Pregnant Inflammatory Bowel Disease Patients Research Articles

Controversies in Venous Thromboembolism Risk Assessment in Inflammatory Bowel Disease: A Narrative Review.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract with increasing rates of incidence and prevalence across the world. Complex inflammatory and prothrombotic pathophysiology in IBD makes venous thromboembolism (VTE) a common complication with significant morbidity and mortality. This risk is increased in pregnancy. As we continue to understand the pathogenesis of IBD, this article highlights the continued risk of VTE following discharge, for which there is currently no clear guidance, yet the risk of VTE remains high. Furthermore, we discuss this increased VTE risk in the context of pregnant IBD patients and the relevant current guidelines. Alongside this, medications that are used to manage IBD carry their own thrombotic risk, which clinicians should be aware of. Assessing VTE risks in IBD populations using newer medications should be a focus of future research.

SAGES guidelines for the use of laparoscopy during pregnancy

BackgroundWhen pregnant patients present with nonobstetric pathology, the physicians caring for them may be uncertain about the optimal management strategy. The aim of this guideline is to develop evidence-based recommendations for pregnant patients presenting with common surgical pathologies including appendicitis, biliary disease, and inflammatory bowel disease (IBD).MethodsThe Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee convened a working group to address these issues. The group generated five key questions and completed a systematic review and meta-analysis of the literature. An expert panel then met to form evidence-based recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Expert opinion was utilized when the available evidence was deemed insufficient.ResultsThe expert panel agreed on ten recommendations addressing the management of appendicitis, biliary disease, and IBD during pregnancy.ConclusionsConditional recommendations were made in favor of appendectomy over nonoperative treatment of appendicitis, laparoscopic appendectomy over open appendectomy, and laparoscopic cholecystectomy over nonoperative treatment of biliary disease and acute cholecystitis specifically. Based on expert opinion, the panel also suggested either operative or nonoperative treatment of biliary diseases other than acute cholecystitis in the third trimester, endoscopic retrograde cholangiopancreatography rather than common bile duct exploration for symptomatic choledocholithiasis, applying the same criteria for emergent surgical intervention in pregnant and non-pregnant IBD patients, utilizing an open rather than minimally invasive approach for pregnant patients requiring emergent surgical treatment of IBD, and managing pregnant patients with active IBD flares in a multidisciplinary fashion at centers with IBD expertise.Graphical abstract

Prescribing in pregnant women with inflammatory bowel disease and its relationship to congenital malformations in Japan.

Inflammatory bowel disease (IBD) frequently affects younger patients and poses various challenges concerning pregnancy and childbirth. Maintaining good disease control throughout pregnancy is crucial, but expectant and pregnant patients may worry about the fetal impact of medications, leading to treatment discontinuation due to uncertainty about this issue. This study investigated the real-world drug-prescribing practices for pregnant patients with IBD in Japan and their potential connection to major congenital malformations (MCMs). Overall, 277 female IBD patients who gave birth between 2010 and 2019 were selected from the JMDC claims database. The prescribing patterns of IBD medications and MCMs in the patients' offspring were analyzed. Among pregnant IBD patients, 74.4% received at least one medication from 90days before pregnancy to 90days after delivery. Trends in medication prescriptions during pregnancy in 2010-2019 revealed consistent use of oral 5-ASA, variable use of topical medications, a decrease in systemic steroids, and an increase in biologics. The prevalence of MCMs in children born to IBD-affected mothers did not differ significantly between those who did and did not receive IBD medications (8.6% vs 6.8%). Although circulatory system MCMs were slightly more common in the IBD medication group (4.9% vs 1.4%), this difference was not significant. Logistic regression analysis did not reveal an association between MCM risk and first-trimester use of IBD medications, including corticosteroids and biologics. This study provides insights into medication patterns in pregnant IBD patients and suggests no increased risk of MCMs associated with first-trimester IBD medication use.

Managing Inflammatory Bowel Disease in Pregnancy: Health Care Professionals' Involvement, Knowledge, and Decision Making.

