Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
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Incidence of Dental Discoloration After Tetracycline Exposure in Korean Children: A Nationwide Population-Based Study

  • Ji Young Lee (Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine) ;
  • Eun Hwa Kim (Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine) ;
  • Myeongjee Lee (Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine) ;
  • Jehee Shin (Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine) ;
  • Sung Min Lim (Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine) ;
  • Jee Yeon Baek (Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine) ;
  • MinYoung Kim (Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine) ;
  • Jong Gyun Ahn (Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine) ;
  • Chung-Min Kang (Department of Pediatric Dentistry, Yonsei University College of Dentistry) ;
  • Inkyung Jung (Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine) ;
  • Ji-Man Kang (Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine)
  • Received : 2022.11.10
  • Accepted : 2023.09.07
  • Published : 2024.04.25
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Abstract

Purpose: Tetracycline is not recommended for children under 12 by guideline due to the risk of tooth discoloration. We aimed to assess the incidence of dental discoloration in Korean children prescribed tetracyclines and investigate whether its risk was greater in tetracycline-exposed children than in the general population. Methods: This population-based cohort study using the Health Insurance Review and Assessment service database included children aged 0-12 years exposed to tetracyclines for at least 1 day between January 2008 and December 2020. The primary outcome was the incidence rate of dental discoloration ≥6 months after prescription, and the standardized incidence ratio (SIR) was evaluated as secondary outcome. Results: 56,990 children were included-1,735 and 55,255 aged <8 and 8-12 years, respectively. 61% children were prescribed tetracycline for <14 days with mostly second-generation tetracyclines, doxycycline (61%) and minocycline (35%). The 5- and 10-year cumulative incidence rates of dental discoloration were 4.1% (95% confidence interval [CI], 3.0-5.7%) and 5.7% (95% CI, 4.1% to 7.8%), respectively, in the 0-7 years age group and 0.8% (95% CI, 0.7% to 0.9%) and 1.3 (95% CI, 1.1% to 1.4%), respectively, in the 8-12 years age group. Tetracycline exposure did not increase such risk compared to that in the general population (SIR, 1.08; 95% CI, 0.69 to 1.60). Conclusions: The incidence of dental discoloration was lower than previously suggested. Relieving the age restriction for prescribing tetracyclines may be considered.

목적: 테트라사이클린 (tetracycline, TC)은 소아청소년을 대상으로 복용하였을 시 영구적 치아 변색의 위험이 증가된다는 보고에 따라 미국에서는 8세 이하, 국내에서는 12세 미만으로 처방이 가이드라인상 추천되지 않고 있는 실정이다. 이에 본 연구에서는 TC에 노출된 소아청소년을 대상으로 치아 변색의 발생률을 분석하고, TC에 노출되지 않은 일반 인구 집단과의 발생률 차이를 비교하고자 하였다. 방법: 본 코호트 연구는 2008년 1월부터 2020년 12월 사이 최소 1일 이상 TC에 노출된 소아청소년(0-12세)에 대한 건강보험심사평가원 데이터베이스 정보를 기반으로 분석하였다. TC 노출 6개월 이후 치아 변색 관련 진단코드의 입력여부를 기준으로 치아 변색 발생률을 도출하였고, 추가적으로 연령 보정이 된 TC에 노출되지 않은 일반 인구집단을 추출하여 이를 변수로 한 표준화한 치아 변색 발병률(standardized incidence ratio, SIR)을 구하였다. 결과: 총 56,990명이 포함되었으며, 이 중 8세 미만은 1,735명, 그리고 8-12세는 55,255명이었다. 이 중 61%가 14일 미만 동안 TC를 처방받았으며, 독시사이클린(61%)과 미노사이클린(35%)을 포함한 2세대 TC가 가장 많은 비중을 차지하였다. 0-7세 연령군에서의 5년 및 10년 누적발생률은 4.1% (95% confidence interval [CI], 3.0% to 5.7%) 및 5.7% (95% CI, 4.1% to 7.8%)으로 확인되었고, 이에 비해 8-12세 연령군에서는 0.8% (95% CI, 0.7 to 0.9%) 및1.3 (95% CI, 1.1% to 1.4%)으로 상대적으로 낮았다. TC노출 후 치아 변색의 발생률은 연령 보정된 일반 인구 집단과 비교하였을 때 통계학적으로 유의미한 차이는 없었다 (SIR, 1.08; 95% CI, 0.69 to 1.60). 결론: TC 노출은 일반 인구에 비해 치아 변색 위험을 유의하게 증가시키지 않았으며, 특히 8-12세 사이의 TC 노출군은 그 이하 연령군에 비해 유의미하게 낮은 발생률을 보였다. 따라서, 국내에서 TC 처방에 대한 연령 제한 완화를 고려할 필요가 있다.

Keywords

Acknowledgement

The authors thank Medical Illustration & Design, part of the Medical Research Support Services of Yonsei University College of Medicine, for all artistic support related to this work.

