Search

Parenteral nutrition (PN) is recognized as a complex high-risk therapy. Its practice is highly variable and frequently suboptimal in pediatric patients. Optimizing care requires evidence, consensus-based guidelines, audits of practice, and standardized strategies. Several pediatric scientific organizations, expert panels, and authorities have recently recommended that standardized PN should generally be used over individualized PN in the majority of pediatric patients including very low birth weight premature infants. In addition, PN admixtures produced and validated by a suitably qualified institution are recommended over locally produced PN. Licensed multi chamber bags are standardized PN bags that comply with Good Manufacturing Practice and high-quality standards for the finished product in the frame of their full manufacturing license. The purpose of this article is to review the practical aspects of PN and the evidence for using such multi-chamber bags in pediatric patients. It highlights the safety characteristics and the limitations of the different PN practices and provides some guidance for ensuring safe and efficient therapy in pediatric patients., Competing Interests: Conflict of Interest VC, MD, NH, JR, MSDP, ST, FV, DW, and CvdA have received honoraria from Baxter Healthcare Corporation for symposium participation or scientific education activity. HA has received honoraria from Baxter Healthcare Corporation and Fresenius Kabi for symposium participation or scientific education activity. MP has received honoraria from Baxter Healthcare Corporation, Fresenius Kabi, and B. Braun for symposium participation or education scientific activity. MD, VC and MT have received investigator-initiated research grants from the Baxter Healthcare Corporation (money paid to their institutions). TS is an employee of Baxter Healthcare Corporation. PL and LO have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Previous research shows that a lung ultrasound score (LUS) can anticipate CPAP failure in neonatal respiratory distress syndrome., Research Question: Can LUS also predict the need for surfactant replacement?, Study Design and Methods: Multicenter, pragmatic study of preterm neonates who underwent lung ultrasound at birth and those given surfactant by masked physicians, who also were scanned within 24 h from administration. Clinical data and respiratory support variables were recorded. Accuracy of LUS, oxygen saturation to Fio 2 ratio, Fio 2 , and Silverman score for surfactant administration were evaluated using receiver operating characteristic curves. The simultaneous prognostic values of LUS and oxygen saturation to Fio 2 ratio for surfactant administration, adjusting for gestational age (GA), were analyzed through a logistic regression model., Results: Two hundred forty infants were enrolled. One hundred eight received at least one dose of surfactant. LUS predicted the first surfactant administration with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, 0.81-0.91), cut off of 9, sensitivity of 0.79 (95% CI, 0.70-0.86), specificity of 0.83 (95% CI, 0.76-0.89), positive predictive value of 0.79 (95% CI, 0.71-0.87), negative predictive value of 0.82 (95% CI, 0.75-0.89), positive likelihood ratio of 4.65 (95% CI, 3.14-6.89), and negative likelihood ratio of 0.26 (95% CI, 0.18-0.37). No significant difference was shown among different GA groups: 25 to 27 weeks' GA (AUC, 0.91; 95% CI, 0.84-0.99), 28 to 30 weeks' GA (AUC, 0.81; 95% CI, 0.72-0.91), and 31 to 33 weeks' GA (AUC, 0.88; 95% CI, 0.79-0.95), respectively. LUS declined significantly within 24 h in infants receiving one surfactant dose. When comparing Fio 2 , oxygen saturation to Fio 2 ratio, LUS, and Silverman scores as criteria for surfactant administration, only the latter showed a significantly poorer performance. The combination of oxygen saturation to Fio 2 ratio and LUS showed the highest predictive power, with an AUC of 0.93 (95% CI, 0.89-0.97), regardless of the GA interval., Interpretation: LUS is a reliable criterion to administer the first surfactant dose regardless of GA. Its association with oxygen saturation to Fio 2 ratio significantly improves the prediction power for surfactant need., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: To study the association of hypertriglyceridemia and of lipid tolerance with clinical and nutritional data in preterm infants receiving routine parenteral nutrition., Design: We retrospectively studied 672 preterm infants (gestational age <32 weeks) with birth weight <1250 g, consecutively admitted to our NICU, born between 2004 and 2018. Selected prenatal data and interventions, parenteral intakes and diseases were considered. Hypertriglyceridemia was defined as plasma triglycerides >250 mg⋅dL -1 . Lipid tolerance was defined as the ratio of plasma triglycerides to the intravenous lipid intake at the time of sampling. Variables associated to hypertriglyceridemia and to lipid tolerance were identified by multiple logistic and linear regression analyses., Results: Hypertriglyceridemia occurred in 200 preterm infants (30%), ranging from 67% at 23 weeks to 16% at 31 weeks' gestation. In 