Postpartum nonsteroidal anti-inflammatory drug exposure does not increase risk for flare in patients with inflammatory bowel disease

Loren G. Rabinowitza*, Tina Deyhima*, Joyce Leeb, Jessica D. Leeb, Amelia Hernc, Nicole Lueb, Grace Geeganagea, Alessandra Saragaa, Ajay Gadea, Jacqueline Shenb, Sarah Balloua, Lauren K. Burdinea, Benjamin Mecsas-Faxona, Laurie Grossberga, Samantha Zullowa, Sarah Fliera, Scott A. Shainkerd, Konstantinos Papamichaela, Joseph D. Feuersteina**, Adam S. Cheifetza,**

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA

aCenter for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (Loren G. Rabinowitz, Tina Deyhim, Grace Geeganage, Alessandra Saraga, Ajay Gade, Sarah Ballou, Lauren K. Burdine, Benjamin Mecsas-Faxon, Laurie Grossberg, Samantha Zullow, Sarah Flier, Konstantinos Papamichael, Joseph D. Feuerstein, Adam S. Cheifetz); bDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (Joyce Lee, Jessica D. Lee, Nicole Lue, Jacqueline Shen); cBoston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts (Amelia Hern); dDepartment of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (Scott A. Shainker), USA

Correspondence to: Loren G. Rabinowitz, MD, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA, e-mail: lrabinow@bidmc.harvard.edu

*Co-first authors

**Co-final authors

Received 18 August 2025; accepted 25 January 2026; published online 24 March 2026
DOI: https://doi.org/10.20524/aog.2026.1054
© 2026 Hellenic Society of Gastroenterology

Abstract

Background Postpartum pain management is an important part of maternal healthcare. Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are typically offered as first-line pharmacologic therapies for postpartum pain. There is a belief that NSAIDs may play a role in exacerbating inflammatory bowel disease (IBD); as a result, some obstetricians avoid NSAIDs for postpartum pain management in patients with IBD. However, data concerning the relationship between short-term NSAID use and IBD flares are inconsistent. The aim of this study was to assess whether hospital postpartum NSAID use is associated with postpartum IBD flare within 9 months from delivery.

Methods This single-center retrospective cohort study included patients with IBD, aged 18 years or older, who had singleton live births between January 1, 2016, and November 30, 2023. Chart review data for each eligible patient were collected for a 9-month postpartum period.

Results Among the 187 patients included in the study, there was no difference between NSAID-exposed and non-exposed patients in postpartum IBD flare: 10/114 (9%) vs. 10/73 (14%), respectively, P=0.335. Based on multivariate regression analysis, NSAID exposure was not associated with postpartum IBD flare, adjusted for active disease at conception and IBD flare during pregnancy: adjusted odds ratio (aOR) 0.6, 95% confidence interval (CI) 0.2-1.7; P=0.327. The same was true for mode of delivery and inpatient opioid exposure: aOR 0.6, 95%CI 0.1-1.5; P=0.291.

Conclusions Postpartum NSAID use for pain control is not associated with IBD flare 9 months after delivery. Large prospective studies are needed to confirm this finding.

Keywords Nonsteroidal anti-inflammatory drugs, pregnancy, inflammatory bowel disease, flare

Ann Gastroenterol 2026; 39 (3): 372-377

Introduction

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, relapsing, and potentially debilitating disorder of the gastrointestinal (GI) tract affecting approximately 2.39 million individuals in the United States [1,2]. The peak incidence of IBD typically occurs in early adulthood and, since approximately 55% of affected individuals are women, a significant proportion of patients require disease management during their reproductive years. Despite this, data on the optimal management of IBD during pregnancy and lactation remain limited [3], though this is changing rapidly.

Effective pain management in the postpartum period is a critical component of maternal care. Given the well-documented risks associated with opioid use—including dependency, overdose and other adverse outcomes—the use of non-opioid analgesics is increasingly prioritized. According to a 2011 report by the Institute of Medicine, 60% of women report experiencing severe pain during and after their first childbirth, underscoring the need for effective and safe postpartum analgesia [4]. In the context of the ongoing opioid crisis, and the well-studied association between opioid exposure and poor IBD outcomes, optimizing pain control strategies is essential—not only to improve patient outcomes, but also to enhance the overall quality of postpartum healthcare [5,6].

