High hydrostatic pressure is similar to Holder pasteurization in preserving donor milk antimicrobial activity.

BACKGROUND: The microbiological safety of donor milk (DM) is commonly ensured by Holder pasteurization (HoP, 62.5 °C for 30 min) in human milk banks despite its detrimental effects on bioactive factors. We compared the antimicrobial properties of DM after Holder pasteurization treatment or High Hydrostatic Pressure processing (HHP, 350 MPa at 38 °C), a non-thermal substitute for DM sterilization. METHODS: We assessed lactoferrin and lysozyme concentrations in raw, HHP- and HoP-treated pools of DM (n = 8). The impact of both treatments was evaluated on the growth of Escherichia coli and Group B Streptococcus in comparison with control media (n = 4). We also addressed the effect of storage of HHP treated DM over a 6-month period (n = 15). RESULTS: HHP milk demonstrated similar concentrations of lactoferrin compared with raw milk, while it was significantly decreased by HoP. Lysozyme concentrations remained stable regardless of the condition. Although a bacteriostatic effect was observed against Escherichia coli at early timepoints, a sharp bactericidal effect was observed against Group B Streptococcus. Unlike HoP, these results were significant for HHP compared to controls. Stored DM was well and safely preserved by HHP. CONCLUSION: Our study demonstrates that this alternative sterilization method shows promise for use with DM in human milk banks. IMPACT: Antimicrobial activity of donor milk after High Hydrostatic Pressure treatment has not been clearly evaluated. Donor milk lactoferrin is better preserved by High Hydrostatic Pressure than conventional Holder pasteurization, while lysozyme concentration is not affected by either treatment. As with Holder pasteurization, High Hydrostatic Pressure preserves donor milk bacteriostatic activity against E. coli in addition to bactericidal activity against Group B Streptococcus. Donor milk treated by High Hydrostatic Pressure can be stored safely for 6 months.

Short-chain fatty acids levels in human milk are not affected by holder pasteurization and high hydrostatic pressure processing.

Sterilized donor milk (DM) is frequently used for feeding preterm infants. To date, the effect of different modes of DM sterilization on short-chain fatty acids (SCFAs) remains unknown. We aimed to quantify SCFAs in DM samples after two types of milk sterilization: the Holder pasteurization (HoP) and a high hydrostatic pressure (HP) processing. Eight pooled DM samples were sterilized by HoP (62.5°C for 30 min) or processed by HP (350 MPa at 38°C). Raw DM was used as control. Six SCFAs were quantified by gas chromatography/mass spectrometry. Compared to raw milk, both HoP and HP treatment did not significantly modulate the concentration of acetate, butyrate, propionate and isovalerate in DM. Valerate and isobutyrate were undetectable in DM samples. In conclusion, both HoP and HP processing preserved milk SCFAs at their initial levels in raw human milk.

The Sterilization of Human Milk by Holder Pasteurization or by High Hydrostatic Pressure Processing Leads to Differential Intestinal Effects in Mice.

BACKGROUND: Human milk banks (HMBs) provide sterilized donor milk (DM) for the feeding of preterm infants. Most HMBs use the standard method of Holder pasteurization (HoP) performed by heating DM at 62.5 °C for 30 min. High hydrostatic pressure (HHP) processing has been proposed as an alternative to HoP. This study aims to evaluate intestinal barrier integrity and microbiota composition in adult mice subjected to a chronic oral administration of HoP- or HHP-DM. METHODS: Mice were treated by daily gavages with HoP- or HHP-DM over seven days. Intestinal barrier integrity was assessed through in vivo 4 kDa FITC-dextran permeability assay and mRNA expression of several tight junctions and mucins in ileum and colon. Cecal short chain fatty acids (SCFAs) and microbiota were analyzed. RESULTS: HHP-DM mice displayed decreased intestinal permeability to FITC-dextran and increased ileal mRNA expression levels of two tight junctions (Ocln and Cdh1) and Muc2. In the colon, mRNA expression levels of two tight junctions (Cdh1 and Tjp1) and of two mucins (Muc2 and Muc4) were decreased in HHP-DM mice. Cecal SCFAs and microbiota were not different between groups. CONCLUSIONS: HHP processing of DM reinforces intestinal barrier integrity in vivo without affecting gut microbiota and SCFAs production. This study reinforces previous findings showing that DM sterilization through HHP might be beneficial for the intestinal maturation of preterm infants compared with the use of HoP for the treatment of DM.

