Introduction

The maternal safety of thiopurines (TP), including azathioprine (AZA) and mercaptopurine (6MP), in pregnancy for IBD management is well established. However, intrahepatic cholestasis of pregnancy (ICP) occurs more commonly in TP exposed IBD pregnancies^1,2,. TP ‘shunting’ with a 6-methylmecrcaptopurine (MMP) to 6-thiogaunine (TGN) ratio of >11, is associated with hepatotoxicity, and increasingly occurs in later pregnancy³. We aimed to explore the mechanisms behind TP exposure and ICP, and identify risk minimisation strategies.

Aims & Methods

Pregnant or preconception participants with IBD receiving 6MP, AZA or biologic monotherapy (BM) were recruited to this prospective multi-centre cohort study. Demographic and disease activity data, as well as TP metabolites, biochemical and haemotologic parameters were obtained prior to conception (PC), in each trimester of pregnancy (T1, T2, T3), at delivery (D), and 6 weeks post-partum (PP). Bile acids (BA) were collected in T2 and T3 in TP exposed pregnancies. ICP was defined by BA >10 with clinical symptoms and LFT derangement. Obstetric outcomes were compared between TP and BM exposed controls. TP metabolites were assessed with high performance liquid chromatography and reported in pmol/8 x 10⁸ RBCs.

Results

131 TP and 147 BM exposed pregnancies were included. 63% of TP pregnancy (82) received AZA and 60% (78) had CD. 12% receiving TP (13/109) had a pre-existing shunting phenotype. 59% (77) received concomitant biologics. 60% (75) had a prior pregnancy, with 5.3% (4) of those having had ICP. TP pregnancies were more likely to be exposed to aminosalycylates (39 vs 14%, p<0.01), and infliximab (32 vs 10, <0.01) and less likely exposed to ustekinumab (8 vs 44, <0.01) and vedolizumab (3 vs 29, <0.01). The median AZA dose was 100mg (IQR 75-150) and 6MP 50mg (IQR 50-75).
Rates of biochemically active disease were equivalent between TP and BM pregnancies. The median faecal calprotectin (FC) for TP exposed pregnancies was 42mg/ml (95% CI 11.9-126.5, n=72) PC, 45mg/ml (9.3-149, 89) in TI, 27mg/ml (12-74, 109) in T2, 21mg/ml (9.8-76, 86) in T3 and 19.7mg/ml (7.9-82.6, 72) PP. For BM pregnancies, the FC was 58mg/ml (95% CI 18.2-251, n=51) PC, 39mg/ml (18.6-150, 75) in T1, 38mg/ml (14.8-106, 80) in T2, 49.9mg/ml (17-189, 68) in T3 and 60mg/ml (13.9-156, 33) PP. FC did not change over the course of pregnancy in TP (p=0.63, Skilling’s Mack) and BM exposed (p=0.73) participants. In TP pregnancies, FC and TGN weakly negatively correlated prior to conception (-0.36, p=0.02, Spearman coefficient), but not at any other timepoint (first trimester; r=-0.07 p=0.59, second trimester; -0.09 p=0.39, third trimester; r=-0.09 p=0.44, postpartum; -0.14 p=0.29).

In those with no dose changes, MMP/TGN increased from PC to T3 (Skilling's Mack p<0.01) (Table 1).

Table: Thiopurine metabolites over the course of pregnancy (median, IQR)

