Reevaluating the FDA's warning against the use of probiotics in preterm neonates: A societal statement by ESPGHAN and EFCNI.

The recent advisory issued by the United States Food and Drug Administration, cautioning against the routine administration of probiotics in preterm neonates, has sparked a lively debate within the scientific community. This commentary presents a perspective from members of the Special Interest Group on Gut Microbiota and Modifications within the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and other authors who contributed to the ESPGHAN position paper on probiotics for preterm infants, as well as representatives from the European Foundation for the Care of Newborn Infants. We advocate for a more nuanced and supportive approach to the use of certain probiotics in this vulnerable population, balancing the demonstrated benefits and risks.

Jejunal Feeding by Gastrojejunal Tube in Pediatric Refractory Gastroesophageal Reflux Disease.

OBJECTIVES: The objective of this study is to determine whether jejunal nutrition by gastrojejunal tube (GJT) could be a therapeutic option for refractory gastroesophageal reflux disease (GERD), avoiding further antireflux surgery. METHODS: A monocentric retrospective study was conducted for all children <18 years who underwent GJT placement to treat GERD. We collected data at the first GJT placement, 5 months after last GJT withdrawal, and at the end of the follow-up (June 2021). RESULTS: Among 46 GERD patients with 86 GJT, 32 (69.6%) and 30 (65.2%) avoided antireflux surgery 5 and 28 months, respectively, after the definitive GJT removal. Five months after GJT removal, discharge from hospital, transition to gastric nutrition, GERD complications, and treatment were significantly improved. Median age and weight at the first GJT placement were 7 months and 6.8 kg. Patients had digestive comorbidities or complicated GERD in 69.6% and 76.1% patients, respectively. The median duration of jejunal nutrition using GJT was 64.5 days. GJT had to be removed in 63 (75.9%) cases for technical problems. CONCLUSIONS: Jejunal nutrition by GJT could be an alternative to antireflux surgery avoiding sustainably antireflux surgery in most of complicated GERD patients. The high frequency of mechanical complications raises that these devices should be technically improved.

Synbiotics in the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.

BACKGROUND: Synbiotics are a mixture comprising of live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There is an increasing number of studies investigating their role in different diseases and disorders. AIM: The purpose of this article is to provide recommendations for the use of synbiotics in the management of pediatric gastrointestinal disorders. The recommendations are developed by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications. METHODS: From existing literature databases, we searched and appraised all systematic reviews and/or meta-analyses, and subsequently published randomized controlled trials (RCTs) that compared the use of synbiotics, in all delivery vehicles and formulations, at any dose, compared to no synbiotics. Synbiotics which are part of infant formula were not assessed. The recommendations were formulated only if at least 2 RCTs that used a well-defined synbiotic were available. RESULTS: Based on the currently available evidence, no recommendation can be formulated in favor or against the use of evaluated synbiotic combination in the treatment of acute gastroenteritis, prevention of necrotizing enterocolitis, Helicobacter pylori infection, inflammatory bowel disease, functional gastrointestinal disorders, and allergy in infants and children. CONCLUSIONS: There is a need for more, well-designed RCTs on the role of synbiotics in gastrointestinal disorders with the same outcome measures to enable the inter-studies comparisons.

Probiotics for the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.

BACKGROUND: Probiotics, defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are widely used despite uncertainty regarding their efficacy and discordant recommendations about their use. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Gut Microbiota and Modifications provides updated recommendations for the use of probiotics for the management of selected pediatric gastrointestinal disorders. METHODS: All systematic reviews and/or meta-analyses, as well as subsequently published randomized controlled trials (RCTs) (until December 2021), that compared the use of probiotics in all delivery vehicles and formulations, at any dose, with no probiotic (ie, placebo or no treatment), were eligible for inclusion. The recommendations were formulated only if at least 2 RCTs on a similar well-defined probiotic strain were available. The modified Delphi process was used to establish consensus on the recommendations. RESULTS: Recommendations for the use of specific probiotic strains were made for the management of acute gastroenteritis, prevention of antibiotic-associated diarrhea, nosocomial diarrhea and necrotizing enterocolitis, management of Helicobacter pylori infection, and management of functional abdominal pain disorders and infant colic. CONCLUSIONS: Despite evidence to support the use of specific probiotics in some clinical situations, further studies confirming the effect(s) and defining the type, dose, and timing of probiotics are still often required. The use of probiotics with no documented health benefits should be discouraged.

A European Survey on Digestive Perianastomotic Ulcerations, a Rare Crohn-like Disorder Occurring in Children and Young Adults.

