Dissecting Allele Architecture of Early Onset IBD Using High-Density Genotyping.

Background: The inflammatory bowel diseases (IBD) are common, complex disorders in which genetic and environmental factors are believed to interact leading to chronic inflammatory responses against the gut microbiota. Earlier genetic studies performed in mostly adult population of European descent identified 163 loci affecting IBD risk, but most have relatively modest effect sizes, and altogether explain only ~20% of the genetic susceptibility. Pediatric onset represents about 25% of overall incident cases in IBD, characterized by distinct disease physiology, course and risks.

Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn's disease.

Background & Aims: Standard therapy for children newly diagnosed with Crohn's disease (CD) includes early administration of immunomodulators after initial treatment with corticosteroids. We compared the effectiveness of early (≤3 mo after diagnosis) treatment with an anti-tumor necrosis factor (TNF)α with that of an immunomodulator in attaining clinical remission and facilitating growth of pediatric patients.

Methods: We analyzed data from the RISK study, an observational research program that enrolled patients younger than age 17 diagnosed with inflammatory (nonpenetrating, nonstricturing) CD from 2008 through 2012 at 28 pediatric gastroenterology centers in North America.

Report of the CCFA pediatric bone, growth and muscle health workshop, New York City, November 11-12, 2011, with updates.

Growth retardation, delayed puberty, decreased bone mass, altered bone architecture, hypovitaminosis D and skeletal muscle mass deficits are common in children with inflammatory bowel diseases. The Crohn's and Colitis Foundation of America sponsored a multidisciplinary workshop on the subject of Bone and Skeletal Growth in Pediatric IBD, held in New York City in November 2011. The topic of the workshop was a key recommendation of the Foundation's Pediatric Challenges meeting in 2005.

Is mechanical ventilation associated with intraventricular hemorrhage in preterm infants?

Background: The impact of mechanical ventilation on the incidence of intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants is unknown, simply because the vast majority of these infants have been routinely intubated and mechanically ventilated. There is a growing interest in the use of early nasal continuous positive airway pressure (ENCPAP) and avoiding mechanical ventilation.

Objectives: To examine the role of mechanical ventilation since delivery room in determining severe IVH in VLBW infants in two neonatal units that follow the same strategy of respiratory management using ENCPAP.

Association of linear growth impairment in pediatric Crohn's disease and a known height locus: a pilot study.

The etiology of growth impairment in Crohn's disease (CD) has been inadequately explained by nutritional, hormonal, and/or disease-related factors, suggesting that genetics may be an additional contributor. The aim of this cross-sectional study was to investigate genetic variants associated with linear growth in pediatric-onset CD. We genotyped 951 subjects (317 CD patient-parent trios) for 64 polymorphisms within 14 CD-susceptibility and 23 stature-associated loci.

Genome-wide association identifies multiple ulcerative colitis susceptibility loci.

Ulcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation underlying ulcerative colitis risk, we present two distinct genome-wide association studies of ulcerative colitis and their joint analysis with a previously published scan, comprising, in aggregate, 2,693 individuals with ulcerative colitis and 6,791 control subjects. Fifty-nine SNPs from 14 independent loci attained an association significance of P < 10(-5).

Common variants at five new loci associated with early-onset inflammatory bowel disease.

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.

Genetic determinants of pediatric inflammatory bowel disease: is age of onset genetically determined?

Inflammatory bowel disease (IBD) is thought to develop as a result of dysregulation of the immune response to normal gut flora in a genetically susceptible host. Approximately 25% of incident cases of IBD occur during childhood and the rest occur throughout adulthood, peaking in the second and third decades of life. What determines the age of onset remains unexplained currently.

Early nasal continuous positive airway pressure and necrotizing enterocolitis in preterm infants.

Background: The use of early nasal continuous positive airway pressure (ENCPAP) as the mode of initial respiratory support for very low birth weight (VLBW) infants has been increasing. The impact of CPAP and oxygen on gut mucosa and perfusion in premature infants is not known. The relation between ENCPAP and necrotizing enterocolitis (NEC) has not been adequately addressed.

Established genetic risk factors do not distinguish early and later onset Crohn's disease.

Background: Early-onset disease is frequently examined in genetic studies because it is presumed to contain a more severe subset of patients under a higher influence of genetic effects. In light of the dramatic success of Crohn's disease (CD) gene discovery efforts, we aimed to characterize the contribution of established common risk variants to pediatric CD.

Methods: Using 35 confirmed CD risk alleles, we genotyped 384 parent-child trios (mean age of onset 11.

Male sex and intraventricular hemorrhage.

Background: Neonatal mortality and morbidity are sex biased in low birth weight infants. The "Y chromosome effect" has been suggested to be responsible for these maturational differences.

Objective: To examine the association of sex and neonatal outcomes.