Inflammatory bowel disease and pregnancy: Lack of knowledge is associated with negative views

BackgroundEnabling women with inflammatory bowel diseases (IBD) to have successful pregnancies requires complex decisions. The study aimed to assess patients' views on IBD and pregnancy and to evaluate any association with subject knowledge.MethodsGeneral attitudes of females with IBD were assessed on fertility, medication use, delivery mode and pregnancy outcomes. Attitudes regarding personal situation were assessed in participants nulliparous since IBD diagnosis. Knowledge of pregnancy-related issues in IBD was assessed by the Crohn's and Colitis Pregnancy Knowledge Score ‘CCPKnow’.ResultsOf 145 participants 68% of participants agreed with need for medical therapy for flares during pregnancy, but 24% felt it more important to tolerate symptoms. 36% believed that all IBD medication is harmful to unborn children. Of 96 women nulliparous after IBD diagnosis, 46% were worried about infertility, 75% expressed concern about passing IBD to offspring and 30% considered not having children. Nearly all participants worried about the effects of IBD on pregnancy and the effects of pregnancy on IBD. General attitudes that ‘medication should be stopped prior to conception’ (P < 0.001), ‘pregnant women should avoid all IBD drugs’ (P < 0.001), and ‘put up with symptoms’ (P < 0.001) were associated with significantly lower CCPKnow scores.ConclusionOver a third of patients considered IBD medication harmful to unborn children. Fear of infertility and concerns about inheritance may explain high rates of voluntary childlessness. Attitudes contrary to medical evidence were associated with significantly lower knowledge. Young women with IBD, particularly those with poor knowledge, should be offered education and counselling about pregnancy-related issues.     

Inflammatory Bowel Disease During Pregnancy

Opinion statement The management of both male and female patients with inflammatory bowel disease (IBD) who wish to have a baby is challenging. For women, the most important factor to bear in mind is that the outcome of pregnancy is largely influenced by disease activity at the time of conception. Women with quiescent disease are likely to have an uncomplicated pregnancy with the delivery of a healthy baby, whereas women with active disease are more likely to have complications such as spontaneous abortions, miscarriages, stillbirths, and exacerbation of the disease. This is more true of patients with Crohn’s disease than of patients with ulcerative colitis. Although the safety of medications used during pregnancy is an important issue, the impact of the medications used to treat IBD is less important in comparison to disease activity itself. 5-Aminosalicylic acid (5-ASA) products appear to be safe during pregnancy; corticosteroids are probably safe; 6-mercaptopurine and azathioprine should be used with caution; and methotrexate is contraindicated. There are inadequate data on the use of infliximab during pregnancy. In regard to men with IBD, the disease itself does not seem to have any negative impact on fertility. However, there is controversy about the effects of using 6-mercaptopurine and azathioprine prior to and during fertilization. In view of possible adverse pregnancy outcomes, it would be prudent to withhold 6-mercaptopurine and azathioprine therapy in men with IBD for 3 months prior to conception, when feasible. Most IBD medications should be continued before, during, and after pregnancy, with careful attention to the known cautions and exceptions. If IBD in a pregnant patient is in remission, the prognosis for pregnancy is the same as if she did not have IBD. Active disease should therefore be treated aggressively and remission accomplished before pregnancy is attempted. Similarly, a woman who unexpectedly becomes pregnant while her IBD is active should be treated aggressively, as remission remains the greatest investment for a favorable pregnancy outcome.     

Management of inflammatory bowel disease during pregnancy and nursing.

The peak age of onset for inflammatory bowel disease (IBD) coincides with the peak age for conception and pregnancy, and gastroenterologists will frequently be called on to treat pregnant IBD patients. The greatest threat to a normal conception and pregnancy is active disease, not active medicine. The majority of IBD medications are safe in pregnancy and nursing and should be used as needed. When in remission, ulcerative colitis and Crohn's disease usually do not affect fertility. Fertility may be impaired, however, by pelvic adhesions and scarring from old operations or disease. Pregnant IBD patients should be followed in a facility where diagnostic tests, such as sigmoidoscopy and ultrasound, and surgery can be performed if necessary.     