The management of pregnant women with inflammatory bowel disease (IBD) is complex. We aimed to assess health care professionals' (HCPs) theoretical and applied knowledge of pregnancy-related IBD issues. A cross-sectional international survey was distributed to HCPs providing IBD care between October 2020 and March 2021. Knowledge was assessed using the validated Crohn's and Colitis Pregnancy Knowledge Score (CCPKnow; range, 0-17). Decision-making was assessed by free text responses to 3 clinical scenarios scored against predetermined scoring criteria (maximum score 70). Among 81 participants, median CCPKnow score was 16 (range, 8-17), and median total scenario score was 29 (range, 9-51). Health care professionals who treat >10 IBD patients per week (CCPKnow P = .03; scenarios P = .003) and are more regularly involved in pregnancy care (CCPKnow P = .005; scenarios P = .005) had significantly better scores. Although CCPKnow scoring was consistently high (median score ≥15) across all groups, consultants scored better than trainees and IBD nurses (P = .008 and P = .031). Median scenario scores were higher for consultants (32) and IBD nurses (33) compared with trainees (24; P = .018 and P = .022). There was a significant positive correlation between caring for greater numbers of pregnant IBD patients and higher CCPKnow (P = .001, r = .358) and scenario scores (P = .001, r = .377). There was a modest correlation between CCPKnow and scenario scores (r = .356; P < 0.001). Despite "good" theoretical pregnancy-related IBD knowledge as assessed by CCPKnow, applied knowledge in the scenarios was less consistent. There is need for further HCP education and clinical experience to achieve optimal standardized care for IBD in pregnancy.

Thiopurine pharmacogenomics and pregnancy in inflammatory bowel disease

The thiopurine drugs azathioprine and 6-mercaptopurine are widely used for the maintenance of clinical remission in steroid-dependent inflammatory bowel disease (IBD). Thiopurines are recommended to be continued throughout pregnancy in IBD patients, but conclusive safety data in pregnant patients remain still insufficient. On the other hand, a strong association between a genetic variant of nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15 p.Arg139Cys) and thiopurine-induced myelotoxicity has been identified. Pharmacokinetic studies have revealed that thiopurine metabolism is altered in pregnant IBD patients and suggested that the fetus may be exposed to the active-thiopurine metabolite, 6-thioguaninetriphosphate, in the uterus. A recent study using knock-in mice harboring the p.Arg138Cys mutation which corresponds to human p.Arg139Cys showed that oral administration of 6-MP at clinical dose induces a severe toxic effect on the fetus harboring the homozygous or heterozygous risk allele. This suggests that NUDT15 genotyping may be required in both women with IBD who are planning pregnancy (or pregnant) and their partner to avoid adverse outcomes for their infant. The risk to the fetus due to maternal thiopurine use is minimal but there are some concerns that are yet to be clarified. In particular, a pharmacogenomic approach to the fetus is considered necessary.

P331 The safety of tioguanine exposure during pregnancy: a case series of seventy-three pregnancies

