Ozturk O, Durak MB, Cagir Y, Ergul M, Keskin ET, Yilmaz E, Acun KC, Atay A, Yuksel I. Influence of pregnancy on outcomes of inflammatory bowel disease and treatment discontinuation. World J Gastroenterol 2026; 32(43): 120573 [DOI: 10.3748/wjg.120573]
Corresponding Author of This Article
Ilhami Yuksel, MD, Professor, Department of Gastroenterology, Faculty of Medicine, Ankara Yildirim Beyazit University, İhsan Doğramacı Caddesi, Bilkent, Ankara 06800, Türkiye. yukselilhami@hotmail.com
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Ozturk O, Durak MB, Cagir Y, Ergul M, Keskin ET, Yilmaz E, Acun KC, Atay A, Yuksel I. Influence of pregnancy on outcomes of inflammatory bowel disease and treatment discontinuation. World J Gastroenterol 2026; 32(43): 120573 [DOI: 10.3748/wjg.120573]
Oguz Ozturk, Mucahit Ergul, Emir Tugrul Keskin, Eren Yilmaz, Kadir Can Acun, Ali Atay, Ilhami Yuksel, Department of Gastroenterology, Ankara Bilkent City Hospital, Ankara 06800, Türkiye
Muhammed Bahaddin Durak, Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara 06120, Türkiye
Yavuz Cagir, Department of Gastroenterology, Ankara Yildirim Beyazit University Yenimahalle Training and Research Hospital, Ankara 06105, Türkiye
Ilhami Yuksel, Department of Gastroenterology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara 06800, Türkiye
Author contributions: Ozturk O, Durak MB, Cagir Y, Ergul M, Keskin ET, Yilmaz E, Acun KC, Atay A, and Yuksel I performed the data collection; Ozturk O and Yuksel I conceptualized the study, planned the design of the study, performed data analysis, interpreted the data, and drafted the manuscript. All authors revised and approved the final version of the manuscript to be submitted.
AI contribution statement: To ensure clarity, grammatical accuracy, and fluency in academic English, we used DeepL and QuillBot solely for language polishing and paraphrasing. These AI tools were only applied to refine the authors’ original ideas and were not used to generate any scientific arguments, interpretations, or data.
Institutional review board statement: The study received approval from the Ethics Committee of Ankara Bilkent City Hospital (Approval No. TABED 1-24-373) and was conducted in accordance with the principles set out in the Declaration of Helsinki.
Informed consent statement: All participants have signed the relevant informed consent forms.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The technical appendix, statistical code, and dataset are available from the corresponding author. This approach was reviewed and approved by the institutional ethics committee.
Corresponding author: Ilhami Yuksel, MD, Professor, Department of Gastroenterology, Faculty of Medicine, Ankara Yildirim Beyazit University, İhsan Doğramacı Caddesi, Bilkent, Ankara 06800, Türkiye. yukselilhami@hotmail.com
Received: March 5, 2026 Revised: March 23, 2026 Accepted: May 19, 2026 Published online: November 21, 2026 Processing time: 207 Days and 20.1 Hours
Abstract
BACKGROUND
Treatment of inflammatory bowel diseases (IBDs) is challenging due to the maintenance of remission and associated fetal safety concerns during pregnancy. While existing literature emphasizes the importance of achieving remission prior to conception, optimal management of IBD during pregnancy remains underexplored, especially regarding medication continuation and efficacy.
AIM
To evaluate the effect of treatment discontinuation on disease activation and pregnancy outcomes in a cohort of patients with IBD.
METHODS
This observational study was performed with pregnant patients with IBD between March 2019 and June 2023. Clinical features, treatment details, disease activation and outcomes were collected and analyzed.
