Safety profile of Td vaccination in Indonesian pregnant women: a post-marketing surveillance study
BACKGROUND The Indonesian Expanded Program of Immunization has implemented tetanus and diphtheria (Td) vaccination to replace the tetanus toxoid vaccine in pregnant women since the year 2016. Td vaccine is administered to protect against diphtheria and tetanus to the mother and her baby as well. This prospective study was conducted to assess the adverse reactions after Td immunization; besides, a retrospective study was conducted to observe the presence of severe local reaction (Arthus reaction), premature birth, and low birth weight history in the medical records of pregnant women who had received Td immunization in the past year.
METHODS A prospective observational study was conducted in 200 pregnant women. Local reactions and systemic events occurring within 28 days after immunization were recorded in the diary card and were confirmed by the health worker in the follow-up visit. A retrospective study was also conducted to evaluate 750 medical records of pregnant women who had received Td immunization. The study was conducted from September 2017 to January 2018. The study has been registered at ClinicalTrials.gov ID: NCT03383653.
RESULTS In 185 pregnant women who completed the study, the most common local reaction was pain, occurring in 33.5% of subjects within 24 hours after vaccination. Fever, other systemic reactions, and serious adverse events were not reported during the observation. In the retrospective study, 647 medical records were validated. No Arthus reaction was observed. The prevalence of premature birth was 1.24%, and that of low birth weight was 2.63%, which were below the normal rates.
CONCLUSIONS Td vaccination in pregnant women was safe and well-tolerated.
World Health Organization. Safety of immunization during pregnancy. A review of the evidence. Global Advisory Committee on Vaccine Safety [Internet]. Geneva: World Health Organization; 2014 [cited 2018 Oct 8]. Available from: https://www.who.int.
Indonesian Ministry of Health. Indonesia health profile 2015 [Internet]. Jakarta: Indonesian Ministry of Health; 2015 [cited 2017 Apr 9]. Available from: http://www.depkes.go.id/resources/download/pusdatin/profil-kesehatan-indonesia/Profil-Kesehatan-Indonesia-2015.pdf. Indonesian.
Sur DK, Wallis DH, O'Connell TX. Vaccinations in pregnancy. Am Fam Physician. 2003;68(2):299-304.
Centers of Disease Control and Prevention (CDC). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women-Advisory Committee on Immunization Practices (ACIP), 2012. MMWR Morb Mortal Wkly Rep. 2013;62(7):131-5.
Galazka A. The changing epidemiology of diphtheria in the vaccine era. J Infect Dis. 2000;181 (Suppl 1):S2-9. https://doi.org/10.1086/315533
Muchlastriningsih E. Vaccine preventable disease in Indonesia. Cermin Dunia Kedokteran. 2005;148:5-11. Indonesian.
Kajian vaksin Td untuk penanggulangan kejadian luar biasa difteri di daerah risiko tinggi. Komite Penasehat Ahli Imunisasi Nasional. SK. Menkes No. 904/MENKES/SK/VII/2010 (Mei.31, 2010).
Kementerian Kesehatan RI Direktorat Jenderal Pencegahan dan Pengendalian Penyakit (Jakarta, Indonesia). Letter to: Kepala Dinas Kesehatan Provinsi Seluruh Indonesia (Indonesia). 2016 Apr 11. 1 leaf. Pemberitahuan peralihan penggunaan vaksin TT ke Td pada wanita usia subur. No.:HK.03.03/D.1/II.2/2511/2016.
Fulton TR, Narayanan D, Bonhoeffer J, Ortiz JR, Lambach P, Omer SB. A systematic review of adverse events following immunization during pregnancy and the newborn period. Vaccine. 2015;33(47):6453-65. https://doi.org/10.1016/j.vaccine.2015.08.043
Marcy SM, Kohl KS, Dagan R, Nalin D, Blum M, Jones MC, et al. Fever as an adverse event following immunization: case definition and guidelines of data collection, analysis, and presentation. Vaccine. 2004;22(5-6):551-6. https://doi.org/10.1016/j.vaccine.2003.09.007
Gidudu J, Kohl KS, Halperin S, Hammer SJ, Heath PT, Hennig R, et al. A local reaction at or near injection site: case definition and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2008;26(52):6800-13. https://doi.org/10.1016/j.vaccine.2008.10.006
US Food and Drug Administration. Guidance for industry: toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials [Internet]. 2007. [cited October 8 2018]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/toxicity-grading-scale-healthy-adult-and-adolescent-volunteers-enrolled-preventive-vaccine-clinical.