Abstract Background Azathioprine and mercaptopurine exposure during conception and pregnancy has been considered safe in patients with inflammatory bowel disease (IBD). Its use is not associated with a higher risk of preterm birth or low birthweight. Data on the safety of tioguanine, an alternative thiopurine-derivate, in pregnant IBD patients is limited. In a small case series, tioguanine appeared safe for both mother and fetus. In this study, we describe the teratogenicity and safety of tioguanine during pregnancy in a large group of IBD patients. Methods We performed a preliminary analysis of our ongoing multicenter descriptive case series of female IBD patients who were treated with tioguanine at some point during their pregnancy. Data regarding disease and medication history, pregnancy course and neonatal outcomes, such as preterm birth, miscarriage, birthweight, Apgar scores and congenital abnormalities were collected by the treating physician. Results Seventy-three pregnancies, including three twin pregnancies were collected. Most women (80%) had Crohn’s disease and the mean age during delivery was 31 years (range 21-42). Tioguanine was used throughout the entire pregnancy in 89% with a median daily dose of 20 mg. Five (6.8%) of these pregnancies resulted in a miscarriage, all within the first 13 weeks. No congenital abnormalities were reported in all seventy-one live born children. In the singleton pregnancies the median birthweight was 3375 gram (IQR 3075-3739, N=61, 4 missing values) with a median gestational age of 39.0 weeks (IQR 38.3-40.0, N=61). Four children (6.5%) were born prematurely (&amp;lt;37 weeks). Two of them were born after a spontaneous onset of labor with respectively 33 + 6 and 35 + 6 weeks, while in the other two labor was induced due to a placental abruption (32 + 1 weeks) or HELLP syndrome (31 + 4 weeks). Three children (4.9%) had a low birthweight (&amp;lt;2500 gram), all of them born prematurely, and five patients (8.3%, N=60, 5 missing values) were born small for gestational age (&amp;lt;10th percentile). The median Apgar score after 1 and 5 minutes was respectively 9 (IQR 8-9, N=58) and 10 (IQR 9-10, N=59). Two neonates (3.4%), one born pre-and dysmature and the other a premature second-born twin, had an Apgar score (&amp;lt;7) after 5 minutes. Conclusion In this large case-series, tioguanine exposure during pregnancy was not associated with an increased risk of congenital abnormalities, low birthweight or preterm birth in IBD patients. These data support the safe use of tioguanine during pregnancy in IBD.

A185 THE IMPACT OF PRIOR SURGERY ON ADVERSE PREGNANCY OUTCOMES IN PREGNANT PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract Background During the course of inflammatory bowel disease (IBD), approximately 20% of patients with ulcerative colitis (UC) and 80% of Crohn’s disease (CD) patients will require surgery. The most common operation is total proctocolectomy and ileoanal pouch anastomosis (IPAA) for UC patients and ileocecal (IC) resection for CD. In pregnant IBD patients, guidelines name the presence of IPAA as a relative indication for Cesarean section (C-section). The effect of prior IBD-related surgery on mode of delivery and pregnancy-related outcomes remains unknown. Aims To describe pregnancy-related outcomes in pregnant women with IBD who have undergone prior IBD-related surgery. Methods We performed a retrospective cohort study of pregnant women with IBD including those with prior IBD-related surgeries including IPAA, IC resection, total or partial colectomy and ileostomy formation who delivered an infant at our medical center from 2016 to 2020. We assessed the mode of delivery, delivery characteristics (emergency vs. planned C-section) and maternal and neonatal outcomes Results Fifty-six UC patients and 64 CD patients were included in the analysis, of which 10 and 24 had undergone prior IBD-related surgery, respectively. The mean age at conception was 34.10 years in the surgical UC group and 30.30 years in the surgical CD group. Mode of delivery: C-section rates were higher in post-surgical compared to non-surgical UC patients (70% vs. 30.4%, p = 0.02). Similar numbers of C-sections were performed emergently in the surgical compared to non-surgical UC group (10% vs. 18%, p = 0.53). Comparatively, there was no significant difference in C-section rates in post -surgical compared to non-surgical CD mothers (50% vs. 40%, p = 0.44), with 13% performed emergently in both groups. Maternal outcomes: Gestational diabetes developed in 10% of surgical UC and 4.5% of surgical CD patients. Premature rupture of membranes developed in 10% of surgical UC and 9.1% of surgical CD patients. There was no difference in pre-eclampsia rates in the surgical and non-surgical CD groups (9.1% vs 13.2%, p = 0.64). Neonatal outcomes: There was no significant difference in pre-term birth rates in post-surgical compared to non-surgical UC mothers (10% vs. 15.2%, p = 0.67) or in surgical compared to non-surgical CD mothers (13.6% vs. 5.1%, p = 0.29). Neonatal Intensive Care Unit (NICU) requirements were higher in infants born to post-surgical CD compared to non-surgical CD mothers (18.2% vs. 2.7%, p = 0.04). More low birth weight (LBW) infants were born to post-surgical CD vs non-surgical CD mothers (13.6% vs. 0%, p = 0.02). Conclusions Women with IBD who have had prior IBD-related surgery may be at increased risk of developing adverse gestational and neonatal outcomes. Women with surgical UC have an increased incidence of Cesarean delivery. Funding Agencies None

Safety of ustekinumab or vedolizumab in pregnant inflammatory bowel disease patients: a multicentre cohort study.