Prebiotic Supplementation during Lactation Affects Microbial Colonization in Postnatal-Growth-Restricted Mice.

BACKGROUND: An inadequate perinatal nutritional environment can alter the maturation of the intestinal barrier and promote long-term pathologies such as metabolic syndrome or chronic intestinal diseases. The intestinal microbiota seems to play a determining role in the development of the intestinal barrier. In the present study, we investigated the impact of consuming an early postnatal prebiotic fiber (PF) on growth, intestinal morphology and the microbiota at weaning in postnatal-growth-restricted mice (PNGR). METHODS: Large litters (15 pups/mother) were generated from FVB/NRj mice to induce PNGR at postnatal day 4 (PN4) and compared to control litters (CTRL, 8 pups/mother). PF (a resistant dextrin) or water was orally administered once daily to the pups from PN8 to PN20 (3.5 g/kg/day). Intestinal morphology was evaluated at weaning (PN21) using the ileum and colon. Microbial colonization and short-chain fatty acid (SCFA) production were investigated using fecal and cecal contents. RESULTS: At weaning, the PNGR mice showed decreased body weight and ileal crypt depth compared to the CTRL. The PNGR microbiota was associated with decreased proportions of the Lachnospiraceae and Oscillospiraceae families and the presence of the Akkermansia family and Enterococcus genus compared to the CTRL pups. The propionate concentrations were also increased with PNGR. While PF supplementation did not impact intestinal morphology in the PNGR pups, the proportions of the Bacteroides and Parabacteroides genera were enriched, but the proportion of the Proteobacteria phylum was reduced. In the CTRL pups, the Akkermansia genus (Verrucomicrobiota phylum) was present in the PF-supplemented CTRL pups compared to the water-supplemented ones. CONCLUSIONS: PNGR alters intestinal crypt maturation in the ileum at weaning and gut microbiota colonization. Our data support the notion that PF supplementation might improve gut microbiota establishment during the early postnatal period.

The metabolome of human milk is altered differentially by Holder pasteurization and high hydrostatic pressure processing.

The milk metabolome is composed of hundreds of molecules that can impact infant development. In preterm infants, sterilized donor milk (DM) is frequently used for their feeding. We aimed to identify differences in the metabolome of DM after two types of milk sterilization: the Holder pasteurization (HoP) and a high hydrostatic pressure (HP) processing. DM samples were sterilized by HoP (62.5°C for 30 min) or processed by HP (350 MPa at 38°C). 595 milk metabolites were analyzed using an untargeted metabolomic analysis. Both treatments differentially altered several classes of compounds. The major changes noted included decreased levels of free fatty acids, phospholipid metabolites, and sphingomyelins. Decreases were more strongly noted in HP samples rather than in HoP ones. Both HoP and HP treatments increased the levels of ceramides and nucleotide compounds. The sterilization of human milk altered its metabolome especially for lipids.

Efficacy and tolerance of enteral nutrition in children with biliary atresia awaiting liver transplantation.