RESULTS
A total of 57 pregnant woman was included, of whom 37 (64.9%) had ulcerative colitis (UC) while 20 (35.1%) had Crohn’s disease (CD). Before pregnancy, medical treatments for UC patients included mesalazine in 29 (78.4%) patients, thiopurine in 20 (54.1%) and biologic therapy in 6 (16.2%). Among the CD patients, 13 (65%) received biologic therapy and 7 (35%) received thiopurine. The most commonly prescribed biologic agent was infliximab for both diseases. During pregnancy, 16 (28.1%) patients, including 6 (18.8%) with UC and 10 (50%) with CD, had a history of treatment discontinuation. Thirteen (81%) medications were discontinued in line with the patient’s preference, with the vast majority of these discontinuations occurring immediately after confirmation of pregnancy rather than during the preconception planning phase. Notably, the majority of cases of patients discontinuing their treatment independently occurred prior to any structured medical counseling regarding the safety of IBD medications during pregnancy. Disease activation occurred for 25 (43.9%) patients, including 10 (50%) with CD and 15 (40.5%) with UC. Twelve (48%) patients required steroids due to activation. There were 54 (94.7%) live births and no statistically significant difference in the live birth rate according to whether disease activation developed or not [23 (92%) vs 31 (96.9%), P = 0.576]. The abortion rate was not associated with disease activation (P > 0.05). No serious infections occurred in the first month following birth.
CONCLUSION
The discontinuation of medical treatment during pregnancy at the patient’s discretion was significantly correlated with disease exacerbations, particularly in patients with UC, and subsequent salvage steroid treatment. These findings underscore the vital role of patient counseling prior to and during pregnancy, with the objective of ensuring medication compliance and optimizing maternal and fetal outcomes.
Core Tip: This study indicates that treatment discontinuation during pregnancy constitutes a substantial and preventable cause of disease exacerbation in women diagnosed with inflammatory bowel diseases, particularly ulcerative colitis. The related increase in the need for salvage steroid therapy reflects the critical importance of pre-pregnancy counseling to ensure treatment compliance and improve maternal and fetal outcomes.
Citation: Ozturk O, Durak MB, Cagir Y, Ergul M, Keskin ET, Yilmaz E, Acun KC, Atay A, Yuksel I. Influence of pregnancy on outcomes of inflammatory bowel disease and treatment discontinuation. World J Gastroenterol 2026; 32(43): 120573
Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD), are chronic relapsing conditions that typically affect people of reproductive age, with a rising incidence worldwide[1,2]. Globally, IBD onset most commonly occurs in the 3rd and 4th decades of life, with a second peak in the 6th and 7th decades. In a recent large cohort study conducted in Türkiye, the peak age of IBD onset was between 23 years and 27 years for CD and 28 years and 32 years for UC. Because the peak incidence happens during the reproductive years, optimizing disease management during pregnancy is all the more essential[3-5]. The principal objective in the management of IBDs is to ensure that the disease remains in remission both before and during pregnancy, as demonstrated by extensive trials. Studies indicate that active disease raises the risk of negative pregnancy outcomes such as preterm birth, low birth weight, and cesarean delivery[5-7].
As outlined in guidelines, the vast majority of IBDs drugs are considered safe during pregnancy and should be continued to ensure optimal disease management, with only a few exceptions, such as methotrexate. Despite these proven safety profiles, there is often a significant discrepancy between the recommendations in guidelines and patient behavior in clinical practice[7-9]. In spite of the evidence, however, many female patients discontinue their treatment unilaterally during pregnancy planning or upon learning of a pregnancy. Such decisions are largely driven by concerns regarding the potential harm that medications may inflict on the fetus. Fear of prenatal drug exposure is often fueled by inadequate health literacy or culturally rooted beliefs[7,9,10]. Unfortunately, the results often include preventable disease flare-ups and heightened risks for both the mother and the infant. To date, there is a paucity of literature addressing the specific reasons and frequency of self-discontinuation of medications in real-world settings and the effects on maternal and infant outcomes[11,12].
This observational study aimed to analyze real-world data and assess how the discontinuation of IBD treatment affects disease flare-ups and outcomes in pregnant patients. The consequences of non-adherence due to patient preference are highlighted and the importance of pre-pregnancy counseling and patient education is emphasized.