The prevalence of inflammatory bowel diseases (IBD) is high in women of childbearing age. Achieving clinical remission from conception to delivery using current medications is a major issue in IBD. To assess maternal and neonatal complications and management of vedolizumab or ustekinumab) in pregnant women with IBD receiving these agents. We performed a retrospective cohort study among GETAID centres including women with IBD who received ustekinumab or vedolizumab during pregnancy or within the 2months before conception and compared outcomes to women exposed to anti-TNF treatment during pregnancy. Seventy-three pregnancies in 68 women with IBD were analysed: 29 on ustekinumab resulting in 26 (90%) live births, two (7%) spontaneous abortions and one (3%) elective termination; 44 on vedolizumab resulting in 38 (86%) live births, five (11%) spontaneous abortions and one (3%) medical interruption. The control group included 88 pregnancies exposed to anti-TNF in 76 women with IBD. The median age at conception, the proportion of women who smoked or in clinical activity at conception was comparable between groups. Only the proportion of patients exposed to >2 anti-TNF agents was significantly increased among the ustekinumab and vedolizumab groups compared to control group (22% and 10% vs 3%, P<0.005). Rates of prematurity, spontaneous abortion, congenital malformations and maternal complications were comparable between groups. We report 73 pregnancies in patients receiving vedolizumab or ustekinumab without a negative signal on maternal or neonatal outcomes. Further prospective studies are needed on the outcomes of pregnancies with new biologic drugs.

Management of Pregnant Inflammatory Bowel Disease Patients During the COVID-19 Pandemic.

The rapid emergence of the novel coronavirus [SARS-CoV2] and the coronavirus disease 2019 [COVID-19] has caused significant global morbidity and mortality. This is particularly concerning for vulnerable groups such as pregnant women with inflammatory bowel disease [IBD]. Care for pregnant IBD patients in itself is a complex issue because of the delicate balance between controlling maternal IBD as well as promoting the health of the unborn child. This often requires continued immunosuppressive maintenance medication or the introduction of new IBD medication during pregnancy. The current global COVID-19 pandemic creates an additional challenge in the management of pregnant IBD patients. In this paper we aimed to answer relevant questions that can be encountered in daily clinical practice when caring for pregnant women with IBD during the current COVID-19 pandemic.PodcastThis article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

P430 Feasibility and reliability of gastrointestinal ultrasound in pregnant inflammatory bowel disease patients

Abstract Background Disease activity during pregnancy in women with inflammatory bowel disease (IBD) is associated with miscarriage, preterm delivery and low birth weight. Monitoring disease activity throughout the pregnancy is therefore important. Gastrointestinal ultrasound (GIUS) has a high potential as a point-of-care tool for monitoring disease activity in IBD as it has been shown to correlate well with endoscopy and magnetic resonance imaging. However, data are scarce on the use of GIUS in IBD throughout pregnancy. The aim of this prospective study is to determine the feasibility and reliability of GIUS in pregnant IBD patients. Methods Patients were included when visiting the outpatient IBD pregnancy clinic. At each trimester, clinical and biochemical disease activity was evaluated and GIUS was performed. Feasibility was assessed by the ability to visualise each bowel segment (terminal ileum (TI), ascending (AC), transverse (TC), descending (DC) and sigmoid colon (SC)). Reliability was evaluated by using clinical and biochemical disease activity as a gold standard. This was defined as a Harvey–Bradshaw Index ≥4 in Crohn’s disease (CD) or a Simple Clinical Colitis Activity Index ≥5 in ulcerative colitis and a faecal calprotectin (FCP)³ 250 mg/g. Bowel wall thickness (BWT) of &amp;gt; 3 mm in the colon and &amp;gt; 2mm in the terminal ileum was considered as signs of active inflammation on ultrasound. A Mann–Whitney U-test and chi-square were used for statistical analysis. Results Thirty-two IBD patients (54% CD) were studied. Both a GIUS and FCP was available in 18, 11 and 6 patients for the first, second and third trimester, respectively. Eleven of 32 (34%) patients had clinically active disease at least at one time point during the pregnancy. Table 1 shows the visibility per segment. When the active disease was defined as an FCP ≥ 250 mg/g, GIUS could distinguish active from the non-active disease in the first, second and third trimester with a sensitivity of 80%, 75% and 75% and specificity of 85%, 86% and 100%, respectively. FCP levels were significantly higher in patients with an active disease on GIUS regardless of the trimester (mean 1095.5 ± 1453.8 mg/g vs. 265.25 ± 649.8 mg/g, p &amp;lt; 0.0001). Conclusion GIUS is accurate to distinguish active from the quiescent disease in pregnancy. Feasibility to visualise the TI and the SC decreased during the second and third trimester, although active disease could still be detected. Consequently, GIUS is feasible and reliable to assess disease activity throughout pregnancy in IBD.

