Efficacy and safety of medical and nutritional management of gastroesophageal reflux in formula-fed infants: a narrative review.

PURPOSE OF REVIEW: The prescription of proton pump inhibitors has an increasing trend, despite that guidelines recommend nutritional management as first-line management. A thickened antiregurgitation formula is recommended in formula-fed infants. In this review we focus on the novel insights in management of formula-fed infants with gastroesophageal reflux disease (GERD). RECENT FINDINGS: New data are limited. Concerning thickened antiregurgitation formula, locust bean gum has been the most studied and has limited adverse effects. However, positive results were also obtained with pectin. The effect of pro- and prebiotics on regurgitation is unclear. The overlap between cow's milk allergy and gastroesophageal reflux remains a challenge. SUMMARY: Very limited new data were published during the last 18 months. Thickened antiregurgitation formula is the first-line approach in formula-fed infants with GERD. No specific thickening agent can be recommended because of lack of comparative trials. Proton pump inhibitors are over prescribed in infants.

Are pro- and/or synbiotics beneficial in Helicobacter pylori eradication therapy in children? A narrative review.

To assess the effect of pro- and synbiotics in the eradication therapy of Helicobacter pylori (Hp), as well as their effect on adverse effects and therapy compliance in children, a review was performed. We searched for relevant studies published in the English language in PubMed in the last 5 years. Articles were extracted using subject heading and keywords of interest to the topic. There is low-quality evidence that Lactobacillus casei, Bifidobacterium infantis, and Clostridium butyricum (only one RCT for all three) and Saccharomyces boulardii (more than 1 RCT) increase the eradication rate and decrease the adverse effects. Data with synbiotics report only a trend towards a better eradication. Heterogeneity in study designs and outcomes is a major limitation to propose evidence-based recommendations. A reduced incidence of antibiotic-associated diarrhoea is reported. Therapy compliance has been poorly studied.   Conclusion: Due to study heterogeneity, there is very low evidence that some specific probiotics strains increase the eradication rate of Hp when added to standard eradication therapy in children. Whether this is related to immunological effects of the strain or a decrease of adverse effects is not known. More studies, especially comparative trials, are needed before the addition of pro- or synbiotics to Hp eradication treatment can be recommended in daily routine. What is Known: • Eradication treatment of Helicobacter pylori in children has a low success rate and induces frequently adverse effects. • The addition of probiotics might improve eradication and decrease adverse effects, but no paediatric guideline does recommend probiotics as part of the eradication treatment. What is New: • There is low-quality evidence that Lactobacillus casei, Bifidobacteria infantis, and Clostridium butyricum (only one randomized controlled trial (RCT) for all three) and Saccharomyces boulardii (more than 1 RCT) increase the eradication rate and decrease the adverse effects. • Data with synbiotics report only a trend towards a better eradication.

How to manage irritable bowel syndrome in children.

AIM: This paper discusses the risk factors and management of paediatric irritable bowel syndrome (IBS), with a focus on the role of the gastrointestinal microbiome. METHODS: English articles of interest published in PubMed and Google Scholar were searched using subject heading and keywords of interest. RESULTS: Only few randomised controlled trials on the management of IBS in children have been published. The vast majority of these intervention trials target to change the composition of the gastrointestinal microbiome. Most studies are underpowered. Major heterogeneities in study designs such as differences in inclusion criteria, including patients with different pain-related functional gastrointestinal disorders and differences in primary outcomes, make it impossible to formulate recommendations. Overall, few adverse events are reported what could indicate safety or point to suboptimal conduction of clinical trials and safety reporting. However, it can also not be excluded that some interventions such as the administration of selected probiotic products may result in benefit. CONCLUSION: There is insufficient evidence to recommend any therapeutic intervention in paediatric IBS, including manipulation of the gastrointestinal tract microbiome, despite the evidence that dysbiosis seems an associated pathophysiologic factor. More designed prospective trials are needed since IBS is not a rare condition during childhood.

A narrative review on the diagnosis and management of constipation in infants.