24% (18/76), 25% (26/103), 26% (24/92) and 17% (12/72) were shunting in T1, T2, T3 and at D respectively. 2.6% (3/116) were receiving split dose TP PC, and of these with bloods taken, 50% (3/6) were shunting in T1, 75% (2/8) in T2, 43% (3/7) in T3 & 20% (1/5) at D. Of PC shunters, 38.5% (5/13) had their dose split over pregnancy; 7.7% (1/13) PC, 23% (3/13) in T1 and 8% (1/13) in T2. Overall, 4% had their dose split (4/100) in T1, 7% in T2 (8/111) and 2% in T3 (2/105). In those who had their dose split in T2 for shunting management, the median MMP/TGN ratio decreased from 18 (IQR 6-57) in T2 to 7 (IQR 3-8) in T3 (p<0.01 Wilcoxon sign-rank) and 3 (IQR 2-3.5) at D (p=0.04).
Elevated ALT was observed in 8.1% (5/62) of TP pregnancies in T1, 5.7% (5/89) in T2, 18.3% (15/82) in T3 and 34.5% (20/38) at D. Increasing MMP was associated with an increasing ALT in T1 (0.001, 0.03), T3 (coeff. 0.002, p=0.001), PP (0.003, p=0.02) and at D (0.002, p<0.01). 60% (3/5), 50% (6/12) and 21.1% (4/19) with elevated ALT in T2, T3 and at D were diagnosed with ICP. The risk of ICP was increased in TP (6.7%, 7/105) vs BM (0%, 0/112) pregnancies (p<0.01). With multivariate binary linear regression, ICP risk was increased with shunting in T3 (RR 8.9, 95% CI 1.2-65.6 p=0.03) and at D (11.4,1.18-110.3, 0.04), TP dose increase antenatally (5.3, 1.4-23.5, <0.01) and prior ICP (21.1, 1.8-249.0, 0.02). Increasing MMP in T2 (0.011, 0.03), T3 (0.001, <0.01) and at D (0.006, <0.01) were associated with increasing bile acids. Of the 7 TP pregnancies with ICP, 1 had a history of shunting PC, and 1 had a prior history of ICP. All were shunting in pregnancy, with 2/7 having an MMP/TGN >75 in T3. 4 cases occurred following a TP dose increase. There was no increased risk of adverse obstetric outcomes, including preterm delivery (RR 0.40, 95% CI 0.05-2.79, p=0.3) and low birth weight (0.61, 0.14-2.62, 0.5) in TP vs BM pregnancies.

Conclusion

TP exposure was associated with an increased risk of ICP. In particular, TP shunting in late pregnancy, TP dose increases and prior ICP were associated with increased ICP risk. Shunting can be effectively managed with TP split dosing. TP dose increases should be avoided in pregnancy, and TP metabolites routinely monitored.

References

1.Jharap B, de Boer NK, Stokkers P, Hommes DW, Oldenburg B, Dijkstra G, van der Woude CJ, de Jong DJ, Mulder CJ, van Elburg RM, van Bodegraven AA, Dutch Initiative on C, Colitis. Intrauterine exposure and pharmacology of conventional thiopurine therapy in pregnant patients with inflammatory bowel disease. Gut. 2014;63(3):451-457.
2. Kanis SL, Modderman S, Escher JC, Erler N, Beukers R, de Boer N, Bodelier A, Depla ACTM, Dijkstra G, van Dijk A-BRM, Gilissen L, Hoentjen F, Jansen JM, Kuyvenhoven J, Mahmmod N, Mallant-Hent RC, van der Meulen-de Jong AE, Noruzi A, Oldenburg B, Oostenbrug LE, Ter Borg PCJ, Pierik M, Romberg- Camps M, Thijs W, West R, de Lima A, van der Woude CJ. Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life. Gut. 2021;70(7):1266.
3. Flanagan E, Wright EK, Hardikar W, Sparrow MP, Connell WR, Kamm MA, De Cruz P, Brown SJ, Thompson A, Greenway A, Westley I, Barclay M, Ross AL, Kiburg KV, Bell SJ, Group PS. Maternal thiopurine metabolism during pregnancy in inflammatory bowel disease and clearance of thiopurine metabolites and outcomes in exposed neonates. Aliment Pharmacol Ther. 2021.

Disclosure

Nil

Introduction

Active inflammatory bowel disease in pregnancy is associated with an increased risk of adverse maternal and neonatal outcomes. Understanding patterns of disease activity may inform strategies for improving outcomes.

Aims & Methods

A retrospective cohort study was conducted of pregnancies managed through an IBD–antenatal clinic between August 2020 and January 2025. Patients were stratified into 2 groups based on disease activity during pregnancy. Active disease was defined using the Physician Global Assessment, symptoms, and biomarkers (CRP and/or FCP). Disease flare was defined by an increase in symptoms and/or biomarkers from their baseline. Disease activity was assessed pre-conception (within 6 months before pregnancy) during pregnancy and post-partum (up to 6 months post birth).

