EXPERT ANALYSIS AT THE PREGNANCY MEETING
SAN DIEGO – In inflammatory bowel disease, it’s active disease – not therapy – that poses the greatest risk to pregnancy.
“You want quiescent disease at the time of conception,” Dr. Chad A. Grotegut said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
Women in remission from IBD at the time of conception face a 20%-25% increased risk of flare during the course of their pregnancy, said Dr. Grotegut of the division of maternal-fetal medicine in the department of obstetrics and gynecology at Duke University, Durham, N.C. But IBD patients with active disease at the time of conception face a 50%-70% increased risk of flare.
Two confounding factors that influence a woman’s risk for flare during pregnancy are smoking cessation and the cessation of medications to control symptoms.
“Interestingly, there is no correlation of symptoms from one pregnancy to another,” said Dr. Grotegut, who added that IBD patients who become pregnant appear to be at increased risk for poor pregnancy outcomes, compared with women who don’t have the disorder.
“Many of the studies on that topic are problematic, though,” he said. “They’re typically small, there may be conflicting results, but the most consistent findings are increased rates of preterm birth, low birth weight, and cesarean delivery.”
Active disease seems to increase the risk of adverse outcomes, especially in those who have active disease at the time of conception.
“It’s unclear what drives the association with adverse outcomes,” Dr. Grotegut said. “It may be the disease itself, disease activity, the generalized inflammatory state, medications, and other factors. The most consistent outcome associated with IBD disease activity in pregnancy is preterm birth.”
He said that women with IBD who wish to become pregnant often ask him about the safety of medications they’re taking. The main classes used for IBD are corticosteroids, aminosalicylates, antibiotics, immunomodulators, and biologics.
Corticosteroids are safe and used only for flares, while aminosalicylates are often used as frontline agents for inducing remission, primarily in ulcerative colitis.
Common aminosalicylates used in IBD include sulfasalazine, balsalazide, mesalamine, and olsalazine. Sulfasalazine is a pro-drug of 5-ASA linked to sulfapyridine, which allows passage to the colon. It potentially interferes with folic acid metabolism, “so expert opinion is that women who are on sulfasalazine have increased folic supplementation 2 mg daily preconception,” he said.
Antibiotics are primarily used for flares and complications, not for maintenance. Common agents include metronidazole and ciprofloxacin, though ciprofloxacin is not typically used in pregnancy due to potential concerns for fetal arthropathies.
Immunomodulators are primarily used to maintain remission. From this category of agents Dr. Grotegut and his associates at Duke most commonly use azathioprine and 6-mercaptopurine.
“They are closely related medications [that] interfere with DNA synthesis and both are classified as FDA pregnancy category D,” he said. “There was initial concern for anomalies in transplant populations but current data suggest no increased risk. Discontinuation results in a high rate of relapse.”
Cyclosporine is used for severe flares in severe steroid-refractory ulcerative colitis. The experience with this agent is largely among transplant recipients but it does not seem to be associated with congenital anomalies, Dr. Grotegut said.
The use of methotrexate is contraindicated during pregnancy and it is advised to wait 3-6 months for conception following discontinuation. Thalidomide is also contraindicated.
As for the safety of biologic agents, the most data exist for infliximab, which crosses the placenta and is detected in cord blood, Dr. Grotegut said. Infliximab is used for both induction and maintenance of IBD remission. It is not associated with congenital anomalies, “but it theoretically may increase the risk of infection, and it may decrease responsiveness to vaccination,” he said. “Because of this, expert opinion is to avoid live vaccinations in newborns exposed to perinatal infliximab.”
There is also increasing recognition that IBD is an independent predictor of venous thromboembolism (VTE), Dr. Grotegut said.
In the nonpregnant population, all IBD patients have a threefold increased risk of VTE, compared with the general population. The relative risk rises to 15- to 20-fold during flares, he said.
VTE prophylaxis and IBD are not currently addressed in guidelines from the American College of Chest Physicians, but the Canadian Association of Gastroenterology recommends anticoagulation prophylaxis during moderate to severe outpatient flare with history of VTE, hospitalization for flare, and during hospitalization for other indications, including those in remission and those undergoing major pelvic surgery.
The Canadian Association of Gastroenterology goes on to recommend anticoagulant prophylaxis for “women with IBD who have undergone cesarean delivery while hospitalized,” Dr. Grotegut said.