Liver enzyme profiles after initiating biological treatment in children with inflammatory bowel diseases.

OBJECTIVES: Biological treatments (BTs) are essential in managing pediatric inflammatory bowel diseases (PIBDs). Elevated liver enzymes sometimes succeed BT, yet elucidating studies are scarce. We addressed liver biochemistry after introducing BT and searched for their determinants. METHODS: We identified PIBD patients receiving infliximab, adalimumab, vedolizumab, or ustekinumab at the Children's Hospital, University of Helsinki, Finland, in 2000-2023, and followed their alanine transaminase (ALT) and γ-glutamyl transpeptidase (GT) levels for 24 months. ALT was categorized based on the age- and sex-specific upper limit of normal. We disregarded 46 patients with underlying primary sclerosing cholangitis with/without autoimmune hepatitis (AIH), pretreatment AIH diagnosis, and elevated liver enzymes at the beginning of BT from the analyses. RESULTS: Of 618 BT episodes in 403 patients, 22.2% exhibited increased ALT or GT (ALT in 117, GT in 4, and both ALT/GT in 16 episodes). Of all ALT elevations (n = 133), 41.4% occurred within the first 3 months. ALT elevation was more common after infliximab (representing 59.5% of BTs) than other BTs (25.9% vs. 14.2%, adjusted odds ratio [OR]: 2.41, 95% confidence interval [CI]: 1.23-4.72). AIH followed 1.5% (n = 9) of BT episodes. Ninety-five percent of ALT elevations resolved within 6 months. Antibiotic exposure (particularly to metronidazole) was associated with ALT elevation in general (adjusted OR: 5.76, 95% CI: 2.40-13.9) and short disease duration before starting BT with notable ALT elevation (adjusted OR: 1.10, 95% CI: 1.01-1.22). CONCLUSIONS: Benign ALT elevation is common within 3 months after starting BT (especially infliximab) and scarcely led to cessation of the treatment. AIH is a rare finding during the first year of BT.

Pre-Diagnostic Saliva Microbiota of School-Aged Children Who Developed Type 1 Diabetes or Inflammatory Bowel Diseases.

Altered commensal microbiota composition has been associated with pediatric type 1 diabetes mellitus (T1D) and inflammatory bowel diseases (IBD), but the causal relationship is still unclear. To search for potential pre-diagnostic biomarkers for pediatric T1D or IBD, we compared microbiota in saliva samples in a nested case-control design comprising children developing T1D (nchildren = 52) or IBD (nchildren = 21) and controls with a similar age, sex, and residential area (nchildren = 79). The pre-diagnostic saliva microbiota alpha- and beta-diversity of children who would develop T1D (nsamples = 27) or IBD (nsamples = 14) minimally varied from that of controls. The relative abundances of Abiotrophia were higher, while those of Veillonella, Actinomyces, Megasphaera, Butyrivibrio, and Candidatus ancillula were lower in children who would develop T1D. Within 2 years before diagnosis, the metabolic PWY-5677 pathway (converting succinate into butyrate) was lower in pre-T1D samples than in controls (q = 0.034). No significant pre-IBD differences were found. In conclusion, saliva microbiota diversity or composition were not successful predictors for pediatric T1D nor IBD. Intriguingly, the succinate fermentation pathway was predicted to be lowered before the onset of T1D. Thus, investigating functional pathways might provide a better approach in searching for biomarkers for autoimmune disease in the future.

Exposure to proton pump inhibitors is associated with the development of pediatric autoimmune diseases.

Proton pump inhibitors (PPIs) have been associated with decreased gut microbiota diversity. Disrupted gut microbiota composition has been reported in several autoimmune diseases (ADs), such as type 1 diabetes mellitus (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD). We investigated whether PPIs are associated with the development of ADs in children and concluded that PPI exposures could be related to the onset of ADs, especially IBD and potentially AIT as well.

Antibiotic exposures and the development of pediatric autoimmune diseases: a register-based case-control study.

