Skip to main content

Advertisement

SpringerLink
Log in

Non-adherence to Medications in Pregnant Ulcerative Colitis Patients Contributes to Disease Flares and Adverse Pregnancy Outcomes

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Adherence to medications is important to maintain disease under control and to prevent complications in pregnant patients with ulcerative colitis (UC). To evaluate the incidence of non-adherence during pregnancy and its effect on relapse and pregnancy outcomes, we conducted a multicenter prospective study using a patient self-reporting system without physician interference.

Methods

Sixty-eight pregnant UC women were recruited from 17 institutions between 2013 and 2019. During the course of pregnancy, questionnaires were collected separately from patients and physicians, to investigate the true adherence to medications, disease activity, and birth outcomes. Multivariable logistic regression analysis was performed to identify the risk factors for the relapse or adverse pregnancy outcomes.

Results

Of 68 pregnancy, 15 adverse pregnancy outcomes occurred in 13 patients. The rate of self-reported non-adherence was the greatest to mesalamines in the first trimester, which was significantly higher than physicians’ estimate (p = 0.0116), and discontinuation was observed in 42.1% of non-adherent group. Logistic regression analysis revealed non-adherence as an independent risk factor for relapse [odds ratio (OR) 7.659, 95% CI 1.928–30.427, p = 0.038], and possibly for adverse pregnancy outcome (OR 8.378, 95% CI 1.350–51.994, p = 0.023). Among the subgroup of patients treated with oral mesalamine alone, the non-adherence was confirmed to be an independent risk factor for relapse (p = 0.002).

Conclusion

Non-adherence to mesalamine was underestimated by physicians in pregnant UC patients and contributed to disease relapse and possibly on pregnancy outcomes. Preconceptional education regarding safety of medications and risk of self-discontinuation is warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

OR:

Odds ratio

CI:

Confidence interval

IBD:

Inflammatory bowel disease

UC:

Ulcerative colitis

LBW:

Low birth weight

VAS:

Visual analogue scale

TNF:

Tumor necrosis factor

References

  1. Haynes RB, Sackett DL, Taylor DW. How to detect and manage low patient compliance in chronic illness. Geriatrics. 1980;35:91–97.

    CAS  PubMed  Google Scholar 

  2. Jackson CA, Clatworthy J, Robinson A, et al. Factors associated with non-adherence to oral medication for inflammatory bowel disease: a systematic review. Am J Gastroenterol. 2010;105:525–539.

    Article  CAS  Google Scholar 

  3. Kane S, Huo D, Aikens J, Hanauer S. Medication nonadherence and the outcomes of patients with quiescent ulcerative colitis. Am J Med. 2003;114:39–43.

    Article  Google Scholar 

  4. Kawakami A, Tanaka M, Nishigaki M, et al. Relationship between non-adherence to aminosalicylate medication and the risk of clinical relapse among Japanese patients with ulcerative colitis in clinical remission: a prospective cohort study. J Gastroenterol. 2013;48:1006–1015.

    Article  CAS  Google Scholar 

  5. Pedersen N, Bortoli A, Duricova D, et al. The course of inflammatory bowel disease during pregnancy and postpartum: a prospective European ECCO-EpiCom Study of 209 pregnant women. Aliment Pharmacol Ther. 2013;38:501–512.

    Article  CAS  Google Scholar 

  6. Gallinger ZR, Rumman A, Nguyen GC. Perceptions and attitudes towards medication adherence during pregnancy in inflammatory bowel disease. J Crohns Colitis. 2016;10:892–897.

    Article  Google Scholar 

  7. Perry J, Chen A, Kariyawasam V, et al. Medication non-adherence in inflammatory bowel diseases is associated with disability. Intest Res. 2018;16:571–578.

    Article  Google Scholar 

  8. Rahimi R, Nikfar S, Rezaie A, et al. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis. Reprod Toxicol. 2008;25:271–275.

