Inflammatory Bowel Disease (IBD)
/We’re joined back today by Dr. David Abel, an assistant professor in OB/GYN at Oregon Health and Sciences University. Newly joining us today is Dr. Rachel Madding, who is a PGY-2 at OHSU. Together they share with us some pearls about IBD and IBD in pregnancy, specifically!
Overview of IBD
Comprised of two major disorders:
Ulcerative Colitis (UC)
Affects the colon and is characterized by inflammation of the mucosal layer.
Key defining symptom is bloody diarrhea.
UC can also be associated with systemic findings including uveitis, scleritis, erythema nodosum, pyoderma gangrenosum, arthritis, lung disease, and venous thromboembolic disease.
Notable for rectal involvement, with a continuous pattern of inflammation.
Crohn’s disease.
Can involve any component of the gastrointestinal tract from the oral cavity to the anus.
Characterized by transmural inflammation often with skip lesions.
It may also include perianal and rectal involvement about 50% of the time.
Symptoms of Crohn’s are highly variable and include fatigue, diarrhea, abdominal pain, weight loss, rectal bleeding, fistula, perianal abscess formation and aphthous ulcers.
Epidemiology of IBD
Approximately 1.6 million Americans have IBD.
About 70,000 new cases diagnosed in the US each year.
More than 50% of those with IBD are women and will carry the diagnosis during their reproductive years.
For every 100,000 deliveries, approximately 130 will be complicated by IBD.
Crohn’s disease in particularly seems to carry a slight female preponderance.
IBD and Pregnancy-Specific Risks
Patients with IBD appear to be at increased risk of preterm delivery, low birth weight, and cesarean delivery.
Active disease, particularly at the time of conception, seems to increase the risk of adverse outcomes.
Preterm delivery is the most consistent adverse outcome associated with IBD disease activity in pregnancy.
A meta-analysis of over 3900 pregnant women with IBD showed an increased rate of preterm delivery and low birth weight by approximately 2-fold, regardless of disease activity as compared with patients without IBD.
Large population-based studies have also shown that patients with IBD have a 1.5- to twofold increase in the rate of cesarean delivery.
The etiology of the association of IBD with adverse pregnancy outcomes remains unclear.
One theory is that IBD represents a generalized inflammatory state.
With regards to other adverse perinatal outcomes, the data is conflicting.
Possible increased risks of spontaneous abortion, preeclampsia, eclampsia, placental abruption, fetal distress, placenta previa, and premature rupture of membranes.
VTE Risk
Increased risk of venous thromboembolism in patients with IBD
The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy recommends consideration of prophylactic anticoagulation when a pregnant patient with IBD is hospitalized for an IBD flare, or after undergoing a cesarean section.
The American College of Chest Physicians does not consider IBD specifically as a venous thromboembolism risk factor, however it does recommend post-cesarean prophylactic anticoagulation for those with one major or at least two minor risk factors for VTE.
Pregnancy’s Impact on IBD
Risk of having a flare during pregnancy in patients with quiescent disease is similar to the nonpregnant patient.
For those who conceive when their disease is quiescent, disease tends to remain in remission throughout the pregnancy and postpartum.
Among patients with Crohn’s disease who conceive while their disease is active, the disease goes into remission in one-third, remains stably active in one-third, and worsens in one-third.
Patients with UC in pregnancy often have more active disease compared with Crohn’s.
Medication Use:
Greatest risk to their pregnancy is active disease at the time of conception, so discontinuing their medication during this time can have adverse effects.
Most medications are not associated with congenital anomalies and adverse perinatal outcomes.
There are several classes of medications including corticosteroids, which are used to treat flares mostly, aminosalicylates, antibiotics, immunomodulators and biologics.
Aminosalicylates i.e., sulfasalazine and mesalamine
Commonly used in UC to reduce intestinal inflammation.
Not associated with fetal risks, but may increase nausea and gastrointestinal reflux in pregnancy.
Should be given with at least 2 mg folic acid during pregnancy because of antifolate effects.
Antibiotics primarily used for flares and complications such as pouchitis and perianal disease.
Generally avoid fluoroquinolone.
Immunomodulators
Azathioprine, cyclosporine, 6-mercaptopurine can be used.
Data suggests a high rate of relapse when these drugs are discontinued.
Methotrexate and thalidomide are contraindicated
For those who are taking methotrexate, the recommendation is to wait 3-6 months after discontinuation before trying to conceive.
Biologics / anti-TNF agents
Increasingly used in the treatment of both IBD and autoimmune conditions
Infliximab, also known as remicade, adalimumab, also known as humira, and certolizumab, also known as cimzia.
These agents are IgG antibodies and cross the placenta
Exception: certolizumab, which does not cross the placenta because it lacks the necessary Fc receptor to facilitate placental transfer.
Safety data from prospective trials and large nationwide cohorts of women who continued taking biologics in pregnancy have not shown an increase in adverse fetal outcomes.
The greatest amount of safety data is for infliximab and adalimumab, which have shown no increased rates of congenital anomalies or infections among infants up to 1 year of age who were exposed to these agents in utero.
PIANO study (Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes): no increase in adverse events based on drug exposure during pregnancy or placental transfer of biologics.
Biologics may result in B cell suppression in the infant; however, this appears to subside after 4-6 months.
Mode of Delivery Considerations with IBD
All patients have the option of having an elective primary cesarean section.
For most patients, a vaginal delivery is encouraged as the risks of a cesarean section are greater.
For those with Crohn’s disease and a history of perianal disease but no current active disease, a vaginal delivery is reasonable, although some may still elect to undergo cesarean section.
For those with active perianal disease, a cesarean section is often performed due to concerns for complicated perianal and/or sphincter injury and healing.
For those with UC who have undergone an ileal pouch anal anastomosis, also referred to as an IPAA or J-pouch, a cesarean delivery is often performed due to concerns for anal sphincter injury and pouch dysfunction.
However, a history of an IPAA is not an absolute contraindication to a vaginal delivery.
Preconception Counseling Pearls
Stress the importance of remaining on their medications, unless taking MTX.
Patients need to know that if their disease is quiescent prior to pregnancy, this portends a more favorable course during pregnancy.
Most patients with inactive disease do well during pregnancy.
It is important to watch for a flare in the postpartum period.
For patients who have active disease, ideally contraception until disease is controlled is important to reduce the risk of adverse perinatal outcomes.
Most patients should be under the care of a gastroenterologist
If not, it is important to reestablish care, as a multidisciplinary approach serves to optimize outcomes.