138 infants (69%) hypertriglyceridemia occurred at a lipid intake of 2.5 g⋅kg -1 or less. Lipid tolerance was reduced especially in infants of less than 28 weeks' gestation (14.3 ± 9.3 vs 18.8 ± 10.2, respectively, p < 0.001). Lipid tolerance was negatively associated with respiratory distress syndrome (OR = -1.14, p = 0.011), patent ductus arteriosus (OR = -1.73, p < 0.001), small for gestational age (OR = -2.96, p < 0.001), intraventricular haemorrhage (OR = -3.96, p < 0.001), late onset sepsis (OR = -8.56, p = 0.039)., Conclusion: Preterm infants on routine parenteral nutrition were able to tolerate markedly lower intravenous lipid intakes than the recommended target values of current guidelines. Lipid tolerance was associated with some of the major complication of prematurity, possibly at risk of developing hypertriglyceridemia., Competing Interests: Conflict of interest The authors report no conflicts of interest. No conflicts of interest to declare. This study was partially supported by an unrestricted grant from Baxter International Corporation., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Preterm infants are at increased risk of long-term neurodevelopmental disabilities (NDD). Long chain n-3 fatty acids play a key role during the development of the central nervous system and some studies in preterm infants showed benefits of docosahexaenoic acid and arachidonic acid supplementation for visual and cognitive development. In recent years fish oil has been added to the fat blend of intravenous (IV) lipid emulsions (LE) but to date scanty data are available on neurodevelopmental outcome of preterm infants that received fish oil containing LE. We studied the effect of fish oil containing IV LE vs standard IV LE on neurodevelopment in a large cohort of preterm infants who received routine parenteral nutrition (PN) from birth., Methods: We retrospectively reviewed the neurodevelopmental outcome of 477 preterm infants (birth weight (BW): 400-1249 g and gestational age (GA) at birth: 24 +0 - 35 +6 weeks (W)) admitted to our NICU between Oct-2008 and June-2017, who received routine PN with different LE, with and without fish oil (IV-FO vs CNTR). We compared neurodevelopment at 2 years corrected age by the Bayley III development scale and the incidence of NDD., Results: Demographics, birth data and the incidence of the main clinical short-term outcomes of prematurity were similar in the two groups (IV-FO: n = 178, GA 197 ± 14 days, BW 931 ± 182 g; CNTR: n = 192, GA 198 ± 15 days, BW 944 ± 194 g). No differences were found in maternal demographics nor in parental education between the two groups. Cognitive score was not significantly different between IV-FO and CNTR (92 ± 15 vs 93 ± 13, p = 0.5). No differences were found in motor and language scores, and in the incidence of NDD in the two groups., Conclusions: Contrary to our hypothesis, the use of fish oil containing LE in a large cohort of preterm infants on routine PN did not result in better neurodevelopment. Large randomized controlled trials powered for neurodevelopment are needed to clarify the impact of the widely used fish oil containing LE on neurodevelopment of preterm infants., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Few studies evaluated the efficacy of pharmacological therapy for gastro-esophageal reflux disease (GERD) in newborns, whose safety has been questioned. Esophageal basal impedance (BI) is a marker of mucosal integrity, and treatment with proton pump inhibitors significantly increases BI in infants; however, no correlation with clinical improvement was reported., Aims: To evaluate the relationship between BI and other esophageal pH-impedance parameters and clinical response to therapy in newborns with GERD., Study Design: Multicenter retrospective study., Subjects: Infants who received omeprazole or ranitidine for GERD., Outcome Measures: Complete response to therapy was defined as symptom decrease by ≥50% compared to baseline, partial response as symptom decrease <50%, no response as no symptom decrease based on chart analysis. Response to therapy was assessed 2 and 4 weeks after the onset of therapy. Univariate and multivariate statistics were performed to assess associations between response to therapy and clinical/pH-impedance parameters., Results: We studied 60 infants (51 born preterm): 47 received omeprazole, 13 ranitidine. Response to therapy was associated with decreasing esophageal clearance time: odds ratio 0.308, 95%CI 0.126-0.753, p = 0.010 at 2 weeks, odds ratio 0.461, 95%CI 0.223-0.955, p = 0.037 at 4 weeks., Conclusions: Clinical response to therapy among infants with GERD was associated with esophageal clearance but not with esophageal BI level., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Blood urea is considered a marker of amino acid utilization in preterm infants on routine parenteral nutrition. However, the association between blood urea and intravenous amino acid intake remains debated., Aims: To evaluate the association between blood urea and both nutrition and clinical data, in a large cohort of preterm infants., Methods: Consecutively admitted preterm infants with