Childhood Functional Gastrointestinal Disorders: Neonate/Toddler

doi:10.1053/j.gastro.2016.02.016

Gastroenterology

Volume 150, Issue 6, May 2016, Pages 1443-1455.e2

https://doi.org/10.1053/j.gastro.2016.02.016 Get rights and content

In 2006, a consensus concerning functional gastrointestinal intestinal disorders in infants and toddlers was described. At that time, little evidence regarding epidemiology, pathophysiology, diagnostic workup, treatment strategies, and follow-up was available. Consequently, the criteria for the clinical entities were more experience based than evidence based. In the past decade, new insights have been gained about the different functional gastrointestinal intestinal disorders in these age groups. Based on those, further revisions have been made to the criteria. The description of infant colic has been expanded to include criteria for the general pediatrician and specific criteria for researchers. The greatest change was the addition of a paragraph regarding the neurobiology of pain in infants and toddlers, including the understanding of the neurodevelopment of nociception and of the wide array of factors that can impact the pain experience.

Section snippets

G1. Infant Regurgitation

Reflux refers to retrograde involuntary movement of gastric contents in and out of the stomach, and is often referred as gastroesophageal reflux.² When the reflux is high enough to be visualized it is called regurgitation. Regurgitation of stomach contents into the esophagus, mouth, and/or nose is common in infants and is within the expected range of behaviors in healthy infants. Infant regurgitation is the most common FGID in the first year of life.³ Recognition of infant regurgitation avoids

II. Neurobiology of Pain in Infants and Toddlers

Because pain is a complex symptom often associated with FGIDs, an understanding of the neurodevelopment of nociception and of the wide array of factors that may impact the pain experience, and an appreciation for pain assessment in infants and toddlers is important for the clinician addressing functional pain in children. The model that most individuals use to understand pain is that of acute pain in which the pain functions as a signal of anatomic or biochemical pathology. The underlying

Recommendations for Future Research

1.
Epidemiological cross-cultural studies are needed to ascertain the impact on quality of life, and medical consultation across cultures.
2.
Pathophysiology in the majority of FGIDs in young children is still poorly understood and multicenter prospective genetic, metabolic, and neurophysiologic characterizations of large numbers of patients are needed.
3.
Among key questions for research is what the primary outcome measures should be for trials that seek to resolve it.
4.
Validated measures, especially for

References (50)

M.A. Van Tilburg et al.
Prevalence of functional gastrointestinal disorders in infants and toddlers
J Pediatr
(2015)
S.R. Orenstein et al.
Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease
J Pediatr
(2009)
M. Saps et al.
Prevalence of functional gastrointestinal disorders in Colombian school children
J Pediatr
(2014)
P.E. Hyman et al.
Childhood functional gastrointestinal disorders: neonate/toddler
Gastroenterology
(2006)
L.D. Scherer et al.
Influence of “GERD” label on parents' decision to medicate infants
Pediatrics
(2013)
Y. Vandenplas et al.
Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)
J Pediatr Gastroenterol Nutr
(2009)
B. Hegar et al.
Natural evolution of regurgitation in healthy infants
Acta Paediatr
(2009)
S.P. Nelson et al.
Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group
Arch Pediatr Adolesc Med
(1997)
R. Rosen
Gastroesophageal reflux in infants: more than just a phenomenon
JAMA Pediatr
(2014)
A. Horvath et al.
The effect of thickened-feed interventions on gastroesophageal reflux in infants: systematic review and meta-analysis of randomized, controlled trials
Pediatrics
(2008)

Y. Vandenplas et al.

Double-blind comparative trial with 2 antiregurgitation formulae

J Pediatr Gastroenterol Nutr

(2013)

M.P. van Wijk et al.

Small volumes of feed can trigger transient lower esophageal sphincter relaxation and gastroesophageal reflux in the right lateral position in infants

J Pediatr

(2010)

R.Y. Moon

SIDS and other sleep-related infant deaths: expansion of recommendations for a safe infant sleeping environment

Pediatrics

(2011)

D.R. Fleisher

Infant rumination syndrome: report of a case and review of the literature

Am J Dis Child

(1979)

R. Bryant-Waugh et al.

Feeding and eating disorders in childhood

Int J Eat Disord

(2010)

E. Fitzpatrick et al.

The incidence of cyclic vomiting syndrome in children: population-based study

Am J Gastroenterol

(2008)

M. Haghighat et al.

Cyclic vomiting syndrome in children: experience with 181 cases from southern Iran

World J Gastroenterol

(2007)

D.R. Fleisher et al.

