78 results on '"Carnielli VP"'
Search Results
2. Role of cardiopulmonary bypass in the acute lung injury of children with congenital heart diseases
- Author
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Maggiolo, A., Luca Vedovelli, Tonazzo, V., Manuela Simonato, Carollo, C., Carnielli, Vp, GIOVANNI STELLIN, Massimo Padalino, and Cogo, P.
- Published
- 2019
Catalog
3. Influence of the type of congenital heart defects on epithelial lining fluid composition in infants undergoing cardiac surgery with cardiopulmonary bypass
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Simonato, M, Baritussio, A, Carnielli, Vp, Vedovelli, L, Falasco, G, Salvagno, M, Padalino, M, Cogo, P., and Vedovelli, Luca
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Heart Septal Defects, Ventricular ,Male ,Pulmonary Circulation ,Heart disease ,Transposition of Great Vessels ,030204 cardiovascular system & hematology ,Pediatrics ,Epithelium ,Hypoplastic left heart syndrome ,law.invention ,0302 clinical medicine ,law ,Hypoplastic Left Heart Syndrome ,Postoperative Period ,Child ,Lung ,Phospholipids ,Tetralogy of Fallot ,Cardiopulmonary Bypass ,Lung Injury ,respiratory system ,Perinatology and Child Health ,Cardiac surgery ,Trachea ,medicine.anatomical_structure ,Great arteries ,Models, Animal ,Cardiology ,Female ,Heart Defects, Congenital ,medicine.medical_specialty ,Heart Ventricles ,Lung injury ,03 medical and health sciences ,Surface-Active Agents ,Internal medicine ,Albumins ,medicine ,Cardiopulmonary bypass ,Animals ,Humans ,Cardiac Surgical Procedures ,Peroxidase ,business.industry ,Heparin ,Pulmonary Gas Exchange ,Hemodynamics ,Infant, Newborn ,Infant ,Pulmonary Surfactants ,medicine.disease ,Pulmonary Alveoli ,030228 respiratory system ,Pediatrics, Perinatology and Child Health ,business - Abstract
BackgroundIn children with congenital heart disease (CHD), altered pulmonary circulation compromises gas exchange. Moreover, pulmonary dysfunction is a complication of cardiac surgery with cardiopulmonary bypass (CPB). No data are available on the effect of different CHDs on lung injury. The aim of this study was to analyze epithelial lining fluid (ELF) surfactant composition in children with CHD.MethodsTracheal aspirates (TAs) from 72 CHD children (age 2.9 (0.4-5.7) months) were obtained before and after CPB. We measured ELF phospholipids, surfactant proteins A and B (SP-A, SP-B), albumin, and myeloperoxidase activity. TAs from 12 infants (age 1.0 (0.9-2.9) months) with normal heart/lung served as controls.ResultsHeart defects were transposition of great arteries (19), tetralogy of Fallot (TOF, 20), atrial/ventricular septal defect (ASD/VSD, 22), and hypoplastic left heart syndrome (11). Increased levels of ELF SP-B were found in all defects, increased myeloperoxidase activity in all except the TOF, and increased levels of ELF albumin and SP-A only in ASD/VSD patients. Postoperatively, ELF findings remained unchanged except for a further increase in myeloperoxidase activity.ConclusionELF composition has distinctive patterns in different CHD. We speculate that a better knowledge of the ELF biochemical changes may help to prevent respiratory complications. more...
- Published
- 2017
4. Assessment of cardio-respiratory rates by non-invasive measurement methods in hospitalized preterm neonates
- Author
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Antognoli, L., primary, Marchionni, P., additional, Nobile, S., additional, Carnielli, VP., additional, and Scalise, L., additional
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- 2018
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5. The Real-World Routine Use of Caffeine Citrate in Preterm Infants: A European Postauthorization Safety Study
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Lista, G, Fabbri, L, Polackova, R, Kiechl-Kohlendorfer, U, Papagaroufalis, K, Saenz, P, Ferrari, F, Lasagna, G, Carnielli, VP, and Peyona PASS Grp
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Apnea ,Preterm infants ,Caffeine citrate - Abstract
Background: Caffeine citrate is the treatment of choice for apnea of prematurity (AOP). Regulatory agencies have requested real-world data on drug utilization and safety, a postauthorization safety study, of a pharmaceutical-grade caffeine citrate, Peyona (R), to confirm its benefit for preterm infants. Objectives: To investigate the clinical use, outcomes, and safety profile of this pharmaceutical-grade caffeine citrate in the routine treatment of preterm infants with a gestational age (GA) more...
