pertussis immunization and high vaccination coverage such as Spain [1], the USA [2] and the UK [3]. Although the reasons have not been fully elucidated, the improved availability of methods to confirm diagnoses (e.g., PCR), the increased awareness for diagnosis and reporting among health professionals, the different efficacy against disease and infection between whole cell and acellular vaccine, the pathogen adaptation or waning of natural or vaccine immunity during periods of low pertussis activity are thought to play an important role in the current trends of the disease [4]. Neither pertussis natural infection nor vaccination induces lifelong immunity; it has been estimated that only 10% of children will be protected 8.5 years after last dose of Tdap [5]. However, vaccination is the most effective way to combat whooping cough epidemics.

Cases increased in several countries in 2011, including high incidence in adulthood. Severe morbidity and mortality from pertussis are concentrated in infants aged <3 months. For example, in 2010, California reported an incidence of 445.9 per 100,000 infants <6 months of age [2], and in 2011, Spain reported an incidence of clinically reported cases higher than 500 cases per 100,000 infants <3 months of age. In the period between 2007 and 2010, there was an increase in infant mortality due to pertussis, being 3.75 deaths per year, compared to 1 death per year in the period 1997–2007 [1]. In UK, 48 deaths in infants under 1 year of age were identified between 2001 and 2011 [3]. In adolescents and adults, pertussis almost always presents as persistent cough, often of undiagnosed cause, and these cases (mainly the parents) are the main sources of infection to susceptible children [1].

The current situation requires consideration of alternative immunization strategies to protect newborns. In 2014, WHO and SAGE established a new working group in pertussis, which provided an opportunity of global review of pertussis epidemiology, as well as newly available data on effectiveness of various vaccination strategies aimed at reducing infant mortality, including pertussis vaccination for pregnant women [6]. Maternal immunization confers both direct and indirect protection. The direct, through a dose of pertussis vaccine during pregnancy that boosts maternal antibody levels, thus providing passive protection to the newborn prior to commencing the primary infant schedule at 2 months of age [7]; and indirect as part of the cocooning strategy (vaccination of close contacts of infants aiming to reduce exposure) protecting the mother as a frequent source of infection. Another additional protective effect could be through transfer of antibodies by breast milk [7].

The concept of maternal immunization is not new and the potential role of whole-cell pertussis containing vaccine (DTwP) in pregnancy was first explored in studies in the early 1940s [8] showing higher levels of antibodies in women with a history of pertussis infection or those immunized during pregnancy with DTwP. Recently, results from PERTU study [9] showed that >94% of infants of 132 mothers who received Tdap vaccination during the late second or third trimester of pregnancy presented levels of anti-pertussis ≥ 10 IU/ml. These findings are consistent with results from other studies [10,11] that have shown that maternal vaccination during pregnancy is associated with significantly higher levels of pertussis antibodies at birth, both in mothers and newborns. Although an accepted serological correlate of protection has not been established [12], high levels of pertussis antibodies in the cord blood have been associated with clinical protection against pertussis [13].

Vaccination of pregnant women with acellular pertussis-containing vaccine was recommended in the USA in 2011 [14] and as an outbreak response measure in the UK in 2012 [3]. In the last 2 years, various countries, agencies and scientific societies have incorporated this recommendation. In December 2012, the CDC issued interim recommendations indicating that women should be revaccinated during each pregnancy, with optimal timing for Tdap administration between 27 and 36 weeks of gestation [11]. Some countries have recommended only the cocooning strategy; however, this option has proven challenging to implement [14], requiring significant resources in order to vaccinate multiple family contacts. Other strategies have been considered, such as adolescent vaccination; however, this one is unlikely to show clear benefits to infants by itself [1].

The available scientific evidence indicates that maternal pertussis vaccination with Tdap is safe among pregnant women, their fetus and the newborn [10,15]. In a clinical trial with crossover design assessing the safety and immunogenicity of Tdap, local reactions were reported during pregnancy in 79% of vaccinated women, versus 80% after pregnancy. Most symptoms were mild and resolved within 72 h. Systemic reactions were noted in 36% of women vaccinated during pregnancy, in 73% of women vaccinated during the postpartum period and in 53% of vaccinated non-pregnant women, with headache, myalgia and malaise being the most common reactions [10].

Although it has been hypothesized that high levels of maternal antibodies may be associated with a poor immune response to vaccination in the infant [16], two studies showed that neither the immune response (humoral and cellular) to DTaP nor safety is influenced by residual maternal antibodies [10,16]. Nevertheless, it has been observed that immunization with Tdap during pregnancy slightly decreased immune responses after primary doses of DTaP to the infants but the difference did not persist after the following booster doses [17]. The main objective should be to protect infants from severe pertussis, which outweighs the potential risk of suffering the more benign form of pertussis at older ages. There are no data suggesting increased risk of pertussis in vaccinated infants aged 6–11 months in those countries who have implemented a maternal pertussis vaccination program (with a vaccine containing diphtheria, tetanus, polio and pertussis antigens) [18].

A recently published case–control study has estimated that the vaccine effectiveness of pertussis vaccination among pregnant women to protect newborn and infants is 93% [19]. The observed vaccine effectiveness is likely to be a combination of the direct effect of transplacental antibody transfer from mother to infant, and the indirect effect of protecting the mother from pertussis. Moreover, it would potentially reduce household transmission and further prevent infant infection. The high vaccine efficacy is consistent with the reduction in reported infant pertussis cases in the UK and Spain following the introduction of maternal vaccination programs [18]. These findings should be conveyed to both pregnant women and health professionals as a means to promote higher uptake [19].

High vaccination coverage among pregnant women is challenging; however, the UK has achieved coverage of pertussis vaccination of around 60% [19] and in Catalonia (Spain), preliminary data show 56% coverage during the first year after implementation of the pregnancy vaccination program (unpublished data). Successful implementation of vaccination programs among pregnant women requires support from healthcare providers, improved access to vaccines and appropriate organizational structures [19]. In Catalonia, vaccination costs are fully funded and access to primary health care is free for the pregnancy follow-up visits, including in private healthcare facilities. The engagement and training of midwives, nurses, obstetricians and pediatric teams are crucial to ensure a high vaccination uptake. The role of healthcare professional advice, perceived susceptibility to disease by healthcare workers and pregnant women, and social norms surrounding healthcare practice have been identified as factors associated with vaccination coverage in pregnancy [20]. Demand among pregnant women for pertussis vaccination is driven by the will of protecting the baby [20].

The value of this strategy will need to be further assessed in other contexts, such as low-income countries. As shown by tetanus, influenza and pertussis vaccination during pregnancy, maternal immunization is a safe and effective approach for prevention of infection in neonates, and could be a promising strategy to address other vaccine preventable diseases of pregnancy and the neonatal period.

In the absence of a vaccine that confers long-lasting immunity, pertussis vaccination of pregnant women seems to be a safe, immunogenic, effective and accepted strategy to protect newborns during the first weeks of life. The existing scientific evidence provides the grounds for pregnant women and healthcare workers to make informed decisions, as well as for countries with high infant morbidity and mortality due to pertussis that should consider implementation of this measure to protect newborns.

Acknowledgements

The authors would like to thank E Parker for reviewing the manuscript for content and grammar.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.