Inflammatory bowel disease meets fertility: A physician and patient survey

Background and aimsInflammatory bowel disease (IBD) can affect patients during their childbearing years. Literature evidence is scarce regarding the level of knowledge among health care professionals (HCPs) and patients about the impact of IBD on fertility. The aim of this survey was to investigate HCPs' and patients' knowledge on fertility, pregnancy, and sexual function, to evaluate how HCPs approach this topic and to report patients’ reproductive outcomes.MethodsSubjects were invited to anonymously complete an online questionnaire collecting data on demographics, patients' disease characteristics, Crohn's and colitis pregnancy-specific disease-related knowledge (CCPKnow), family planning, reason of childlessness, pregnancy outcomes, need for assisted reproductive technology, impact on sexual function, and availability of patients’ information regarding IBD and pregnancy.ResultsA total of 257 HCPs from 40 countries and 793 patients (615 females, 176 males and 2 who preferred not to disclose their gender; 396 (50%) with ulcerative colitis, 381 (48%) with Crohn's disease, 14 (1.8%) with undetermined IBD) from 4 countries completed the survey. In total, 98.4% of HCPs had good or very good pregnancy-specific knowledge according to CCPKnow score, compared to only 29.3% of patients. Of the women surveyed, 56.3% had no children (14.1% due to a voluntary choice). A total of 427 pregnancies and 401 live births were reported in 266 women. Twenty-four pregnancies (5.6%) in 22 women required assisted reproductive technologies (ART). There were no more complications in pregnancies resulting from ART compared with spontaneous conception (5/24; 20.8% vs 81/401; 20.2%). Three quarters of IBD patients (75.6%) had breastfed. An impaired sexual function was found in one-fifth (21.9%) of men with IBD, while two-thirds (66.1%) of the women reported sexual function impairment. Surprisingly, 63% of patients reported not having received any information about IBD and pregnancy, and only 10% of patients had received information from their IBD specialist. In addition, 42.1% and 36% of HCPs had already referred a patients to a medically assisted reproduction center to receive general information about their reproductive health and about options of fertility preservation (e.g., cryopreservation), respectively.ConclusionIBD patients have a poor knowledge about the impact of IBD on fertility and pregnancy and HCPs do not sufficiently inform their patients. More information on these topics is needed for IBD patients.     

Inflammatory bowel disease during pregnancy

Opinion statement Physicians treating patients with Crohn’s disease and ulcerative colitis will often need to care for them throughout pregnancy and deal with the surrounding issues of fertility, childbirth, and sexuality. Patients often worry about continuing medications during pregnancy and feel particularly at risk for poor birth outcomes. However, because pregnancy outcomes are most closely tied to disease activity at the time of conception, patients who are in remission when they conceive will have the most successful pregnancies. The overriding principle in treating pregnant patients with inflammatory bowel disease (IBD) is continued and close surveillance of disease activity, with aggressive medical, and if indicated, surgical treatment. With few exceptions, medicines used to induce remission before pregnancy should be continued throughout pregnancy. Pregnant women with active IBD should be followed by a gastroenterologist with experience in the issues surrounding pregnancy, and by an obstetrician with access to a tertiary referral center. Properly treated and followed, patients with IBD can expect outcomes from their pregnancies that approximate those of patients without the disease.     