Results

Of 209 pregnancies (Table 1), 76.3% (n=158) were in remission and 23.7% (n=49) had active disease pre-conception. Among those with active disease, 81.6% (n=40) remained active into pregnancy, while 18.4% (n=9) achieved remission. Of those in remission at pre-conception, 73.4% (n=116) stayed in remission during pregnancy, and 24.7% (n=39) flared. 2 patients with no pre-conception data were active in pregnancy.
Of 125 patients in remission during pregnancy, 73.6% (n=92) stayed in remission post-partum and 12.0% (n=15) flared. Among 81 patients with active disease in pregnancy, 39.5% (n=32) remained active, and 53.0% (n=43) achieved remission post-partum.
Patients in remission through pregnancy had a higher mean BMI (24.5 vs 23.0 kg/m², p=0.027), were more likely to be of white ethnicity compared to minority ethnic groups (61.0% vs 38.4% p=0.0026), have a diagnosis of Crohn’s disease (58.6% vs 37.0%, p=0.0088), and be nulliparous (51.2% vs 35.0%, p=0.0414).
At conception, approximately 30% of patients in both groups were not receiving any treatment. During pregnancy, this proportion fell to 8.6% in the active group, reflecting therapy escalation. Use of biologics increased from 22.2% to 38.2% in the active group and remained stable at 36.0% in the remission group. Corticosteroid use was exclusive to the active disease cohort (6.2% at conception; 23.5% during pregnancy).
Active disease in pregnancy was associated with higher rates of adverse outcomes: gestational diabetes (12.3% vs 8.0%, p=0.001), fetal growth restriction (4.9% vs 0%, p=0.044), and low birth weight (<2500g: 14.6% vs 2.4%, p=0.015). While rates of small for gestational age infants were higher in the active group (9.9% vs 4.0%), this was not statistically significant.
Emergency c-sections were more common in the active group (29.9% vs 15.0%, p=0.03), while elective c-sections were more frequent in the remission group (27.5% vs 13.4%, p = 0.03). Women in remission more often had an intact perineum (63.6% vs 54.7%), while episiotomy was more frequent in those with active disease (18.8% vs 11.7%); both did not reach statistical significance.

	Pre-conception % of available data (n)	Pregnancy % of available data (n)	Post-partum % of available data (n)
Active disease	23.7% (49)	39.3% (81)	25.2% (47)
Remission	76.3% (158)	60.7% (125)	74.2% (135)
Excluded (pregnancy loss)	0	3	3
Missing data points	2	0	24

Conclusion

This study underscores the impact of active IBD on maternal and neonatal outcomes.
Nearly 1 in 4 women in remission at preconception flared during pregnancy. This highlights the need for effective pre-conception counselling, access to disease monitoring tools, multidisciplinary management and timely treatment optimisation to sustain remission during pregnancy.

Disclosure

No disclosures

Introduction

Infant outcomes are favourable post in-utero exposure to thiopurines (TP), with no increase in infant infections or adverse growth and developmental outcomes^1-2. However, infant thrombocytosis, anaemia, lymphopenia and liver function derangement have been observed in small studies^1,3,4. We aimed to identify the frequency of and associations with these abnormalities in TP exposed infants and determine the clinical impact.

Aims & Methods

Infants born to participants in the multi-centre prospective PICCOLO-X study receiving TP were compared to infants exposed to biologic monotherapy (BM) in-utero. TP metabolites (6-thiogaunine (TGN) and 6-methylmercaptopurine (MMP)), liver function tests (LFT) and full blood examination (FBE) were taken from cord blood at delivery, and repeated at 6 weeks (6W). Abnormal parameters were repeated thereafter until normalization and infants reviewed by a paediatric gastroenterologist. Infants are followed for 2 years. TGN and MMP levels were assessed using high performance liquid chromatography. The lower limit for detection was 15 for TGN and 100pmol/8 x 10⁸ RBCs for MMP. Age specific biochemical and haematological reference ranges were used.

Results

78 TP and 52 BM infants (IFX 5, ADA 9, 23 UST and 15 VDZ) were included. Delivery outcomes were equivalent between the groups. TGN and MMP were undetectable at delivery in 6/55 and 47/55 respectively, and all tested cleared both at 6W (n=44). The median delivery infant:maternal TGN and MMP ratios were 0.38 (IQR 0.24-0.50, n=49) and 0.18 (0.05-0.45, n=8). Thrombocytosis was seen in 80% (62/77) of all infants at 6W and 77% (49/64) at 3 months (3M). Elevated ALT was seen in >50% of infants at 3M and 6 months (6M), and anaemia in 12% (8/67) at delivery. There was no increased risk of thrombocytosis or transaminitis in TP exposed infants vs controls (Table). Maternal TP shunting (RR 2.06, 95% CI 1.33-3.18, p<0.01) and MMP (coef. 0.03, 0.02) at delivery and preceding infection (RR 1.65, 1.01-2.70, 0.05) were associated with increasing ALT at 6W, as were preceding infection and elevated ALT (1.25, 1.14-1.37, <0.01) and ALP (1.89, 1.49-2.40, <0.01) at 3M. Vaccination prior to bloods increased the risk of elevated ALP at 6W (1.87, 1.11-3.13, 0.02). Neutropenia risk was increased in those with preceding infection (1.94, 1.05-3.59, 0.04) and vaccination (6.33, 1.09-36.83, <0.04) at 3M. Neutropenia at 6W was associated with an increased risk of infection at 3M (4.89, 1.64-14.57, <0.01). Maternal CRP in trimester 2 was associated with increasing ALT at 6W (coef. 0.7, 95% CI 0.4-1.0, p<0.01), 3M (1.6, 1.2-2.1, <0.01) and 6M (1.6, 1.2-2.0, <0.01), as was maternal calprotectin in trimester 3 and infant 6W platelets (0.08, 0.02-1.5, <0.01). There was no increased risk of infection, chronic disease, allergy or growth <10^th percentile in TP vs BM exposed infants at 6W, 3M and 6M.

