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Background It is proposed that the development of parenteral nutrition-associated cholestasis (PNAC) was significantly associated with preterm birth, low birth weight, infection, etc.; however, the etiology and pathogenesis of PNAC are not fully understood. Most of the studies examining PNAC-associated risk factors were single-center studies with relatively small sample sizes. Objective To analyze the risk factors associated with PNAC in preterm infants in China. Methods This is a retrospective multicenter observational study. Clinical data on the effect of multiple oil-fat emulsions (soybean oil-medium chain triglycerides-olive oil-fish oil, SMOF) in preterm infants were collected from a prospective multicenter randomized controlled study. A secondary analysis was performed in which preterm infants were divided into the PNAC group and the non-PNAC group based on the PNAC status. Results A total of 465 cases very preterm infants or very low birth weight infants were included in the study in which 81 cases were assigned to the PNAC group and 384 cases were assigned to the non-PNAC group. The PNAC group had a lower mean gestational age, lower mean birth weight, longer duration of invasive and non-invasive mechanical ventilation, a longer duration oxygen support, and longer hospital stay (P < 0.001 for all). The PNAC group had higher respiratory distress syndrome, hemodynamically significant patent ductus arteriosus, necrotizing enterocolitis (NEC) with stage II or higher, surgically treated NEC, late-onset sepsis, metabolic bone disease, and extrauterine growth retardation (EUGR) compared to the non-PNAC group (P < 0.05 for all). In contrast with the non-PNAC group, the PNAC group received a higher maximum dose of amino acids and fat emulsion, more medium/long-chain fatty emulsion, less SMOF, had a longer duration of parenteral nutrition, lower rates of breastfeeding, higher incidence of feeding intolerance (FI), more accumulated days to achieve total enteral nutrition, less accumulated days of total calories up to standard 110 kcal/kg/day and slower velocity of weight growth (P < 0.05 for all). Logistic regression analysis indicated that the maximum dose of amino acids (OR, 5.352; 95% CI, 2.355 to 12.161), EUGR (OR, 2.396; 95% CI, 1.255 to 4.572), FI (OR, 2.581; 95% CI, 1.395 to 4.775), surgically treated NEC (OR, 11.300; 95% CI, 2.127 ~ 60.035), and longer total hospital stay (OR, 1.030; 95% CI, 1.014 to 1.046) were independent risk factors for the development of PNAC. SMOF (OR, 0.358; 95% CI, 0.193 to 0.663) and breastfeeding (OR, 0.297; 95% CI, 0.157 to 0.559) were protective factors for PNAC. Conclusions PNAC can be reduced by optimizing the management of enteral and parenteral nutrition and reducing gastrointestinal comorbidities in preterm infants.

Objective This study compared the clinical effects of two different lipid emulsions in premature infants with gestational age < 32 weeks (VPI) or birth weight < 1500 g (VLBWI) to provide an evidence-based medicine basis for optimizing intravenous lipid emulsion. Methods This was a prospective multicenter randomized controlled study. A total of 465 VPIs or VLBWIs, admitted to the neonatal intensive care unit of five tertiary hospitals in China from March 1, 2021 to December 31, 2021, were recruited. All subjects were randomly allocated into two groups, namely, medium-chain triglycerides/long-chain triglycerides (MCT/LCT) group (n = 231) and soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) group (n = 234). Clinical features, biochemical indexes, nutrition support therapy, and complications were analyzed and compared between the two groups. Results No significant differences were found in perinatal data, hospitalization, parenteral and enteral nutrition support between the two groups (P > 0.05). Compared with the MCT/LCT group, the incidence of neonates with a peak value of total bilirubin (TB) > 5 mg/dL (84/231 [36.4% vs. 60/234 [25.6%]), a peak value of direct bilirubin (DB) ≥ 2 mg/dL (26/231 [11.3% vs. 14/234 [6.0%]), a peak value of alkaline phosphatase (ALP) > 900 IU/L (17/231 [7.4% vs. 7/234 [3.0%]), and a peak value of triglycerides (TG) > 3.4 mmol/L (13/231 [5.6% vs. 4/234[1.7%]]) were lower in the SMOF group (P < 0.05). Univariate analysis showed that in the subgroup analysis of < 28 weeks, the incidence of parenteral nutrition-associated cholestasis (PNAC) and metabolic bone disease of prematurity (MBDP) were lower in the SMOF group (P = 0.043 and 0.029, respectively), whereas no significant differences were present in the incidence of PNAC and MBDP between the two groups at > 28 weeks group (P = 0.177 and 0.991, respectively). Multivariate logistic regression analysis revealed that the incidence of PNAC (aRR: 0.38, 95% confidence interval [CI]: 0.20–0.70, P = 0.002) and MBDP (aRR: 0.12, 95% CI: 0.19–0.81, P = 0.029) in the SMOF group were lower than that in the MCT/LCT group. In addition, no significant differences were recorded in the incidence of patent ductus arteriosus, feeding intolerance, necrotizing enterocolitis (Bell’s stage ≥ 2), late-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity and extrauterine growth retardation between the two groups (P > 0.05). Conclusions The application of mixed oil emulsion in VPI or VLBWI can reduce the risk of plasma TB > 5 mg/dL, DB ≥ 2 mg/dL, ALP > 900 IU/L, and TG > 3.4 mmol/L during hospitalization. SMOF has better lipid tolerance, reduces the incidence of PNAC and MBDP, and exerts more benefits in preterm infants with gestational age < 28 weeks.

