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: Nutritional deficiency soon after birth is a risk factor of chronic lung disease (bronchopulmonary dysplasia, BPD). Afflicted infants are further prone to inadequate growth during hospitalization (extrauterine growth restriction, EUGR). This multi-center retrospective study investigated risk factors of EUGR, specifically in very preterm infants with BPD. Method: Data of infants with BPD who were born less than 32 weeks gestation (n = 1010) were collected from 7 regions of China. All infants were non-small for gestational age at birth. Infants were characterized as EUGR or non-EUGR at 36 weeks gestation or discharge, or stratified by gestational age or birthweight. Logistic regression analysis was applied. Results: In 65.5% of the population, the BPD was mild. Infants with severe BPD (8.3%) had the highest rate of EUGR (72.6%, P < 0.001). Groups stratified by gestational age did not differ in rates of EUGR, but the birthweight of the EUGR group was significantly lower than that of the non-EUGR (P < 0.001). Birthweights of < 1000, 1000–1499, and ≥ 1500 g showed EUGR rates of 65.9%, 43.4%, and 23.8%, respectively (P < 0.001). Overall, the independent risk factors of EUGR were: moderate-to-severe BPD, gestational hypertension, cesarean section, cumulative fasting time, time required to achieve 110 kcal/kg/d, and hemodynamically significant patent ductus arteriosus (hsPDA). Conclusion: In very preterm infants with BPD, the lower the birthweight or the more severe the BPD, the greater the risk of EUGR. In those with hsPDA, or moderate-to-severe BPD, it is especially important to prevent EUGR through perinatal management, enteral nutrition, and nutritional strategies.

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 AND PURPOSE: Neonatal hypocalcemia is the most common metabolic disorder, and whether asymptomatic disease should be treated with calcium supplements remains controversial. We aimed to quantify neonatal hypocalcemia’s global CBF and cerebral metabolic rate of oxygen (CMRO₂) using physiologic MR imaging and elucidate the pathophysiologic vulnerabilities of neonatal hypocalcemia. MATERIALS AND METHODS: A total of 37 consecutive patients with neonatal hypocalcemia were enrolled. They were further divided into subgroups with and without structural MR imaging abnormalities, denoted as neonatal hypocalcemia-a (n = 24) and neonatal hypocalcemia-n (n = 13). Nineteen healthy neonates were enrolled as a control group. Brain physiologic parameters determined using phase-contrast MR imaging, T2-relaxation-under-spin-tagging MR imaging, and brain volume were compared between patients with neonatal hypocalcemia (their subgroups) and controls. Predictors for neonatal hypocalcemia–related brain injuries were identified using multivariate logistic regression analysis and expressed as ORs with 95% CIs. RESULTS: Patients with neonatal hypocalcemia showed significantly lower CBF and CMRO₂ compared with controls. Furthermore, the neonatal hypocalcemia-a subset (versus controls or neonatal hypocalcemia-n) had significantly lower CBF and CMRO₂. There was no obvious difference in CBF and CMRO₂ between the neonatal hypocalcemia-n subset and controls. CBF and CMRO₂ were independently associated with neonatal hypocalcemia. The ORs were 0.80 (95% CI, 0.65–0.99) and 0.97 (95% CI, 0.89–1.05) for CBF and CMRO₂, respectively. CONCLUSIONS: Neonatal hypocalcemia with structural damage may exhibit lower hemodynamics and cerebral metabolism. CBF may be useful in assessing the need for calcium supplementation in asymptomatic neonatal hypocalcemia to prevent brain injury.