a gestational age of less than 32 weeks and a birth weight lower than 1250 g on routine parenteral nutrition from the first hour of life were studied. Clinical and nutrition data collected hourly during the hospitalization were used in multiple linear regression analysis., Results: We studied 674 patients and 1863 blood urea determinations. Blood urea concentration was positively associated with blood creatinine concentration, intravenous amino acid intake, patent ductus arteriosus and respiratory distress syndrome, and negatively associated with intravenous non-protein energy intakes, daily weight change, gestational age, being small for gestational age, antenatal steroids therapy and reverse flow in the umbilical artery (p < 0.001; R = 0.7)., Conclusions: From a nutrition perspective, in our large cohort of small preterm infants blood urea was positively correlated with intravenous amino acid intake and negatively correlated with intravenous non-protein energy intake. This is in line with current knowledge in human physiology and suggest that a reduction of intravenous amino acid intake based on blood urea concentrations was justified., Competing Interests: Conflicts of interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Long chain n-3 fatty acids (n-3 LCPUFA) play a pivotal role during central nervous system development and the provision of docosahexaenoic acid (DHA) is recommended for the preterm infant. However, there are concerns that oral fish oil, which is a good source of DHA, may adversely affect growth of preterm infants, as it decreases arachidonic acid (ARA). It has been about ten years since fish oil was added to the fat blend of intravenous (IV) lipid emulsions (LE) but information on growth and other clinical outcomes of preterm infants is still scarce. We studied the effect of fish oil containing IV LE vs standard IV LE on growth in a large cohort of preterm infants who received routine parenteral nutrition (PN)., Methods: We retrospectively reviewed growth data of 546 preterm infants with a birth weight (BW) < 1250 g consecutively admitted to our NICU between Oct-2008 and Jun-2017 who received PN starting from the first day of life. Individual patients received only one of 5 commercially available IV LE. For the purpose of this study we grouped the patients who received the fish oil containing LE (IV-FO) and those who received conventional LE (CNTR). We compared PN and enteral nutrition (EN) intakes, and growth from birth to 36 +0 weeks post-menstrual age (W PMA)., Results: Demographics, birth data and the incidence of the main complications of prematurity were similar between the two groups (IV-FO: n = 240, Gestational age (GA) 197 ± 16 d, BW 942 ± 181 g; CNTR: n = 237, GA 199 ± 17 d, BW 960 ± 197 g). No difference was found in PN and EN energy and macronutrient intakes from birth to 36 +0 W PMA, as well as in the proportion of human milk to infant milk formula. Weight gain from the regained BW to 36 +0 W PMA was slightly but significantly higher in IV-FO group: 17.3 ± 2.8 and 16.8 ± 2.7 g∙kg -1 ∙d -1 , IV-FO and CNTR respectively (p = 0.03). There was no difference in length gain and head growth nor in body size at 36 +0 W PMA between the two groups., Conclusions: The use of IV fish oil did not negatively affect weight gain in a cohort of preterm infants. Large randomized controlled trials are needed to assess the effect of IV fish oil on the complication of prematurity and on selected domains of infant development., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The association between cardiorespiratory events (CRE) and gastro-esophageal reflux (GER) among neonates is still controversial., Aims: To test such an association in preterm and term infants., Study Design: Prospective observational study., Subjects: Forty-seven infants with suspected GER and recurrent CRE admitted at a neonatal intensive care unit, who underwent simultaneous and synchronized 24-hour recording of heart rate (HR), peripheral oxygen saturation (SpO2) and pH-impedance monitoring (MII-pH). HR/SpO2 data were filtered to avoid artefactual episodes of hypoxia and hypoperfusion., Outcome Measures: The main outcome measure was the symptom association probability (SAP), with a 2-minute time window. Infants with positive (>95%) and negative (≤95%) SAP index tests were compared by univariate and multivariate statistics., Results: Median gestational age at birth was 29 4/7 weeks, median age at study 36 days. We recorded 3341 GER events and 4936 CRE (4710 desaturations, 226 bradycardias); 609/4936 (12%) CRE were temporally associated with GER episodes: 338 preceded and 271 followed GER events. The SAP index was significant in 5/47 (11%) patients. The SAP index including only CRE following GER events was significant in 3/47 (6%). There was no significant difference in the number of acid, weakly acid, non-acid, pH-only events preceding or following CRE between infants with SAP-positive and SAP-negative tests. Infants with positive SAP-index tests compared to those with SAP-negative tests had lower weight gain in the three days preceding the test and tended to have lower birth weight., Conclusions: GER