Incidence Of Parenteral Nutrition-associated Cholestasis Research Articles

Comparison of Two Lipid Emulsions on the Incidence of Parenteral Nutrition Associated Cholestasis in Neonates.

Lipid emulsion contributes to parenteral nutrition associated cholestasis (PNAC). For decades, soybean oil-based intravenous lipid emulsion (SO-ILE) was the predominant product. Recently, a multicomponent lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil and fish oil (SMOF-ILE) has been used off-label in neonatal care. This study evaluates the incidence of PNAC in neonates who received SMOF-ILE or SO-ILE. This was a retrospective review of neonates who received SMOF-ILE or SO-ILE for at least 14 days. Patients receiving SMOF-ILE were matched based on gestational age (GA) and birth weight to a historical cohort receiving SO-ILE. The primary outcomes were the incidences of PNAC among all patients and patients without intestinal failure. The secondary outcomes were clinical outcomes and incidence of PNAC stratified by GA. Clinical outcomes included liver function tests, growth parameters, and development of retinopathy of prematurity and intraventricular hemorrhage. Forty-three neonates who received SMOF-ILE were matched to 43 neonates who received SOILE. There were no significant differences in baseline characteristics. The incidence of PNAC in the total population was 12% in the SMOF-ILE cohort and 23% in the SO-ILE cohort (p = 0.26). The lipid dosage of SMOF-ILE was significantly higher at time of peak direct serum bilirubin concentration compared with SO-ILE cohort (p = 0.05). Clinically significant differences were noted in laboratory endpoints in several subgroups. There was no significant difference in the incidence of PNAC among neonates in a SMOFILE cohort compared with a historical SO-ILE cohort.

Clinical effect of multi-oil fat emulsion for parenteral nutrition support in extremely low birth weight infants

OBJECTIVE To study the clinical effect of multi-oil fat emulsion for parenteral nutrition support in extremely low birth weight (ELBW) infants. METHODS A retrospective analysis was performed for 49 ELBW infants who were admitted from January 1, 2018 to July 30, 2020, with an age of ≤14 days on admission and a duration of parenteral nutrition of > 14 days. According to the type of lipid emulsion received, the ELBW infants were divided into two groups: soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) (n=26) and medium-chain triglycerides/long-chain triglycerides (MCT/LCT) (n=23). The two groups were compared in terms of clinical features, complications, nutrition support therapy, and outcome. RESULTS The 49 ELBW infants had a mean birth weight of (892±83) g and a mean gestational age of (28.2±2.3) weeks. There was no significant difference between the two groups in the incidence rates of hemodynamically significant patent ductus arteriosus, intraventricular hemorrhage, neonatal necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia (BPD), grade Ⅲ BPD, sepsis, and pneumonia (P > 0.05). There was also no significant difference in the duration of parenteral nutrition, the age of total enteral nutrition, and head circumference/body length/body weight at discharge between the two groups (P > 0.05). Of all the infants, 22 (45%) had parenteral nutrition-associated cholestasis (PNAC), with 13 (50%) in the SMOF group and 9 (39%) in the MCT/LCT group but there was no significant difference in the incidence of PNAC between the two groups (P > 0.05); however, the infants with PNAC in the SMOF group had significantly lower peak values of direct bilirubin and alanine aminotransferase than those in the MCT/LCT group (P < 0.05). CONCLUSIONS The application of multi-oil fat emulsion in ELBW infants does not reduce the incidence rate of complications, but compared with MCT/LCT emulsion, SMOF can reduce the severity of PNAC in ELBW infants.