Infant outcome	Timepoint	Thiopurines (%, n)	Biologic monotherapy (%,n)	Relative risk (95%) p, univariate binary regression	Adjusted coefficient (95%CI) p, Ordinary multivariate linear regression
Thrombocytosis/ Platelet count	6 weeks	80.7 (42/52)	80 (20/25)	1.01 (0.80 – 1.28) 0.93	38.3 (-330.2-406.7) 0.76
	6 months	59.5 (22/37)	62.5 (10/16)	0.95 (0.60-1.51) 0.83	360.8 (-370.8-1092.4) 0.24
Neutropaenia/neutrophil count	3 months	2.94 (1/33)	26.3 (5/19)	0.11 (0.01-0.89) 0.04	1.82 (-4.02-7.67) 0.39
Elevated ALT/ALT level	6 weeks	51.9 (28/54)	50 (13/26)	1.04 (0.65-1.65) 0.88	14.3 (-66.2-94.8) 0.67
	6 months	18.2 (6/33)	7.14 (1/14)	2.55 (0.37-19.24) 0.37	22.7 (-599.1-644.5) 0.89
Elevated ALP/ALP count	3 months	12.5 (5/40)	40 (8/20)	0.3 (0.11-0.83) 0.02	-71.9 (-317.1-173.3) 0.46
Anaemia/Haemaglobin	Delivery	11.7 (6/51)	12.5 (2/16)	0.94 (0.21-4.21) 0.94	-36.5 (-91.7-18.3 0.2

Conclusion

Abnormal biochemical and haematologic outcomes were seen in infants born to women with IBD, but not more commonly in those exposed to TP in-utero, and with favourable clinical outcomes. Abnormalities were associated antenatal maternal inflammation, altered maternal thiopurine metabolism and preceding infant infection and vaccination.

References

1. Kanis SL, de Lima-Karagiannis A, de Boer NKH, van der Woude CJ. Use of Thiopurines During Conception and Pregnancy Is Not Associated With Adverse Pregnancy Outcomes or Health of Infants at One Year in a Prospective Study. Clin Gastroenterol Hepatol. 2017;15(8):1232-1241.e1231.
2. Mahadevan U, Long MD, Kane SV, Roy A, Dubinsky MC, Sands BE, Cohen RD, Chambers CD, Sandborn WJ. Pregnancy and Neonatal Outcomes After Fetal Exposure to Biologics and Thiopurines Among Women With Inflammatory Bowel Disease. Gastroenterology. 2021;160(4):1131-1139.
3. Thomas C, Monteil-Ganiere C, Mirallié S, Hémont C, Dert C, Léger A, Joyau C, Caldari D, Audrain M. A Severe Neonatal Lymphopenia Associated With Administration of Azathioprine to the Mother in a Context of Crohn’s Disease. Journal of Crohn's and Colitis. 2018;12(2):258-261.
4. Flanagan E, Wright EK, Hardikar W, Sparrow MP, Connell WR, Kamm MA, De Cruz P, Brown SJ, Thompson A, Greenway A, Westley I, Barclay M, Ross AL, Kiburg KV, Bell SJ, Group PS. Maternal thiopurine metabolism during pregnancy in inflammatory bowel disease and clearance of thiopurine metabolites and outcomes in exposed neonates. Aliment Pharmacol Ther. 2021.

Disclosure

Nil

Introduction

Pregnancy in women with Inflammatory Bowel Disease (IBD) is associated with increased risk of complications, particularly when disease activity is uncontrolled. Antenatal hospital admissions may reflect underlying disease activity or pregnancy-related complications and may adversely affect pregnancy outcomes.

Aims & Methods

The aim of this retrospective observational study was to describe the causes and outcomes of hospital admissions during pregnancy in women with IBD.We included completed pregnancies in women with a confirmed diagnosis of Crohn’s disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBD-U), followed between May 2014 and March 2025, who had at least one hospital admission during pregnancy. Data were collected on IBD history, disease activity, assessed according to the Global Physician Assessment (GPA), treatment, reasons for admission, investigations, and pregnancy outcomes.