and CRE were associated in <11% of patients. The evaluation of ponderal growth might be helpful in predicting such an association., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: High dietary intakes of phytosterols (Phyto), such as those consumed by vegans and vegetarians, are not recommended for cholesterol-lowering in pregnant women (PW) because the safety of their use during pregnancy has not been fully established [1]. Information on Phyto in pregnancy is very limited., Objective: To characterize the maternal-fetal gradient of free and esterified Phyto at the time of delivery in humans., Design: PW who had a term delivery at the Obstetrics and Gynecology Unit of the University Hospital of Padua (Padua, Italy), between November 2016 and March 2017, participated in the study. Fatty acids (FA), cholesterol (Chol), Chol metabolites (7-dehydrocholesterol, 7-DHChol; lathosterol, Latho; 7α-hydroxycholesterol, 7α-OHChol), and Phyto (campesterol, Camp; stigmasterol, Stigma; sitosterol, Sito) were measured in both maternal (MB) and cord blood (CB) at the time of delivery. Non-pregnant adult volunteers (Ref-NA) served as a reference., Results: Thirty-four term PW and 12 Ref-NA signed informed consent and were studied. Plasma total Phyto concentrations in CB were up to 20-fold lower than in MB (p < 0.05). Positive and significant correlations were found between total Phyto of MB-CB pairs (p < 0.01), and between total FA and Camp of MB (p < 0.05). Interestingly, free Chol to Chol ester ratio of CB did not differ from that of MB, and free Phyto to Phyto ester ratios were higher in CB than in MB (p < 0.001). No differences were found between Phyto concentrations of MB and Ref-NA. However, free Chol to Chol ester ratio, and free Phyto to Phyto ester ratios were higher in MB than in Ref-NA (p < 0.05). Chol synthesis, as indicated by 7-DHChol to 7α-OHChol, Latho to 7α-OHChol, and Latho to Sito ratios, was greatest in CB and lowest in Ref-NA., Conclusion: Our data suggest that free Phyto cross the human placenta more easily than Phyto ester. An elevated Stigma to Chol ratio in CB than in MB was also described for the first time. The impact of these findings on the neonatal outcomes remains to be elucidated., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: In total, 930 urine samples obtained on 2nd and 3rd day from birth have been analyzed for the early diagnosis of Mucopolysaccharidoses., Methods: Dimethylmethylene blue (DMB) assay and one-dimensional electrophoresis were performed in all urine samples. Agarose gel electrophoresis, before and after treatment with chondroitinase ABC and heparinases, was used for a comprehensive characterization., Results: Out of 930 urine samples 7 showed anomalous electrophoretic pattern; 5 of them had high GAG levels by DMB test. Atypical samples (n = 7) were analyzed by agarose gel electrophoresis. After enzymatic digestion, some slow bands were still visible. A second urine sample of the above 7 newborns was analyzed at the age of 1 month, demonstrating both a normal pattern and normal GAG levels. Additional urine and vaginal mucus samples from 10 term neonates with vaginal bleeding showed the same electrophoretic pattern observed in the 7 false positive samples., Conclusions: The altered electrophoretic pattern may be due to the presence of glycoproteins and not to specific GAGs, due to high levels of maternal hormones exposure during pregnancy. To our knowledge, this is the first time maternal estrogen hormones are proposed as a likely cause of false-positive urinary glycosaminoglycan screen test in healthy newborns., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Neurocognitive deficits at school starting age may affect as many as 50% of children who underwent cardiac surgery for complex congenital heart disease (CHD). The aim of this study was to identify which phases of cardiopulmonary bypass (CPB) are associated with an increased risk of impaired neurodevelopmental skills in children with complex CHD. This was assessed by means of glial fibrillary acidic protein (GFAP) plasma levels during CPB for CHD surgery, as a marker of neurologic insult. We correlated GFAP levels with clinical parameters and neurodevelopmental outcome., Methods: We studied 45 children undergoing surgery for complex CHD. We measured plasma GFAP levels by enzyme-linked immunosorbent assay at the following steps: anesthesia induction, CPB start, end of hypothermia, end of rewarming, and end of CPB. Neurologic assessment and Vineland Adaptive Behavior Scales (VABS-I) were administered to patients at least 18 months after surgery., Results: GFAP was undetectable before surgery and it peaked at the end of hypothermia or rewarming. Multiple regression analyses showed that GFAP peak level and preoperative neurologic comorbidity were significant independent predictors of neurologic impairment, as showed by VABS-I communication domain intelligence quotient (IQ). Receiver operating characteristic curve showed that the model was highly significant., Conclusions: Impaired neurodevelopment was associated with increase of GFAP plasma levels during cardiac surgery in infants. The identification