Management of Inflammatory Bowel Disease in Pregnancy: A Practical Approach to New Guidelines
Inflammatory bowel disease (IBD) affects patients in their adolescent and adult years of life, during a time when they may be contemplating pregnancy or are pregnant. Maternal IBD and, specifically, active IBD during pregnancy are associated with an increased risk of adverse maternal and fetal outcomes including prematurity, low birth weight, and cesarean delivery . Thus optimization and management of IBD before and during pregnancy are important in improving maternal and fetal outcomes. Nevertheless, patients and physicians are challenged on balancing the benefits of therapy for active maternal IBD with the potential risks of these therapies to the fetus.
The medical literature has demonstrated that significant gaps in knowledge about the management of IBD during pregnancy exist in both patients and their physicians, resulting in misperceptions about IBD therapies during pregnancy [2–4]; “voluntary childlessness” as a consequence of fear of infertility, the ability to cope with the pregnancy in the presence of disease, heritability of the disease, and adverse fetal outcomes [2–4]; medication nonadherence [3–7]; and misdirected physician-led modification or cessation of therapies in this cohort [7–9]. Further, in a recent Canadian survey of physicians, less than 50% of surveyed physicians felt comfortable managing IBD during pregnancy . In Canada, family physicians and nurses are often the primary initial contact for the IBD patient in their journey from preconception to pregnancy. Once pregnant, women in the Canadian healthcare system are cared for by a multidisciplinary team that includes family physicians, obstetricians, nurses, and midwives. Acknowledging the knowledge gap and changing landscape of IBD management, “The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy” were developed, integrating up-to-date evidence vetted by the GRADE approach and tailored to North American clinical practice .
“The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy”  consist of 29 recommendations (27 statements, of which two statements have two parts, i.e., 4A, 4B, 10A, and 10B) spanning preconception, pregnancy, and postpartum care. The recommendations can be viewed in Table 1 or within the hyperlink provided: https://www.cag-acg.org/images/publications/PIIS0016508515017734.pdf. The working group comprised experts from multiple disciplines which included (1) gastroenterologists with expertise in the management of IBD; (2) obstetricians; (3) specialists in maternal-fetal medicine; (4) pharmacologists; and (5) female IBD patient representation. The consensus panel was also well represented by Motherisk, an internationally recognized program that provides information and advice to pregnant women and their healthcare providers on the safety of medications during pregnancy and breastfeeding. As adverse events such as preterm delivery can lead to higher rates of infant mortality, appropriate and timely diagnostic and treatment interventions during pregnancy can be considered lifesaving measures. Taking this into consideration and the highly favorable benefit-harm profile, the working group designated 21 of the 29 recommendations as strong despite the very low quality of evidence presented.
In contrast to previously published guidelines, the Toronto consensus is very explicit in its recommendations for management of flares during pregnancy. These recommendations are stratified by disease phenotype and current medication(s) at the time of the flare. Statements 14–16 emphasize the use of induction agents that include corticosteroid therapy or anti-TNF therapy. Additionally, the consensus statements help to guide care providers on the use of concomitant thiopurine therapy, making the distinction between a patient who is naïve to thiopurine therapy in the event of a flare (Statement 16) and the scenario of a patient already on combination therapy (Statement 11).
Recognizing that controversy surrounds the use of anti-TNF therapy, the Toronto consensus provides clear recommendations that anti-TNF therapy is to be continued throughout pregnancy (Statement 10A). This differs from various editorials, guidelines, and review articles that have focused on discontinuation of anti-TNF in the late second trimester or early third trimester [12–14]. There is no doubt that the current Toronto guidelines place disease remission as top priority based on solid evidence that inactive disease portends the best prognosis for both maternal and fetal health. Further, consensus members discussed that the common practice of modifying the dosing schedule during the third trimester (e.g., providing an infusion of infliximab at weeks 30–32 and adalimumab at weeks 34–36 and then resuming therapy postpartum) to minimize drug hiatus may help minimize disease flare in the mother but does not minimize fetal exposure, as transplacental drug transfer is very efficient in the second and third trimesters. There is, however, little evidence of an increased risk of infection or developmental delay (at least in the short-term) with continued anti-TNF therapy. However, recognizing a variety of individual factors such as theoretical concerns or strong patient preference, Statement 10B makes the conditional recommendation that, in order to minimize fetal exposure, one could administer the last dose at 22 to 24 weeks of gestation in patients who are at low risk for relapse. Strict criteria for determining patients who are at low risk for relapse are explicitly stated and include sustained symptomatic remission during the 12 months before conception, no active disease on endoscopy or imaging during the preconception period, no prior secondary loss of response to anti-TNF therapy or dose escalation, demonstrated therapeutic levels of anti-TNF therapy, no prior intestinal resections, and no hospitalizations in the past 36 months .
These statements make strong recommendations for objective assessments before conception and close monitoring during pregnancy, though it is recognized that some jurisdictions may have limited access to endoscopy, specialized gastroenterology care, or high-risk obstetrical consultation. However, these guidelines provide a framework from which healthcare providers can make decisions regarding the management of IBD during pregnancy and provide a common algorithm that can be followed by the multidisciplinary care team that manages the pregnant woman with IBD.
G. C. Nguyen
C. H. Seow
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