World Health Organization. Information sheet observed rate of vaccine reactions diphtheria, pertussis, tetanus vaccines. Global Vaccine Safety [Internet]. Geneva: World Health Organization; 2014 [cited 2018 Oct 15]. Available from: https://www.who.int/vaccine_safety/initiative/tools/DTP_vaccine_rates_information_sheet.pdf.
Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable disease. 13th ed. Washington D.C: Public Health Foundation; 2015.
Quinn JA, Munoz FM, Gonik B, Frau L, Cutland C, Mallett-Moore T, et al. Preterm birth: case definition & guidelines for data collection, analysis, and presentation of immunisation safety data. Vaccine. 2016;34(49):6047-56. https://doi.org/10.1016/j.vaccine.2016.03.045
Cutland CL, Lackritz EM, Mallett-Moore T, Bardají A, Chandrasekaran R, Lahariya C, et al. Low birth weight: case definition & guidelines for data collection analysis, and presentation of maternal immunization safety data. Vaccine. 2017;35(48 Pt A):6492-500. https://doi.org/10.1016/j.vaccine.2017.01.049
Sawyer, M. Pertussis vaccine. Summary Report. Department of Health and Human Services. Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP) [Internet]. 2012 [cited 2018 Oct 8]. p. 170. Available from: https://www.cdc.gov.
Fadlyana E, Rusmil K, Garna H, Sumarman I, Adi SS, Bachtiar NS. Immunogenicity and Safety Td Vaccine in adolescent to prevent re-emerging disease in Indonesia. Sari Pediatri. 2013;15(3):141-9. Indonesian. https://doi.org/10.14238/sp15.3.2013.141-9
Sundoro J, Bachtiar NS, Syafriyal, Sari RM. Protectivity, local reactions, and systemic reaction following td vaccination among elementary school students in Indonesia. MKB. 2014;46(3):155-61. Indonesian. https://doi.org/10.15395/mkb.v46n3.315
Petousis-Harris H, Walls T, Watson D, Paynter J, Graham P, Turner N. Safety of Tdap vaccine in pregnant women: an observational study. BMJ Open. 2016;6:e010911. https://doi.org/10.1136/bmjopen-2015-010911
World Health Organization. Immunization, vaccine and biologicals. Tetanus [Internet]. 2018 [cited 2018 Oct 15]. Available from: https://www.who.int/immunization/diseases/tetanus/en/.
Zheteyeva YA, Moro PL, Tepper NK, Rasmussen SA, Barash FE, Revzina NV, et al. Adverse event reports after tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines in pregnant women. Am J Obstet Gynecol. 2012;207(1):59.e1-7. https://doi.org/10.1016/j.ajog.2012.05.006
World Health Organization. Preterm birth [Internet]. 2018 [cited 2018 Oct 15]. Available from: https://www.who.int/news-room/fact-sheets/detail/preterm-birth.
Indonesian Ministry of Health. Indonesia health profile 2014 [Internet]. Jakarta: Indonesian Ministry of Health; 2015 [cited 2018 Oct 8]. Available from: https://www.google.com/url?sa=t&source=web&rct=j&url=http://www.depkes.go.id/resources/download/pusdatin/profil-kesehatan-indonesia/profil-kesehatan-indonesia-2014.pdf&ved=2ahUKEwix0dDwp57mAhV56nMBHcmbDw0QFjAAegQICBAC&usg=AOvVaw12rtDRtuGUjSCdBhhmOMDr.
Sukumaran L, McCarthy NL, Kharbanda EO, McNeil MM, Naleway AL, Klein NP, et al. Association of Tdap vaccination with acute events and adverse birth outcomes among women with prior tetanus-containing immunizations. JAMA. 2015;314(15):1581-7. https://doi.org/10.1001/jama.2015.12790
Copyright (c) 2019 Mita Puspita
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.