OBJECTIVES: Digestive perianastomotic ulcerations (DPAU) resembling Crohn disease lesions are long-term complications of intestinal resections, occurring in children and young adults. They are known to be uncommon, severe and difficult to treat. METHODS: In the absence of recommendations, we performed a large European survey among the members of the ESPGHAN working group on inflammatory bowel disease (IBD) in order to collect the experience of expert pediatric gastroenterologists on DPAU. RESULTS: Fifty-one patients (29 boys and 22 girls) were identified from 19 centers in 8 countries. Most patients were followed after necrotizing enterocolitis (n = 20) or Hirschsprung disease (n = 11). The anastomosis was performed at a median age (interquartile range) of 6 [1-23] months, and first symptoms occurred 39 [22-106] months after surgery. Anemia was the most prevalent symptom followed by diarrhea, abdominal pain, bloating, and failure to thrive. Hypoalbuminemia, elevated CRP, and fecal calprotectin were common. Deep ulcerations were found in 59% of patients usually proximally to the anastomosis (68%). During a median follow-up of 40 [19-67] months, treatments reported to be the most effective included exclusive enteral nutrition (31/35, 88%), redo anastomosis (18/22, 82%), and alternate antibiotic treatment (37/64, 58%). CONCLUSIONS: Unfortunately, persistence of symptoms, failure to thrive, and abnormal laboratory tests at last follow-up in most of patients show the burden of DPAU lacking optimal therapy and incomplete understanding of the pathophysiology.

Concomitant gastrostomy tube insertion during laparoscopic Nissen fundoplication for gastro-esophageal reflux disease: analysis of risk factors for fundoplication failure.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) and gastrostomy tube (GT) placement may be performed concomitantly in children with gastro-esophageal reflux disease (GERD) and failure to thrive. We aimed to evaluate the rate and risk factors for LNF failure in children undergoing concomitant LNF/GT. METHODS: A retrospective multi-institutional cohort study was conducted, reviewing patients that underwent LNF (2005-2014). Data collected included patient demographics, comorbidities, and type of GT (laparoscopy- or endoscopy-assisted). The primary outcome measure was LNF failure. Data was compared using contingency tables or Mann-Whitney tests, when appropriate. An exploratory analysis by Kaplan-Meier survival and Cox proportional hazards analysis was performed to determine predictors of time to LNF failure after LNF/GT. RESULTS: Of 189 children that underwent LNF, 99 (52%) had a concomitant GT (55% laparoscopy-, 45% endoscopy-assisted). LNF failed in 15% after LNF/GT and in 17% after LNF alone (p = 0.84), at a median age of 23 months (IQR 8-41). Using univariate analysis, we found that a younger age at the time of surgery (p = 0.05), prematurity (p = 0.0018), esophageal atresia (p = 0.01), and endoscopy-assisted GT (p = 0.02) were potential predictors of LNF failure after LNF/GT. After multivariate regression analysis, prematurity (p = 0.007) remained significantly associated with LNF failure after LNF/GT. No predictive factors for LNF failure after LNF alone were identified. CONCLUSIONS: Concomitant GT insertion and LNF is a common practice, as half of the children that undergo LNF also received GT insertion. Children born preterm or with esophageal atresia comprise a fragile population at high-risk of LNF failure after LNF/GT. Prospective, multicentric studies are needed to evaluate the best GT technique to use in children undergoing LNF.

Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection and Other Conditions in Children: A Joint Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.

Role of Lactoferrin in Neonates and Infants: An Update.

Lactoferrin is one of the most represented and important bioactive proteins in human and mammal milk. In humans, lactoferrin is responsible for several actions targeting anti-infective, immunological, and gastrointestinal domains in neonates, infants, and young children. Evidence-based data vouch for the ability of supplemented lactoferrin to prevent sepsis and necrotizing enterocolitis in preterm infants and to reduce the burden of morbidity related to gastrointestinal and respiratory pathogens in young children. However, several issues remain pending regarding answers and clarification related to quality control, correct intakes, optimal schedules and schemes of supplementations, interactions with probiotics, and different types of milk and formulas. This review summarizes the current evidence regarding lactoferrin and discusses the areas in need of further guidance prior to the adoption of strategies that include a routine use of lactoferrin in neonates and young children.

Postsurgical Perforation of the Esophagus Can Be Treated Using a Fully Covered Stent in Children.