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed analgesics globally, with agents such as ketorolac, ibuprofen and naproxen commonly used for postpartum pain control. However, NSAIDs are known to pose GI risks, and their impact on IBD disease activity remains a subject of ongoing debate [7-11]. Previous data suggested that NSAID exposure may precipitate clinical relapse in up to 20% of patients with quiescent IBD [12,13]. Furthermore, a case–control study by Evans et al reported an association between NSAID use and increased risk of emergency hospital admission among IBD patients; however, the study lacked detailed data on the dosage and duration of NSAID exposure [14]. Newer studies have suggested that NSAID use, particularly over a short duration, is not associated with worsened clinical outcomes or risk of flare in patients with IBD [7,15]. These uncertainties highlight the clinical dilemma of selecting appropriate analgesic regimens for patients with IBD during the postpartum period.

The primary aim of this study was to assess whether hospital postpartum NSAID use is associated with postpartum IBD flare within 9 months from delivery. A secondary aim was to investigate the association of NSAID use with postpartum IBD-related hospitalizations, patients needing postpartum GI visits, and the number of such visits made.

Patients and methods

Study design and population

This was a single-center retrospective cohort study of postpartum patients aged 18 years or older who had singleton live births between January 1, 2016, and November 30, 2023. Patients with IBD were identified using International Classification of Diseases (ICD)-10 codes from the electronic medical record, and the study was further limited to those who were diagnosed with IBD at least 1 year prior to conception. Patients who had spontaneous or elective terminations, multiple gestations, those with missing data (i.e., patients who did not receive IBD care at the primary site), and those without accessible inpatient medication administration records of NSAIDs were excluded. This study was approved by the Institutional Review Board of the Beth Israel Deaconess Medical Center, with a waiver of consent for retrospective analysis of de-identified data (approved on September 25, 2024: IRB#2021P000725).

Study outcomes

The primary aim of the study was the association of NSAID exposure with postpartum IBD flare within 9 months after delivery. Flare was defined as the addition of steroids (oral/rectal); change in medical treatment (including advanced therapies, treatment optimization not based on proactive therapeutic drug monitoring); surgical intervention; or IBD-related hospitalization. Medication use during inpatient course was determined based on inpatient administration records, any history of taking NSAIDs, either selective or non-selective, including but not limited to ibuprofen, ketorolac, and naproxen. Secondary outcomes were postpartum IBD-related hospitalizations, patients needing postpartum GI visits, and the number of such visits made within 9 months after delivery.

Statistical analysis

A per-pregnancy event analysis was performed. Categorical variables were described as frequency with percentage and compared between groups using chi-square or Fisher’s exact test, as appropriate. Continuous variables were described as median with interquartile range (IQR), and were compared between groups using the Mann-Whitney U test. Multivariable binary regression analyses were performed to determine the independent effect of NSAID use associated with postpartum IBD flare. In view of the small number (n=20) of events (postpartum flares), we restricted the multivariable analyses to a maximum of 2 covariates, as follows: model 1 (IBD medication at conception and IBD flare during pregnancy; model 2 (active disease at conception and corticosteroids at the time of delivery; model 3 (mode of delivery and inpatient opioid exposure); model 4 (active disease at conception and IBD flare during pregnancy). Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CI) were also provided. All analyses were performed using SPSS version 28.0 (SPSS, Chicago, IL, USA) and GraphPad Prism version 5.03 for Windows (GraphPad Software, San Diego, CA, USA).

Results

Demographic and clinical characteristics

A total of 398 pregnancies in 336 patients were screened. Including only the patients with accurate inpatient medication administration and available GI and obstetric charts, a total of 187 pregnancies were ultimately included in the analysis, with 114 exposed to NSAIDs during the postpartum hospitalization and 73 unexposed (Table 1). The median maternal age at delivery was 32 years (IQR: 35-38), and the median length of hospitalization was 3 days (IQR: 3-5) in both groups, with no significant differences between NSAID users and non-users (P=0.986 and P=0.718, respectively). Regarding IBD subtype, UC, CD and IBD-unclassified (IBD-U) were present in 47%, 48% and 5% of the cohort, respectively. Distribution by IBD type did not significantly differ in relation to NSAID exposure (P=0.151). The median disease duration was 10 years (IQR: 6-16), comparable across groups (P=0.416). Median preconception body mass index was similar between NSAID and non-NSAID users (21.6 vs. 21.0 kg/m2, P=0.198).