Background: In recent years, a lot of research has been conducted on the risk factors and prevention measures associated with parenteral nutrition-associated cholestasis (PNAC). It is proposed that the development of PNAC was significantly associated with preterm birth, low birth weight, infection, long duration of fasting, necrotizing enterocolitis (NEC), extrauterine growth retardation (EUGR) and nutritional factors, including the use of amino acids and fat emulsion; however, the etiology and pathogenesis of PNAC are not fully understood. Most of the studies examining PNAC-associated risk factors were single-center studies with relatively small sample sizes. Objective: To analyze the risk factors associated with PNAC in preterm infants in China. Methods: This is a retrospective multicenter observational study. Clinical data on the effect of multiple oil-fat emulsions (soybean oil-medium chain triglycerides-olive oil-fish oil, SMOF) in preterm infants were collected from a prospective multicenter randomized controlled study. The study was conducted at five tertiary care hospitals with a neonatal intensive care unit (NICU) of IIIB or higher in China between January 2021 and December 2021. A secondary analysis was performed in which preterm infants were divided into the PNAC group and the non-PNAC group based on the PNAC status. Risk factors for the development of PNAC in preterm infants were analyzed using the χ2 test (or Fisher's exact probability method), Student’s t-test or rank sum test, and logistic regression analysis. Results: A total of 465 very preterm infant (VPI) or very low birth weight infant (VLBWI) cases were included in the study in which 81 (17.4%) were assigned to the PNAC group and 384 (82.6%) were assigned to the non-PNAC group. Compared with the non-PNAC group, the PNAC group had a lower mean gestational age, lower mean birth weight, longer duration of invasive and non-invasive mechanical ventilation, a longer duration oxygen support, and longer hospital stay (P < 0.001 for all). The PNAC group had higher respiratory distress syndrome (RDS), hemodynamically significant patent ductus arteriosus (hsPDA), NEC with stage II or higher or surgically treated NEC, late-onset sepsis (LOS), metabolic bone disease (MBD), and extrauterine growth retardation (EUGR) compared to the non-PNAC group (P < 0.05 for all). In contrast with the non-PNAC group, the PNAC group received a higher maximum dose of amino acids and fat emulsion, more medium/long-chain fatty emulsion, less SMOF, had a longer duration of parenteral nutrition, lower rates of breastfeeding, higher incidence of feeding intolerance (FI), more accumulated days to achieve total enteral nutrition, less accumulated days of total calories up to standard 110 kcal/kg/day, and slower velocity of weight growth (P < 0.05 for all). Logistic regression analysis indicated that the maximum dose of amino acids (OR, 5.352; 95% CI, 2.355 to 12.161), EUGR (OR, 2.396; 95% CI, 1.255 to 4.572), FI (OR, 2.581; 95% CI, 1.395 to 4.775), surgically treated NEC (OR, 11.300; 95% CI, 2.127~60.035), and longer total hospital stay (OR, 1.030; 95% CI, 1.014 to 1.046) were independent risk factors for the development of PNAC. SMOF (OR, 0.358; 95% CI, 0.193 to 0.663) and breastfeeding (OR, 0.297; 95% CI, 0.157 to 0.559) were protective factors for PNAC. Conclusions: Increasing breastfeeding rates in VPI or VLBWI can reduce the incidence of PNAC by promoting feeding tolerance using fat emulsion (SOMF), avoiding excessive parenteral amino acid intake, preventing the development of severe NEC requiring surgery, and reducing the incidence of EUGR.