Inflammatory Bowel Disease in Pregnancy Clinical Care Pathway: A Report From the American Gastroenterological Association IBD Parenthood Project Working Group

In the United States, approximately 0.5% of the population, or 1.6 million people, have inflammatory bowel disease (IBD)—Crohn’s disease (CD) and ulcerative colitis (UC).1,2 Of those, roughly half are women, and most will carry the diagnosis during their reproductive years.3 Caring for this complex population is a challenge for the multidisciplinary group of providers involved, compounded by misinformation and differences in priorities. There is fear surrounding the impact of IBD and its therapies on pregnancy and infant outcomes, as well as fear surrounding the impact of pregnancy on IBD and maternal health.4–6 Oftentimes, the default is to stop all therapies through pregnancy and lactation, despite the significant risk of worsening disease activity, which is the greatest known risk to pregnancy outcome.7 By looking at only one part of the puzzle, the greater picture of maternal and infant health is missed. The challenge of improving care to the woman with IBD is best met with the power of information, collaboration, and shared decision-making. The goal of the IBD in Pregnancy Clinical Care Pathway is to provide guidance on the continuum of care and best practices for managing patients with IBD who are either pregnant or have a desire to become pregnant. The Pathway outlines the entire care process—from preconception counseling through the postpartum phase. The Pathway was developed by a multidisciplinary working group, encompassing the full spectrum of providers that a pregnant female with IBD may seek treatment from before, during, and after pregnancy. The working group included representatives from the fields of gastroenterology, maternal–fetal medicine (MFM), teratology, and lactation, as well as patient stakeholders, and is backed by a multisociety team. The Pathway provides a practical resource for clinicians and health systems to guide the treatment for these patients and ensure a consistent and high level of care. (Figure 1 outlines the scope of the IBD in Pregnancy Clinical Care Pathway.) Overview of IBD in Pregnancy Clinical Care Pathway. LARC, long-acting, reversible contraception. Ideally, a pregnant patient with IBD is monitored by both a gastroenterologist specializing in IBD and an MFM specialist, with assistance from nutritionists, lactation counselors, and colorectal surgeons, as needed. However, due to variations in access, availability, and preference, patients may receive their IBD care from a general gastroenterologist, nurse practitioner, physician’s assistant, surgeon, primary care provider, or even the emergency department. Similarly, obstetric care may be provided by an MFM, general obstetrician, midwife, family practitioner, or no one at all for much of the pregnancy.8 Some patients are newly diagnosed with IBD during pregnancy and may be directed to a gastroenterologist after an emergency department visit, hospital admission, or visit with their primary care provider or obstetrician/gynecologist (OB/GYN). We understand that many patients and providers do not have access to IBD experts and MFM specialists, particularly outside of urban centers. However, any gastroenterologist, OB/GYN, or specialized physician’s assistant, nurse practitioner, or midwife can follow the Care Pathway to optimize outcomes in this population. The risks of IBD to a pregnancy are significant and manifold, including miscarriage, delivery of a small-for-gestational-age infant, premature delivery, poor maternal weight gain, and complications of labor and delivery (eg, preeclampsia, placental abruption, increased probability of cesarean delivery).9–14 Therefore, we recommend consultation with an MFM specialist, if available, for every pregnant patient with IBD. This is especially relevant to those with prior laparotomy, ostomy, ileal pouch-anal anastomosis (IPAA, or “J-pouch”) surgery, and presentation suggesting the need for cesarean delivery, prior cesarean delivery, treatment with biologic or combination therapy, current active disease or recent hospitalization, perianal disease, or a history of adverse pregnancy outcomes.15 The MFM specialist can determine the type of monitoring needed and the frequency of return visits. In most cases, it will be the general obstetrician who attends the delivery. The patient’s gastroenterologist should coordinate her IBD care and see the patient once in the first or second trimester and thereafter during her pregnancy, as appropriate for her disease severity and pregnancy status. The gastroenterologist should also coordinate with the patient’s obstetric provider who will lead the pregnancy-related care. Finally, the patient should be provided with a clear and easily understandable consensus plan for managing her disease during conception, pregnancy, and postpartum. As the patient may see multiple covering providers during her pregnancy, a clear plan can help empower her to obtain the very best care for herself and her child. Although not all patients will have access to specialty care, additional care providers during pregnancy and postpartum may include a nutritionist, particularly in patients with active disease, significant surgical changes, or inadequate maternal