P853 The gut microbiota of pregnant inflammatory bowel disease patients shows a low diversity, but stable profile throughout pregnancy

P853 The gut microbiota of pregnant inflammatory bowel disease patients shows a low diversity, but stable profile throughout pregnancy

Maternal and foetal adverse events with tumour necrosis factor-alpha inhibitors in inflammatory bowel disease.

Transplacental transfer of tumour necrosis factor-alpha (TNF-α) inhibitors has been shown in mothers receiving therapy for inflammatory bowel disease (IBD). To examine reports of adverse events of these medications in pregnancy. Individual Safety Reports of adverse events (Jan 2003-June 2012) were accessed from the Food and Drug Administration Adverse Event Reporting System. The study data set was constructed by searching for cases with an indication for medication usage of IBD. The data set was then queried for key terms indicating pregnancy, followed by elimination of cases with potentially teratogenic exposures (FDA category X concomitant medications) as well exposures to study medications through partner or if the medications were discontinued prior to pregnancy. Logistic regression analysis was performed to detect signals for maternal/foetal adverse events with TNF-α inhibitors and/or thiopurines (compared to aminosalicylates). A total of 1097 individual Safety Reports in pregnant IBD patients were identified with the majority reported among patients receiving TNF-α inhibitor monotherapy (783 cases, 71.4%). Thiopurine monotherapy (OR 2.55, CI 0.95-6.88) and in combination with TNF-α inhibitors (OR 0.97, CI 0.49-1.93) were not associated with increased odds of maternal/foetal adverse events. Decreased odds for maternal/foetal adverse events were seen with TNF-α inhibitor monotherapy (overall) and specifically with certolizumab monotherapy (OR 0.11, CI 0.05-0.23). In this analysis of adverse events from the Food and Drug Administration Adverse Event Reporting System, use of thiopurine monotherapy or in combination with TNF-α inhibitors was not associated with an increase in maternal/foetal adverse events. Certolizumab monotherapy was associated with a decrease in maternal/foetal adverse events.

Su1091 State of Trainee Inflammatory Bowel Disease Education in the United States: A National Survey

