Long-term follow-up for pediatric intestinal pseudo-obstruction patients in China.

BACKGROUND: Pediatric intestinal pseudo-obstruction (PIPO) is a heterogeneous and severe group of disorders with a high mortality rate. Patients with PIPO often develop malnutrition and need long-term nutrition support. This study aimed to determine the nutrition status, particularly micronutrients, during the long-term follow-up of patients with PIPO. METHODS: Fifty-eight patients with PIPO were followed up for at least 6 months between January 2008 and December 2020 in our hospital. PIPO was diagnosed based on the European society for pediatric gastroenterology, hepatology, and nutrition consensus. Data on clinical characteristics, medical and surgical management, nutrition support, serum vitamins, and mineral concentrations were collected. The patients were divided into the early-onset PIPO (EO-PIPO; neonatal-onset) and late-onset PIPO (LO-PIPO; infant- or child-onset) groups. RESULTS: The mean follow-up was 29.5 months (6-153 months). The overall survival rate was 63.8% (37 out of 58 participants) (EO-PIPO, 48.6% [17 out of 35 participants]; LO-PIPO, 87.0% [20 out of 23 participants]). Mortality in the EO-PIPO group was higher than in the LO-PIPO group (P = 0.002). Twenty-one patients died, of which 18 (85.7%) patients had EO-PIPO and 14 (66.7%) patients died under 1 year of age. Infection was the major cause of death. Severe malnutrition was observed at baseline and during follow-up in 25 (43.1%) and 6 (16.2%) patients, respectively. At baseline and during follow-up, the zinc deficiency rates were 29.6% and 26.3%, and those of vitamin D were 26.9% and 52.6%, respectively. CONCLUSIONS: Zinc and vitamin D deficiencies are common in patients with PIPO during follow-up. Therefore, additional supplements should be recommended.

Micronutrient deficiencies in pediatric short bowel syndrome: a 10-year review from an intestinal rehabilitation center in China.

PURPOSE: Vitamins and trace elements are essential nutrients for growth and intestinal adaptation in children with short bowel syndrome (SBS). This study aimed to assess micronutrients' status during and after weaning off PN in pediatric SBS. METHODS: This retrospective study evaluated the follow-up of 31 children with SBS between Jan 2010 and Sep 2019. Clinical data were reviewed from the patients' electric medical record. Serum electrolytes, trace elements, vitamin B12, vitamin D, and folate concentrations were collected before and after enteral autonomy. RESULTS: Thirty-one SBS cases were reviewed (median onset age 11 days after birth, 51.6% boys, mean PN duration 4 months, and mean residual small intestine length 58.2 cm). Median duration of follow-up was 10 months (interquartile range [IQR]: 4, 19). The common micronutrient deficiencies were zinc (51.6%), copper (38.7%), vitamin D (32.3%), and phosphorus (25.8%) after the transition to EN. The proportion of patients deficient in vitamin D decreased dramatically from 93.5% to 32.3% (P < 0.001), and serum concentrations of vitamin D increased significantly (27.4 ± 12.3 vs. 60.3 ± 32.9 nmol/l, P = 0.03) after achieving full enteral feeding more than 1 month. Additionally, serum magnesium levels significantly increased (0.76 ± 0.17 vs. 0.88 ± 0.14 mmol/l, P = 0.03). Hemoglobin levels elevated significantly after weaning off PN (104.3 ± 10.7 vs. 117.8 ± 13.7 g/l, P = 0.03). CONCLUSIONS: Micronutrient deficiencies remain a common problem in pediatric SBS through intestinal rehabilitation. Therefore, we strongly recommend supplementation of more vitamin D and trace elements (zinc, copper, and phosphorus) under regular monitoring during long-term intestinal rehabilitation.

Effect of a fish oil-based lipid emulsion on intestinal failure-associated liver disease in children.

