Introduction to and Screening Visit Results of the Multicenter Pediatric Crohn’s Disease Growth Study

Gupta, Neera; Lustig, Robert H.; Andrews, Howard; Sylvester, Francisco; Keljo, David J.; Goyal, Alka; Gokhale, Ranjana; Patel, Ashish; Guthery, Stephen L.; Leu, Cheng-Shiun

doi:10.1093/ibd/izaa023

Cited by 8 publications

(5 citation statements)

References 37 publications

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“…The incidence of IBD is high and increasing, especially in early life (Benchimol et al, 2017(Benchimol et al, , 2014Ng et al, 2017). IBD is particularly challenging when it develops in children; delay in the onset and progression through puberty is common in this population, and can result in reduced adult height and sexual immaturity (Gupta et al, 2020). In this study, we assessed the microbiome, intestinal, endocrine, brain, and behavioral effects of repeated DSS-induced gut inflammation in early life.…”

Section: Discussionmentioning

confidence: 99%

Early-Life Gut Inflammation Drives Sex-Dependent Shifts in the Microbiome-Endocrine-Brain Axis

Sullivan,

Sie,

et al. 2024

Preprint

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Despite recent advances in understanding the connection between the gut microbiota and the brain, there remains a wide knowledge gap in how gut inflammation impacts brain development. Microbiota-derived metabolite signaling from the gut to the brain is required for normal development of microglia, the brain's resident immune cells. Disruption of the microbiota-brain communication has been linked to impaired behaviours and Autism Spectrum Disorder. We hypothesized that intestinal inflammation in early life would negatively affect neurodevelopment through dysregulation of microbiota communication to brain microglia. To test this hypothesis, we developed a novel pediatric model of Inflammatory Bowel Disease (IBD). IBD is an incurable condition affecting millions of people worldwide, characterized by chronic intestinal inflammation, and has comorbid symptoms of anxiety, depression and cognitive impairment. Significantly, 25% of IBD patients are diagnosed during childhood, and the effect of chronic inflammation during this critical period of development is largely unknown. We developed a chemical model of pediatric chronic IBD by repeatedly treating juvenile mice with dextran sodium sulfate (DSS) in drinking water. DSS-treated mice displayed increased intestinal inflammation, altered microbiota and changes in circulating metabolites. We also found that alterations in gut microbiota had long-term impacts on female microglia and male sex-specific behaviours and testosterone regulation, consistent with delayed puberty observed in male IBD patients. Our research expands our understanding of microbiota-microglia communication underlying development. The gut-brain axis is an exciting target for personalized medicine as microbiome manipulations could be feasible for early intervention to reverse deficits due to juvenile inflammation.

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Section: Discussionmentioning

confidence: 99%

Early-Life Gut Inflammation Drives Sex-Dependent Shifts in the Microbiome-Endocrine-Brain Axis

Sullivan,

Sie,

et al. 2024

Preprint

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“…Gupta et al (6,7) observed that the median onset of menarche was delayed from 12.5 years to 13.9 years in girls with CD and suggested that delayed BA could allow for continued growth in patients with older CA. This was later supported by retrospective data from the ImproveCareNow registry where girls aged >15 years grew a median of 1.8 cm with CD and 1.5 cm with UC (27).…”

Section: Discussionmentioning

confidence: 99%

“…Growth impairment is a well-recognized multifactorial complication of pediatric-onset inflammatory bowel disease (IBD) and associated with the age of onset of IBD, severity of disease, nutritional insufficiency, disease location, and medication exposure (1–8). Confounding factors such as familial short stature, which is identified by low mid-parental height (MPH), can also play a role in final height (FHt).…”

mentioning

confidence: 99%

“…The onset of menarche is often recognized by patients and their families as being followed by slowing of linear growth, which is concerning to shorter patients with already impaired growth (9,10). Data describing the association between age at menarche and growth in pediatric IBD patients is limited, often based on patient recall and without concurrent height measurements (6,7,11). We hypothesized that pediatric IBD patients with early menarche might have lower FHt secondary to epiphyseal closure while those with late menarche will have time to grow.…”