weight gain; a psychologist to provide support for the anxiety and depression that are increased in both IBD and pregnancy16,17; and a lactation specialist knowledgeable in IBD medications. When the infant is born, a pediatrician will need to be involved and should be aware of potential complications the infant may experience, as well as vaccination and breastfeeding recommendations. Family planning for all women with IBD should include consultation with their gastroenterologist, OB/GYN, and, if appropriate, an MFM specialist and a colorectal surgeon. Three- to six-month remission before conception reduces the risk of a flare-up during pregnancy and in the postpartum period, making contraception an important part of the discussion.18 In-person preconception care improves adherence to medications, enhances smoking-cessation efforts, reduces relapse during pregnancy, and lowers the risk of having a low-birth-weight infant.19 Such care should focus on optimizing nutrition status, maintaining iron and folic acid supplementation, and achieving an ideal weight, if possible. The patient’s OB/GYN should be actively engaged in decisions regarding contraception. The safest and most effective birth control option is long-acting, reversible contraception, which may include a hormonal or nonhormonal intrauterine device or a contraceptive implant. The authors prefer non–estrogen-containing contraception, given the increased risk of venous thromboembolism in IBD. However, low-dose estrogen oral contraceptive pills may be an option if the patient does not have a personal or family history of blood clots or other risk factors for thromboembolic events. Active small bowel inflammation, extensive resection, or rapid bowel transit may decrease oral contraceptive pill efficacy.20 Preconception counseling and evaluation are key components of the care of the woman with IBD who is of child-bearing age (Figure 2).19 The genetic risk of IBD is an important topic that will frequently arise during preconception counseling, and patients typically overestimate the risk of having a child affected by IBD. In European cohort studies, the genetic risk of CD is higher than that of UC. Incidence rate ratios represent the relative risk of IBD; however, absolute risk is an easier and more comprehensible concept to discuss with patients. The concordance rates in monozygotic twins range from 20%–56% for CD and from 6%–19% for UC.21 With maternal CD, the incidence rate ratio for CD in offspring is 6.3, whereas the incidence rate ratio for UC in an offspring with maternal UC is 3.7. Having multiple family members affected by IBD will increase the risk, as will young age at diagnosis. The absolute risk of an offspring developing CD in the setting of maternal CD is 2.7%, whereas the risk of UC in the setting of maternal UC is 1.6%.22 Based on 2 small studies, the risk of IBD has been suggested to exceed 30% when both parents have the disease.23,24 These rates may be higher in cases of multiple affected family members and in certain ethnic groups. Studies suggest that the risk of IBD is 3-fold higher in non-Hispanic whites25 and 2- to 4-fold higher in Ashkenazi Jews compared to non-Jewish ethnic groups, although the risk among non-European populations has not been well-characterized amid rising global incidence.26 Numerous genetic associations with IBD have been identified, but the development of IBD is only rarely attributable to single genes, and there are no genetic tests available to predict whether one’s offspring will develop IBD. Pregnancy planning and conception. ACOG, American College of Obstetricians and Gynecologists; LARC, long-acting, reversible contraception. Among women with CD and UC whose disease is in remission and who have never had surgery, fertility rates are equal to those in the general population. However, women who have had IPAA surgery, proctectomy, and permanent ostomies have decreased fertility due to inflammation and scarring of the fallopian tubes.27–30 Laparoscopic rather than open IPAA surgery may improve fertility rates.31,32 Women with active IBD may also have decreased fertility.33 A review of fertility in IBD reported that 17% of women with IBD are voluntarily childless5 compared to 6% of women in the general population.34 The choice to remain childless appears to be largely due to incorrect information about pregnancy and IBD. Medical therapy for IBD, including all biologic therapies, steroids, thiopurines, methotrexate, and mesalamine, does not decrease fertility.15,35–37 Referral for assisted reproductive technology (ART) treatments should be individualized, depending on the patient’s age, IBD type, and history of IBD surgery. Women with CD who are over the age of 30 years may have decreased ovarian reserve.38,39 In general, IBD patients who have tried unsuccessfully to conceive for 6 months should be referred for infertility evaluation, particularly if they have had pelvic surgery.40 IBD medications have no effect on egg freezing or ART efficacy; in the authors’ experience, hormones used as part of ART have no adverse effect on IBD activity. ART in women with CD and UC is not as effective as in infertile women in the general population.41–43 Similarly, among women with CD who have had CD surgery, ART is less effective than in women with CD who have never had surgery.41 