Results

Of 57 pregnant women that were included (mean age: 32 years; 27 CD, 27 UC, 3 IBD-U), 6 patients (10.52%) were diagnosed during pregnancy. Prior to pregnancy, 20 patients (35.08%) had undergone IBD-related surgery, and 10 of these had a stoma. Among CD patients, 14.28% (n=4) had a history of previously active perianal disease, and 21.43% (n=6) had active perianal disease during pregnancy. Disease activity, before conception, was as follows: 66.67% (n=37) in remission, 12.28% (n=7) with mild disease, 7.02% (n=4) with moderate disease, and 1.75% (n=1) with severe disease. During pregnancy, 73.68% (n=42) remained in remission, while 12.28% (n=7) had moderate disease, 8.77% (n=5) mild disease, and 5.26% (n=3) severe disease. Regarding maintenance therapy during pregnancy, 38.6% (n=22) received aminosalicylates, 29.82% (n=17) thiopurines, and 36.84% (n=21) biologics. 13 patients (22.8%) remained on no maintenance therapy. Steroids were used at least once during pregnancy in 36.84% (n=21). In total, 64.91% (n=37) of admissions were IBD-related (n=19 flare, n=7 stoma complications, n=6 abdominal pain in the absence of active IBD, n=2 perianal complications, n=2 gastrointestinal bleeding, n=1 perforation). Among non-IBD-related admissions, 45% (n=9) were due to obstetric complications, 15% (n=3) due to infections, 30% (n=6; biliary sepsis, cholestasis, migraine, suspected venous thromboembolism ,hemoptysis and suspected pulmonary embolism) due to other causes, and 10% (n=2) due to undocumented reasons. Radiological investigations were performed in 38.6% (n=22) of patients, 21.05% (n=12) underwent endoscopic evaluation, and 10.52% (n=6) required surgical intervention. Pre-eclampsia or eclampsia was documented in 4 patients (7.01%), and gestational diabetes was observed in 5 patients (8.77%). Delivery outcomes included 61.4% vaginal births (n=25 spontaneous vaginal deliveries; n=10 assisted vaginal deliveries) and 36.84% caesarean sections (n=11 elective; n=9 emergency). Two stillbirths were recorded. The mean birth weight was 3,135 grams and 49.12% (n=28) of mothers initiated breastfeeding. Preterm delivery, defined as birth before 37 weeks of gestation, occurred in 14.03% (n=8) of cases.

Conclusion

Hospital admissions in pregnant women with IBD often reflect disease flares, stoma complications or abdominal pain. Most pregnancies complicated by IBD hospital admissions had favorable outcomes. These findings underline the importance of multidisciplinary care and close monitoring to manage both IBD-related issues and pregnancy-specific complications.

Disclosure

C.P.S. has received unrestricted research grants from Celltrion, Warner Chilcott, Janssen, and AbbVie, has provided consultancy to Warner Chilcott, Dr. Falk, AbbVie, Takeda, Fresenius Kabi, Galapagos, Ferring, Arena, and Janssen, and had speaker arrangements with Warner Chilcott, Dr. Falk, AbbVie, MSD, Pfizer, Celltrion, and Takeda.

Introduction

Inflammatory bowel disease (IBD) often affects patients during their reproductive years. The management of patients wishing to conceive or during pregnancy requires specialized counseling.

Aims & Methods

Our aim was to have a global perspective on the management of IBD by gastroenterologists (GIs) during preconception, pregnancy, breastfeeding and neonatal period.
An anonymous survey (75 questions) was developed to investigate different facets of clinical practice concerning the management of pregnant and breastfeeding in patients with IBD. A national representative from each European country, USA, Latin America, Australia and New Zealand was selected to distribute the survey to their GIs colleagues who treat IBD patients (irrespectively of their experience).