The cyclic vomiting syndrome: a report of 71 cases and literature review

J Pediatr Gastroenterol Nutr

(1993)

B.U. Li et al.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition consensus statement on the diagnosis and management of cyclic vomiting syndrome

J Pediatr Gastroenterol Nutr

(2008)

The International Classification of Headache Disorders, 3rd edition (beta version)

Cephalalgia

(2013)

M. Saps et al.

Parental report of abdominal pain and abdominal pain-related functional gastrointestinal disorders from a community survey

J Pediatr Gastroenterol Nutr

(2012)

N.M. Devanarayana et al.

Prevalence of functional gastrointestinal diseases in a cohort of Sri Lankan adolescents: comparison between Rome II and Rome III criteria

J Trop Pediatr

(2011)

M.A.L. Van Tilburg et al.

Prevalence of child/adolescent functional gastrointestinal disorders in a national US community sample

Gastroenterology

(2014)

S. Tarbell et al.

Psychiatric symptoms in children and adolescents with cyclic vomiting syndrome and their parents

Headache

(2008)

B.U. Li

Cyclic vomiting: the pattern and syndrome paradigm

J Pediatr Gastroenterol Nutr

(1995)

Cited by (460)

Cognitive Bias in an Infant with Constipation
2024, Journal of Pediatrics
Prevalence and determinants of constipation in children in Asia: a systematic review and meta-analysis
2024, eClinicalMedicine
Constipation is prevalent worldwide, significantly increasing healthcare costs and diminishing the quality of life in children affected. Current studies have yielded mixed results regarding the factors associated with constipation, and mainly focusing on patients outside of Asia. Moreover, most of these studies lack focus on the paediatric population. This study aimed to identify the prevalence and associated factors of constipation among children in Asia.
In this systematic review and meta-analysis, we systematically searched PubMed, Scopus, and Cochrane for cohort and cross-sectional studies published from database inception up to October 12, 2022, and continued with manual searching until September 2, 2023. Eligible studies were those that included children in Asia aged 0–18 years old suffering from idiopathic constipation, with prevalence value provided in the English abstract. The analysis included clinical and general population. Children with organic constipation, who had undergone gastrointestinal surgery, or with congenital defects were excluded, as these factors affect the incidence of constipation. Data included in the analysis were extracted from published reports only. The extracted data were pooled using random-effects model to analyse the prevalence of constipation in children in Asia. This study is registered with PROSPERO, CRD42022367122.
Out of 4410 systematically searched studies and 36 manually searched ones, a total of 50 studies were included in the final analysis, encompassing data from 311,660 children residing in Asia. The pooled prevalence of constipation was 12.0% (95% CI 9.3–14.6%, I² = 99.8%). There was no significant difference in constipation prevalence observed by sex and geographical location. Nonetheless, adolescents and children aged 1–9 years exhibited a significantly higher prevalence constipation compared to infants (p < 0.0001) Additionally, significant differences in constipation rates were observed across various diagnostic methods, population sources, and mental health conditions.
Despite the high heterogeneity resulting from varying diagnostic tools or definitions used among studies, our review adds to the literature on constipation among children in Asia. It reveals a notably high prevalence of constipation in this demographic. Diagnostic methods, age, and compromised mental health emerged as significant influencers of constipation among children in Asia, highlighting potential strategies to mitigate constipation prevalence in children in Asia.
The National Science and Technology Council, Taiwan.
Position paper on transanal irrigation in chronic non-organic constipation
2024, Digestive and Liver Disease
The practice of recto-colonic water irrigation to treat constipation has been used since ancient times with different, uncontrolled, and variably performing methods which have been considered interchangeably all alike. The use of better-performing devices with a standardized methodology is relatively recent, and the term Trans Anal Irrigation (TAI) defines a methodology performed with devices able to control the timing, volume, and pressure of the water introduced into the rectum and colon utilizing a catheter or a cone through the anus. Such practice has been implemented with favorable responses in patients with refractory chronic constipation secondary to neurological diseases.
However, since the role of Trans Anal Irrigation as a therapeutic aid in chronic functional constipation and functional evacuation disorders is not yet fully clarified and standardized, a group of clinical investigators with recognized expertise in these clinical conditions intends to clarify the elements that characterize a TAI procedure that can benefit patients with functional constipation and functional defecation disorders defined according to the lastly updated Rome Diagnostic Criteria. Finally, the paper deals with adherence and practical implementation of TAI.
Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
2024, The Lancet Gastroenterology and Hepatology
Linaclotide, a guanylate cyclase C agonist, has been approved in the USA for the treatment of chronic idiopathic constipation and irritable bowel syndrome with predominant constipation in adults. We aimed to assess the efficacy and safety of linaclotide in paediatric patients aged 6–17 years with functional constipation.
This randomised, double-blind, placebo-controlled, multicentre, phase 3 study was done at 64 clinic or hospital sites in seven countries (USA, Canada, Israel, Italy, the Netherlands, Ukraine, and Estonia). Patients aged 6−17 years who met modified Rome III criteria for functional constipation were randomly assigned (1:1), with a block size of four and stratified by age (6–11 years and 12–17 years), to receive either oral linaclotide 72 μg or placebo once daily for 12 weeks. Participants, investigators, and data assessors were masked to assignment. The primary efficacy endpoint was change from baseline (CFB) in the 12-week frequency rate of spontaneous bowel movements (SBMs; occurring in the absence of rescue medication on the calendar day of or before the bowel movement) per week and the secondary efficacy endpoint was CFB in stool consistency over the 12-week treatment period; efficacy and safety were analysed in all patients in the randomised population who received at least one dose of study intervention (modified intention-to-treat population and safety population, respectively). The study is registered with ClinicalTrials.gov, NCT04026113, and the functional constipation part of the study is complete.