The decreased efficacy of ART is likely due to a lesser chance of achieving a chemical pregnancy (positive human chorionic gonadotropin 2 weeks after embryo transfer).43 Once pregnant, women with CD and UC have equal chances of achieving a live birth compared to women in the general population who underwent ART.43 Women need to be up-to-date with their Papanicolaou smears, vaccines, and routine health care maintenance before pregnancy. Cessation of smoking, alcohol, opioids, and recreational drug use should be encouraged. Meta-analyses of have that can not only the of women during pregnancy, but also improve birth from during pregnancy the risks of birth and and of or recreational should also be has been used in patients with IBD to improve and However, due to for adverse outcomes in the developing and the American College of Obstetricians and and the of use during pregnancy and it is to a of use in pregnancy, it is best to be these during pregnancy. A review of that are not suggesting that and may be in IBD and any as well as folic use may increase the risk of and adverse pregnancy and should not be a maintenance therapy for pregnancy. to be at months before due to its an is on the for at months should be before conception. Based on available and the risk to pregnancy of active disease, and used in the treatment of IBD are risk during pregnancy and In the authors’ drug of should be and or as before conception. the American on drug monitoring not include a on monitoring of patients in a level may lead to in this population and may lead to increased the given the of of during having a level before conception is and may There are human on the use of in pregnancy. a clear risk of at suggesting that this should be at in the first The of the drug is a of 1 should be before conception. In the patient with treatment who pregnancy, the information should be with all and a consensus should be regarding of the The visit should include a of nutrition and weight gain, disease activity, monitoring of maternal and status, as well as Ideally, this is a at the preconception consultation and during the with IBD should follow the of for the general obstetric population, which include a for In women, iron may the that pregnancy. patients with IBD, this may also should be that (eg, are with use during pregnancy and also to increase their however, is due to increased with IBD are at risk for iron and given increased iron during pregnancy, iron and should be in the first trimester and provided as needed. to may need to on other supplementation, as folic acid or may also be to with a for on a The consultation may include guidance on as well as on folic which is important for development during pregnancy. should be in patients with IBD on with ileal or on medications that with folic acid of for pregnant women with IBD is not achieving the weight for their The and that with CD and UC had a and a increased risk of inadequate weight on the of recommendations. with IBD with inadequate weight had a risk of small-for-gestational-age compared with The also a with disease and weight In a cohort women with IBD and inadequate weight also had a increased risk of outlines of the key to IBD disease and its impact on maternal and is of CD or which of A of a higher risk ratio of active disease during pregnancy in patients with UC who pregnancy with active disease compared with those whose disease was in remission at conception this risk was also higher in patients with CD are consistent with a recent European of patients in remission at conception during pregnancy, whereas of those with active disease Having active disease is with a significant increase in the rate of In a cohort the impact of CD on birth outcomes, of had disease during pregnancy and had or disease activity. The relative risk of birth was higher in women with or disease during pregnancy compared with women Active disease may as or When active disease is there is to a increased risk for routine pregnancy care, group provides an to the for active disease and counseling as particularly if the patient with or has a history of perianal women who have of IBD, or those a may be for or surgery if the and surgery, as the type of use of medications for and age at the of the should be in consultation with an OB/GYN or MFM specialist, as well as an In general, a may be or as well as any after weeks the of a with the patient about monitoring and need for cesarean one should the patient in the to of the and which may lead to maternal and placental for for of during pregnancy is on best available the risk of maternal disease and the that on these is not or therapies may be during pregnancy and through delivery can also be as an therapy for disease but are for maintenance therapy, to increased risks for or are as an for patients with or perianal human of and human no are used for IBD and should be when When maintenance therapy in pregnancy, is of biologic therapy in pregnancy has been with decreased disease activity, and postpartum with a incidence of adverse pregnancy most from actively the from and of women who in pregnancy have not an increase in adverse The greatest of are for and which have no increased rates of or among to 1 of age who to these in combination therapy and is due to increased risk of in the infant, this has not been the is an on