Objectives: Malnutrition is common in children with biliary atresia (BA) awaiting liver transplantation (LT). Few studies have evaluated the effectiveness of enteral nutrition (EN) in these patients. The objective of this work was to assess the efficacy and tolerance of EN in children with BA awaiting LT. Methods: A total of 31 patients with BA followed between 1995 and 2018 were retrospectively included. Anthropometric indicators (weight, length, and head circumference) and adverse effects of EN were noted at the start (T0) and the end (T1) of EN. The z-scores for anthropometric indicators were compared between T0 and T1. Results: The median age at T0 was 7 months (interquartile range [IQR] 5-9), and the median duration of EN was 9 months (IQR 3-17). The z-scores for anthropometric variables improved from T0 to T1: -1.6 (IQR -2.5 to -1.0) to -0.5 (IQR -1.8 to 0.3) for median weight for age; -1.3 (IQR -2.4 to 0) to -0.4 (IQR -2.0 to 0.7) for length for age; -0.9 (IQR -2.3 to -0.3) to -0.3 (IQR -1.2 to 0.1) for weight for length; and -1.2 (IQR -2.1 to -0.6) to -0.2 (IQR -1.6 to 0.4) for body mass index (p < 0.05 for all comparisons). Nearly all (94%) of the patients had a weight-for-length z-score > -2 at the end of EN; 23% had adverse effects and 10% had complications leading to the cessation of EN. Conclusion: EN is effective and well tolerated in infants with BA awaiting LT.

Comparison of Endoscopic Dilatation and Heller's Myotomy for Treating Esophageal Achalasia in Children: A Multicenter Study.

OBJECTIVE: To compare the efficacy of, and complications from, the 2 main treatments for achalasia: endoscopic dilatation and surgical cardiomyotomy (Heller's myotomy). STUDY DESIGN: We retrospectively collected data on children treated for achalasia over an 11-year period from 8 tertiary pediatric centers. A line of treatment was defined as performing either Heller's myotomy or 1-3 sessions of endoscopy dilatation over 3 months. Treatment success was a priori defined as clinical improvement and no need for new treatment. RESULTS: Ninety-seven children (median age, 12 years; 57% boys) were included. The median time to diagnosis was 10.5 months, and the median follow-up period was 27 months. Thirty-seven children were treated by Heller's myotomy and 60 by endoscopy dilatation as the first-line treatment. After adjustment for potentially confounding factors, Heller's myotomy was significantly more successful than endoscopy dilatation (hazard ratio, 3.93 [1.74; 8.88]; P = .001), with a median survival without failure of 49 and 7 months, respectively, and with no significant difference in the occurrence of complications (35.2% for Heller's myotomy, 29.7% for endoscopy dilatation, P = .56). Hydrostatic dilatation was as successful as pneumatic dilatation (hazard ratio, 1.35 [0.56; 3.23]; P = .50). CONCLUSIONS: Heller's myotomy is more successful than endoscopy dilatation, with no significant difference in the occurrence of serious complications. This raises the potential role of peroral endoscopic myotomy as an alternative treatment to Heller's myotomy.

Noninvasive Pediatric Liver Fibrosis Measurement: Two-Dimensional Shear Wave Elastography Compared With Transient Elastography.

Objectives: Although transient elastography (TE) is the primary noninvasive method for assessing liver fibrosis, its use remains to be validated in children. This study aims to evaluate the agreement between two-dimensional ultrasound shear wave elastography (2D-SWE) and TE to assess pediatric liver stiffness method. Methods: During the 18-month study, we prospectively included 101 consecutive children (median age: 8.5 years, range: 1 month to 17 years) who required TE for medical reasons, and in whom 2D-SWE measurement was performed within a 3-month follow-up during a routine ultrasound. Liver elasticity values were classified according to the Metavir score using published pediatric norms for TE and according to the manufacturer's reference values for 2D-SWE. The Spearman's correlation coefficient was used to assess the relationship between the elasticity measured by the two techniques. Concordance was described by the Bland-Altman method. Results: A strong correlation (rho = 0.70, p < 0.001) was found between 2D-SWE and TE for the elasticity measures. The strength of correlation was higher among patients older than 6 years (rho = 0.79, p < 0.001). Concordance between liver fibrosis stages assessed by these techniques was moderate [weighted kappa = 0.46, (95% CI: 0.35-0.57)]. When considering stages over F2, 2D-SWE diagnostic performances showed a sensitivity of 85% (95% CI: 74-92) and a specificity of 57% (95% CI: 42-70) compared with TE. Conclusion: Measurements of the liver stiffness using 2D-SWE and TE are strongly correlated. The moderate concordance between these techniques for assessing the liver fibrosis stage provides evidence against alternating between these methods during follow-up of patients with the chronic liver diseases.