Parenteral nutrition associated cholestasis

Parenteral nutrition (PN) is life saving for many preterm infants and other neonates with severe illness, but prolonged use of PN can lead to intrahepatic cholestasis, referred to as parenteral nutrition–associated cholestasis (PNAC). It is defined as direct bilirubin greater than 2.0 mg/dL persistent for at least 2 consecutive tests duringthe administration of PN, not associated with other known causes of cholestasis [1-3]. With the increasing survival of preterm infants and neonates requiring intensive care, PNAC has become a more common clinical challenge. The incidence of PNAC varywidely depending on the population studied, with high incidencein populations carrying several risk factors for PNAC. It increases with duration of PN and ranges from 10% to 85% in infants [4-8]. A multifactorial aetiology has been proposed for the development of PNAC. Recognized risk factors for PNAC include low birth weight, low gestational age, necrotizing enterocolitis, intestinal malformations, and intestinal surgery. A further risk factor is the occurrence ofsevere infections, due to the requirement for central line for infusion of PN, and bacterial overgrowth caused by enteralstarvation and immature immune function[9-13]. However, exposure to PN is demonstratedas the main factor in the development of PNAC. Intravenous hyper-alimentationhas been implicated, such as thetotal caloric overload, the quality of aminoacid solutions, the cumulative amount and the quality of lipid infusion, the presence of excessivealuminium in the PN solution, and the high manganese intake with PN [1,14-17]. Ursodeoxycholic acid, cyclic PN, light protection for PN, tapering the soybean-based lipid emulsion, and antibiotics to decontaminate bacterial overgrowth are used to treat PNAC [18-21]. In recent years, increasing attention has been paid to the lipid content in PN. It has been found that fish oil–containing lipid emulsions could be useful in infants to reverse PNAC for whom enteral feeding is intolerable. However, no evidence supports the use of fish oil–containing lipid emulsions to prevent PNAC in neonates, including preterm infants [22]. Enteral feeding remains the best strategy to reverse and prevent PNAC, with as little as 10% of caloric intake showing beneficial effects [5,22].

PP282-SUN POOR NUTRITION AND SOCIOECONOMIC STATUS – MAIN RISK FACTORS FOR EARLY DEATHS IN YOUNG CYSTIC FIBROSIS PATIENTS

Methods: Clinical data of 523 preterm infants who had received PN for more than 7 days were reviewed. Among them, 250 cases were preterm infants without any complications (group 1). Two hundred and seventy-three cases were preterminfants with complications (including asphyxia, septicemia, pneumonia, hyaline membrane disease, and necrotizing enterocolitis) (group 2). The incidence of parenteral nutrition-associated cholestasis (PNAC) between these two groups was compared and risk factors of PNAC were analyzed. Results: Total incidence of PNAC in preterm infants was 8.8%. The incidence of PNAC in group 1 and that in group 2 were 4.4% and 12.8%, respectively. The average gestational age and birth weight of PNAC group were less and lower than those of the non-PNAC group. The time to start enteric feeding was delayed, and daily weight gain was less in the PNAC group. Average PN duration was longer, calorie intake was higher in the PNAC group. Age of starting oral nutrition and birth weight regain time were earlier in the preterm infants without complications. Conclusion: The incidence of PNAC was associated with lower gestational age, lower birth weight, longer duration of PN, higher calorie intake, later enteric feeding, and complications of prematurity.

Randomized Controlled Trial of Early Parenteral Nutrition Cycling to Prevent Cholestasis in Very Low Birth Weight Infants

To compare the incidence of cholestasis in very low birth weight infants receiving cycled versus continuous parenteral nutrition, and to determine factors that predispose to parenteral nutrition-associated cholestasis (PNAC). Preterm infants weighing ≤ 1250 g (n = 70) at birth were randomly assigned within the first 5 postnatal days to either cycle (n = 34) or continuous (n = 36) parenteral nutrition. Liver function tests were obtained at baseline, and sequentially thereafter. Cholestasis was defined as direct bilirubin >2 mg/dL. Infants with major congenital anomalies, congenital hepatic disease, clinically apparent congenital viral infection, and those who required major abdominal surgery were excluded. The incidence of PNAC was similar in the 2 groups (cycle 32% vs continuous 31%; P = 1.0). Bilirubin and transaminases were similar in both groups by repeated measures of ANOVA. Gestational age, birth weight, and Apgar scores were significantly lower, and Clinical Risk Index for Babies II scores were significantly higher in infants who developed PNAC. Using backward selection logistic regression, bronchopulmonary dysplasia, duration of parenteral nutrition, and days to full enteral nutrition emerged as factors independently associated with PNAC. Early prophylactic parenteral nutrition cycling in very low birth weight infants in this study did not reduce cholestasis. Time to full feedings is a significant predictor for PNAC in very low birth weight infants. Preterm infants with bronchopulmonary dysplasia are more likely to have PNAC as a comorbidity. The Clinical Risk Index for Babies II score may help identify those preterm infants who might benefit from future prospective prevention trials.

