Hyperadiponectinemia During Infliximab Induction Therapy in Pediatric Crohn Disease

Objectives: The inflammatory process in Crohn disease (CD) involves the visceral fat, characterized by adipocyte hyperplasia and altered adipose tissue and serum concentrations of tumor necrosis factor (TNF), leptin, adiponectin and resistin. We investigated the effect of anti-TNF therapy with infliximab (IFX) on serum adipokine levels in pediatric CD. Methods: Serum concentrations of resistin (ng/mL), leptin (ng/mL), and total adiponectin (mu g/mL) were assessed by enzyme-linked immunosorbent assays (ELISA) in 18 pediatric CD patients (mean age 15.0 +/- 1.5 years) before first, second, and fourth IFX infusion (weeks 0, 2, and 14) and compared with baseline values from sex- and BMI-matched healthy controls (HC, mean age 13.4 +/- 1.6 years). Results: At baseline, CD patients (mean age 15.0 +/- 1.5 years, 10 of 18 boys) compared with HC (13.4 +/- 1.6 years, 7 of 15 boys) had higher resistin levels (median 14.7 ng/mL, range 5.1-50.5 vs 7.3 ng/mL, 0.5-14.5);P = 0.0002). At weeks 2 and 14, resistin decreased to 6.9 ng/mL (2.9-16.8) (P < 0.0001) and 9.2 ng/mL (4.1-20.6;P = 0.0011), respectively. Leptin and adiponectin were comparable between patients and HC at baseline. Leptin increased in girls from 9.5 ng/mL (4.0-30.1) to 16.0 ng/mL (7.9-35.2;P = 0.0156) and 17.2 ng/mL (10.8-26.8;P = 0.1953) at weeks 0, 2, and 14 respectively;with a trend in boys from 2 (0.6-12.9) to 2.8 (1.7-8.6;P = 0.0840) and 3.3 (1.34.6;P = 0.1309). Adiponectin peaked initially from 7.8 mu g/mL (4.6-11.9) at week 0 to 9.2 mu g/mL (4.1-20.7;P = 0.0005) at week 2 and thereafter fell to 6.5 mu g/mL (3.0-12.7;P = 0.0182) at week 14. Conclusions: TNF blockade is associated with changes in circulating adipokines. The marked early increase of the potent anti-inflammatory adiponectin may contribute to the rapid response to IFX in CD

Incidence and Risk Factors for Perianal Disease in Pediatric Crohn Disease Patients Followed in CEDATA-GPGE Registry

Objectives:Perianal disease (PD) with fistula and/or abscess formation is a severe complication in Crohn disease (CD). We examined prevalence, incidence, and risk factors for PD development in a pediatric CD cohort.Methods:Patients with CD from the prospective, multicenter registry for inflammatory bowel disease from Germany and Austria (CEDATA-GPGE) were included if diagnosed at the age of 18 years or younger, registered within 3 months after diagnosis, and having at least 2 follow-up visits within the first year of registration. We examined potential risk factors for PD with Kaplan-Meier analysis and a final Cox model considering sex, family history of inflammatory bowel disease, extraintestinal manifestations, disease location, and induction therapy (corticosteroids or nutritional therapy).Results:Of 2406 patients with CD, 742 fulfilled inclusion criteria (59% boys, mean age at diagnosis 12.43.4 years). PD was present at diagnosis in 41 patients (5.5%;80.9% boys), whereas 32 patients (4.3%, 81.3% male) developed PD during follow-up (mean 2.0 +/- 1.6 years). The cumulative incidence of PD at 12 and 36 months after diagnosis was 3.5% and 7.5%, respectively. Potential risk factors for PD development during follow-up were male sex (hazard ratio=3.2, [95%;confidence interval 1.2-7.8]) and induction therapy with corticosteroids (hazard ratio=2.5 [1.1-5.5]). Diagnostic evaluation at PD diagnosis was incomplete in 40% of affected subjects. PD resolved within 1 year in 50% of cases.Conclusions:Approximately 10% of CD patients in our cohort suffered from PD within the first 3 years of their disease. Male sex and initial corticosteroid therapy were associated with an increased risk to develop PD after diagnosis

Characteristics of the infant/mother pairs studied with breast milk samples available at month 1 and month 4.

<p>Characteristics of the infant/mother pairs studied with breast milk samples available at month 1 and month 4.</p

Associations between breast milk macronutrient classes and hormones to infant serum metabolites at 4 months of age.

<p>Breast milk components were measured at month 1 (a) or month 4 (b). Negative log-transformed P-values are plotted for each metabolite arranged by metabolite group and species. Higher values represented in the outer circles present a higher association between metabolite and predictor. P-values were calculated by linear regression models with the milk compound as independent variable, adjusted for infant sex, breastfeeding status at 4-month blood withdrawal (exclusively BF yes/no), and the infant’s age at blood withdrawal. Random intercepts were modelled for batch number and study centre. P-values were corrected (PLME) for multiple testing using Bonferroni’s methods, this is by dividing the p-value with number of metabolites (n = 184).</p

Correlations between breast milk fatty acids percentages to infant serum metabolites at 4 months of age.

<p>Breast milk components were measured at month 1 (a) or month 4 (b). Spearman correlation coefficients are plotted for each metabolite arranged by metabolite group. AA, amino acids; Carn, acylcarnitines; LPC, lysophosphatidylcholines; PC aa, diacyl-phosphatidylcholines; PC ae, acyl-alkyl-phosphatidylcholines SM, sphingomyelins.</p

CONSORT flow diagram.

<p>Of 944 children in the PreventCD-cohort, 196 complete mother/infant pairs with complete sample sets were analysed. 136 pairs were studied for the associations between <i>month 1</i> breast milk composition and infant serum metabolites at age of 4 months and 137 were studied for the associations between <i>month 4</i> breast milk composition and infant serum metabolites at age of 4 months. 87 were studied at both time points.</p