OBJECTIVES: Surgery and conservative treatment of esophageal or gastric perforations are both often associated with poor results and carry a high morbidity and mortality rate. The aim of the present study was to evaluate the effectiveness and safety of using fully covered self-expending metallic stents (SEMS) in children with upper digestive leaks. METHODS: This retrospective study reviewed all children with esophageal or gastric perforation who were treated with placement of an SEMS from January 2011 to January 2015. Closure of the perforation was the primary outcome measured. Secondary outcomes were the duration of antibiotic therapy and parenteral nutrition, adverse events, and length of hospitalization. RESULTS: A total of 19 SEMS were placed in 10 patients (median age: 5.5 years; 5 girls) treated for postanastomotic leaks of esophageal atresia (n = 3), esophagogastroplasty (n = 4), resection of esophageal duplication (n = 1) or perforation during Toupet surgical dismantling (n = 1), and gastric rupture after Nissen surgery (n = 1). The perforation closed in 9 out of 10 patients in a mean of 36 days after stenting (range: 13-158 days). All patients received antibiotic therapy for an average of 17.5 days (3-109 days) and parenteral nutrition for 49 days (17-266 days). During a median follow-up of 8.9 months, 4 out of 9 sealed perforations developed stenosis, which was efficiently treated by endoscopic dilations in 2 patients and surgical redo in 2 patients with dilation-resistant stenosis. CONCLUSIONS: Covered stents appear to be beneficial in closing esophageal perforations in children and can avoid the high morbidity of a surgical repair. Stenosis, however, occurred frequently after larger leakages.

Clinical Manifestation of Cytomegalovirus-Associated Protein-Losing Enteropathy in Children.

In children, CMV-associated protein-losing enteropathy (PLE) is characterised by a benign course and spontaneous healing but can lead to generalised oedema. Poorly defined, it is diagnosed after unnecessary invasive tests. Children with CMV-associated PLE between 2009 and 2019 in two French hospitals are retrospectively described. Clinical and biological signs, CMV identification, endoscopy and histological findings, disease management and course are analysed. CMV-associated PLE is proven in 21 immunocompetent and 22 immunosuppressed patients, with ages consistent with primo-infection and reactivation, respectively. The digestive symptoms prevail in immunocompetent children, mainly with vomiting (85.7% versus 50%, CI [1.2; 39.2], p = 0.02). Immunocompetent patients show more oedema (61.9% versus 4.5%, CI [3.6; 1502.4], p < 0.001), linked to more severe hypoalbuminemia (21.2 g/L [17.6-25.7] versus 29.6 g/L [24.9-33.9], p = 0.01). A severe course is observed in 23.8% of the immunocompetent patients and 54.5% of the immunosuppressed ones (p = 0.06). Evidence of CMV infection based on non-invasive methods is found on 88.9% of immunocompetent and 95.5% of immunosuppressed patients (p = 0.58), while endoscopy was performed on 95.2% and 100% of them, respectively (p = 0.48), without any therapeutic change. Thus, CMV-associated PLE should be suspected in children with generalised oedema. Not as benign as previously described, it can be confirmed using non-invasive tests.

The clinical evidence for postbiotics as microbial therapeutics.

An optimally operating microbiome supports protective, metabolic, and immune functions, but disruptions produce metabolites and toxins which can be involved in many conditions. Probiotics have the potential to manage these. However, their use in vulnerable people is linked to possible safety concerns and maintaining their viability is difficult. Interest in postbiotics is therefore increasing. Postbiotics contain inactivated microbial cells or cell components, thus are more stable and exert similar health benefits to probiotics. To review the evidence for the clinical benefits of postbiotics in highly prevalent conditions and consider future potential areas of benefit. There is growing evidence revealing the diverse clinical benefits of postbiotics in many prevalent conditions. Postbiotics could offer a novel therapeutic approach and may be a safer alternative to probiotics. Establishing interaction mechanisms between postbiotics and commensal microorganisms will improve the understanding of potential clinical benefits and may lead to targeted postbiotic therapy.

Interplay Between Exercise and Gut Microbiome in the Context of Human Health and Performance.

Gut microbiota and exercise have recently been shown to be interconnected. Both moderate and intense exercise are typically part of the training regimen of endurance athletes, but they exert different effects on health. Moderate exercise has positive effects on the health of average athletes, such as a reduction in inflammation and intestinal permeability and an improvement in body composition. It also induces positive changes in the gut microbiota composition and in the microbial metabolites produced in the gastrointestinal tract. Conversely, intense exercise can increase gastrointestinal epithelial wall permeability and diminish gut mucus thickness, potentially enabling pathogens to enter the bloodstream. This, in turn, may contribute to the increase in inflammation levels. However, elite athletes seem to have a higher gut microbial diversity, shifted toward bacterial species involved in amino acid biosynthesis and carbohydrate/fiber metabolism, consequently producing key metabolites such as short-chain fatty acids. Moreover, rodent studies have highlighted a bidirectional relationship, with exercise impacting the gut microbiota composition while the microbiota may influence performance. The present review focuses on gut microbiota and endurance sports and how this interconnection depends upon exercise intensity and training. After pointing out the limits of the studies so far available, we suggest that taking into account the microbiota composition and its metabolic contribution to human host health could help in monitoring and modulating athletes' health and performance. Such an integrated approach should help in the design of microbiome-based solutions for health or performance.