MATERIALS AND METHODS
Study design
This study entailed an observational analysis of pregnant women with IBDs treated at a single tertiary center between March 2019 and June 2023. The study received approval from the institutional ethics committee. The analyzed dataset was obtained from electronic database containing information on patient demographics, clinical characteristics, disease history, laboratory findings, medication information, and pregnancy-related outcomes.
The inclusion criteria included a confirmed diagnosis of CD or UC, documentation of pregnancy, and availability of adequate clinical records regarding pregnancy and the perinatal period.
At the time of pregnancy diagnosis, the medications used, as well as clinical, biochemical, and endoscopic remission, were noted. Disease type, location, and behavior were determined based on the Montreal classification[13]. Immunomodulatory therapy included azathioprine (AZA), and biologic therapy included infliximab (IFX), adalimumab (ADA), and vedolizumab (VDZ). Methotrexate was not administered to any patients due to its teratogenic properties, and ustekinumab (UST) and upadacitinib were not administered due to insufficient data on their use during pregnancy. Patients receiving mesalazine, AZA, IFX, ADA, or VDZ were advised to continue their current treatment for 24 weeks, while those receiving methotrexate, UST, or upadacitinib were advised to switch to a different treatment. While the decision to use medication was left to the discretion of the patient, strong recommendations were made for those with active disease. Disease activation was assessed using the Truelove-Witts score, the partial Mayo endoscopic score for UC, and the CD Activity Index for CD. Clinical disease activity was defined as a partial Mayo score of > 2 for UC and a CD Activity Index score of > 150 for CD. These evaluations were methodically performed at the time of pregnancy confirmation, during periodic follow-up visits during each trimester, and promptly upon the manifestation of any symptoms. This approach was of critical significance in establishing a clear temporal relationship between the discontinuation of treatment and subsequent disease activity. During disease activation, all patients underwent intestinal ultrasonography, and in cases of severe UC, rectosigmoidoscopy was performed. Remission induction therapy with steroids was administered in cases of moderate to severe active disease. Abortion, intrauterine growth restriction (IUGR), birth complications, low birth weight, and postpartum infections were noted. The primary endpoint of the study was disease activation, while secondary endpoints were abortion, IUGR, low birth weight, and postpartum infections.
Statistical analysis
Statistical analysis was conducted using IBM SPSS Statistics 25.0 for Windows (IBM Corp., Armonk, NY, United States). The normality of the numerical data was assessed using the Kolmogorov-Smirnov test. As the numerical variables did not demonstrate normal distribution, they were transformed into medians (interquartile ranges) prior to comparison using the Mann-Whitney U test, which is a non-parametric test. Categorical variables were presented as frequency counts and percentages and subjected to comparisons using the χ2 test or Fisher exact test as appropriate. Statistically significant findings were accepted at P < 0.05.
RESULTS
A total of 57 patients with IBD were analyzed, including 37 (64.9%) with UC and 20 (35.1%) with CD (Figure 1), and the median age was 22 years. UC was most commonly left-sided at 51.4%, while ileal and ileocolonic involvement was common at 40% for CD. Perianal involvement was also observed in 40% of CD cases. In the entire study group, 42 (73.7%) patients received mesalazine, 24 (42.1%) AZA, 8 (14%) IFX, 5 (8.8%) ADA, and 2 (3.5%) VDZ as the most frequently prescribed medications. Comprehensive demographic and clinical characteristics are presented in Table 1.
Figure 1
Inclusion criteria for the study and treatment details.
Table 1 Demographics, clinical characteristics, and laboratory data of the entire study group and subgroups according to inflammatory bowel disease type, median (interquartile range)/n (%).
