A study found that neonatal cytokine levels measured shortly after birth may be associated with an increased risk of developing very early–onset inflammatory bowel disease prior to the age of 6 years.
In the study, published in Gastroenterology, researchers analyzed dried blood spots collected 4 to 6 days following birth from 464 individuals who later developed pediatric-onset inflammatory bowel disease (IBD) and matched controls.
The study included 243 patients with Crohn's disease (CD) (46% female) and 221 patients with ulcerative colitis (UC) (50% female), diagnosed at a median age of 11 years (interquartile range [IQR] = 7–15 years). A subcohort of 88 patients with very early–onset IBD (VEO-IBD) (diagnosed before age 6 years) was also analyzed separately. Among these, 36 had CD (28% female), 52 had UC (54% female), and their median age at diagnosis was 2 years (IQR = 0–5 years).
Among the key findings were:
- Lower interleukin (IL)-4 levels at birth were significantly associated with increased risk of VEO-IBD (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.19–0.83, P = .02).
- Higher IL-17A levels showed a marginally significant association with increased VEO-IBD risk (OR = 1.17, 95% CI = 1.01–1.42, P = .06).
- No statistically significant associations were found between neonatal cytokine levels and overall pediatric-onset IBD risk in the full cohort.
In the overall cohort, 35 individuals (3.8%) had mothers with IBD, and 26 of these individuals developed IBD later in life. In the VEO subcohort, 4.5% of them had a mother with IBD, and 75% of these patients developed IBD later in life.
The researchers measured levels of interferon-γ, tumor necrosis factor-α, IL-1β, IL-4, IL-6, and IL-17A using a highly sensitive multiplex immunoassay (S-PLEX, MesoScale). These six cytokines were measurable in at least 20% of individuals. Logistic regression models were used to assess associations between cytokine levels and IBD risk, adjusting for gestational age, birth year, delivery mode, and sex.
The measured concentration in fg/mL was divided by 100, with the reported OR corresponding to the risk associated with an increase of 0.1 pg/mL (or 100 fg/mL). Correction for multiple testing by false discovery rate (FDR) was performed in all analyses.
While significance was lost after multiple testing correction in the VEO-IBD analysis, likely because of low statistical power, the findings suggested potential early inflammatory changes in patients who develop IBD at a very young age.
The study leveraged unique access to neonatal blood spots from the Danish National Biobank linked to nationwide health data from the Danish National Patient Registry. Limitations included potential variations in measured concentrations caused by varying sample storage time, differences in hematocrit levels, and differences in handling of samples over time.
Conflict of interest disclosures can be found in the study.