Between Oct 1, 2019, and March 21, 2022, 330 patients were enrolled and randomly assigned to linaclotide (n=166) or placebo (n=164). Two patients in the linaclotide group did not receive any treatment; thus, efficacy and safety endpoints were assessed in 328 patients (164 patients in each group). 293 (89%) patients completed the 12-week treatment period (148 in the linaclotide group and 145 in the placebo group). 181 (55%) of 328 patients were female and 147 (45%) were male. At baseline, the mean frequency rate for SBMs was 1·28 SBMs per week (SD 0·87) for placebo and 1·16 SBMs per week (0·83) for linaclotide, increasing to 2·29 SBMs per week (1·99) for placebo and 3·41 SBMs per week (2·76) for linaclotide during intervention. Compared with placebo (least-squares mean [LSM] CFB 1·05 SBMs per week [SE 0·19]), patients treated with linaclotide showed significant improvement in SBM frequency (LSM CFB 2·22 SBMs per week [0·19]; LSM CFB difference 1·17 SBMs per week [95% CI 0·65−1·69]; p<0·0001). Linaclotide also significantly improved stool consistency over placebo (LSM CFB 1·11 [SE 0·08] vs 0·69 [0·08]; LSM CFB difference 0·42 [95% CI 0·21−0·64]; p=0·0001). The most reported treatment-emergent adverse event (TEAE) by patients treated with linaclotide was diarrhoea (seven [4%] of 164 vs three [2%] of 164 patients in the placebo group) and by patients treated with placebo was COVID-19 (five [3%] vs four [2%] in the linaclotide group). The most frequent treatment-related TEAE was diarrhoea (linaclotide: six [4%] patients; placebo: two [1%] patients). One serious adverse event of special interest (treatment-related severe diarrhoea resulting in dehydration and hospitalisation) occurred in a female patient aged 17 years in the linaclotide group; this case resolved without sequelae after administration of intravenous fluids. No deaths occurred during the study.
Linaclotide is an efficacious and well tolerated treatment for functional constipation in paediatric patients and has subsequently been approved by the US Food and Drug Administration for this indication.
AbbVie and Ironwood Pharmaceuticals.
Diagnostic and therapeutic approach to children with chronic refractory constipation: Consensus report by the SIGENP motility working group
2024, Digestive and Liver Disease
Constipation is a common problem in children, accounting for about 3% of all primary care visits and up to 25% of referrals to paediatric gastroenterologists. Although polyethylene glycol often proves effective, most children require prolonged treatment and about 50% of them have at least one relapse within the first 5 years after initial recovery. When conventional treatment fails, children are considered to have refractory constipation.
Children with refractory constipation deserve specialist management and guidance. Over the last decades, there has been a remarkable increase in our knowledge of normal and abnormal colonic and anorectal motility in children, and a number of different techniques to measure transit and motility have been developed. The present review analyses the possible diagnostic investigations for children with refractory constipation, focusing on their actual indications and their utility in clinical practice. Moreover, we have also analytically reviewed medical and surgical therapeutic options, which should be considered in selected patients in order to achieve the best clinical outcome.
Plasma GDNF levels in spinal dysraphism and its relation with neurological impairment in children: A point of care study
2024, Journal of Pediatric Urology
GDNF plays a crucial role in the stimulation of recovery, neuroplasticity and synaptic reorganization after spinal cord injury providing neuroprotection and neuroregeneration. Plasma GDNF levels are upregulated in cases of spina bifida owing to the intrauterine damage of the exposed spinal cord. Our aim was to compare the plasma GDNF levels in patients of spina bifida with non-spina bifida cases and assess the correlation with neurological impairment at one year of follow up.
Single centre prospective analysis of cases of spina bifida from 2020 to 2022 at presentation and after one year of follow up post-surgery. Cases with hernia and hydrocele without any other disorders were recruited into the control group. Plasma GDNF levels were assessed with immunoassay kits and compared with neurological involvement.
85 cases were included in the study. GDNF levels were elevated in cases compared to controls (mean 6.62 vs 1.76) with significant p value (<0.01). Same was observed for open and closed defects (mean 7.63 vs 4.86: p < 0.01). At follow up of 52 cases post-surgery cases with neurogenic bladder with abnormal urodynamic studies, sphincter involvement and motor impairment had significantly elevated baseline levels of GDNF compared with those who did not have this neurological impairment (p < 0.01).
The neurotrophic factor up-regulation can reflect an endogenous attempt at neuroprotection against the biochemical and molecular cascades triggered by the spinal cord damage. This upregulation can be represented as important biochemical markers of severe spinal cord damage and can be associated with severity of spine injury in MMC patients. Our results are in keeping with these findings, that, there were increased levels of plasma GDNF levels in cases of spinal dysraphism compared to control population. Also, the type of lesion reflecting the severity whether a closed or an open dysraphism, showed significant difference in levels between them suggesting, yet again, more damage in open defect as expected. The levels were higher with involvement of bladder, sphincter and lower limb power.
There is significant elevation of plasma GDNF levels in cases of spina bifida and this elevation is proportional to the degree of spinal damage and hence the neurological impairment. GDNF levels are a good predictor for assessing the severity of the lesion and thus the outcome in these cases. Additional prospective and long-term studies with a larger cohort are needed for a better understanding of neurotrophin pattern modulation in MMC.