Table 1 Demographic and clinical characteristics (per pregnancy analysis)

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Fourteen percent (14%) of subjects were current smokers, with no difference between groups (P=0.835). Medicaid insurance coverage was reported in 9% of patients, and insurance status did not differ significantly by NSAID use (P=0.424). At conception, 16% of patients were on no IBD medications, 45% were on non-biologic therapy and 39% on biologics. There was no significant difference between groups in IBD medication use at conception (P=0.559). Use of low-dose aspirin during pregnancy occurred in 18% of participants and did not differ between groups (P=0.193). Active disease at conception was present in 15% of the cohort, and 22% of the cohort flared during pregnancy, with no differences between NSAID-exposed and non-exposed groups (14/96 [15%] vs. 10/59 [17%] P=0.820, and 22/114 [19%] vs. 20/73 [27%] P=0.212, respectively). Inpatient narcotic use during delivery hospitalization occurred in 40% of cases and was similar between NSAID users and non-users (43/114 [38%] vs. 32/73 [44%], P=0.446), as was acetaminophen use (93% overall, P=0.768). No statistically significant difference was observed in morphine equivalent dosage use between NSAID users and non-users (30 mg [10-76.3], P=0.511). Vaginal delivery was more common overall (65% vs. 35%), but the mode of delivery did not differ significantly in relation to NSAID exposure (P=0.115).

NSAIDs and postpartum IBD flare

Among the 187 pregnancies analyzed, postpartum IBD flare occurred in 9% of cases, with no statistically significant difference between NSAID-exposed and unexposed groups (P=0.335) (Table 2). Based on multivariate regression analysis (Table 3), NSAID exposure was not associated with postpartum IBD flare, adjusted for active disease at conception and IBD flare during pregnancy (aOR 0.6, 95%CI 0.2-1.7; P=0.327), as well as mode of delivery and inpatient opioid exposure (aOR 0.6, 95%CI 0.1-1.5; P=0.291).

Table 2 Postpartum outcomes by NSAID exposure

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Table 3 Association of NSAID use with postpartum IBD flare

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NSAIDs and other outcomes

Postpartum IBD-related hospitalizations were reported in 13% of cases overall, and rates were identical among NSAID exposed and non-exposed patients (13% in each group, P>0.99 with 0% risk difference between groups). Most patients (89%) had postpartum GI visits, with a median of 2 visits (IQR: 1-3). Visit frequency and proportion of patients seen post-delivery were similar between groups, with a 1% risk difference between exposed and non-exposed patients (P=0.796 and P=0.264, respectively) (Table 2).

Discussion

This study’s findings indicate that short-term NSAID use appears to be a safe and effective approach to postpartum pain control for patients with IBD, and is in alignment with current American College of Obstetricians and Gynecologists’ (ACOG) first-line recommendations [16,17]. In this study, the use of NSAIDs for postpartum analgesia was not associated with an increased risk of IBD flare in the 9 months following delivery, and NSAID use was not linked to IBD-related hospitalizations in the postpartum period.

ACOG recommends NSAIDs as a first-line therapy for postpartum pain management, with opioids added only if needed, and for the shortest reasonable duration [17]. The recommendation of non-opioid analgesics for the general postpartum patient population is intended to minimize the risk of development of opioid use disorders among opioid-naïve patients, and to reduce the chances of opioid-induced side-effects. Furthermore, although both NSAIDs and opioids are excreted into breastmilk, breastfed infants of individuals prescribed opioids may experience central nervous system depression and neonatal sedation, making non-opioid analgesics a safer option for breastfed infants. Despite this, and perhaps as a result of the widely held belief that NSAIDs increase the likelihood of IBD flares, many patients with IBD and their obstetricians may avoid NSAIDs during postpartum recovery.