In the subgroup analysis of patients with UC, 25 patients (67.6%) had continued their current treatment, whereas 12 patients (32.4%) had discontinued treatment (Figure 1). The age at disease onset [23 (11-32) years vs 21.5 (14-25) years, P = 0.235], total disease duration, smoking status, body mass index, and extent of the disease were statistically comparable between the two groups (P > 0.05 for all). Hemoglobin [12 (6.2-14.6) g/dL vs 10.1 (8.4-13) g/dL, P = 0.037] and serum albumin levels [4 (3.5-5.1) g/dL vs 4 (3.5-4.4) g/dL, P = 0.033] were significantly higher among patients who continued treatment, whereas the partial Mayo score [5 (1-9) vs 7 (4-8), P = 0.018] and disease activity were significantly higher among patients who discontinued treatment. Among the UC patients receiving treatment, including both monotherapy and combination therapies, 29 (78.4%) received mesalazine, 20 (54.1%) received AZA, and 2 (5.4%) received IFX, while among the CD patients, 3 patients (15%) received AZA and 5 patients (25%) received IFX. There were no significant differences between the treatment continuation and discontinuation groups regarding the rates of abortion [9 (36%) vs 4 (33.3%), P = 1], IUGR [2 (8%) vs 1 (8.3%), P = 1], and low birth weight [3 (12%) vs 2 (16.7%), P = 1]. Infant infections did not occur in either group (Table 2).
Table 2 Clinical outcomes and demographic data of patients with ulcerative colitis who continued and discontinued therapy, median (interquartile range)/n (%).
Table 3 presents the subgroup analysis of patients with CD according to treatment continuation status. During the study period, 16 pregnant patients (80%) with CD continued treatment, whereas 4 patients (20%) discontinued treatment (Figure 1). Age at disease onset, total disease duration, smoking status, body mass index, and extent of the disease (P = 0.535) were comparable between these two groups (P > 0.05 for all). All patients who continued treatment were receiving biologic therapy. No statistically significant difference was observed between the groups with respect to abortion rates [5 (31.3%)vs 1 (25.0%), P = 1]. IUGR, low birth weight, and infection were not observed in either group (Table 3).
Table 3 Clinical outcomes and demographic data of patients with Crohn’s disease who continued and discontinued therapy, median (interquartile range)/n (%).
Of the total 57 patients, 25 (43.9%) experienced disease activation during pregnancy. The remaining 32 patients (56.1%) remained in remission. Upon comprehensive analysis of the entire cohort, it was observed that medical treatment discontinuation occurred with greater frequency in the group with disease activation compared to the group without activation (40% vs 18.8%), although the difference was not statistically significant (P = 0.076). Upon further analysis of the data, exacerbation was observed in 10 (62.5%) of the 16 patients who had discontinued their treatment, while exacerbation was detected in 15 (36.6%) of the 41 patients who had continued their treatment. The need for salvage steroid therapy was considerably elevated in patients who experienced activation (48% vs 3.1%, P < 0.001). A comparison of the baseline characteristics of the activation and non-activation groups yielded no significant differences.
Univariate and multivariate analyses showed that discontinuing medication predicted activation for both UC and CD during pregnancy. Similarly, the need for steroid salvage therapy was significantly higher among patients who experienced activation (Table 4). Analysis of fetal and maternal outcomes indicated a median gestational age of 37.9 weeks. Preterm birth occurred in 9 (15.8%) cases. Of the 13 patients who received anti-tumor necrosis factor (TNF) therapy before pregnancy, 9 (69%) continued treatment, while 4 (31%) discontinued it. Descriptive analysis showed that the preterm birth rate was lower in the group continuing anti-TNF therapy (11.1%) than in those who discontinued or did not receive such treatment.
Table 4 Demographics, clinical characteristics, and laboratory data of the whole study group and subgroups according to treatment discontinuation, median (interquartile range)/n (%).
This study has highlighted the consequences of discontinuing medical treatment during pregnancy as an important problem in the management of IBDs. Our findings demonstrated that treatment interruption, especially in UC patients, is statistically significantly associated with the likelihood of disease activation and the need for salvage steroid therapy. Treatment interruption appeared to occur predominantly based on the patient’s preference. The CD group did not demonstrate similar statistical significance regarding disease activation, most likely due to the small number of participants. However, this study has confirmed that discontinuing IBD medication is an avoidable source of risk for clinical deterioration, even though the overall live birth rate remained high throughout the entire cohort.