References

  1. Weisblum B, Davies J. Antibiotic inhibitors of the bacterial ribosome. Bacteriol Rev 1968;32:493-528. https://doi.org/10.1128/br.32.4_pt_2.493-528.1968
  2. Okada T, Morozumi M, Tajima T, Hasegawa M, Sakata H, Ohnari S, et al. Rapid effectiveness of minocycline or doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011 outbreak among Japanese children. Clin Infect Dis 2012;55:1642-9. https://doi.org/10.1093/cid/cis784
  3. Tanaka T, Oishi T, Miyata I, Wakabayashi S, Kono M, Ono S, et al. Macrolide-resistant Mycoplasma pneumoniae infection, Japan, 2008-2015. Emerg Infect Dis 2017;23:1703-6. https://doi.org/10.3201/eid2310.170106
  4. D'Alessandro M, Loy A, Castagnola E. Management of lyme disease in european children: a review for practical purpose. Curr Infect Dis Rep 2017;19:27.
  5. Anderson A, Bijlmer H, Fournier P, Graves S, Hartzell J, Kersh G, et al. Diagnosis and management of Q fever - United States, 2013: recommendations from CDC and the Q Fever Working Group. Atlanta: Center for Disease Control and Prevention, 2013.
  6. Center for Disease Control and Prevention (CDC). Research on doxycycline and tooth staining [Internet]. Atlanta: CDC; 2019 [cited 2022 Apr 1]. Available from: https://www.cdc.gov/rmsf/doxycycline/index.html.
  7. Pereyre S, Goret J, Bebear C. Mycoplasma pneumoniae: current knowledge on macrolide resistance and treatment. Front Microbiol 2016;7:974.
  8. 2019 Acute respiratory infection Control Guideline. Cheongju: Korea Disease Control and Prevention Agency, 2019:127-31.
  9. Todd SR, Dahlgren FS, Traeger MS, Beltran-Aguilar ED, Marianos DW, Hamilton C, et al. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever. J Pediatr 2015;166:1246-51.
  10. Ministry of Food and Drug Safety (MFDS). Announcement on contraindications for combination and contraindications for certain ages [Internet]. Cheongju: MFDS; 2007 [cited 2022 May 9]. Available from: https://www.mfds.go.kr/docviewer/skin/doc.html?fn=d8253ddac3dd4204f9a36d5527077d90&rs=/docviewer/result/ntc0004/9574/1/202205.
  11. Wallman IS, Hilton HB. Teeth pigmented by tetracycline. Lancet 1962;1:827-9. https://doi.org/10.1016/S0140-6736(62)91840-8
  12. Swallow JN, De Haller J, Young WF. Side-effects to antibiotics in cystic fibrosis: dental changes in relation to antibiotic administration. Arch Dis Child 1967;42:311-8. https://doi.org/10.1136/adc.42.223.311
  13. Shwachman H, Fekete E, Kulczycki LL, Foley GE. The effect of long-term antibiotic therapy in patients with cystic fibrosis of the pancreas. Antibiot Annu 1958-1959;6:692-9.
  14. Conchie JM, Munroe JD, Anderson DO. The incidence of staining of permanent teeth by the tetracyclines. Can Med Assoc J 1970;103:351-6.
  15. Porter PJ, Sweeney EA, Golan H, Kass EH. Controlled study of the effect of prenatal tetracycline on primary dentition. Antimicrob Agents Chemother 1965;5:668-71.
  16. Forti G, Benincori C. Doxycycline and the teeth. Lancet 1969;1:782.
  17. Volovitz B, Shkap R, Amir J, Calderon S, Varsano I, Nussinovitch M. Absence of tooth staining with doxycycline treatment in young children. Clin Pediatr (Phila) 2007;46:121-6. https://doi.org/10.1177/0009922806290026
  18. Kimberlin DW, Lynfield R, Sawyer MH. Red book: 2021 report of the Committee on Infectious Diseases. 32th ed. Itasca: American Academy of Pediatrics, 2021.
  19. Health Insurance Review and Assessment (HIRA). Drug utilization review (DUR) [Internet]. Wonju: HIRA; c2023 [cited 2022 Apr 20]. Available from: https://www.hira.or.kr/dummy.do?pgmid=HIRAA990001000330.
  20. Gaillard T, Briolant S, Madamet M, Pradines B. The end of a dogma: the safety of doxycycline use in young children for malaria treatment. Malar J 2017;16:148.
  21. Reid DJ, Dean MC. Variation in modern human enamel formation times. J Hum Evol 2006;50:329-46. https://doi.org/10.1016/j.jhevol.2005.09.003
  22. Ha SG, Oh KJ, Ko KP, Sun YH, Ryoo E, Tchah H, et al. Therapeutic Efficacy and safety of prolonged macrolide, corticosteroid, doxycycline, and levofloxacin against macrolide-unresponsive Mycoplasma pneumoniae pneumonia in children. J Korean Med Sci 2018;33:e268.
  23. Atar M, Korperich EJ. Systemic disorders and their influence on the development of dental hard tissues: a literature review. J Dent 2010;38:296-306. https://doi.org/10.1016/j.jdent.2009.12.001
  24. Son M, Jo S, Lee JS, Lee DH. Association between oral health and incidence of pneumonia: a population-based cohort study from Korea. Sci Rep 2020;10:9576.