of the neurologic high-risk phases of CPB run could support the application of new neuroprotective strategies for CHD repair., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Phytosterols in vegetable oil (VO)-based lipid emulsions (LE) likely contribute to parenteral nutrition-associated cholestasis (PNAC) in preterm infants. No characterization of plasma phytosterol half-lives has been done in very low birth weight (VLBW) preterm infants receiving parenteral nutrition (PN) with LE., Methods: In a prospective cohort study, 45 VLBW preterm infants who received PN underwent serial blood sample measurements of sitosterol (SITO), campesterol (CAMP), and stigmasterol (STIGM). Plasma phytosterol half-lives were calculated from the phytosterol concentrations-decay curves by using a single-compartment model., Results: After the stop of the intravenous LE, study infants had significantly lower plasma total CAMP, STIGM and SITO concentrations. The decay of plasma phytosterol concentrations was monoexponential. Half-life of plasma total CAMP, STIGM and SITO was 13.5 ± 6.9, 10.3 ± 4.5 and 10.3 ± 4.0 days, respectively. Plasma phytosterol half-lives did not correlate with gestational age, birth weight, cumulative phytosterol intakes and plasma conjugated bilirubin., Conclusion: VLBW preterm infants on PN with LE had rather long plasma phytosterol half-lives similar to hypercholesterolemic adults and phytosterolemic homozygotes patients. We speculate that the accumulation of phytosterols could contribute to their vulnerability to PNAC., Clinical Trial Registry: The Ethics Committee of Marche-Italy (DG/469); www.clinicaltrials.gov (identification number NCT02758834)., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Acute respiratory distress syndrome (ARDS) is undefined in neonates, despite the long-standing existing formal recognition of ARDS syndrome in later life. We describe the Neonatal ARDS Project: an international, collaborative, multicentre, and multidisciplinary project which aimed to produce an ARDS consensus definition for neonates that is applicable from the perinatal period. The definition was created through discussions between five expert members of the European Society for Paediatric and Neonatal Intensive Care; four experts of the European Society for Paediatric Research; two independent experts from the USA and two from Australia. This Position Paper provides the first consensus definition for neonatal ARDS (called the Montreux definition). We also provide expert consensus that mechanisms causing ARDS in adults and older children-namely complex surfactant dysfunction, lung tissue inflammation, loss of lung volume, increased shunt, and diffuse alveolar damage-are also present in several critical neonatal respiratory disorders., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background & Aims: Provision of long chain polyunsaturated fatty acids (LCP) both of the omega-3 and omega-6 families is recommended for preterm infants (PI). Fish oil (FO) contains omega-3 and omega-6 LCP and it is incorporated in the fat blend of the new generation lipid emulsions (LE). Omega-3 LCP have been shown to reduce the expression of genes involved in lipogenesis, which could be important for several organs development. The aim of this study was to ascertain if the use of intravenous FO has an effect on lipogenesis in PI., Methods: Forty PI were randomized to receive two LE: MSF (50:40:10 Medium Chain Triglycerides (MCT): Soybean oil (SO): FO) or MS (50:50 MCT:SO). We measured plasma lipids on day 7 and the fractional and absolute synthesis rates (FSR and ASR) of cholesterol and of selected fatty acids (FA) after (2)H2O body water labeling., Results: Plasma phospholipids (PL), free cholesterol (FC), and cholesterol esters (CE) concentrations were all lower in MSF than in MS. In spite of lower plasma FC and CE concentrations, cholesterol biosynthesis was similar between the two study groups (FC: FSR 16.0 ± 1.4 vs 14.1  ± 1.1%/d, p = 0.74; ASR 6.8 ± 0.6 vs 7.1 ± 0.6 mg kg(-1) d(-1), p = 0.93; CE: FSR 3.6 ± 0.5 vs 4.2 ± 0.4%/d, p = 0.38; ASR: 3.3 ± 0.4 vs 4.4 ± 0.5 mg kg(-1) d(-1), p = 0.13, in MSF and MS respectively). FSR and ASR of selected FA were, or tended to be, lower in MSF than in MS. ASR of PL palmitate (4.0 ± 0.3 vs 4.8 ± 0.4 mg kg(-1) d(-1), p = 0.045), PL oleate (0.2 ± 0.04 vs 0.4 ± 0.05 mg kg(-1) d(-1), p = 0.02) and CE oleate (0.5 ± 0.1 vs 0.9 ± 0.1 mg kg(-1) d(-1), p = 0.03) were significantly lower in MSF than in MS. There were no differences in plasma TG FA biosynthesis., Conclusions: Cholesterol biosynthesis was not affected by 10% FO during neonatal parenteral nutrition. Ten percent FO caused a statistically significant reduction in the lipogenesis of selected FA and an overall tendency towards a reduced lipogenesis. The magnitude seems to be limited and the biological significance is unknown. Our data warrant follow-up studies in PI who receive intravenous FO, especially in those infants who receive larger doses than in the present study. Since this trial started in 2007, trial registration was not required., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Univentricular