Patient preference appears to be the main factor influencing treatment discontinuation. The use of medications by pregnant women with IBDs may be a concern arising from the instinctive desire to protect the fetus. Methotrexate, a well-documented teratogenic agent, is not given to pregnant women with IBDs, and UST, VDZ, and upadacitinib are also not given to these patients due to insufficient safety studies[14]. However, mesalazine, AZA, and anti-TNF agents (certolizumab, ADA, and IFX) have sufficient data regarding their safe use in pregnancy[15,16].
This study found no evidence of an increased risk of abortion, IUGR, low birth weight, or infant infection in pregnant patients with IBDs who continued using their medication during pregnancy. Furthermore, discontinuation of medication was found to be associated with disease activation and increased steroid requirements. These findings are supported by the multicenter prospective study conducted by Watanabe et al[10], who concluded that treatment non-adherence regardless of physician advice constituted an independent risk factor for flare-ups in UC patients and could contribute to adverse pregnancy outcomes. A meta-analysis by Nielsen et al[7] provided crucial evidence that the continuation of biologic therapy during pregnancy does not increase the risk of adverse maternal or fetal outcomes compared to the general population. Our findings indicated a significant correlation between treatment discontinuation and the deterioration of objective clinical parameters in UC patients, including lower hemoglobin and albumin levels and significantly higher partial Mayo and endoscopic scores. Regarding the low hemoglobin levels observed in these patients, previous research has revealed that anemic pregnant patients face elevated risks of preeclampsia, maternal mortality, and infection and more complications from hemorrhage during childbirth[17-19].
As demonstrated in previous studies, the most important risk during pregnancy in this population is IBD exacerbation rather than the medications used for maintenance therapy[14-17]. Active disease significantly increases the likelihood of spontaneous abortion, preterm birth, and low-birth-weight infants[18,19]. Systemic inflammation, impaired placental perfusion, anemia, malnutrition, and increased steroid requirements are possible causes of increased preterm birth risk in pregnant women with IBDs[20-22]. Studies have shown that disease activation in IBD increases the risk of preterm labor by 1.8-3 times[23,24]. In the present study, the rate of preterm birth was higher among patients who discontinued their medication. Disease activation and increased steroid requirements likely contribute to preterm birth in unison. Furthermore, increased steroid requirements during pregnancy are associated with gestational diabetes, hypertension, preeclampsia, weight gain, osteoporosis, and premature birth[25,26].
Our study demonstrated that the predominant reason for treatment discontinuation in this population is patient preference, highlighting one of the most fundamental challenges in this field of medicine: Concerns regarding drug safety and a lack of information among patients[27]. Within the Turkish context, this behavior is often exacerbated by cultural tendencies to avoid all pharmacological interventions during pregnancy, varying levels of health literacy, and, at times, limited access to specialized counseling for preconception and pregnancy health. The high rate of unplanned pregnancies within our cohort further complicated this underlying issue. Individuals who do not receive adequate counseling prior to conception may not fully understand the risks associated with active disease or the importance of maintaining medication regimens[28]. The dangers of treatment discontinuation arising from patient preference are similarly emphasized in the literature, and these decisions generally stem from patients’ concerns about the potential harm of medications to the fetus. However, recent meta-analyses have indicated a twofold higher probability of IBD exacerbations during pregnancy in women who were experiencing active disease at the onset of pregnancy[2,27,29,30]. The value of preconception counseling in enhancing medication adherence has been demonstrated, with favorable outcomes for the mother and fetus obtained in our study with the continuation of medications. The overall live birth rate was 90% in both groups. The lack of statistical significance in this regard may be attributable to the small sizes of the respective subgroups.
