麻豆传媒

Children diagnosed with inflammatory bowel disease (IBD) had triple the risk of death as adults compared with members of the general population, Swedish investigators reported.

And although the absolute number of deaths in the study was small, the relative risk for death has not decreased over the past few decades despite use of new immunomodulatory and biologic treatments, according to Ola Olén, MD, PhD, of the Karolinska Institute in Stockholm, and colleagues.

Their study online in found that the most common cause of death in childhood-onset IBD was malignancy, followed by digestive diseases and infections. While the majority of IBD patients lived as long as their counterparts in the general population, patients with ulcerative colitis (UC) with primary sclerosing cholangitis (PSC) or a first-degree relation with UC had the highest risk of premature death.

Asked for his perspective, Ryan Ungaro, MD, MS, of the Icahn School of Medicine at Mount Sinai in New York City, who was not involved with the research, said the study is important and shows the major impact IBD has on patients' lives.

"While the absolute risk of death is low, it is alarming that the relative risk is quite elevated," he told 麻豆传媒. "This study highlights the need for further investigation into treatments and strategies, such as earlier diagnosis and intervention, that may decrease the risk of death in order to optimize care for IBD patients."

The Swedish researchers found hazard ratios (HRs) in UC patients that were almost double those in patients with Crohn's disease (CD), and the HRs were elevated for patients with all three IBD types:

• UC 4.0 (95% CI 3.4-4.7)
• CD 2.3 (95% CI 1.8-3.0)
• IBD-unclassified (IBD-U) 2.0 (95% CI 1.2-3.4).

"Individuals diagnosed with IBD in childhood need to be monitored carefully," Olén told 麻豆传媒. "But we're still talking small differences in the number of deaths. Most young people with IBD do not die earlier than their peers, but a few with severe IBD and serious complications such as cancer have a greatly elevated relative risk."

Study Details

For the study, Olén and co-authors identified children diagnosed before age 18 in Swedish national health registers during 1964 to 2014 (n=9,442) and matched them for sex, age, calendar year, and place of residence with a large reference group from the general population (n=93,180). The mean age at IBD diagnosis was 13.7, and 55.3% were boys.

Cox regression HRs for death were estimated separately for UC (n=4,671), CD (n=3,780), and IBD-U (n=991), and compared by calendar period.

The mean age of participants at the end of the 50-year follow-up was 30. During 138,690 person-years of follow-up, 294 deaths, or 2.1 per 1,000 person-years, occurred in IBD patients versus 940 in the reference group, or 0.7 per 1,000 person-years (adjusted HR 3.2, 95% CI 2.8-3.7). That corresponded to one extra death per 694 patients with childhood-onset IBD through adulthood for 1 year, the researchers reported.

In patients younger than 18, there were 27 deaths from IBD, for an HR of 4.9 (95% CI 3.0-7.7). Among young adults with IBD, no evidence emerged that the HRs for death decreased from 1964 through 2014 (P=0.90).

Data on pediatric-onset IBS have been scarce, the team pointed out, noting that case series from the 1920s to the 1970s found a cumulative mortality at 18-20 years of follow-up of 42-25%. When follow-up was stopped at the participant's 18th birthday, there were 27 deaths in IBD patients (0.9/1,000 person-years) compared with 55 deaths in large reference group (0.2/1,000 person-years), corresponding to one extra death per 1,333 IBD patients followed for 1 year.

Childhood absolute mortality decreased over time, falling from 2.6/1,000 during 1964-1979 to 0.8/1,000 during 2002-2014), partly reflecting, the investigators said, a general decline in Swedish child mortality in this time frame -- 0.3/1,000 in 1964-1979 versus 0.2/1,000 in 2002-2014.

Mortality was highest during the first year of follow-up (HR=10.5), but was based on only a few deaths (n=18), of which seven were due to gastrointestinal disease. Five of these individuals died of cancer, and six of non-IBD causes. HRs remained elevated after >5 years of follow-up. The very high HR for GI mortality was mainly due to patients with severe colitis or complications such as short bowel syndrome or liver failure.

There was also a six-fold increased risk of death from infectious disease, the researchers found. Again, however, the absolute number of deaths was low at six, and the 95% confidence intervals were wide. Especially high mortality (HR 12.2) emerged in UC patients with PSC and was largely due to cancer and digestive diseases.

Olén and colleagues noted that recent European case series such as those by and identified 57 deaths in children with IBD, with infections (n=19) and cancer (n=14) the two most common causes.

Study limitations, Olén and co-authors said, included lack of information on medications and the insufficient power of the study to directly assess the effects of immunomodulators and biologics on mortality. The analysis also lacked power to detect potential changes in mortality patterns -- for example, possible increased mortality from infections due to medications and decreased mortality due to better treatment of colitis and inflammation-related cancers. In addition, the group's definitions of disease extent, location, behavior, and severity have not been validated.

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