congenital heart defects require open-heart surgery soon after birth, and are associated with risk of brain injury and poor neurologic outcome., Methods: This is a prospective, observational study on children undergoing cardiac surgery. Plasma glial fibrillary acidic protein (GFAP), as an early marker of brain injury, was measured by ELISA at the end of anaesthesia induction, initiation of cardiopulmonary bypass (CPB), the end of cooling, the end of rewarming, the end of CPB, and after protamine administration. We recorded clinical and surgical parameters to assess which CPB phase and clinical parameters were associated with a GFAP increase., Results: We studied 13 children less than 50 months of age: 8 underwent Norwood or Damus-Kaye-Stansel palliation (group 1) and 5 underwent Fontan procedure (group 2). A GFAP increase was only observed in group 1, with the highest median value at the end of rewarming. No quantifiable levels of GFAP were measured at pre-bypass and the start of CPB stages in all patients. End of cooling and CPB-end GFAP, GFAP maximum value, and GFAP area under the curve all correlated with the CPB time spent at a cerebral regional saturation < 45% (P = 0.021, 0.028, 0.007, 0.021, respectively)., Conclusions: Children with univentricular heart defects exhibit a CPB plasma-GFAP increase only after stage 1 palliation. The maximum GFAP increase occurred at the end of rewarming. Further studies are needed to identify which clinical or surgical parameter(s) could reflect a GFAP increase during surgery for congenital heart defects, and whether GFAP levels correlate with the neurologic outcome., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Lipid emulsions containing fish oil, as source of long chain omega 3 fatty acids, have recently became available for parenteral nutrition in infants, but scanty data exist in extremely low birth weight preterms. The objective of this study was to compare plasma fatty acids and lipid tolerance in preterm infants receiving different doses of a 15% fish oil vs. a soybean oil based lipid emulsion., Methods: Preterm infants (birth weight 500-1249 g) were randomized to receive parenteral nutrition with MOSF (30% Medium-chain triglycerides, 25% Olive oil, 30% Soybean oil, 15% Fish oil) or S (S, 100% Soybean oil) both at two levels of fat intake: 2.5 or 3.5 g kg(-1) d(-1), named 2.5Fat and 3.5Fat respectively. Plasma lipid classes and their fatty acid composition were determined on postnatal day 7 and 14 by gas chromatography together with routine biochemistry., Results: We studied 80 infants. MOSF infants had significantly higher plasma phospholipid Docosahexaenoic acid and Eicosapentaenoic and lower Arachidonic acid. Plasma phospholipids, triglycerides and free cholesterol were all significantly higher in the MOSF-3.5Fat group, while cholesterol esters were lower with MOSF than with S. The area under the curve of total bilirubin was significantly lower with MOSF than with S., Conclusions: The use of a lipid emulsion with 15% FO resulted in marked changes of plasma long-chain fatty acids. Whether the benefits of increasing Docosahexaenoic acid outweigh the potential negative effect of reduced Arachidonic acid should be further studied. MOSF patients exhibited reduced lipid tolerance at 3.5 g kg(-1) d(-1) fat intake. The trial was conducted between January 2008 and December 2012 so we had not registered it in a public trials registry as it is now required for trials that started after July 2008., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Elevated plasma phytosterol concentrations are an untoward effect of parenteral nutrition (PN) with vegetable oil-based lipid emulsions (LEs). Phytosterols are elevated in neonatal cholestasis, but the relation remains controversial., Objective: The objective was to study the effect of 5 LEs on plasma phytosterols in preterm infants., Design: One hundred forty-four consecutive admitted preterm infants (birth weight: 500-1249 g) were studied. Patients were randomly assigned to receive 1 of 5 different LEs: S [100% soybean oil (SO)], MS [50% medium-chain triglycerides (MCTs) and 50% SO], MSF (50% MCTs, 40% SO, and 10% fish oil (FO)], OS (80% olive oil and 20% SO), or MOSF (30% MCTs, 25% olive oil, 30% SO, and 15% FO). Phytosterols in the LEs and in plasma (on postnatal day 7 and day 14) were measured by gas chromatography-mass spectrometry., Results: Patients in the S group had significantly higher total phytosterol intakes than did the other study groups. On PN days 7 and 14, plasma phytosterol concentrations were highest in the S group and lowest in the MOSF group. Despite similar β-sitosterol intakes between the MS and MSF groups, plasma concentrations were significantly lower in the MSF than in the MS group. Only 3 patients (2.1%) developed cholestasis: 1 in the MS, 1 in the MSF, and 1 in the MOSF group. No cases of cholestasis were observed in the S and OS groups., Conclusions: In uncomplicated preterm infants receiving routine PN, we found a correlation between phytosterol intake and plasma phytosterol concentrations; however, cholestasis was rare and no difference in liver function at 6 wk was observed.