for combination therapy and severity of patient’s therapy for the first in pregnancy is not due to the risk of and the to In the trimester of pregnancy, appropriate IBD medications, including biologic therapy, should be However, to the of delivery, biologic can be not to or drug at the of The of maintaining disease remission and delivery may any risks with biologic for Pregnancy and of small for pregnancy Pregnancy and of small for pregnancy In pregnancy by IBD, the of focus on obstetric (Figure A patient may delivery in most of IBD, there is active disease the of delivery or patient delivery has not been to risk for development of IBD in the those labor and delivery, care should include and of or delivery on obstetric for of delivery. group venous weeks and before delivery for of delivery planning to disease We recommend cesarean delivery for women with prior to its on the prior surgical as well as higher rates of of the with in complex in cases of or prior surgery may or or through cesarean delivery also the and are less certain given the of is given to women who have had IPAA surgery, which does not to pregnancy does of delivery to However, cesarean delivery is to important due to the increased risk of the of delivery, one should a consultation with a with the of an as cesarean delivery may or of the bowel to delivery. for cesarean delivery in women with IPAA include of surgical and surgical for bowel surgery at the of delivery. of shared should be when counseling patients regarding of delivery. The care should to ensure regarding counseling and planning for of delivery, as this will patient and anxiety regarding delivery. In to ensure disease control through the postpartum period, it is important to planning the postpartum of biologic therapy before delivery. This may and the appropriate for the with both the and gastroenterologist should be for disease monitoring and therapy as women for IBD are for given the higher risks of venous thromboembolic disease in patients with IBD, as well as the that This patients for an IBD as well as those patients cesarean the a of should be after delivery, with with and may be to weeks to the of greatest risk for venous thromboembolic disease, in patients with a history of venous thromboembolic disease or other risk and are appropriate to to breastfeeding women, oral and should be there is no of and the is appropriate, may be after delivery and after cesarean When for and during pregnancy and the we recommend weight to the appropriate can be as needed on disease activity, drug and postpartum weight as medications should be in the postpartum period, with the of (Figure care for and American of and for and LARC, long-acting, reversible venous delivery, women with IBD should receive monitoring and of of can be used for postpartum of in with OB/GYN and pediatrician and are the Some should be during lactation due to the increased risk of infant or As may therapy for maintaining (eg, with should be may be used for a however, therapy has been to IBD and should be A more of of medications during lactation is in the on Care for Finally, before there should be a regarding contraception plan to pregnancy and as In the patient cesarean delivery, and are the of increased of hospital and may the risk of The risk of may also be increased in patients with an IPAA if the was during cesarean delivery. bowel is a in women with an IPAA after cesarean In patients who have an ostomy, as and may with of the in the of the should with a nutritionist, if to weight during pregnancy. care may with a colorectal and an a cesarean is covering the with is to the with IBD who are breastfeeding should follow recommendations. 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However, should be given to as that may increase the risk of developing CD in There are no for from to other than the American of for all breastfeeding for 6 with of breastfeeding for 1 or as by and should be given on to the for and However, if the is to any biologic therapy, other than during the trimester of pregnancy after weeks of live is for the first 6 months of The is the only live that is before 6 months in the United is given in 2 at 2 and be most the first should be before an infant weeks of age, which the The and live vaccines, which are given at 1 of age, are to the infant is actively whether a who is and breastfeeding at the the and are due should the for a of to any effect on the child who is the are needed before any can be with to There is no to suggest that to with IBD of have any on monitoring can be at the American of and for and The on support the of effect of IBD medications on The of inflammation in on the developing is an of that is has been that both and during The of inflammatory control during pregnancy should be when counseling women with IBD. The of in the years has provided to women with IBD who to be to conceive a child. However, a of information and poor among providers has the patient with and This Clinical Care Pathway has all available and an multidisciplinary multiple to it all in a that is easily and we understand that are needed and may over we that every woman with IBD who is pregnancy or is pregnant will have access to that are by her and obstetric provider, working in to ensure the pregnancy. 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