BACKGROUND: Antibiotics have been associated with several individual autoimmune diseases (ADs). This study aims to discover whether pre-diagnostic antibiotics are associated with the onset of ADs in general. METHODS: From a cohort of 11,407 children, 242 developed ADs (type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis (JIA), or inflammatory bowel diseases) by a median age of 16 years. Antibiotic purchases from birth until the date of diagnosis (or respective date in the matched controls n = 708) were traced from national registers. RESULTS: Total number of antibiotic purchases was not related to the onset of ADs when studied as a group. Of specific diagnoses, JIA was associated with the total number of antibiotics throughout the childhood and with broad-spectrum antibiotics before the age of 3 years. Intriguingly, recent and frequent antibiotic use (within 2 years before diagnosis and ≥3 purchases) was associated with the onset of ADs (OR 1.72, 95% CI 1.08-2.74). Regardless of frequent use in childhood (40% of all antibiotics), penicillin group antibiotics were not related to any ADs. CONCLUSIONS: Use of antibiotics was relatively safe regarding the overall development of ADs. However, broad-spectrum antibiotics should be used considerately as they may associate with an increased likelihood of JIA. IMPACT: Increasing numbers of antibiotic purchases before the age of 3 years or throughout childhood were not associated with the development of pediatric autoimmune diseases. Broad-spectrum antibiotics were related to the development of autoimmune diseases, especially juvenile idiopathic arthritis in children, while penicillin group antibiotics were not. The use of broad-spectrum antibiotics in children should be cautious as they may carry along a risk for autoimmune disease development.

Central obesity in school-aged children increases the likelihood of developing paediatric autoimmune diseases.

BACKGROUND: The incidences of both paediatric obesity and autoimmune diseases have been increasing, but their relationship with one another is unclear. OBJECTIVE: To determine whether obesity or particular dietary patterns in school-aged children are potential risk factors for autoimmune diseases during adolescence. METHODS: This matched case-control study included 525 children, followed up from a median age of 11.3 to 16.7 years. Of them, 105 children received primary autoimmune diagnoses (diabetes, thyroiditis, arthritis, or inflammatory bowel diseases) after baseline and generated the case group. Four children with matching age, sex, and residential area generated the control group of 420 children. At baseline, age- and sex-specific body mass index categories were acquired and waist-to-height ratio (WHTR) was calculated. Central obesity was present when WHTR ≥0.5. Dietary patterns were analysed using a food frequency questionnaire (FFQ). RESULTS: School-aged children with central obesity were 2.11 (OR, 95% CI 1.11-3.98) times more likely to develop autoimmune diseases before age of 19 years than those without central obesity. Being overweight was not related to the onset of these diseases (OR 1.60, 95% CI 0.89-2.87, nor were dietary patterns. CONCLUSION: Central obesity in school-aged children was related to the development of autoimmune diseases, while being overweight and dietary patterns were not.

Perinatal risk factors for pediatric onset type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis, and inflammatory bowel diseases.

Type 1 diabetes mellitus (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD) are common pediatric autoimmune diseases with unknown risk factors. Using nationwide registers, we searched for their perinatal risk factors. Our study followed up 11,407 children (born 2000-2005) for a median of 16.6 years (from birth to 2018). Of them, 2.15% received primary diagnosis and 0.08% also secondary: 0.89% had DM, 0.60% had AIT, 0.48% had JIA, and 0.25% had IBD. The incidences per 100,000 children/year were 106.1 for DM, 46.0 for AIT, 55.0 for JIA, and 23.7 for IBD. There were more preterm births (< 37 weeks) among children with studied autoimmune diseases compared with the rest of the cohort (8.6% vs. 5.3%, p = 0.035). Among those born preterm, children with studied autoimmune diseases received more postnatal antibiotics compared with other preterm children in the cohort (47.6% vs. 27.7%, p = 0.046). Children with IBD were born to older mothers compared with those without studied diagnoses (33.0 vs 30.2, p = 0.004).Conclusion: Preterm birth was a shared risk factor for autoimmune diseases in our study, especially when combined with postnatal antibiotic treatments. High maternal age was associated with IBD. What is Known: • Type 1 diabetes (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD) are common pediatric autoimmune diseases • It is unclear whether these diseases have shared risk factors, since there are no previous simultaneous epidemiological nor follow-up studies on them in one cohort  What is New: • Preterm births were more common in children with DM, AIT, JIA, or IBD compared with other children in the cohort, and preterm children who developed these diseases recieved more postnatal antibiotics compared with other preterm children • High maternal age was associated with IBD.