INTRODUCTION: Functional constipation is one of the common disorders of gut-brain interaction in infancy, and decreases the quality of life of infants and parents. AREAS COVERED: Relevant articles up to November 2022 were reviewed. We searched in PubMed, Google Scholar, and MEDLINE for guidelines, position papers, reviews, and randomized controlled trials on infant constipation. EXPERT OPINION: Randomized controlled trials in this specific age group are mostly limited to trials with infant formula. The prevalence of infant constipation in formula-fed infants is decreasing, and can be associated with adaptations in formula composition. While the supplementation of infant formula with pro-, pre- and/or synbiotics decreases the prevalence of constipation, their efficacy in constipated infants is disappointing. There is limited evidence to support the addition of magnesium to infant formula to treat constipation. The evidence for the efficacy and safety of polyethylene glycol in children < 2 years has expanded over the past years. The administration of lactulose or polyethylene glycol is the preferred medical management, in case nutritional management does result in insufficient improvement.

Diagnosis and Management of Ménétrier Disease in Children: A Case Series Review.

PURPOSE: Ménétrier disease (MD) was first described in 1888, and 50 cases have been reported until now. We aimed to discuss the etiology, diagnostics, and management of MD in children. METHODS: We searched for case reports published from 2014 till 2019 in English using PubMed. Articles were selected using subject headings and key words of interest to the topic. Interesting references of the included articles were also included. RESULTS: The pathophysiology of MD is still uncertain. However, overexpression of transforming growth factor alpha with transformation of the gastric mucosa has been observed, which may be mediated by genetics and provoked by an infectious trigger. Clinically, MD is diagnosed by abdominal pain, vomiting, anorexia, and edema secondary to hypoalbuminemia. A gastroscopy with biopsy is the gold standard for the diagnosis of MD. In children, the disease is self-limiting and only requires supportive treatment. In general, children have a good prognosis and recover spontaneously within a few weeks. CONCLUSION: Few pediatric cases of MD have been described in recent years, and with all different etiology. Endoscopy with biopsy remains the golden standard for the diagnosis of MD, and in children, the disease is self-limiting.

Prevention and Management with Pro-, Pre and Synbiotics in Children with Asthma and Allergic Rhinitis: A Narrative Review.

Allergic diseases including allergic rhinitis and asthma are increasing in the developing world, related to a westernizing lifestyle, while the prevalence is stable and decreasing in the industrialized world. This paper aims to answer the question if prevention and/or treatment of allergic rhinitis and asthma can be achieved by administrating pro-, pre- and/or synbiotics that might contribute to stabilizing the disturbed microbiome that influences the immune system through the gut-lung axis. We searched for relevant English articles in PubMed and Google Scholar. Articles interesting for the topic were selected using subject heading and key words. Interesting references in included articles were also considered. While there is substantial evidence from animal studies in well controlled conditions that selected probiotic strains may offer benefits in the prevention of wheezing and asthma, outcomes from clinical studies in infants (including as well pre- and postnatal administration) are disappointing. The latter may be related to the multiple confounding factors such as environment, strain selection and dosage, moment of administration and genetic background. There is little evidence to recommend administration of pro, pre- or synbiotics in the prevention of asthma and allergic rhinitis in children.

Safety considerations when managing gastro-esophageal reflux disease in infants.

Introduction: Gastro-esophageal reflux disease (GERD) in infants is worldwide diagnosed with increasing frequency, resulting in an increasing number of infants exposed to treatment. In this review, we focus on the safety of therapeutic options. Areas covered: English articles were searched from 1990 until May 2020 in PubMed and Google Scholar. Evidence suggests that non-pharmacological treatment is often effective and safe. Guidelines restrict pharmacological treatment to acid-suppressive medication, which is associated with adverse effects, often related to gastro-intestinal dysbiosis and consequences of the latter. Aluminum-free alginates have some efficacy and are not associated with relevant adverse effects. Especially in infants, GERD is often nonacid related. Prokinetics are not recommended because of lack of efficacy and numerous adverse effects. Expert opinion: Pediatric trials are underpowered regarding adverse effects. The number of infants exposed to anti-secretory agents is increasing worldwide, often without indication. Informing healthcare providers about adverse effects of acid-secretory medication may contribute to a more rational use. Acid inhibiting agents such as alginates are a drug class associated with limited efficacy and devoid of serious adverse effects. Regarding prokinetics, the risk of adverse effects outweighs the benefit. Reassurance of parents and nutritional management of GERD in infants is effective and safe.

