Pertussis vaccination during pregnancy in Belgium: Results of a prospective controlled cohort study
Introduction
Pertussis, caused by Bordetella pertussis, is a highly contagious respiratory illness and a major cause of infant morbidity and mortality. Global pertussis vaccination programs have been introduced with success and approximately 86% of infants worldwide have received 3 doses of the diphtheria-tetanus–pertussis (DTP3) vaccine [1].
However, a decade after the switch from the whole-cell (wP) vaccine to the acellular pertussis (aP) vaccine, a cyclic resurgence has been reported in several industrialized countries. The reason is presumed to be multifactorial, with waning immunity after the primary or booster vaccination as the primary cause. A resurgence has been observed in all age categories; however, severe morbidity and mortality occurs primarily in young infants who are not fully vaccinated [2], [3]. The majority of cases are found in adolescents and adults, due to waning immunity [4], and these populations represent sources of infection for young infants.
In Belgium, pertussis vaccination with a hexavalent aP-containing vaccine is offered at 8, 12, and 16 weeks and 15 months of age. Booster doses for children at 4–6 years of age (since 2004) and for adolescents at 14–16 years of age have been recommended (since 2009). Additionally, receiving a booster dose once during adulthood has been recommended since 2013 [5]. Nevertheless, the total number of confirmed cases increased in Belgium from 93 in 2005 to 843 cases in 2013 [6], of which many (25.4% in 2013) were found in infants under the age of 1 year.
Partial primary protection against infectious diseases is offered at birth by maternal immunoglobulin G (IgG) antibodies [7], [8], with an estimated half-life of 6 weeks for pertussis [8]. The amount of transmitted antibodies depends on the placental function and the concentration of maternal antibodies in the pregnant woman [9]. The latter depends on the time lapse since the last vaccination or infection [10] and the titer of passively transmitted pertussis maternal antibodies is often low [11]. Thus, increasing the load of maternal antibodies by vaccination during pregnancy is, with the currently available vaccines, the only way to offer passive protection to the newborn at birth [12]. During the first weeks of life, these maternal antibodies disappear in the newborn due to natural clearance [9], [13].
Vaccination during pregnancy is recommended in an increasing number of countries (e.g. UK, USA, Belgium, New Zealand, etc.). Research has been performed on the immunological and safety aspects of the strategy [14], [15], [16], [17], [18]; nevertheless, many aspects are still unknown, and the possible interference of maternal antibodies with the infant's immune responses is one of the concerns.
To the best of our knowledge, no other data have been published on the effects of using the combined tetanus, diphtheria and acellular pertussis vaccine Boostrix® (GSK, Rixensart, Belgium) during pregnancy. The primary aim was to measure the influence of this booster vaccination on the titer and the duration of maternal antibodies in infants and to assess possible interference.
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Material and methods
A prospective controlled cohort study was conducted in accordance with the Declaration of Helsinki, ICH-GCP, and the procedures established by Belgian law and was approved by the ethics committee of the University of Antwerp, Belgium (Clinicaltrials.gov identifier: NCT01698346). Written informed consent was obtained from all participants and from both parents of the participating infants (in accordance with the Belgian law and IRB regulations).
Healthy pregnant women and their healthy offspring
General characteristics of the study population (Table 1)
In total, 57 healthy pregnant women were vaccinated (the vaccine group), and 42 women were identified as controls (the control group). The children were born between April 2, 2012 and April 16, 2014. Blood samples were taken between February 6, 2012 and September 18, 2014. The mean interval between the Tdap immunization and delivery was 77.1 days (39–117 days). The mean gestational age at vaccination was 28.6 (22–33) weeks. After delivery, 55 children were included in the vaccine group
Discussion
This study is the first to investigate the effect of the administration of Boostrix® in pregnant women on transmitted maternal antibodies and to assess the immune responses of infants administered acellular pertussis-containing vaccines (Infanrix hexa®) according to a schedule of 8, 12 and 16 weeks of age. The presented data show that vaccinating during pregnancy closes the susceptibility gap for pertussis infection.
Safety data have been reported from far larger studies [16], [27], showing that
Conclusion
The pertussis vaccination has been recommended for every pregnant woman during each pregnancy by the Superior Health Council in Belgium since August 2013 and many other countries in Western Europe and North America; the results of this study support these recommendations and provide additional scientific evidence to continue this vaccination strategy. The susceptibility gap for pertussis in the youngest age group, before immunization starts, was closed. Blunting was found for the anti-PT
Conflict of interest statement
Authors do not have a commercial or other association that might pose a conflict of interest (e.g., pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding).
Acknowledgments
The authors would like to thank all participating women and their children. We would also like to thank all participating hospitals for their recruitment assistance and Mrs. Aline Bontenakel for performing the blood sampling in the infants. The excellent technical assistance for the laboratory testing of Caroline Rodeghiero and Christophe Van den Poel is gratefully acknowledged.
This work was supported by Vlir-UOS (Flemish Interuniversity Council) (ZEIN2012Z131) and FWO (Fund for Scientific
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