    Article  CAS  Google Scholar 

  9. Severs M, Zuithoff PN, Mangen MJ, et al. Assessing self-reported medication adherence in inflammatory bowel disease: a comparison of tools. Inflamm Bowel Dis. 2016;22:2158–2164.

    Article  Google Scholar 

  10. Julsgaard M. Adherence to medical treatment in relation to pregnancy, birth outcome & breastfeeding behavior among women with Crohn’s disease. Dan Med J. 2016; 63pii: B5263.

  11. Burton MJ, Voluse AC, Patel AB, et al. Measuring adherence to hepatitis C direct-acting antiviral medications: using the VAS in an HCV treatment clinic. South Med J. 2018;111:45–50.

    Article  Google Scholar 

  12. Bello C, Belaiche J, Louis E, et al. Evolution and predictive factors of relapse in ulcerative colitis patients treated with mesalazine after a first course of corticosteroids. J Crohn’s Colitis. 2011;5:196–202.

    Article  CAS  Google Scholar 

  13. Romberg-Camps MJ, Dagnelie PC, Kester AD, et al. Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease. Am J Gastroenterol. 2009;104:371–383.

    Article  CAS  Google Scholar 

  14. https://www.mhlw.go.jp/file/05-Shingikai-10801000-Iseikyoku-Soumuka/0000134652.pdf Accessed 15 Apr 2019

  15. Fukuda T, Naganuma M, Sugimoto S, et al. The risk factor of clinical relapse in ulcerative colitis patients with low dose 5-aminosalicylic acid as maintenance therapy: a report from the IBD registry. PLoS ONE. 2017;12:e0187737.

    Article  Google Scholar 

  16. Wang Y, Parker CE, Feagan BG, et al. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2016;5:CD000544. https://doi.org/10.1002/14651858.cd000544.pub4.

    Article  Google Scholar 

  17. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487–497.

    Article  CAS  Google Scholar 

  18. Nguyen TM, La Caze A, Cottrell N. What are validated self-report adherence scales really measuring?: a systematic review. Br J Clin Pharmacol. 2014;77:427–445.

    Article  Google Scholar 

  19. Kleinman NJ, Manhart LE, Mohanraj R, et al. Antiretroviral therapy adherence measurement in non-clinical settings in South India. AIDS Care. 2015;27:248–254.

    Article  Google Scholar 

  20. Selinger CP, Ochieng AO, George V, et al. The accuracy of adherence self-report scales in patients on thiopurines for inflammatory bowel disease: a comparison with drug metabolite levels and medication possession ratios. Inflamm Bowel Dis. 2018;25:919–924.

    Article  Google Scholar 

  21. Bröms G, Granath F, Linder M, et al. Birth outcomes in women with inflammatory bowel disease: effects of disease activity and drug exposure. Inflamm Bowel Dis. 2014;20:1091–1098.

    PubMed  Google Scholar 

  22. Shivhare SB, Bulmer JN, Lash GE. Immunity at the maternal–fetal interface. In: Mestecky J, Strober W, Russell M, eds. Mucosal immunology. 4th ed. New York: Academic Press; 2015:2231–2250.

    Chapter  Google Scholar 

  23. Soler A, Morales C, Mademont-Soler I, et al. Overview of chromosome abnormalities in first trimester miscarriages: a series of 1,011 consecutive chorionic villi sample karyotypes. Cytogenet Genome Res. 2017;152:81–89.

    Article  CAS  Google Scholar 

  24. Bressler B, Marshall JK, Bernstein CN, et al. Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the toronto consensus. Gastroenterology. 2015;148:1035–1058.

    Article  Google Scholar 

  25. Haynes RB, Ackloo E, Sahota N, et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2008;. https://doi.org/10.1002/14651858.CD000011.pub3.

    Article  PubMed  Google Scholar 

  26. D’Incà R, Bertomoro P, Mazzocco K, et al. Risk factors for non-adherence to medication in inflammatory bowel disease patients. Aliment Pharmacol Ther. 2008;27:166–172.