Efficacy of Intermediate-Dose Oral Erythromycin on Very Low Birth Weight Infants With Feeding Intolerance

Erythromycin is generally used as a prokinetic agent for the treatment of feeding intolerance in preterm infants; however, results from previous studies significantly vary due to different medication dosages, routes of administration, and therapy durations. The effectiveness and safety of intermediate-dose oral erythromycin in very low birth weight (VLBW) infants with feeding intolerance was examined in this study. Between November 2007 and August 2009, 45 VLBW infants with feeding intolerance, who were all at least 14 days old, were randomly allocated to a treatment group and administered 5mg/kg oral erythromycin every 6hours for 14 days (n=19). Another set of randomly selected infants was allocated to the control group, which was not administered erythromycin (n=26). The number of days required to achieve full enteral feeding (36.5±7.4 vs. 54.7±23.3 days, respectively; p=0.01), the duration of parenteral nutrition (p<0.05), and the time required to achieve a body weight ≥2500g (p<0.05) were significantly shorter in the erythromycin group compared with the control group. The incidence of parenteral nutrition-associated cholestasis (PNAC) and necrotizing enterocolitis (NEC) ≥ stage II after 14 days of treatment were significantly lower (p<0.05) in the erythromycin group. No significant differences were observed in terms of the incidences of sepsis, bronchopulmonary dysplasia, or retinopathy of prematurity. No adverse effects were associated with erythromycin treatment. Intermediate-dose oral erythromycin is effective and safe for the treatment of feeding intolerance in VLBW infants. The incidences of PNAC and ≥ stage II NEC were significant lower in the erythromycin group.

Antibiotics for the newborn

Because of the high susceptibility to infections, antibiotics are the most widely used drugs in newborns. The result of antibiotic use, however, may be strongly influenced by the peculiar physiology of the neonate, characterized by the delicate process of adaptation from intra- to extra-uterine life. Additional important factors that may affect antibiotic therapy are gestational age, birth weight, the intrauterine growth restriction, chronological age and, especially, the kidney and liver function immaturity. Dosing, timing and route of administration must, therefore, take in careful consideration the neonatal variability of bioavailability, distribution, metabolism, biotransformation, and excretion. The fine adjustment of dosing and duration of therapy should be based on pharmacokinetic and pharmacodynamic parameters. In spite of significant variations of sepsis etiology, the best initial empiric therapy of a suspected systemic infection still remains, as several years ago, the association of ampicillin and gentamicin. Other very effective and useful antibiotics, as cephalosporins, carbanepems or glycopeptides should be administered judiciously to infants, following the recommendations of a restricted use, to obtain maximal efficacy and minimal toxicity. Finally, because of their peculiar features, macrolide antibiotics have recently been proposed for different indications than the antibacterial activity. Use of oral erythromycin for the treatment of gastrointestinal dysmotility in preterm infants could reduce the incidence of parenteral nutrition-associated cholestasis by almost 50%, while azithromycin because of the combined antibiotic and anti-inflammatory effects, has been successfully used in a pilot study in the extremely low birth weight infant for the prevention of bronchopulmonary dysplasia.

