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Background: Early continuous positive airway pressure (CPAP) and surfactant replacement are effective treatments for neonatal respiratory distress syndrome (RDS). CPAP is the first line in preterm infants needing respiratory support, with surfactant replacement in case of CPAP failure (CPAP-F)., Objectives: To analyze incidence and factors associated with CPAP-F in preterm infants with RDS., Design, Setting and Patients: Single-center retrospective database analysis (2004-2017) of inborn infants, gestational age (GA) 24 + 0/7-31 + 6/7 weeks, not intubated on admission to the neonatal intensive care unit, managed with CPAP. CPAP-F was defined as intubation and surfactant administration in the first 72 h of life; CPAP success (CPAP-S) was CPAP alone without need for additional RDS treatments. Demographic, respiratory, and clinical data associated with CPAP-F were studied using logistic regression analysis., Results: A total of 562 infants met the inclusion criteria: 252 (44.8%) were CPAP-F and 310 (55.2%) were CPAP-S. The CPAP-F, compared to CPAP-S group, had lower GA and birth weight, and were less likely to receive antenatal steroids or to be vaginal births. Logistic regression showed that the fraction of inspired oxygen (FiO 2 ) ≥ 0.23 between 180 and 240 min of life (FiO 2 180-240 min) was the strongest factor associated with CPAP-F (odds ratio: 16.01 [95% confidence interval: 10.34-24.81])., Conclusion: FiO 2 180-240 min was highly predictive of CPAP-F in preterm infants. With this model for surfactant administration/CPAP-F, 11.2% of infants would have unnecessarily received treatment, but importantly, 27.7% would have been treated much earlier, with a potential reduction in air leaks and duration of mechanical ventilation., (© 2021 Wiley Periodicals LLC.)

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: 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.)

Introduction: The benefits of intravenous (IV) fish oil (FO), as a source of n-3 long-chain polyunsaturated fatty acids, on lung growth in preterm infants, remain controversial., Aim: To evaluate if IV FO improves lung growth in small preterm infants on routine parenteral nutrition (PN)., Materials and Methods: We retrospectively reviewed prospectively collected data of preterm infants with a birth weight <1250 g who received routine PN from birth. We compared patients who received FO containing IV lipid emulsions with infants who received conventional emulsions (CNTR). The oxygen saturation (SpO 2 ) to a fraction of inspired oxygen (FiO 2 ) ratio (SFR) at 36 weeks (W) of gestation was chosen as the primary outcome variable to assess lung growth., Results: Four hundred and seventy-seven infants were studied: 240 received IV FO and 237 CNTR. While exposure to antenatal glucocorticoids was higher in IV FO group than in CNTR (95 vs 90%, P = .04), there were no differences in birth data, enteral and parenteral nutrition intakes, ventilator supports and drug therapies. The incidence of the most common complications of prematurity at 36 W was not different (bronchopulmonary dysplasia was 27 vs 21% in IV FO vs CNTR infants, P = .1). Weight gain from birth to 36 W was marginally, but significantly, higher (+0.5 g/kg/d, P = .03) in IV FO group vs CNTR. SFR increased from 32 W to 36 W in all study patients (P < .001). IV FO infants had significantly lower SpO 2 from 33 W to 35 W (P < .001) and lower (worse) SFR at 36 W (432 ± 57 vs 444 ± 51, P = .026) compared to CNTR., Conclusion: Contrary to our hypothesis, the use of FO containing IV lipid emulsions for the routine PN of the preterm infant did not improve lung growth compared to the infants who received conventional IV lipid emulsions., (© 2020 Wiley Periodicals LLC.)

Objectives: In case of hypertriglyceridemia (HiTG) during parenteral nutrition (PN), the 2018 European Society of Paediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an intravenous (IV) lipid titration, but its consequences in small preterm infants are largely unknown. We compared macronutrient and energy intakes, growth, diseases associated with prematurity, and neurodevelopment in small preterm infants on PN who developed (cases) or did not develop HiTG (controls, CNTR)., Methods: We retrospectively reviewed data of preterm infants with a birth weight (BW) <1250 g consecutively admitted to our neonatal intensive care unit (2004-2016) who received routine PN. HiTG infants were defined by at least 1 triglyceride (TG) measurement >250 mg/dL during the first 10 days of life. Patients with and without HiTG were match-paired for BW and gestational age., Results: A total of 658 infants were analyzed and 196 (30%) had HiTG. One hundred thirty-six HiTG patients were matched with 136 CNTR. In the first 10 days of life, IV lipid, non-protein energy and total energy intakes, but not IV amino acids and carbohydrates, were significantly lower in HiTG infants. We found no differences between groups in diseases associated with prematurity. Anthropometry at 36 weeks (W), anthropometry at 2-year (Y) corrected age (CA), and neurodevelopment at 2Y CA were not different., Conclusions: Growth, diseases associated with prematurity, and neurodevelopment at 2Y CA in HiTG infants were similar to CNTR. This occurred despite a statistically significant albeit small reduction in IV lipid and non-protein energy intakes due to a strict TG monitoring and IV lipid titration at TG levels >250 mg/dL.

[This corrects the article on p. 54 in vol. 5, PMID: 28983481.].

Clinical trials have demonstrated that heparan sulfate (HS) could be used as a therapeutic agent for the treatment of inflammatory diseases. Its anti-inflammatory effect makes it suitable for the development of biomimetic innovative strategies aiming at modulating stem cells behavior toward a pro-regenerative phenotype in case of injury or inflammation. Here, we propose collagen type I meshes fabricated by solvent casting and further crosslinked with HS (HS-Col) to create a biomimetic environment resembling the extracellular matrix of soft tissue. HS-Col meshes were tested for their capability to provide physical support to stem cells' growth, maintain their phenotypes and immunosuppressive potential following inflammation. HS-Col effect on stem cells was investigated in standard conditions as well as in an inflammatory environment recapitulated in vitro through a mix of pro-inflammatory cytokines (tumor necrosis factor-α and interferon-gamma; 20 ng/ml). A significant increase in the production of molecules associated with immunosuppression was demonstrated in response to the material and when cells were grown in presence of pro-inflammatory stimuli, compared to bare collagen membranes (Col), leading to a greater inhibitory potential when mesenchymal stem cells were exposed to stimulated peripheral blood mononuclear cells. Our data suggest that the presence of HS is able to activate the molecular machinery responsible for the release of anti-inflammatory cytokines, potentially leading to a faster resolution of inflammation.