麻豆传媒

Women with inflammatory bowel disease (IBD) had increased risk of adverse outcomes in pregnancy, a systematic review and meta-analysis confirmed.

In an analysis of 53 studies published up to May 2019 and involving a total of 7,917 IBD pregnancies and 3,253 healthy control pregnancies, Vivian Huang, MD, of the University of Toronto, and colleagues found the following odds ratios (OR) for mothers with IBD:

• More frequent cesarean delivery: 1.79 (95% CI 1.16-2.77)

• More frequent gestational diabetes: 2.96 (95% CI 1.47-5.98)

• More frequent preterm rupture of membranes before labor onset: 12.0 (95% CI 2.15-67.98)

As shown in the study online in , the incidence of placenta-related diseases, however, was not elevated, with rates as follows:

• 2.0% (95% CI 0.9-3.1) for pre-eclampsia

• 3.3% (95% CI 0-7.2) for placental abruption

• 0.5% (95% CI 0.2-0.9) for placenta previa

• 0.3% (95% CI 0-0.5) for chorioamnionitis

While there was no significant increased risk for early pregnancy loss (OR 1.63, 95% CI 0.49-5.43), almost a third of all the pregnant IBD patients had C-sections, reflecting an almost twofold increase compared with those of controls, the researchers said. The heightened risk of surgical delivery remained significant for ulcerative colitis (OR 1.80, 95% CI 1.21-2.90) but not Crohn's disease (OR 1.48, 95% CI 0.94-2.34).

"Placental-related disorders, such as pre-eclampsia, placental abruption, and placenta previa, do not appear to be increased in this patient population, although this remains to be confirmed in larger, prospective studies," the authors wrote.

"Regardless, those at high-risk of developing these adverse outcomes, particularly those with active or refractory disease, should be managed by a multi-disciplinary team, including gastroenterologists, obstetricians, and maternal-fetal medicine specialists, in order to reduce overall pregnancy-related morbidity," the team added.

Several studies have reported increased rates of elective and emergent in IBD patients, particularly in Crohn's patients with active perianal disease and ulcerative colitis patients with post-ileal pouch anal anastomosis, Huang and associates noted. Other studies have found an increased risk of and structural disorders such as ectopic pregnancy. These risks remain controversial, however.

And although some recent research has suggested an elevated risk of placental disorders in IBD patients, the study sample sizes have been small, and the specific risk factors remain unknown, Huang and colleagues pointed out.

Encouragingly, the new study found that most nonbiologic IBD therapies such as 5-aminosalicylic acid and thiopurines were not linked to adverse maternal, placental, or obstetric outcomes but, again, the sample sizes were small and control-group comparisons were lacking, the authors cautioned.

Furthermore, anti-tumor necrosis factor (TNF) therapy, whether continued into the third trimester or not, was not associated with abnormal placental diseases. "Although study numbers for these outcomes were again small, these preliminary findings support recent guideline to continue anti-TNF therapy during pregnancy in order to maintain disease remission," the researchers wrote.

In terms of other biologics, the analysis was unable to comment on adverse pregnancy-related outcomes in patients managed with vedolizumab (Entyvio) and ustekinumab (Stelara), nor with newer agents such as tofacitinib (Xeljanz), owing to a lack of case-control or cohort studies addressing placenta-related diseases, the investigators said.

"Female patients of childbearing age will need their providers to give them information on expected outcomes of their IBD during pregnancy. This is an important study that thoroughly evaluated existing literature on a wide range of maternal and fetal outcomes in women with IBD," Richa Shukla, MD, of Baylor College of Medicine in Houston, who was not involved with the study, told 麻豆传媒. "The study will be very helpful in allowing gastroenterologists, particularly those who have a larger population of IBD patients, to effectively counsel pregnant IBD patients."

Last year, the American Gastroenterological Association issued a report aimed at standardizing the management of IBD to ensure safe pregnancy.

Study limitations, Huang and co-authors noted, were that most of the studies included were retrospective and lacked a priori cohorts, which may have resulted in risk-impacting confounding biases. Variables such as advanced maternal age, genitourinary abnormalities, and substance use may have inadvertently affected risk outcomes. In addition, most patient-control comparator studies were observational, case-control, or cohort in nature, and this likely resulted in selection and recall bias. Also, the selection of controls varied across studies, with patients often presenting at tertiary-care centers and hence not being representative of the general IBD population, particularly women in clinical and objective remission throughout pregnancy.

Finally, there was no comparative data on the specific risks in patients with ulcerative colitis or Crohn's disease or on specific medication exposures, nor was there disease activity stratification by trimester, potentially resulting in inter-study heterogeneity, Huang and associates said.

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