    Article  Google Scholar 

  27. Lee J, Jee SR, Kim HW, et al. Factors associated with low adherence to oral 5-aminosalicylic acid in patients with ulcerative colitis. PLoS One.. 2019;. https://doi.org/10.1371/journal.pone.0214129.eCollection2019.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Peduzzi P, Concato J, Kemper E, et al. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49:1373–1379.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a Grant-in-Aid for the Intractable Disease Project of the Ministry of Health, Labour and Welfare of Japan, and by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology. Special thanks to Makiko Oda for her professional help with analyzing data statistically.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Chikako Watanabe & Ryota Hokari

  2. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

    Masakazu Nagahori & Toshimitsu Fujii

  3. Department of Gastroenterology, Kitasato University School of Medicine, 1-15-1 Kitazato, Minami, Sagamihara, Kanagawa, 252-0374, Japan

    Kaoru Yokoyama

  4. Division of IBD, Department of Internal Medicine, Tokyo Yamate Medical Center, 3-22-1 Hyakunincho, Shinjuku-ku, Tokyo, 169-0073, Japan

    Naoki Yoshimura

  5. Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8462, Japan

    Taku Kobayashi & Toshifumi Hibi

  6. Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3, Asahimachi, Abeno-ku, Osaka, 545-8585, Japan

    Hirokazu Yamagami

  7. Department of Gastroenterology, Kanazawa University Hospital, 13-1 Takaracho, Kanazawa, Ishikawa, 920-8641, Japan

    Kazuya Kitamura

  8. Department of Gastroenterology, National Hospital Organization Kanazawa Medical Center, 1-1 Shimoishihikicho, Kanazawa, Ishikawa, 920-8650, Japan

    Kagaya Takashi

  9. Department of Inflammatory Bowel Disease, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan

    Shiro Nakamura

  10. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Makoto Naganuma

  11. Department of Gastroenterology, Shimane University School of Medicine, 1060 Nishikawatsu-cho, Matsue-shi, Shimane, 690-8504, Japan

    Shunji Ishihara

  12. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka City, 812-8582, Japan

    Motohiro Esaki

  13. Department of Internal Medicine and Gastroenterology, Tokyo Women’s Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Maria Yonezawa

  14. Inflammatory Bowel Disease Center, Yokohama City University Medical Center, 4-57 Urafunecho, Minami-ku, Yokohama-City, Kanagawa, 232-0024, Japan

    Reiko Kunisaki

  15. Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, 5841 S. Maryland Ave. MC 4076, Chicago, IL, 60637, USA

    Atsushi Sakuraba

  16. Department of Obstetrics and Gynecology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Naoaki Kuji

  17. International University of Health and Welfare Graduate School, 4-1-26 Akasaka, Minato ku, Tokyo, 107-8402, Japan

    Soichiro Miura

  18. Department of Internal Medicine, Sakura Medical Center, Toho University, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan

    Yasuo Suzuki

Authors
  1. Chikako Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masakazu Nagahori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshimitsu Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kaoru Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naoki Yoshimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Taku Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hirokazu Yamagami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazuya Kitamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kagaya Takashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shiro Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Makoto Naganuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shunji Ishihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Motohiro Esaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Maria Yonezawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Reiko Kunisaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Atsushi Sakuraba
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Naoaki Kuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Soichiro Miura
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Toshifumi Hibi
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Yasuo Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Ryota Hokari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chikako Watanabe.

Ethics declarations

Conflict of interest

None.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Watanabe, C., Nagahori, M., Fujii, T. et al. Non-adherence to Medications in Pregnant Ulcerative Colitis Patients Contributes to Disease Flares and Adverse Pregnancy Outcomes. Dig Dis Sci 66, 577–586 (2021). https://doi.org/10.1007/s10620-020-06221-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-020-06221-6

Keywords

Search

Navigation