Introduction: The incidence of Inflammatory Bowel Disease (IBD) and the complexity of its management are increasing. Identifying shortcomings and defining the core content of IBD education in gastroenterology (GI) fellowship training in the United States (US) are critical to preparing trainees for this challenge. The aim of this study was to perform a needs assessment survey of US GI fellowship program directors (PD) and trainees to understand the current state of IBD training in the US. Methods: A 15-question PD survey and 19question trainee survey was performed using Survey Monkey. Survey content was developed and reviewed together with nationally recognized IBD experts and optimized in a pilot trial with recently graduated GI trainees. Final questionaires were sent to all US PDs with the request to forward the trainee survey to their respective program trainees. Data were analyzed using excel and SAS v9.3. Results: Surveys were completed by 43/161 (27%) PDs and 116 trainees. The majority of PDs (39/43) worked at university or university-affiliated hospitals. IBD specific inpatient and/or outpatient rotations were offered by 63% of PD institutions. All trainee years were equally represented. While most trainees were or with their inpatient and outpatient IBD training, a significant subgroup was unsure or felt their inpatient (33%) or outpatient (43%) training was inadequate. Only 28% of trainees were satisfied with their current level of IBD exposure during training. Monthly IBD didactics was the only variable independently associated with satisfaction with current level of training (OR 4.6, 95% CI 1.8-11.8). Most trainees (62%) were not interested in pursuing an IBD career, but 10% were considering applying for an advanced IBD fellowship. Strikingly, 57% would consider an IBD focus, if offered, in the context of a 3 year GI fellowship. We examined trainee comfort by different competencies in IBD management (Figure 1). Trainees reported the most confidence or comfort in the management of inpatient CD or UC. In contrast, fewer than half the trainees reported comfort in the management of pouch or stoma issues or the pregnant IBD patient. The proportion of PDs viewing a competency as essential training strongly correlated with trainee comfort in that area (correlation co-efficient 0.75, p < 0.001; Figure 2). Conclusions: Over one-third of participating US GI trainees did not feel confident or mostly comfortable with their level of IBD training. More than half would consider choosing an IBD focus during GI fellowship, if offered. There is a wide spectrum of comfort regarding different competencies in IBD management suggesting that specific areas may require additional focus during training. These findings can provide the basis for the development of an IBD core competency curriculum for US GI fellowship programs.

From conception to delivery: managing the pregnant inflammatory bowel disease patient.

Inflammatory bowel disease (IBD) typically affects patients during their adolescent and young adult years. As these are the reproductive years, patients and physicians often have concerns regarding the interaction between IBD, medications and surgery used to treat IBD, and reproduction, pregnancy outcomes, and neonatal outcomes. Studies have shown a lack of knowledge among both patients and physicians regarding reproductive issues in IBD. As the literature is constantly expanding regarding these very issues, with this review, we provide a comprehensive, updated overview of the literature on the management of the IBD patient from conception to delivery, and provide action tips to help guide the clinician in the management of the IBD patient during pregnancy.

Su1139 Awareness Among Practitioners Regarding the Safety of Inflammatory Bowel Disease Medications During Pregnancy

Background: Inflammatory Bowel Disease (IBD) frequently occurs in females of childbearing age. It is important to have the disease in remission at the time of conception and throughout the pregnancy. The benefits of medical therapy to maintain remission during pregnancy outweigh the risks of cessation in majority of the cases. Physicians involved in the care of pregnant IBD patients may not have the correct information regarding the safety of IBD drugs. We conducted a local survey to assess the knowledge and awareness among various practitioners regarding the safety issues of drugs used to treat IBD in the pregnant patients. Methods: 111 practitioners (Family Medicine (FM) n=35, Internal Medicine (IM) n=22, OB/GYN n=22, GI-General n=23, and GI-IBD Specialist n=9) were quizzed on the FDA classification of common IBD drugs and the need for caution with live vaccines in neonates of mothers receiving biologics during pregnancy. They were also given two scenarios in managing a patient with IBD desiring to become pregnant: 1) the patient being managed with thiopurines and 2) the patient being managed with biologics. For each scenario, physicians were asked if they would inform the patient to 1) only take current medications as symptoms arise, 2) not take the medications under any condition, 3) continue taking the medication as previously prescribed, 4 and 5) discontinue one and start a differentmedication. The percentage of practitioners among the different groups was compared using either χ2 or Fisher's exact test as appropriate. The p-value was adjusted for multiple comparisons. Results: GI-General and IM were less likely to answer correctly more than one question regarding the FDA classification of IBD drugs compared to FM and OB/GYN practitioners (27% vs. 74%, p,0.0005) and GI-IBD (27% vs. 56%, p=0.43). GIs (GI-General and GIIBD) are more likely to advise their patients to continue taking their current medications (biologics and thiopurines) during pregnancy compared to non GIs (IM, FM, OB/GYN) (biologics: 84% vs. 45%, p,0.0005; thiopurines: 66% vs. 14%, p,0.0005)( figure). Only 45% of OB/GYN correctly identified the safety issues regarding administration of live vaccines in neonates of mothers receiving biologics. There was no difference between GIs and non GIs with regard to the safety knowledge of administering live vaccines (63% vs. 59%, p= 0.83). Overall, 79% of physicians surveyed said they would change their practice based on the educational section at the end of the survey. Conclusion: Practitioners involved in the care of pregnant patients may not have the correct knowledge regarding the safety and management of IBD drugs during pregnancy. Bringing awareness through appropriate education can result in the greater likelihood of physicians following best practice guidelines.