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confidence: 99%

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Growth After Menarche in Pediatric Inflammatory Bowel Disease

Salguero

Deplewski

Gokhale

et al. 2022

Journal of Pediatric Gastroenterology &Amp; Nutrition

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Objectives: Growth impairment in pediatric patients with pediatric onset inflammatory bowel disease (IBD) is multifactorial. Reports on the effect of age at menarche on adult stature in this population are limited. This study investigated the impact of age at menarche, disease-associated factors, and mid-parental height on growth from menarche to final height (FHt) in pediatric patients with Crohn disease (CD) and ulcerative colitis (UC) and IBD unclassified (IBD-U). Methods: Subjects were enrolled from a prospectively maintained pediatric IBD database when IBD preceded menarche and dates of menarche and FHt measurements were recorded. Results: One hundred forty-six patients: CD 112 and UC 30/IBD-U 4. Mean age (years) at diagnosis (10.9 vs 10.1), menarche (14.4 vs 14.0), and FHt (19.6 vs 19.7). CD and UC/IBD-U patients showed significant association between Chronological age (CA) at menarche and FHt (cm, P < 0.001) but not FHt z score (FHt-Z) < −1.0 (P = 0.42). FHt-Z < −2.0 occurred in only 5 patients. Growth impairment (FHt-Z < −1.0) was associated with surgery before menarche (P = 0.03), jejunal disease (P = 0.003), low mid-parental height z score (MPH-Z) (P < 0.001), hospitalization for CD (P = 0.03) but not UC, recurrent corticosteroid, or anti-tumor necrosis factor alpha (anti-TNFα) therapy.Conclusions: Early age of menarche was associated with greater potential for linear growth to FHt but not FHt-Z (P < 0.05). Surgery before menarche, jejunal disease, hospitalization for CD, low MPH, and weight z score were associated with FHt-Z < −1.0.

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“…In the Sex Differences in Statural Growth Impairment in Pediatric Crohn's Disease study (also known as the Growth Study), a poorer height growth in males was described: the data suggest that height gain is lower in males than females with skeletal maturation [40].…”

Section: Growth Failurementioning

confidence: 99%

Growth and Puberty in Children with Inflammatory Bowel Diseases

Amaro

Chiarelli

2020

Biomedicines

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Inflammatory bowel diseases (IBD) are gastrointestinal tract pathologies of unknown etiology; they have an alternating trend, with active and silent phases. IBD are classified in two main forms: ulcerative colitis (UC) and Crohn’s disease (CD). Both have chronic and recurrent course, gastrointestinal symptoms, and extraintestinal manifestations. The altered immune response role seems to be important both in UC and CD. In the majority of cases, CD begins with abdominal pain, diarrhea, decrease in appetite, and weight loss; there can be also perianal fistulas, rhagades, and perianal recurrent abscesses. In addition, retarded growth and delayed puberty can precede the development of the disease or can even be predominant at onset. Growth retardation is found in 40% of IBD patients, but the underlying mechanism of this and other extra-intestinal manifestations are partially known: the main hypotheses are represented by malnutrition and inflammatory response during the active phase of the disease. The increased level of pro-inflammatory cytokines can influence growth, but also the onset of puberty and its progression. In addition, it could be essential to clarify the role and the possible effects of all the currently used treatments concerning growth failure and delayed puberty.

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Introduction to and Screening Visit Results of the Multicenter Pediatric Crohn’s Disease Growth Study

Cited by 8 publications

References 37 publications

Early-Life Gut Inflammation Drives Sex-Dependent Shifts in the Microbiome-Endocrine-Brain Axis

Early-Life Gut Inflammation Drives Sex-Dependent Shifts in the Microbiome-Endocrine-Brain Axis

Growth After Menarche in Pediatric Inflammatory Bowel Disease

Growth and Puberty in Children with Inflammatory Bowel Diseases

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