Results

A total of 856 GIs from 36 countries participated in the survey. Among the participants, 63% had over a decade of experience as GIs, and 61% identified themselves as IBD specialists. The most relevant survey results and sub-analyses based on expertise are presented in tables 1 and 2. In the management of pregnant patients in remission, treatment discontinuation occurred either consistently or occasionally as follows: 20% thiopurines, 37% vedolizumab, 31% ustekinumab, and 96% small molecules. Notably, 13% did not always discontinue small molecules in patients contemplating pregnancy. Safety was the main reason for discontinuing IBD therapy during pregnancy. Contrary to the recommendations in clinical practice guidelines, many GIs avoid starting oral or rectal budesonide, anti-TNF, vedolizumab or ustekinumab during a disease flare. Further, a third of GIs would start thiopurines for a flare during pregnancy. Moreover, 13% will never perform a colonoscopy in a pregnant patient to guide decision making. Half of GIs implemented a dedicated outpatient follow-up program for pregnant patients in remission, with 87% enrolling all pregnant patients in this program. Concerning breastfeeding, 14% believed that all drugs can be used while breastfeeding. Regarding offspring’s vaccination, about 20% recommend against the administration of non-live vaccines and only 50% recommended avoiding live vaccines during the first 12 months for children exposed to anti-TNF in-utero. Among those GIs who recommended delaying vaccines in such cases, only 41% recommended testing the infant for detectable anti-TNF levels if live vaccines were required. Among the surveyed GIs, only a minority had a referral obstetrician, and only 35% referred patients with active or complicated IBD, while 45% had a referral paediatrician with expertise in IBD. The main results regarding the medical management and monitoring of IBD during pregnancy, as well as advice on birth outcomes, breastfeeding, and vaccination, are detailed in Table 1.

Conclusion

The management of IBD during pregnancy, lactation, and neonatal period is notably suboptimal, even among GIs specifically dedicated to IBD. It is crucial to address this current need and implement urgent educational measures in this area.

Table 1. Medical management and disease monitoring during pregnancy, advice birth outcomes, breastfeeding, and vaccination.