Our objective was to study the metabolic precursors of surfactant disaturated-phosphatidylcholine (DSPC) in preterm infants with respiratory distress syndrome (RDS) on mechanical ventilation. We performed 46 DSPC kinetic studies in 23 preterms on fat-free parenteral nutrition and mechanical ventilation (birth weight = 1167 +/- 451 g, gestational age = 28.5 +/- 2.0 weeks). Eight infants received a simultaneous intravenous infusion of U(13)C-glucose and [16,16,16](2)H-palmitate, eight infants received U(13)C-glucose and (2)H(2)O, and seven received U(13)C-palmitate and (2)H(2)O. Surfactant DSPC kinetics were calculated from the isotopic enrichments of DSPC-palmitate from sequential tracheal aspirates and its metabolic precursors in plasma or urine. DSPC fractional synthesis rate (FSR) was 17 +/- 11, 21 +/- 16, and 15 +/- 6%/day from glucose, palmitate, and body water, respectively (P = 0.36). DSPC-FSR from U(13)C-glucose and (2)H(2)O were significantly correlated and yielded similar estimates (difference of -0.1 +/- 3%) (P = 0.91). The difference in the 15 infants receiving palmitate versus (2)H(2)O or palmitate versus glucose was +6.0 +/- 12%/day (P = 0.21). There was a significant correlation between DSPC-FSRs from plasma glucose and plasma FFA. The contribution of glucose versus palmitate to DSPC-FSR was 49 +/- 20% versus 51 +/- 20%, respectively. Plasma glucose and FFA showed similar contributions to DSPC-FSR in infants with RDS and fat-free parenteral nutrition. FSRs from (2)H(2)O or glucose were highly correlated.

Background: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are long-chain polyunsaturated fatty acids (LCPs) that play pivotal roles in growth and neurodevelopment., Objective: We aimed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs., Design: Twenty-two preterm infants were randomly assigned to either the no-LCP group (fed formula without LCPs; n = 11) or the LCP group (fed formula with LCPs; n = 11). Dietary LCPs had higher (13)C content than did the endogenously synthesized LCPs, which were derived from linoleic and alpha-linolenic acids. The (13)C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1, 3, and 7 mo. Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated., Results: Percentage AA synthesis was 67.2 +/- 7.8%, 35.9 +/- 9.8%, and 29.0 +/- 10.3%, and that of DHA was 41.7 +/- 14.9%, 10.5 +/- 8.1%, and 7.4 +/- 6.2% at 1, 3, and 7 mo old, respectively. Absolute AA synthesis was 26.7 +/- 4.2, 14.4 +/- 3.9, and 11.6 +/- 4.1 mg x kg(-1) x d(-1) and that of DHA was 12.6 +/- 4.5, 3.2 +/- 2.5, and 2.3 +/- 1.9 mg x kg(-1) . d(-1) at 1, 3, and 7 mo old, respectively. AA and DHA synthesis decreased significantly (P < 0.01) with time, and AA synthesis was significantly (P < 0.01) greater than DHA synthesis., Conclusions: By this novel approach, we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods. By age 7 mo, LCP synthesis was dramatically lower in preterm infants fed LCPs.

We compared kinetic indices of pulmonary surfactant metabolism in premature infants (n = 41) with respect to i) tracer ([1-(13)C1]acetate, [U-(13)C6]glucose, and [1,2,3,4-(13)C4] palmitate), ii) phospholipid (PL) pool (total PLs or disaturated PLs), or iii) instrumentation [gas chromatography/mass spectrometry (GC/MS) or GC-combustion-isotope ratio mass spectometry (GC-C-IRMS)]. Tracer incorporation was measured in PLs extracted from serial tracheal aspirates after a 24 h tracer infusion. The fractional catabolic rate (FCR), representing the total fractional turnover from all sources of surfactant production, was independent of tracer. The fractional synthesis rate of surfactant PL from plasma palmitate was significantly higher than that from palmitate synthesized de novo from acetate, and these two sources of palmitate together accounted for only half of the total surfactant production in preterm infants. [U-(13)C6]glucose showed significant recycling of the (13)C label in intermediary metabolism, distinguishable by GC-MS but not by GC-C-IRMS, resulting in a slower apparent FCR when GC-C-IRMS was used. The extracted PL pool did not affect the surfactant metabolic indices. We suggest that FCR should be used as a primary measure of surfactant turnover kinetics and that tracers labeling both de novo synthesis (acetate and glucose) and preformed pathways (plasma palmitate) can be used to partition the fractional contribution of each pathway to total production.