View all citing articles on Scopus

: Conflicts of interest The authors disclose no conflicts.

^∗: Authors share co-first authorship.

View full text

Section II: FGIDs: Diagnostic GroupsNeonate/ToddlerChildhood Functional Gastrointestinal Disorders: Neonate/Toddler

Section snippets

G1. Infant Regurgitation

II. Neurobiology of Pain in Infants and Toddlers

Recommendations for Future Research

J Pediatr

J Pediatr

J Pediatr

Gastroenterology

Influence of “GERD” label on parents' decision to medicate infants

Pediatrics

Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)

J Pediatr Gastroenterol Nutr

Natural evolution of regurgitation in healthy infants

Acta Paediatr

Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group

Arch Pediatr Adolesc Med

Gastroesophageal reflux in infants: more than just a phenomenon

JAMA Pediatr

The effect of thickened-feed interventions on gastroesophageal reflux in infants: systematic review and meta-analysis of randomized, controlled trials

Pediatrics

Double-blind comparative trial with 2 antiregurgitation formulae

J Pediatr Gastroenterol Nutr

Small volumes of feed can trigger transient lower esophageal sphincter relaxation and gastroesophageal reflux in the right lateral position in infants

J Pediatr

SIDS and other sleep-related infant deaths: expansion of recommendations for a safe infant sleeping environment

Pediatrics

Infant rumination syndrome: report of a case and review of the literature

Am J Dis Child

Feeding and eating disorders in childhood

Int J Eat Disord

The incidence of cyclic vomiting syndrome in children: population-based study

Am J Gastroenterol

Cyclic vomiting syndrome in children: experience with 181 cases from southern Iran

World J Gastroenterol

The cyclic vomiting syndrome: a report of 71 cases and literature review

J Pediatr Gastroenterol Nutr

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition consensus statement on the diagnosis and management of cyclic vomiting syndrome

J Pediatr Gastroenterol Nutr

The International Classification of Headache Disorders, 3rd edition (beta version)

Cephalalgia

Parental report of abdominal pain and abdominal pain-related functional gastrointestinal disorders from a community survey

J Pediatr Gastroenterol Nutr

Prevalence of functional gastrointestinal diseases in a cohort of Sri Lankan adolescents: comparison between Rome II and Rome III criteria

J Trop Pediatr

Prevalence of child/adolescent functional gastrointestinal disorders in a national US community sample

Gastroenterology

Psychiatric symptoms in children and adolescents with cyclic vomiting syndrome and their parents

Headache

Cyclic vomiting: the pattern and syndrome paradigm

J Pediatr Gastroenterol Nutr

Section II: FGIDs: Diagnostic Groups
Neonate/Toddler
Childhood Functional Gastrointestinal Disorders: Neonate/Toddler