High-Dose Oral Erythromycin Decreased the Incidence of Parenteral Nutrition-Associated Cholestasis in Preterm Infants

High-Dose Oral Erythromycin Decreased the Incidence of Parenteral Nutrition-Associated Cholestasis in Preterm Infants

High-Dose Oral Erythromycin Decreased the Incidence of Parenteral Nutrition-Associated Cholestasis in Preterm Infants

Background & Aims: Feeding intolerance because of functional gastrointestinal dysmotility and parenteral nutrition-associated cholestasis (PNAC) are common problems in preterm, very-low-birth-weight (VLBW) infants. This double-blind, randomized, placebo-controlled study aimed to assess the effectiveness of “high-dose” oral erythromycin as a prokinetic agent in decreasing the incidence of PNAC. Two secondary end points, including the time to achieve full enteral feeding and the duration of parenteral nutrition, were also evaluated. Methods: Infants consecutively admitted to the neonatal unit were randomized to receive erythromycin (12.5 mg/kg/dose every 6 hours for 14 days) or an equivalent volume of normal saline (placebo) if they attained less than half the total daily fluid intake (<75 mL/kg/day) as milk feeds on day 14 of life. Results: Of 182 VLBW infants enrolled, 91 received erythromycin. The incidence of PNAC was significantly lower in erythromycin-treated infants (18/91) compared with placebo infants (37/91; P = .003). Treated infants achieved full enteral nutrition significantly earlier (mean, 10.1; SE, 1.7 days; P < .001), and the duration of parenteral nutrition was also significantly decreased by 10 days (P < .001). Importantly, fewer infants receiving erythromycin had 2 or more episodes of septicemia (n = 4) compared with placebo patients (n = 13, P = .03). No serious adverse effect was associated with erythromycin treatment. Conclusions: High-dose oral erythromycin can be considered as a rescue measure for VLBW infants who fail to establish adequate enteral nutrition and in whom anatomically obstructive pathologies of the gastrointestinal tract have been excluded.

Comparison of total parenteral nutrition-associated cholestasis according to amino acid mixtures in very low birth weight infants

Purpose:The purpose of this study was to evaluate the effect of amino acid mixtures on incidence and severity of total parenteral nutrition associated-cholestasis(PNAC) in very low birth weight infants. Methods:Retrospective review of 63 very low birth weight infants(birth weight ≤1,500 g) who received total parenteral nutrition(TPN) in our neonatal intensive care unit from January 2000 to December 2004 was performed. Patients were divided into 2 groups:Group I(n=32, Jan 2000-Jun 2002) and Group II(n=31, Jul 2002-Dec 2004), where infants in Group II received taurine and glutamic acid-rich amino acid mixtures. PNAC was defined as serum direct bilirubin(DB) level greater than 2.0 mg/dL. The incidence and severity of PNAC were compared between these groups. Results:The incidence of PNAC was significantly lower in Group II than in Group I(21.9% vs 6.5%, P

Parenteral nutrition-associated cholestasis in neonates: the role of aluminum.

Parenteral nutrition (PN) is an essential component in the care of premature and ill infants. The incidence of parenteral nutrition-associated cholestasis (PNAC) ranges from 7.4 to 84%. One substance in PN solutions that has been implicated in PNAC is aluminum. Aluminum loading in animals and humans causes hepatic accumulation and damage. The degree of aluminum contamination of PN solutions has decreased over time, but contamination still significantly exceeds levels that are safe for human neonates. Further study into the relationship between aluminum contamination in neonatal PN solutions and the development of PNAC is necessary.

Hyperalimentation‐Associated Neonatal Cholestasis: Effect of Oral Gentamicin

The effect of oral gentamicin on the incidence of parenteral nutrition-associated cholestasis in preterm infants less than 1500 g birth weight was assessed retrospectively. Of 24 patients on parenteral nutrition for more than 10 days, 12 infants who received oral gentamicin (group I) for prophylaxis against neonatal necrotizing enterocolitis were compared to 12 infants who did not (group II). Both mean and peak direct bilirubin levels were significantly higher in group II. The increase in both mean and peak direct bilirubin levels after initiation of total parenteral nutrition (TPN) was significant in group II only. The incidence of cholestasis was significantly higher in group II than in group I. These results suggest that oral gentamicin may have a protective effect against parenteral nutrition-associated cholestasis in the newborn preterm infant.