Use of Hypnosis in Paediatric Gastrointestinal Endoscopy: A Pilot Study.

Objectives: Experience of hypnosis in gastrointestinal (GI) endoscopy is scarce in children. Our aims were to assess the rate of successful GI endoscopy performed using hypnosis alone or in combination with midazolam, with or without additional equimolar mixture of oxygen and nitrous oxide (EMONO), and to identify predictive factors of successful endoscopy in children. Methods: This prospective single-centre study included children older than 6 years requiring a diagnostic esophagogastroduodenoscopy (EGD) or rectosigmoidoscopy. Ericksonian hypnosis was performed alone or in combination with midazolam, with or without additional EMONO. Successful endoscopy was defined by a complete and well-tolerated procedure. Levels of satisfaction of the endoscopist, nurse, and patient were assessed. Results: One hundred forty children [70 boys, median age: 12 years (Q1-Q3: 9-14)] were included over a 14-month period. They underwent EGD in 51.4% (n = 72) and rectosigmoidoscopy in 48.6% (n = 68) of cases. EMONO and midazolam were combined with hypnosis in 136 cases (97.1%). Successful endoscopy rate reached 82.9%. The procedure was interrupted due to poor tolerance and was rescheduled under general anaesthesia in 11 patients (7.9%). Predictive factors for successful endoscopy were older age (13 vs. 8 years, OR: 1.34, CI 95% [1.10-1.62], p = 0.003) and type of endoscopy (EGD vs. rectosigmoidoscopy, OR: 16.34 [2.14-124.68], p = 0.007). A good cooperation of the patient was reported by the endoscopist and the nurse in 88.4 and 86.9% of cases, respectively. Ninety-two per cent of patients mentioned that the procedure went well. Conclusions: Our study suggests that hypnosis combined with EMONO and/or midazolam is of additional value to perform diagnostic EGD or rectosigmoidoscopy in children older than 6 years without systematic need for general anaesthesia.

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.

How good is quality-of-life for children receiving home parenteral nutrition? - A pilot study.

BACKGROUND & AIMS: Children on home parenteral nutrition and their parents not only engage with complex nutritional issues but also have to manage difficult social and financial problems with social and clinical support that may not always meet their needs. Baxter's HPN-QOL questionnaire, assesses the QOL of adult patients treated with HPN, and has been developed rigorously using standard guidelines, measuring various dimensions of QOL. Our aim was to use this tool to explore how HPN influences the QOL of paediatric patients. METHODS: The HPN-QOL questionnaire was modified to suit a paediatric HPN population. Data on demographics, aetiology of intestinal failure and duration of HPN were collected from a departmental database. Quality-of-Life grading of functional and symptom scales, HPN specific items and overall QOL Numerical Rating Scales were determined. RESULTS: Fourteen out of 17 families returned the completed questionnaires. QOL was significantly impaired by increased dependency regarding items of daily living such as eating, dressing, washing, and mobility, but was not affected in the domains of school attendance, general fatigue, pain and body image. There were no significant differences in QOL when patients with and without enterostomy were compared. Patients felt well supported by the hospital nutrition team in managing logistics related to HPN. CONCLUSIONS: QOL in HPN patients was not significantly affected by the medical aspects of care. This descriptive study highlights the need for further integration of medical and social care in order to support families of children receiving HPN as QOL was impaired in relation to activities of daily living and social functioning.