The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: pregnancy and pediatrics

Women with inflammatory bowel disease (IBD) have similar rates of fertility to the general population, but have an increased rate of adverse pregnancy outcomes compared with the general population, which may be worsened by disease activity. Infertility is increased in those undergoing ileal pouch-anal anastomosis. Anti-tumor necrosis factor therapy in pregnancy is considered to be low risk and compatible with use during conception in men and women and during pregnancy in at least the first two trimesters. Infliximab (IFX) and certolizumab pegol are also compatible with breastfeeding, but safety data for adalimumab (ADA) are awaited. The safety of natalizumab during pregnancy is unknown. For children with Crohn's disease (CD), IFX is effective at inducing and maintaining remission. Episodic therapy is not as effective as scheduled infusions. Disease duration in children does not appear to affect the efficacy of IFX. IFX promotes growth in prepubertal and early pubertal Crohn's patients. It is also effective for the treatment of extraintestinal manifestations. ADA is effective for children with active CD and for maintaining remission, even if they have lost response to IFX, although there are fewer data. Vaccination of infants exposed to biological therapy in utero should be given at standard schedules during the first 6 months of life, except for live-virus vaccines such as rotavirus. Inactivated vaccines may be safely administered to children with IBD, even when immunocompromised.     

Medication non-adherence in adult patients affected by inflammatory bowel disease: a critical review and update of the determining factors,consequences and possible interventions

Introduction: Achieving adherence to medications can be a serious challenge for patients affected by inflammatory bowel disease (IBD). Medical treatment is fundamental for inducing and maintaining remission, preventing flares and reducing the risk of colorectal cancer. Non-adherence may affect patients’ quality of life resulting in unfavourable treatment outcomes, more hospitalizations and higher healthcare-related costs. Recognising and improving adherence is therefore a primary aim for the treatment of IBD.

Areas covered: We critically discuss the current knowledge on medication non-adherence in adult patients affected by IBD, also mentioning a few issues concerning the paediatric and adolescent populations. In particular, we reviewed the literature focusing on the definition and detection of non-adherence, on its extent and on the possible non-modifiable and modifiable factors involved (patient-centred, therapy-related, disease-related and physician-related). Furthermore, we analysed the interventional studies performed so far. The literature review was conducted through PubMed addressing medication non-adherence in IBD, using the keywords ‘adherence’ and related terms and ‘IBD, ulcerative colitis or Crohn’s disease’.

Expert commentary: Adherence to therapy for IBD is a complex yet fundamental issue that cannot be solved by addressing a single aspect only. Future studies should focus on patient-tailored and multidimensional interventions.     

Treatment of pregnant women with a diagnosis of inflammatory bowel disease

The frequency of diagnosis of inflammatory bowel disease(IBD) has increased in younger populations.For this reason,pregnancy in patients with IBD is a topic of interest,warranting additional focus on disease management during this period.The main objective of this article is to summarize the latest findings and guidelines on the management of potential problems from pregnancy to the breastfeeding stage.Fertility is decreased in patients with active IBD.Disease remission prior to conception will likely decrease the rate of pregnancy-related complications.Most of the drugs used for IBD treatment are safe during both pregnancy and breastfeeding.Two exceptions are methotrexate and thalidomide,which are contraindicated in pregnancy.Antitumor necrosis factor agents are not advised during the third trimester as they exhibit increased transplacental transmission and potentially cause immunosuppression in the fetus.Radiological and endoscopic examinations and surgical interventions should be performed only when absolutely necessary.Surgery increases the fetal mortality rate.The delivery method should be determined with consideration of the disease site and presence of progression or flare up.Treatment planning should be a collaborative effort among the gastroenterologist,obstetrician,colorectal surgeon and patient.     

Conception outcomes and opinions about pregnancy for men with inflammatory bowel disease

Background and aimsPatients with inflammatory bowel disease (IBD) who want to have children are anxious to receive medical treatment. The consensus regarding pregnancy has not been surveyed for male IBD patients. The present study was investigated opinions among male IBD patients about pregnancy, conception and neonatal outcomes for partners.MethodsSubjects comprised 364 of 386 patients enrolled (94.3%). Subjects received a questionnaire regarding their opinions and thoughts about pregnancy. The course of partner's conceptions and presence of neonatal malformations was also surveyed.ResultsThe rate of live births for partners of male IBD patients was 91.6% (219/239). Most patients with CD (29/33; 88%) had their children after surgery had been performed. The rate of expressing hopes to have a child tended to be higher for patients with UC (93/128; 73%) than for patients with CD (61/97; 63%; p = 0.21). Furthermore, the rate of hesitation was significantly higher in CD patients (34/107; 32%) than in UC patients (38/188; 20%; p = 0.03).Patients considered that safety of medication (51%) and maintenance of remission (41%) was more important than receiving no treatment for IBD (19%) when planning to conceive. Mesalamine and infliximab were more favorable at conception than sulfasalazine and immunomodulators.ConclusionsThis is the first report to survey the thinking of male IBD patients regarding pregnancy. Most male IBD patients considered “maintaining remission” as important at conception. Our study provides important information for IBD patients and for the treating physician when planning to conceive.     