Questions	Global N=856	By expertise
		IBD specialists N=315	General GIs N=521	p
Pregnant patients in remission Discontinued of different types of drugs (always or sometimes), n (%) -Thiopurines -Allopurinol if combination with thiopurines -Thiopurines if combination with anti-TNF -Anti-TNF -Methotrexate -Vedolizumab -Ustekinumab -Small molecules Discontinue small molecules if contemplating pregnancy (always, sometimes), n (%)	162 (20) 244 (75) 337 (45) 354 (43) 698 (99.6) 370 (37) 264 (31) 468 (96) 460 (87)	79 (15) 177 (77) 207 (42) 210 (41) 446 (99.6) 177(36) 178 (38) 336 (97) 328 (88)	79 (27) 64 (70) 122 (49) 113 (39) 238 (100) 90 (40) 82 (43) 125 (95) 124 (87)	<0.001 >0.05 >0.05 0.03 >0.05 >0.05 >0.05 >0.05 >0.05
Pregnant patients with disease flare Initiate the following therapies in case of disease flare during 1st, 2nd or 3rd trimester, n (%) - Systemic steroids - Oral budesonide - Rectal budesonide - Oral 5-ASA - Rectal 5-ASA - Thiopurines - Allopurinol - Methotrexate - Cyclosporine - Anti-TNF - Vedolizumab - Ustekinumab - Tofacitinib - Filgotinib - Upadacitinib - Ozanimod - Risankizumab Recommend urgent surgery, if indicated, n (%) - Yes, if clinically indicated regardless gestational age - Depends on the pregnancy trimester - Only if C-section could be performed Consider C-section indicated (always or if previous episodes of faecal incontinence) in case of, n (%): - Inactive perianal disease - Active perianal disease - Inactive rectovaginal fistula - History of ileal-pouch anastomosis	779 (91) 647 (76) 632 (74) 736 (86) 697 (81) 237 (28) 18 (2) 3 (0.4) 92 (11) 699 (82) 471 (55) 425 (50) 11 (1) 2 (0.2) 7 (0.8) 1 (0.1) 2 (0.2) 726 (94) 25 (4) 19 (3) 500 (71) 745 (98) 642 (90) 565 (84)	488 (94) 410 (79) 402 (77) 471 (90) 446 (86) 152 (29) 11 (2) 1 (0.1) 75 (14) 465 (89) 326 (63) 312 (60) 4 (1) 1 (0.2) 4 (0.8) 1 (0.2) 2 (0.3) 461 (95) 15 (3) 10 (2) 324 (72) 472 (98) 401 (89) 368 (84)	274 (87) 225 (71) 222 (71) 253 (80) 239 (76) 82 (26) 6 (2) 2 (0.2) 17 (5) 222 (70) 135 (43) 107 (34) 6 (2) 0 (0) 2 (0.6) 0 (0) 0 (0) 252 (93) 10 (4) 9 (3) 167 (69) 256 (97) 228 (91) 185 (84)	<0.001 0.01 0.03 <0.001 <0.001 >0.05 >0.05 >0.05 <0.0001 <0.0001 <0.0001 <0.0001 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
Disease monitoring during pregnancy Perform a colonoscopy in case of disease flare if results will change the treatment, n (%) Order a CT scan in case complications or disease activity needs to be ruled out like in a non-pregnant patient, n (%) Order a MRI in case complications or disease activity needs to be ruled out like in a non-pregnant patient, n (%)	725 (87) 290 (36) 787 (93)	444 (87) 77 (20) 461 (94)	267 (87) 50 (21) 255 (91)	>0.05 >0.05 >0.05
Advice about adverse birth outcomes ​ Who is the main person responsible for providing counselling regarding IBD in pregnancy, n (%) -Gastroenterologist -Obstetrician -Both (gastroenterologist and obstetrician) -The nurse -Other Provide pre-conception counselling to fertile patients, n (%) -Yes, to all fertile patients -Yes, but only to those who request it - No, not in generally Provide counselling to pregnant patients, n (%) -Yes, to all pregnant patients -Yes, but only to those who request it - No, not in generally	427 (50) 18 (2) 387 (45) 8 (1) 15 (2) 325 (38) 344 (40) 166 (20) 587 (69) 153 (18) 90 (11)	269 (52) 7 (1) 232 (45) 7 (1) 5 (1) 212 (41) 222 (43) 84 (16) 382 (74) 88 (17) 47 (9)	149 (47) 11 (4) 145 (46) 1 (1) 9 (3) 106 (35) 118 (39) 76 (26) 200 (67) 59 (20) 39 (13)	>0.05 <0.0001 <0.0001
Breastfeeding Advice against the following drugs during breastfeeding, n (%) - 5-ASA - Systemic steroids - Oral budesonide - Thiopurines - Allopurinol - Methotrexate - Cyclosporine - Ciprofloxacin - Metronidazole - Anti-TNF - Vedolizumab - Ustekinumab - Tofacitinib - Filgotinib - Upadacitinib - Ozanimod	11(1) 30 (4) 17 (2) 74 (9) 207 (24) 579 (68) 337 (39) 237 (28) 228 (27) 26 (3) 38 (4) 50 (6) 504 (59) 493 (58) 485 (57) 458 (54)	5 (1) 13 (3) 9 (2) 28 (5) 128 (25) 343 (66) 188 (36) 136 (26) 126 (24) 5 (1) 13 (2) 18 (4) 325 (62) 324 (62) 320 (61) 302 (58)	6 (2) 17 (5) 8 (2) 43 (14) 74 (23) 223 (71) 140 (44) 100 (32) 101 (32) 21 (7) 23 (7) 30 (9) 169 (54) 162 (51) 157 (50) 150 (48)	0.002 0.03 >0.05 <0.0001 >0.05 >0.05 0.02 >0.05 0.01 <0.0001 0.001 <0.0001 0.01 0.002 0.001 0.004
Vaccination Recommend no live vaccines during the first 12 months of life in a child exposed to anti-TNF in-utero, n (%) Recommend no live vaccines during the first 12 months of life in a child exposed to vedolizumab in-utero, n (%) Recommend no live vaccines during the first 12 months of life in a child exposed to ustekinumab in-utero, n (%) Vaccines you recommend against in a child exposed to anti-TNFs in-utero, n (%) - Hepatitis B, tetanus, Haemophilus influenza type B - Tetanus, pertussis, diphtheria - Measles, mumps, rubella, rotavirus - BCG-vaccine - Rotavirus Advice against live-vaccines vaccination beyond 12 months if the child is exposed to the following biologics during breastfeeding, n (%) - Infiximab - Adalimumab - Golimumab - Certolizumab - Vedolizumab - Ustekinumab	423 (50) 303 (35) 332 (39) 181 (21) 196 (23) 373 (44) 405 (47) 351 (41) 120 (14) 120 (14) 109 (13) 88 (10) 72 (8) 77 (9)	288 (55) 214 (41) 241 (46) 114 (22) 119 (23) 239 (46) 262 (50) 253 (49) 71 (14) 71 (14) 67 (13) 49 (9) 37 (7) 41 (8)	129 (41) 84 (27) 87 (28) 62 (20) 72 (23) 125 (40) 133 (42) 91 (29) 46 (15) 46 (15) 39 (12) 36 (11) 33 (10) 34 (11)	<0.0001 <0.0001 <0.0001 >0.05 >0.05 >0.05 0.02 <0.001 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
Anti-TNF: antitumor necrosis factor, GI: gastroenterologist, IBD: inflammatory bowel disease, 5-ASA: 5-aminosalicylates, CT: computed tomography, MRI: magnetic resonance image, BCG: bacillus Calmette-Guérin.