BACKGROUND/OBJECTIVES: The aim of this study was to assess the effects of a fish oil-based lipid emulsion on intestinal failure-associated liver disease (IFALD) in children. SUBJECTS/METHODS: From January 2014 through June 2017, we enrolled 32 children with IF on long-term parenteral nutrition (PN). When the levels of any three of seven liver indicators (TBA, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, gamma glutamyl transferase (γ-GT), total bilirubin (TB), or direct bilirubin (DB)) were two times higher than normal levels, we switched a 50:50 mix of soybean oil and medium-chain triglycerides (MCT) lipid emulsion (with an average dose of 1.30 g/kg/day) to a fish oil-based lipid emulsion (1 g/kg/day) and measured liver function in the children. Meanwhile, inflammation and oxidative stress-related markers were also measured. RESULTS: The average fish oil therapy duration was 26 ± 21 days, and the median duration of PN support was 84 days. With fish oil therapy, levels of TBA, ALT, AST, γ-GT, TB, and DB all significantly decreased. Enteral nutrition was introduced following fish oil resulting in higher energy intake (99.88 ± 31.06 kcal/kg/day) compared with before fish oil (67.90 ± 27.31 kcal/kg/day, P = 0.001). No significant difference was found in average PN energy (P = 0.147). In addition, levels of inflammatory indicators like tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and white blood cell (WBC) significantly decreased. CONCLUSIONS: Fish oil therapy alleviates IFALD in children.

Choline Protects Against Intestinal Failure-Associated Liver Disease in Parenteral Nutrition-Fed Immature Rats.

BACKGROUND: Deficiency of choline, a required nutrient, is related to intestinal failure-associated liver disease (IFALD). Therefore, we aimed to investigate the effects of choline supplementation on IFALD and the underlying mechanisms. METHODS: Male Sprague-Dawley rats (4 weeks old) were fed AIN-93G chow and administered intravenous 0.9% saline (control), parenteral nutrition (PN), or PN plus intravenous choline (600 mg/kg) for 7 days. We evaluated body weight, hepatic histology, biochemical indicators, triglycerides, oxidative status, methylation levels of peroxisomal proliferator-activated receptor alpha (PPARα) gene promoter, expression of PPARα and carnitine palmitoyltransferase 1 (CPT1), and levels of choline metabolites. RESULTS: The PN + choline group exhibited improved body weight compared with the PN group. PN impaired hepatic function, increased hepatic triglycerides, induced dyslipidemia, enhanced reactive oxygen species and malondialdehyde, and reduced total antioxidant capacity. The PN group had higher pathologic scores than the control group. These results were prevented by choline administration. Compared with the control group, PN increased PPARα promoter methylation and hepatic betaine concentration, reduced hepatic choline and phosphatidylcholine (PC) levels, decreased plasma choline and betaine concentrations, and downregulated PPARα and CPT1 mRNA and protein expression. Choline supplementation elevated hepatic choline and PC levels and enhanced plasma choline, betaine, and PC concentrations but reduced hepatic betaine level, reversed PPARα promoter hypermethylation, and upregulated PPARα and CPT1 mRNA and protein expression in PN-fed rats, compared with rats receiving PN alone. CONCLUSION: Choline addition to PN may prevent IFALD by reducing oxidative stress, enhancing hepatic fat export, and promoting fatty acid catabolism in immature rats receiving PN.

Soybean Oil-Based Lipid Emulsion Increases Intestinal Permeability of Lipopolysaccharide in Caco-2 Cells by Downregulation of P-Glycoprotein via ERK-FOXO 3a Pathway.

BACKGROUND AND AIMS: Elevated intestinal permeability of lipopolysaccharide (LPS) is a major complication for patients with parenteral nutrition (PN), but the pathogenesis is poorly understood. Intestinal P-glycoprotein (P-gp) is one of the efflux transporters that contribute to restricting the permeability of lipopolysaccharide via transcellular route. P-gp expression may be regulated by PN ingredients, and thus this study sought to investigate the effect of PN on the expression of P-gp and to elucidate the underlying mechanism in vitro. METHODS: Caco-2 cells were treated with PN ingredients. Changes in P-gp expression and function were determined and the role of ERK-FOXO 3a pathway was studied. Transport studies of FITC-lipopolysaccharide (FITC-LPS) across Caco-2 cell monolayers were also performed. RESULTS: Among PN ingredients, soybean oil-based lipid emulsion (SOLE) exhibited significant inhibitory effect on P-gp expression and function. This regulation was mediated via activation of ERK pathway with subsequent nuclear exclusion of FOXO 3a. Importantly, P-gp participated in antagonizing the permeation of FITC-LPS (apical to basolateral) across Caco-2 cell monolayers. SOLE significantly increased the permeability of FITC-LPS (apical to basolateral), which was associated with impaired P-gp function. CONCLUSIONS: The expression and function of intestinal P-gp is suppressed by SOLE in vitro.