Functional abdominal pain disorders and patient- and parent-reported outcomes in children with inflammatory bowel disease in remission.

BACKGROUND: Chronic abdominal pain occurs frequently in pediatric patients with inflammatory bowel disease (IBD) in remission. AIMS: To assess the prevalence and factors associated with Functional Abdominal Pain Disorders among IBD children in remission (IBD-FAPD). METHODS: Patients with IBD for > 1 year, in clinical remission for ≥ 3 months were recruited from a National IBD network. IBD-FAPDs were assessed using the Rome III questionnaire criteria. Patient- or parent- reported outcomes were assessed. RESULTS: Among 102 included patients, 57 (56%) were boys, mean age (DS) was 15.0 (± 2.0) years and 75 (74%) had Crohn's disease. Twenty-two patients (22%) had at least one Functional Gastrointestinal Disorder among which 17 had at least one IBD-FAPD. Past severity of disease or treatments received and level of remission were not significantly associated with IBD-FAPD. Patients with IBD-FAPD reported more fatigue (peds-FACIT-F: 35.9 ± 9.8 vs. 43.0 ± 6.9, p = 0.01) and a lower HR-QoL (IMPACT III: 76.5 ± 9.6 vs. 81.6 ± 9.2, p = 0.04) than patients without FAPD, and their parents had higher levels of State and Trait anxiety than the other parents. CONCLUSIONS: Prevalence of IBD-FAPD was 17%. IBD-FAPD was not associated with past severity of disease, but with fatigue and lower HR-QoL.

[An acidosis not so basic]. / Une acidose pas si basique.

We present the case of a four-year-old girl, who was hospitalized in intensive care unit for a coma resulting from metabolic acidosis with increased anion gap. The patient was treated for short bowel syndrome, following necrotising enterocolitis, which occurred 51 days after birth. In our initial evaluation of the patient's metabolic acidosis, we were unable to identify the cause of the increased anion gap. Urinary organic acids chromatography identified a large peak of lactate (quantified at 15 mmol/mol of creatiniuria), as well as its metabolites. The discrepancy between normal blood lactate concentration assayed by enzymatic assay, and the large amount of lactate found by gas-chromatography/mass spectrometry (GC/MS) in urine highlights the limit of the stereospecificity of enzymatic assays. Indeed, most lactates assay use enzymatic assays that are specific for L-lactate, whereas organic acids chromatography, whose column is mostly achiral, can detect both stereoisomers, D- and L-lactate. Organic acids in urine analysis, in addition to the clinical context, suggested a diagnosis of D-lactic acidosis. Following a review of the physiopathology and treatment of short bowel syndrome, we will discuss the mechanism and diagnosis of the D-lactic acidosis in our patient. This case highlights the need to perform an organic acid profile in urine in the presence of any unexplained increased anion gap to determine its cause.

Urgent endoscopy in children: epidemiology in a large region of France.

Background and study aims The real burden of urgent endoscopy in children has not been studied yet. Our aim was to evaluate the need for urgent endoscopy in children. Patients and methods Information was collected about all the calls that were received during the 24 hour on-call shift for pediatric endoscopy in the region of Ile-de-France (12.1 million inhabitants) during a 6 months period (February-July 2017). Results A total of 237 calls (19 calls/y/100,000 children) were collected regarding children of an average age of 3.2 years (range 2 days-18 years). Most of the calls (68 %) were for foreign body ingestions. Gastroscopy was required in 32 % of children: 24 % of those calling for foreign body ingestion, 48 % for gastrointestinal bleeding, 63 % for caustic ingestions ( P  = 0.01). The average time between the call and the urgent endoscopy were below the international recommendations for each situation. Conclusions Calling the endoscopist seems to have become a recurrent practice, although in most cases, urgent endoscopy did not appear necessary, especially for foreign body ingestion. This organization of pediatric endoscopy on call was able to guarantee the performance of urgent endoscopy in adequate timing for a highly populated region.

Gut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosystem?