Disclosure

María José Casanova, has received education funding from Pfizer, Takeda, Janssen, MSD, Dr. Falk, Shire, Ferring, Galápagos and Abbvie.
Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma.
Aurelien Amiot has received consulting fees from Pfizer, Janssen, Tillotts Pharma, Takeda, and Adacyte as well as lecture fees and travel accommodations from Abbvie, Janssen, Biogen, Fresenius kabi, Takeda Pfizer, Tillotts pharma, Sandoz and Celltrion.
Hannah Gordon has received speaker fees from Janssen, Ferring, AbbVie, IBDscope and consultancy fees from Galapagos
Paulo Kotze has receive consultancy and speaking honorarium for Abbvie, Janssen, Pfizer and Takeda.
Andreas Blesl has served as speaker, consultant, and advisory member for or has received research funding from Abbvie, Aengus, Boston Scientific, Bristol-Myers Squibb, Dr. Falk Pharma, Genericon, Gilead, Janssen, Lilly, MSD, Olympus, Pfizer, Takeda, Vifo
Ignacio Catalán-Serra has received research grants and/or speaker and advisory fees from: Tillots, Takeda, Ferring, Elli Lilly, Bristol-Myers-Squidd, Janssen and Abbvie
Peter Bossuyt has received financial support for research: AbbVie, Amgen, Janssen, Viatris, Pfizer. Lecture fees: AbbVie, Bristol Myers Squibb, CAG, Celltrion, EPGS, Galapagos, Globalport, Janssen, Lilly, Materia Prima, Pentax, Scope, Takeda. Advisory board fees: AbbVie, Arena, Bristol Myers Squibb, Celltrion, CIRC, Dr Falk Benelux, Galapagos, Janssen, Eli Lilly, Pentax, PSI-CRO, Roche, Takeda, Tetrameros
Ariella Bar Gil Shitrit reports consulting/advisory fees from Takeda, Janssen, Neopharm Pfizer and AbbVie; Speaking and teaching fees from Takeda, Janssen, AbbVie, Neopharm, Rafa, BMS, Lilly and Pfizer, and research support from Takeda and Janssen.
Paulina Molander has received speaker and consultancy fees from Abbvie, Orion Pharma, Pfizer, Sandoz, Takeda, Tillotts Pharma, and advisory board member fees from BMS, Gilead and Janssen-Cilag
G Mantzaris: has served as advisory board member for AbbVie, Celgene, Celtrion, Ferring, Genesis, Hospira, Janssen, Millennium Pharmaceuticals, Merck Sharp & Dohme, Mylan, Pharmacosmos, Pfizer, Takeda, and Vianex; has served as a speaker for AbbVie, Angelini, Falk Pharma, Ferring, Galenica, Cenesis, Hospira, Janssen, Merck Sharp & Dohme, Omega Pharma, Takeda, and Vianex; has served as a consultant for Merck Sharp & Dohme and Takeda; and has received research support from AbbVie, Galenica, Genesis, Menarini Group, and Merck Sharp & Dohme.
Pascal Juillerat has receive research grant from Vifor Pharma, consulting/Board/speaker from AbbVie, Arena, Amgen, BMS, Ferring, Gilead, Janssen, Lilly, MSD, Pfizer, Pierre Fabre, Roche, Sandoz, Takeda, Tillots, UCB Pharma .
Krisztina B. Gecse has received research grants from Abbvie, Pfizer Inc, Celltrion and Galapagos, consultancy fees and speaker’s honoraria from AbbVie, Celltrion, Ferring, Galapagos, Immunic Therapeutics, Janssen Pharmaceuticals, Pfizer Inc., Samsung Bioepis, Takeda and Tillotts.
Pär Mirelyd has received paid lectures from Abbvie, Tillotts, Galapagos, Janssen and Pfizer
Uma Mahadevan has received consultant fees from Abbvie, Arena, BMS, Boeringher Ingerlheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck/Prometheus Laboratories, Pfizer, Rani Therapeutics, Roivant, Takeda.
Beatriz Iade has served as speaker from Abbvie and Janssen.
Dana Duricova has received lecture fee/ consultancy from Janssen, Takeda, Abbvie, Pfizer, Ferring, Eli-Lilly
Mette Julsgaard has received research grants for other investigator-driven studies from Takeda and Novo Nordisk Foundation (grant no. NNF23OC0081717), has received consultation fees from Ferring and Takeda, and has received speaker’s fees from MSD, Ferring, Tillotts Pharma, and Takeda.
María Chaparro has served as speaker, consultant or research or education funding from MSD, Abbvie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Biogen, Gilead and Lilly.