Drug Therapy of Inflammatory Bowel Disease in Fertile Women

Inflammatory bowel disease (IBD) is a disease that affects women of childbearing age. Active disease at conception increases the risk for adverse outcomes and thus postponement of pregnancy until the disease is in remission is the best advice that physicians can give their IBD patients. The majority of medications used to treat IBD are safe in pregnancy and breastfeeding; active, untreated, or undertreated disease is more deleterious than active therapy.     

Pregnancy and nursing in inflammatory bowel disease

The peak age of onset for IBD coincides with the peak age for conception and pregnancy. Women with inactive IBD who become pregnant do not have increased complications compared with age-matched controls. Most medications for IBD are safe in pregnancy. The greatest danger to a normal conception and pregnancy is active disease, not the medicine used to treat it. This article outlines fertility in IBD, the effect of IBD on pregnancy, the effect of pregnancy on IBD, and the medical therapy available.     

Factors associated with pregnancy-related knowledge in women of reproductive age with inflammatory bowel disease

Objective: Inflammatory bowel disease (IBD) usually develops at a young age, and many women experience marriage, pregnancy, and delivery during the disease course. We aimed to evaluate the pregnancy-related knowledge of women with IBD in Korea and investigate the associated factors.

Material and methods: A total of 270 women with IBD, aged 19–45 years, from four tertiary hospitals in Korea were administered a questionnaire comprising 17 questions from the validated Crohn’s and Colitis Pregnancy Knowledge Score (CCPKnow) that were translated into Korean.

Results: The average CCPKnow score of the 270 patients was 7.47?±?3.07; and most of the patients (51.5%) exhibited a poor knowledge level. Younger age at diagnosis, Crohn’s disease rather than ulcerative colitis, longer disease duration, anti-TNF-α medication history, higher household income, and delivery after diagnosis were associated with an appropriate level of pregnancy-related knowledge. Younger age at diagnosis (odds ratio [OR], 1.87; p?=?.036), anti-TNF-α therapy (OR, 1.87; p?=?.047), and delivery while suffering from IBD (OR, 3.07; p?=?.002) were independent factors affecting the pregnancy-related knowledge level. Approximately 69.6% of patients acquired related knowledge from their gastroenterology doctor, whereas 19.4% of patients intended to remain childless.

Conclusions: To our knowledge, this is the first study to assess the pregnancy-related knowledge of women of reproductive-age with IBD and their perceptions by using a questionnaire in Asia. As more than half of the patients showed a poor knowledge level of IBD, a general education program should be conducted by gastroenterology doctors.     

Clinical courses and pregnancy outcomes in Japanese women with inflammatory bowel disease

In this study, we analyzed the clinical courses and the pregnancy outcomes in Japanese women with inflammatory bowel disease (IBD) in our hospital in the recent 10 years. We analyzed 49 pregnancies in 38 patients with ulcerative colitis (UC) and 24 pregnancies in 16 patients with Crohn's disease (CD) retrospectively. The results indicated that pregnancy has less influence on the clinical courses of IBD and that IBD also has less influence on the pregnancy outcomes. However, we should pay attention to the results that the patients with CD tend to deteriorate if conception occurs when CD is active and that patients with active UC tend to have more adverse pregnancy outcomes than patients in remission. In conclusion, patients with IBD are recommended to become pregnant when the diseases are in remission and treatment using selected safe medications should be continued during the pregnancy.     