The importance of long-chain polyunsaturated fatty acids (LCPs) in the development of preterm infants is now well accepted but the source of dietary LCPs to be added to infant formulas remains controversial. We measured dietary intakes, fecal output, and percentages of intestinal absorption of n-6 and n-3 LCPs in healthy preterm infants fed exclusively preterm breast milk (PBM; n = 20), formula without LCPs added (NLCPs; n = 19), formula with LCPs derived from phospholipids (PL-LCPs; n = 19), or formula with LCPs from triacylglycerols (TG-LCPs; n = 19). Intestinal absorption of arachidonic acid was not different in the four groups but docosahexaenoic acid was better absorbed from PL-LCPs than from PBM (88.3 +/- 1.8% compared with 78.4 +/- 4.0%, P < 0.05) Total absorption of n-6 LCPs was not different between groups but total n-3 LCPs were better absorbed from PL-LCPs than from PBM or TG-LCPs (88.7 +/- 1.9%, 79.2 +/- 4.4%, and 80.4 +/- 2.2%, respectively). In conclusion, docosahexaenoic acid and arachidonic acid were absorbed as efficiently from TG-LCPs formula as from breast milk fat. Absorption of docosahexaenoic acid and n-3 LCPs was greater from PL-LCPs formula than from PBM or TG-LCPs formula.

Limited information is available on the metabolic fate of medium-chain triacylglycerols (triglycerides) after intestinal absorption and on their influence on essential fatty acid metabolism. We studied in preterm infants the effect of two infant formulas, one with a high (HMCT) and one with a low (LMCT) medium-chain triacylglycerol content, on plasma fatty acids. The HMCT formula contained 46 mol% 8:0 + 10:0 and the LMCT formula (4.8 mol% 8:0 + 10:0) had approximately twice the amount of long-chain saturated and monounsaturated fatty acids as the HMCT. Both formulas had similar contents of linoleic and linolenic acids. Plasma lipids and fatty acids were determined at birth and on day 24 of life in 20 infants fed the LMCT (n = 12) or HMCT (n = 8) formula. Significant amounts of medium-chain fatty acids were found in the systemic circulation of the infants fed the HMCT formula, mainly in plasma fatty acids and triacylglycerols. Despite striking dietary differences, palmitic and stearic acids were not different between groups, indicating de novo synthesis of long-chain fatty acids with the HMCT formula. Plasma phospholipid docosahexaenoic acid was significantly lower in the HMCT group than in the LMCT infants (1.38 +/- 0.07 compared with 1.73 +/- 0.07 mol%, P = 0.002). Our data indicate that a high MCT intake in preterm infants increases lipogenesis, and dietary nonessential fatty acids interfere with the metabolism of docosahexaenoic acid.

Seven premature infants were each fed, for 1 wk in a crossover design. The beta formula contained triacylglycerols resembling the stereoisomeric structure of human milk fat (25.4% by wt 16:0, 76.1% of which is at the sn-2 position), whereas in the alpha formula 87.3% of total 16:0 (25.7% by wt was at the sn-1,3 positions. Plasma lipids and their fatty acid compositions were determined at the end of each 1 wk study period. Infants fed with the beta formula had higher percentages of palmitic acid in plasma sterol esters, triacylglycerols, and free fatty acids, and lower linoleic acid in triacylglycerols than with the alpha formula. Premature infants fed formulas with triacylglycerols 16:0 predominantly in the sn-2 rather than the sn-1,3 positions had alterations in their plasma fatty acids consistent with enhanced absorption of 16:0 from the sn-2 compared with the sn-1,3 positions.

The effect of the structure of human milk triglycerides on intestinal fat absorption remains controversial. Twelve infants were each fed, for 1 wk in a crossover design, two formulas that differed only in triglyceride configuration. The "beta" formula contained triglycerides similar to those in human milk (26% palmitic acid, esterified predominantly to the sn-2 position) whereas in the "alpha" formula, which contained triglycerides similar to those in formulas currently marketed, palmitate was mainly at the sn-1,3 positions. Fatty acid, fat, and mineral balances were measured at the end of each 1-wk period. Myristic, palmitic, and stearic acids were absorbed better from the beta formula, but total fat excretion was not reduced. During the feeding of beta formula fecal calcium excretion was lower, urinary calcium higher, and urinary phosphate lower. A formula containing triglycerides similar to those in human milk has significant effects on fatty acid intestinal absorption and improves mineral balance in comparison with a conventional formula.