Most of the Human diseases affecting westernized countries are associated with dysbiosis and loss of microbial diversity in the gut microbiota. The Western way of life, with a wide use of antibiotics and other environmental triggers, may reduce the number of bacterial predators leading to a decrease in microbial diversity of the Human gut. We argue that this phenomenon is similar to the process of ecosystem impoverishment in macro ecology where human activity decreases ecological niches, the size of predator populations, and finally the biodiversity. Such pauperization is fundamental since it reverses the evolution processes, drives life backward into diminished complexity, stability, and adaptability. A simple therapeutic approach could thus be to reintroduce bacterial predators and restore a bacterial diversity of the host microbiota.

Long-Term Outcome of Laparoscopic Duhamel Procedure for Extended Hirschsprung's Disease.

BACKGROUND: The aim of our study was to report our experience in extended Hirschsprung's disease (HD) in children operated on by laparoscopy. PATIENTS AND METHODS: Retrospective data collection from a single center from 1991 to 2013 concerned extended forms of HD operated on by laparoscopic Duhamel procedure and included extension of aganglionosis, comorbidities, short and late postoperative outcome, and results of endoscopy when performed. RESULTS: Thirty patients presented an extended form of aganglionosis: 5 involving the transverse colon, 10 the right colon, and 15 the ileum (median length = 15 cm, range 1-60). Short-term outcome showed 13% postoperative complications requiring redo-surgery: occlusion (n = 2), wall abscess (n = 1), and anastomotic leak (n = 1). Median follow-up was of 5 years (range: 1-19 years). Satisfying bowel control was reached in 53%, and 46% had a weight-for-age reference curve up to -1 SD. They had four stools per day on average, 13% of soiling, 6% of constipation, and 26% of recurrent abdominal distention. Late enterocolitis occurred in 22% (n = 7): 6 with ileum involvement and 1 extended to the transverse colon. Endoscopy showed Crohn-like ulcerations in 100% of these cases. CONCLUSION: Laparoscopic Duhamel procedure is a safe and effective surgical technique in the management of extended forms of HD, with a low postoperative morbidity, but the frequent occurrence of late enterocolitis associated with Crohn-like ulcerations impairs the late outcome. Link between HD and Crohn disease still requires to be investigated.

Use of Procalcitonin Assays to Predict Serious Bacterial Infection in Young Febrile Infants.

IMPORTANCE: The procalcitonin (PCT) assay is an accurate screening test for identifying invasive bacterial infection (IBI); however, data on the PCT assay in very young infants are insufficient. OBJECTIVE: To assess the diagnostic characteristics of the PCT assay for detecting serious bacterial infection (SBI) and IBI in febrile infants aged 7 to 91 days. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study that included infants aged 7 to 91 days admitted for fever to 15 French pediatric emergency departments was conducted for a period of 30 months (October 1, 2008, through March 31, 2011). The data management and analysis were performed from October 1, 2011, through October 31, 2014. MAIN OUTCOMES AND MEASURES: The diagnostic characteristics of the PCT assay, C-reactive protein (CRP) concentration, white blood cell (WBC) count, and absolute neutrophil cell (ANC) count for detecting SBI and IBI were described and compared for the overall population and subgroups of infants according to the age and the duration of fever. Laboratory test cutoff values were calculated based on receiver operating characteristic (ROC) curve analysis. The SBIs were defined as a pathogenic bacteria in positive culture of blood, cerebrospinal fluid, urine, or stool samples, including bacteremia and bacterial meningitis classified as IBIs. RESULTS: Among the 2047 infants included, 139 (6.8%) were diagnosed as having an SBI and 21 (1.0%) as having an IBI (11.0% and 1.7% of those with blood culture (n = 1258), respectively). The PCT assay offered an area under the curve (AUC) of ROC curve similar to that for CRP concentration for the detection of SBI (AUC, 0.81; 95% CI, 0.75-0.86; vs AUC, 0.80; 95% CI, 0.75-0.85; P = .70). The AUC ROC curve for the detection of IBI for the PCT assay was significantly higher than that for the CRP concentration (AUC, 0.91; 95% CI, 0.83-0.99; vs AUC, 0.77; 95% CI, 0.65-0.89; P = .002). Using a cutoff value of 0.3 ng/mL for PCT and 20 mg/L for CRP, negative likelihood ratios were 0.3 (95% CI, 0.2-0.5) for identifying SBI and 0.1 (95% CI, 0.03-0.4) and 0.3 (95% CI, 0.2-0.7) for identifying IBI, respectively. Similar results were obtained for the subgroup of infants younger than 1 month and for those with fever lasting less than 6 hours. CONCLUSIONS AND RELEVANCE: The PCT assay has better diagnostic accuracy than CRP measurement for detecting IBI; the 2 tests perform similarly for identifying SBI in febrile infants aged 7 to 91 days.