Real Time Versus Photographic Assessment of Stool Consistency Using the Brussels Infant and Toddler Stool Scale: Are They Telling Us the Same?

PURPOSE: Digital communication is becoming increasingly important in clinical practice and research. The finding that stool consistency can be evaluated similarly using either "in vivo" or photographic material by health care professionals will decrease subjective interpretation by parents. The primary outcome of this study was the reliability of stool consistency scoring using the Brussels Infant and Toddler Stool Scale (BITSS) between fresh stools and their photos; the secondary outcome was the inter-rater reliability based on the fresh stools. METHODS: Fresh stool samples from healthy children were collected in a day care center. These stools, and one month later the corresponding photos presented in a random order, were presented to 14 observers. Reliabilities were analyzed using absolute agreements and weighted and unweighted Cohen's κ. RESULTS: In total, 202 samples were rated 576 times. Absolute agreement between photographic and real time assessment ranged between 71.1% and 83.3% among observers. This corresponded with substantial agreement (unweighted κ=0.70 [95% CI, 0.61-0.78]; weighted κ=0.86 [95% CI, 0.78-0.88]). The inter-observer agreement showed similar percentages of absolute agreement (81.4-82.0%) and κ-values corresponding with fair-to-moderate agreement. CONCLUSION: Our findings suggest that the assessment of fresh stool consistency can also reliably be done on photographic material when using the BITSS. This opens opportunities in scientific surroundings and in our daily life communication with parents and caretakers.

The influence of the gastrointestinal microbiome on infant colic.

INTRODUCTION: Although infantile colic is relatively frequent, its pathophysiology is not yet understood. The aim of this paper is to provide a better understanding of the link between infantile colic and the gastrointestinal microbiome. AREAS COVERED: The gastro-intestinal microbiome may already start to develop in the womb and grows exponentially immediately after birth. Factors influencing the microbiome can cause dysbiosis and precipitate symptoms of colic through several mechanisms such as increased gas production and low grade gut inflammation. Other possible factors are immaturity of the enterohepatic bile acid cycle and administration of antibiotics and other medications during the perinatal period. An effective treatment for all colicky infants has yet to be discovered, but the probiotic Lactobacillus reuteri DSM17938 was shown to be effective in breastfed infants with colic. The scientific databases 'Pubmed' and 'Google scholar' were searched from inception until 02/2020. Relevant articles were selected based on the abstract. EXPERT OPINION: Recent literature confirmed that the composition of the gastrointestinal microbiome is associated with the development of infantile colic. It can be speculated that full sequencing and bioinformatics analysis to identify the microbiome down to the species level may provide answers to the etiology and management of infantile colic.

Functional constipation in children: challenges and solutions.

This review intends to update what is known about and what is still a challenge in functional constipation (FC) in children regarding epidemiology, pathophysiology, diagnosis, and management. Although FC is a common childhood problem, its global burden remains unknown as data from parts of the world are missing. Another problem is that there is a large variation in prevalence due to differences in study methods and defining age groups. The pathophysiology of FC remains unclear to date but is probably multifactorial. Withholding behavior is likely to be the most important factor in toddlers and young children. Genetics may also play a role since many patients have positive family history, but mutations in genes associated with FC have not been found. Over the past years, different diagnostic criteria for FC in infants and children have been proposed. This year, Rome IV criteria have been released. Compared to Rome III, it eliminates two diagnostic criteria in children under the age of 4 who still wear diapers. Physical examination and taking a thorough medical history are recommended, but other investigations such as abdominal radiography, transabdominal recto-ultrasonography, colonic transit time, rectal biopsies, and colon manometry are not routinely recommended. Regarding treatment, guidelines recommend disimpaction and maintenance therapy with polyethylene glycol (PEG) with or without electrolytes. But experience shows that acceptability, adherence, and tolerance to PEG are still a challenge. Counseling of parents and children about causes of FC is often neglected. Recent studies suggest that behavior therapy added to laxative therapy improves the relief of symptoms. Further homogeneous studies, better-defined outcomes, and studies conducted in primary care are needed.