Family planning and inflammatory bowel disease: the patient and the practitioner

Patients with inflammatory bowel disease (IBD) are commonly in their child-bearing years. Maintainance medication, as recommended by international guidelines, is an emotive topic and an anxiety source. This study measures the awareness of patients and primary practitioners of the issues involved. A prospective questionnaire was sent to female patients (18-50 years) with an IBD diagnosis in Kerry General Hospital, Ireland, who were identified from radiology and pathology databases. A seperate questionnaire was sent to General Practitioners (GPs) in the region. About 31 female patients (42%) and 49 GPs (43%) returned completed questionnaires. About 29% had Crohn's disease and 71% ulcerative colitis. A total of 42% of patients would allow having IBD or its treatment to influence decisions about family planning. Most patients were on maintainance medications. Despite this, 68% had not discussed family planning with a doctor. One-third believed all medications should be stopped during pregnancy and 68% reported significant anxiety about future pregnancies. A total of 68% GPs report regular contact with IBD patients, but consultations with pregnant IBD patients are less frequent. About 41% of GPs have not opportunistically raised family planning with this patient group and 67% would refer to a tertiary specialist for advice. About 2% of GP's had need to research the topic in the last 12 months. There is a significant patient knowledge deficit about pregnancy and IBD resulting in unwarranted fears and anxiety. Further evidence based education for GP's with increased gastroenterologist/IBD nurse specialist support should maximize exploitation of health promotion opportunities to electively address this issue.

Letter: thiopurines during pregnancy and intrauterine exposure to metabolites

SIRS, We read with great interest the review of literature and proposed management-algorithm concerning the often challenging questions on fertility and pregnancy in inflammatory bowel disease (IBD) patients. The risks and benefits of continuation of azathioprine (AZA) or mercaptopurine (MP) therapy should indeed be balanced in each pregnant IBD patient. In general, maintenance thiopurine therapy throughout pregnancy is considered safe and there is no necessity for cessation of administration. The authors state that the foetus is protected from potential teratogenic effects of thiopurines, as it lacks the enzyme inosinate phosphorylase, which is required to convert AZA or MP to its active metabolites. We feel that this statement needs some refinement. The unborn child is only marginally exposed to the parent compounds AZA or MP themselves, as these drugs are rapidly absorbed and metabolised intracellularly by enterocytes and hepatocytes into several metabolites. Therefore, it is to be expected that there will be no, or limited, metabolism of AZA or MP in the foetus itself. Recently, we demonstrated that the human foetus is exposed to the pharmacologically active metabolite 6-tioguanine nucleotides generated from maternal AZA use. Surprisingly, in the vast majority of newborns, the thiopurine metabolite 6methylmercaptopurine could not be detected in red blood cells directly drawn from the umbilical cord after delivery. Based on these observations, it appears that the placenta plays a critical role in the transfer of maternal thiopurine metabolites. To our knowledge, the enzyme inosinate phosphorylase does not play a role in the metabolism of thiopurines. Therefore, the statement that the foetus is protected from teratogenic effects as it lacks the enzyme inosinate phosphorylase cannot hold true. Perhaps the manuscript should have stated that maintenance thiopurine therapy during pregnancy is considered safe, despite intrauterine exposure to thiopurine metabolite 6-tioguanine nucleotides.