Given the identified risks, it is clear that the advantages associated with the continuation of treatments such as mesalazine, AZA, and, most notably, biologic agents significantly surpass the associated potential risks during pregnancy[7,12]. Our findings, which provide support for the continuation of anti-TNF treatment in particular, are firmly supported by extensive recent data. For example, the United States-based PIANO registry system repeatedly demonstrated the safety of anti-TNF agents and AZA during pregnancy[6]. Recent data concerning newer biologic agents such as VDZ and UST are equally encouraging. Based on data from the aforementioned PIANO registry system, Chugh et al[31] concluded that exposure to VDZ or UST did not appear to be associated with an elevated risk of adverse maternal or infant outcomes when compared to anti-TNF treatment or a lack of treatment. Our descriptive analysis showed a lower rate of preterm birth with UST; albeit, this finding was not statistically significant due to the small sample size. The accumulation of evidence in this domain, as briefly summarized by Brondfield and Mahadevan[11], resulted in a global consensus. This consensus was formally established in the “Global Consensus Statemen” a seminal document developed by Mahadevan et al[15] that included 39 experts and seven patient advocates from six continents. The establishment of evidence-based standards for global clinical practice is the central tenet of this comprehensive report, which directly supports the core message of our study. The consensus designated preconception counseling as a strong recommendation and advised for the continuation of maintenance therapies, including anti-TNF, VDZ and UST throughout pregnancy to sustain remission. The foundational principle of this global agreement was that active IBDs itself, rather than its treatments, posed the primary threat to maternal and fetal health. This corroborated the conclusion that the benefits of managing disease activity significantly outweigh the potential risks, a finding strongly reinforced by our own study[11,15]. Both North American and updated European guidelines now recommend the continuation of biological therapies throughout pregnancy to maintain remission[27,32,33].
Another significant finding of our study was the absence of reported infections within the first month among infants whose mothers had continued anti-TNF therapy, irrespective of the duration of that therapy. Two cases of infection were documented among the infants of mothers who did not receive anti-TNF therapy. Due to the limited number of patients in these subgroups, no statistical comparisons were conducted for these results. However, the observation of no infections in infants of mothers receiving anti-TNF therapy suggests a potentially superior safety profile for these treatment modalities during pregnancy, a finding corroborated by the existing literature[16].
The study’s observational cohort design, single-center nature, and limited number of patients, particularly in the CD subgroup, constitute significant limitations. The total sample size of 57 is relatively small, inherently limiting the study’s statistical power, especially in conducting subgroup analyses. The small number of CD patients (n = 20) included in the study further limited the ability to generate reliable, statistically significant findings and increased the risk of type II error. Consequently, relationships between treatment discontinuation and disease flares in cases of CD could have gone undetected. In the CD subgroup of our study, we reached a conclusion that initially appeared paradoxical; the relapse rate among patients who discontinued treatment (25%) was lower than among those who continued treatment (56.3%). The observed discrepancy could be considered an idiosyncrasy resulting from the minimal number of patients in the group who discontinued treatment (n = 4), an insufficient sample size to facilitate a statistically significant interpretation. Moreover, this paradox underscores the considerable effect of potential confounding factors, including initial disease severity and the depth of remission. It is possible that patients who chose to discontinue their treatment might have initially exhibited a milder disease course, or they might have experienced a state of deeper, longer-lasting clinical and endoscopic remission prior to pregnancy, which could have created a false sense of security resulting in their discontinuation of treatment. Conversely, those who continued treatment may have had a history of more aggressive or refractory disease, which would necessitate the continued usage of biologic agents and inherently carry a higher baseline risk of relapse. Consequently, it is insufficient to draw definitive conclusions from this study regarding the effects of treatment discontinuation in CD patients.
Moreover, the subgroup analyses investigating fetomaternal outcomes and anti-TNF usage were not amenable to statistical analysis, owing to the insufficient number of participants. Consequently, these analyses were presented in a descriptive capacity. Many studies in this field share these limitations.
CONCLUSION
The study showed that the discontinuation of medical treatment at the patient’s discretion is a primary and preventable risk factor for disease activation and increased steroid requirements in pregnant women with IBDs, particularly those with UC. These findings emphasize the critical role of proactive patient counseling in optimizing maternal and infant outcomes in clinical practice by promoting medication adherence.
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