Algorithms to facilitate shared decision-making for the management of mild-to-moderate ulcerative colitis

ABSTRACT

Introduction: Nonadherence has been a key barrier to the efficacy of medical treatments in ulcerative colitis (UC). Engaging patients in their IBD care via shared decision-making (SDM) to facilitate self-management may improve adherence to therapy.

Areas covered: This review aims to summarize the most recent trial evidence from 2012 to 2017 for mild-to-moderate UC in order to develop clinical algorithms that guide SDM to facilitate self-management. A structured literature search via multiple electronic databases was performed using the search terms ‘ulcerative colitis,’ ‘treatment,’ ‘management,’ ‘medication,’ ‘maintenance,’ ‘remission,’ ‘5-ASA,’ and ‘inflammatory bowel disease.

Expert commentary: Novel formulations of existing oral and topical medications have expanded the treatment options available for the induction and maintenance therapy for mild-to-moderate UC. Daily dosing of 5-ASA therapy is equivalent to twice daily dosing. The combination therapies of oral plus topical 5-ASA therapy and 5-ASA plus corticosteroid therapy are more effective than monotherapy. Budesonide MMX now plays a role in the management of mild-to-moderate UC. This review collates the evidence on drug efficacy and safety, adherence and tolerability, and noninvasive monitoring of mild-to-moderate UC into SDM-orientated algorithms to facilitate self-management.     

Identifying Patient Priorities for Preconception and Pregnancy Counseling in IBD

Background

Inflammatory bowel disease (IBD) commonly affects women of reproductive age. Many patients lacking knowledge about IBD and reproduction make uninformed decisions, such as voluntary childlessness and medication cessation. Education should be individualized to the patient’s knowledge base and include topics of most importance to the patient. Our study aimed to describe the priority rankings of topics selected by patients seeking preconception and pregnancy counseling.

Methods

As part of an ongoing prospective study, patients with IBD were asked to rank, in order of importance, nine a priori preconception, pregnancy, and postpartum topics they would like addressed by our specialized care team, which includes an IBD physician and a high-risk obstetrician. χ² and Fisher’s exact tests were used to assess associations between clinical and demographic characteristics and priority rankings, and a p value cutoff for significance was set as .05.

Results

One hundred and fifty-eight women with IBD (mean (IQR) age; 32 (28–37) years) were seen in consultation, and 116 (70 (60%) CD, 43 (37%) UC, and 3 (3%) IBD-U) completed intake forms were analyzed. There were 78 (68%) women seen in the preconception stage, median age 31 (IQR 28–34), and 38 women (32%) were pregnant, median age 32 (IQR 28–33). Safety of IBD medications during pregnancy was most commonly ranked as top priority (40%) for all patients regardless of pregnancy status, followed by control of IBD disease activity and impact on pregnancy (31%), impact of IBD and surgery on fertility (19%), pregnancy outcomes for the baby (18%), mode of delivery (6%), inheritance of IBD (4%), breastfeeding (2%), nutritional health (2%), and vaccines and newborn care (1%). The impact of IBD and surgery on fertility was ranked as the number one priority more often in the preconception group (p value?<?0.01) and mode of delivery in the pregnancy group (p value 0.04). Conclusion: Safety of IBD medications remains a priority topic for patients seeking preconception and pregnancy counseling.