The literature linking NSAIDs to IBD flares is inconclusive. It is known that NSAIDs are associated with mucosal injury, and several studies have reported an increased likelihood of IBD flares after NSAID exposure [18-20]. However, a meta-analysis of 18 studies that examined the relationship between NSAIDs and IBD exacerbations found no significant association between NSAID use and the risk of UC or CD exacerbation [15]. Additionally, a cohort study published in 2023, which included 15,705 patients with IBD, with and without NSAID exposure, suggested that the relationship between NSAIDs and IBD exacerbations might be attributable to “protopathic bias”, in which NSAIDs might be used to treat early signs of an IBD flare (e.g., joint pain) and consequently their association with the flare cannot be considered causal [7].

Existing literature on postpartum pain control for patients with IBD is limited. In a recent retrospective cohort study, Johnson et al found that postpartum use of ketorolac—a commonly administered intravenous NSAID—was not associated with increased clinical disease activity up to 6 weeks postpartum [21]. In that study, the use of oral (PO) NSAIDs, and the NSAID dosage and frequency, were not reported. A recent grading recommendation by Mahadevan et al emphasized the safety of NSAIDs for postpartum pain management, and recommended them over opiates, considering their safety profile [22]. Our study adds to the existing literature with its inclusion of both IV and PO NSAIDs, and with a longer duration of follow up following delivery to assess for the longitudinal risk of postpartum IBD flare.

This study had some limitations. First, as a retrospective observational analysis, it cannot establish causality between NSAID exposure and postpartum IBD outcomes. Second, because the cohort was derived from a single center, generalizability to other practice settings may be limited. Although NSAID dose, route and duration were abstracted, the sample size limited the statistical power for detailed subgroup comparisons, while direct comparisons across specific NSAIDs are difficult to interpret, given the absence of an accepted standardized potency-equivalence framework. In addition, outpatient NSAID use after discharge was not reliably captured, as many NSAIDs are obtained over the counter and prescription records do not confirm actual use. Consistently with the retrospective design, we did not contact participants to ascertain post-discharge exposure, in order to avoid introducing recall bias that might have led to underestimation of the total postpartum NSAID use. Finally, because we used a more stringent definition of postpartum flare, milder or subclinical changes in disease activity may not have been detected. Importantly, postpartum flare rates were low across the cohort despite these constraints, supporting the conclusion that NSAID use during the delivery hospitalization, as assessed here, was not associated with an increased risk of postpartum flare.

In conclusion, our findings suggest that short-term NSAID use during the postpartum period is not associated with an increased risk of IBD flare within 9 months of delivery. Future research should include larger, prospective, multicenter studies to better characterize how NSAID dosing, duration and formulation may influence disease activity in the postpartum patient population.

Summary Box

What is already known:

  • The diagnosis of inflammatory bowel disease (IBD) peaks in the third decade of life and frequently overlaps with pregnancy

  • Pain management is essential during the postpartum period

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastrointestinal toxicity and their role in IBD exacerbation remains controversial

What the new findings are:

  • Short term NSAID use during postpartum period for pain control was not associated with IBD flare up to 9 months after delivery

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Notes

Conflict of Interest: K.P.: received lecture fees from Physicians Education Resource LLC and Grifols; scientific advisory board fees: ProciseDx Inc, Scipher Medicine Corporation and Celltrion Inc.; and consultant fees from Prometheus Laboratories Inc.; A.S.C.: Consulting: AbbVie, Johnson and Johnson, Prometheus (SAB), Aegirbio (SAB), Artizan (SAB), Fzata, Celltrion, Eli Lilly, Adiso, BMS, Clario, Food is Good, Fresenius Kabi, Pfizer, Procise, Spherix, Samsung; Speaking (nonbranded): AbbVie, Johnson and Johnson, BMS; L.B.G. received scientific advisory board fees from BMS and Pfizer. SAS receives research support from the Chase Koch Foundation and the Roger‘s Family Foundation. The remaining authors disclose no conflicts of interest

Funding: Study was funded by internal institutional grant