Conception and pregnancy outcome in women with inflammatory bowel disease: A multicentre study from Japan

Background Neither conceptions and pregnancy outcomes nor the safety of medications for childbearing inflammatory bowel disease (IBD) patients has been investigated in Asia. The aim of this study is to analyse conception and pregnancy outcomes of Japanese female IBD patients. Methods We conducted a retrospective cohort study of pregnant IBD patients at 6 institutions. The incidences of abortion, Caesarean delivery, low birth weight (LBW) (< 2500 g), and congenital malformation were analysed in these patients. Risk factors associated with adverse outcomes in IBD patients were also assessed. Results A total of 325 patients experienced 534 conceptions. Among these, 303 conceptions (57%) were observed during/after disease onset. Although conceptions and pregnancy outcomes after disease onset were comparable to the observed levels prior to disease onset in UC patients, the incidences of spontaneous abortion (OR 5.3; 95%CI 1.1–25.0) and Caesarean delivery (OR 4.8; 95%CI 1.5–15.0) were significantly higher in Crohn's disease (CD) patients whose conceptions occurred after disease onset compared to CD patients whose conceptions occurred before disease onset. The incidences of spontaneous abortion, LBW, and Caesarean delivery were higher in CD patients who had a history of surgery for perianal lesions than in those who did not have perianal lesions or who had ulcerative colitis (UC). In the IBD patients studied after disease onset, independent risk factors for spontaneous abortions included a history of previous treatment for sterility (OR 2.9; 95%CI 1.2–7.0). Independent risk factors for Caesarean operation (OR 4.1, 95% CI: 1.7–10.1) and LBW (OR 3.5, 95% CI: 1.3–9.1) included a history of bowel resection for the treatment of IBD. Congenital malformation was not associated with the factors of type of disease, smoking, and previous surgery. Conclusion In Japanese UC patients, conception and pregnancy outcomes after disease onset were comparable to the outcomes observed prior to disease onset, whereas CD appeared to be associated with adverse outcomes. Caesarean operation and LBW were more frequently observed in CD patients who had a history of surgery for perianal lesions and bowel resection.

High intra-uterine exposure to infliximab following maternal anti-TNF treatment during pregnancy

Typically, inflammatory bowel disease (IBD) patients are in their reproductive years, raising questions about safely using antitumour necrosis factor antibodies like infliximab (IFX) during pregnancy. IgG antibodies naturally cross the placenta, especially during the last trimester. To prevent foetal intra-uterine exposure, stopping IFX treatment at gestational week 30 is recommended. However, whether this limits intra-uterine and early postnatal IFX exposure is unestablished. To determine the intra-uterine exposure to IFX following maternal treatment with IFX. Four pregnant IBD patients intentionally continued IFX during pregnancy. IFX levels were assessed in newborns' cord blood and the mothers' peripheral blood at delivery. The children's development during the first 3-6 months, infections, vaccine reactions and antibody responses to vaccinations against Haemophilus influenzae type b and Pneumococcus were assessed. The patients stopped IFX therapy at gestational week 21, 26, 26 and 30, respectively. In three infants, therapeutic IFX levels were present in cord blood at levels of 5.5-13.7 μg/mL and were two- to three-fold higher than in the peripheral blood of their mothers. During the 3- to 6-month follow-up, the children developed normally without signs of infections or allergic reactions, and had normal antibody titres after routine childhood vaccinations. The use of IFX until gestational week 30 leads to foetal intra-uterine exposure to IFX at levels that exceed those in the mothers' peripheral blood. Although no short-term complications were detected, the high IFX levels observed in newborns raise concerns about unknown effects of IFX on the developing immune system.

Inflammatory Bowel Disease and Pregnancy: Evidence, Uncertainty and Patient Decision-Making

Inflammatory bowel disease (IBD) often affects women during their child-bearing years. Management of a pregnant IBD patient, or a patient contemplating pregnancy, poses unique challenges and can be quite daunting. Knowledge of the basic interplay among disease, normal host physiology and pregnancy is vital to managing these patients. One of the most important advances in the management of IBD over the past decade has been the finding that normal pregnancy outcomes can be achieved when a woman enters the pregnancy in remission. New insights into the safety of a wider spectrum of drugs in these patients has allowed for increased success in IBD management. The evidence supporting medical interventions including biological therapy such as antibodies to tumour necrosis factor agents is reviewed. Once the treating physician understands this complex relationship, management of the pregnant IBD patient can often become a rewarding experience.