     

Chromogranin A as a biomarker of disease activity and biologic therapy in inflammatory bowel disease: a prospective observational study

Abstract

Objective. To access the correlation of Chromogranin A (CgA) with inflammatory bowel disease (IBD) activity and responsiveness to medical therapy. Material and methods. A prospective observational study was conducted in 56 patients with moderate ulcerative colitis (UC) or Crohn’s disease (CD) (UC, n = 29, CD, n = 27), 17 patients with irritable bowel syndrome and predominant diarrhea (IBS-D) and 40 healthy volunteers. IBD patients were treated by biologics (infliximab or adalimumab) or conventional agents (aminosalicylates, thiopurines or methotrexate and steroids) and were classified according to their treatment in two groups. Serum CgA was measured at baseline and 4-week posttreatment period. Results. Serum CgA was significantly higher in IBD patients than in those with IBS-D or healthy volunteers (p < 0.01). Furthermore, serum CgA was markedly increased in CD patients than in UC patients (p < 0.01). CgA value was significantly reduced in ‘biologic’ group (24 IBD patients, UC, n = 15, CD, n = 9) at 4-week posttreatment period (p < 0.01), while 18/24 (72%) patients were already in remission during that time. In contrast, CgA value was significantly increased in the ‘conventional’ treatment group (32 IBD patients, UC, n = 14, CD, n = 18) between the two visits (p < 0.01), although 22/32 (69%) patients were in remission during the 4-week posttreatment period. Conclusion. CgA appears to be a reliable marker of disease activity in IBD patients and especially in those who received biologic therapy. IBS-D patients presented normal CgA values.     

Long-term outcome of inflammatory bowel disease patients with deep remission after discontinuation of TNFα-blocking agents

Background: Little data exist on the long-term prognosis of patients with inflammatory bowel disease (IBD) after stopping TNFα-blocking therapy in deep remission. Existing data indicate that approximately 50% of patients on combination therapy who discontinued TNFα-blockers are still in remission 24 months later. The aims of this follow-up analysis were to evaluate the long-term remission rate after cessation of TNFα-blocking therapy, the predicting factors of a relapse and the response to restarting TNFα blockers.

Methods: The first follow-up data of 51 IBD patients (17 Crohn’s disease [CD], 30 ulcerative colitis [UC] and four inflammatory bowel disease type unclassified [IBDU]) in deep remission at the time of cessation of TNFα-blocking therapy have been published earlier. The long-term data was collected retrospectively after the first follow-up year to evaluate the remission rate and risk factors for the relapse after a median of 36 months.

Results: After the first relapse-free year, 14 out of the remaining 34 IBD patients relapsed (41%; 5/12 [42%] CD and 9/22 [41%] UC/IBDU). Univariate analysis indicated no associations with any predictive factors. Re-treatment was effective in 90% (26/29) of patients.

Conclusion: Of IBD patients in deep remission at the time of cessation of TNFα-blocking therapy, up to 60% experience a clinical or endoscopic relapse after a median follow-up time of 36 months (95% CI 31–41 months). No individual risk factors predicting relapse could be identified. However, the initial response to a restart of TNFα-blockers seems to be effective and well tolerated.     

Management of the pregnant inflammatory bowel disease patient on antitumour necrosis factor therapy: State of the art and future directions

Antitumour necrosis factor (anti-TNF) therapy has been a major advance in the treatment of inflammatory bowel disease (IBD) by improving rates of mucosal healing, steroid-free remission, and decreasing rates of hospitalization and surgery. Because IBD affects women in their reproductive years, clinicians have and will continue to be asked in the future about the safety profile of these agents and their potential impact on pregnancy, the developing fetus and newborn. Immunoglobulin G transfer from the mother to fetus begins in the second trimester, with an elevation starting at 22 weeks of gestation and the largest amount transferred in the third trimester. Although research investigating the long-term outcomes of children exposed to anti-TNF therapy in utero is limited, there is no known adverse effect on either pregnancy or newborn outcomes including infectious complications with this class of drugs. The World Congress of Gastroenterology consensus statement on biological therapy for IBD considered infliximab and adalimumab to be low risk and compatible with use during conception and during pregnancy in at least the first two trimesters. Based on a clinical algorithm used at the University of Calgary Pregnancy and IBD clinic (Calgary, Alberta), recommendations have been provided on the management of pregnant patients on anti-TNF therapy, particularly with regard to third-trimester dosing, taking into account disease characteristics of individual patients. When educated about the safety of anti-TNF therapy during pregnancy, patients often choose to continue on therapy during the third trimester.