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- 2016
6. Hypothermia and Meconium Aspiration Syndrome: International Multicenter Retrospective Cohort Study
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De Luca, D, Tingay, Dg, van Kaam, A, de Carvalho, Wb, Valverde, E, Roehr, Cc, Mosca, F, Matassa, Pg, Danhaive, O, Carnielli, Vp, Piastra, Marco, Piastra, M (ORCID:0000-0002-3144-8970), De Luca, D, Tingay, Dg, van Kaam, A, de Carvalho, Wb, Valverde, E, Roehr, Cc, Mosca, F, Matassa, Pg, Danhaive, O, Carnielli, Vp, Piastra, Marco, and Piastra, M (ORCID:0000-0002-3144-8970) more...
- Abstract
N/A
- Published
- 2016
7. Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).
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Vento G, Paladini A, Aurilia C, Ozdemir SA, Carnielli VP, Cools F, Costa S, Cota F, Dani C, Davis PG, Fattore S, Fè C, Finer N, Fusco FP, Gizzi C, Herting E, Jian M, Lio A, Lista G, Mosca F, Nobile S, Perri A, Picone S, Pillow JJ, Polglase G, Pasciuto T, Pastorino R, Tana M, Tingay D, Tirone C, van Kaam AH, Ventura ML, Aceti A, Agosti M, Alighieri G, Ancora G, Angileri V, Ausanio G, Aversa S, Balestri E, Baraldi E, Barbini MC, Barone C, Beghini R, Bellan C, Berardi A, Bernardo I, Betta P, Binotti M, Bizzarri B, Borgarello G, Borgione S, Borrelli A, Bottino R, Bracaglia G, Bresesti I, Burattini I, Cacace C, Calzolari F, Campagnoli MF, Capasso L, Capozza M, Capretti MG, Caravetta J, Carbonara C, Cardilli V, Carta M, Castoldi F, Castronovo A, Cavalleri E, Cavigioli F, Cecchi S, Chierici V, Cimino C, Cocca F, Cocca C, Cogo P, Coma M, Comito V, Condò V, Consigli C, Conti R, Corradi M, Corsello G, Corvaglia LT, Costa A, Coscia A, Cresi F, Crispino F, D'Amico P, De Cosmo L, De Maio C, Del Campo G, Di Credico S, Di Fabio S, Di Nicola P, Di Paolo A, Di Valerio S, Distilo A, Duca V, Falcone A, Falsaperla R, Fasolato VA, Fatuzzo V, Favini F, Ferrarello MP, Ferrari S, Nastro FF, Forcellini CA, Fracchiolla A, Gabriele A, Galdo F, Gallini F, Gangemi A, Gargano G, Gazzolo D, Gentile MP, Ghirardello S, Giardina F, Giordano L, Gitto E, Giuffrè M, Grappone L, Grasso F, Greco I, Grison A, Guglielmino R, Guidotti I, Guzzo I, La Forgia N, La Placa S, La Torre G, Lago P, Lanciotti L, Lavizzari A, Leo F, Leonardi V, Lestingi D, Li J, Liberatore P, Lodin D, Lubrano R, Lucente M, Luciani S, Luvarà D, Maffei G, Maggio A, Maggio L, Maiolo K, Malaigia L, Mangili G, Manna A, Maranella E, Marciano A, Marcozzi P, Marletta M, Marseglia L, Martinelli D, Martinelli S, Massari S, Massenzi L, Matina F, Mattia L, Mescoli G, Migliore IV, Minghetti D, Mondello I, Montano S, Morandi G, Mores N, Morreale S, Morselli I, Motta M, Napolitano M, Nardo D, Nicolardi A, Nider S, Nigro G, Nuccio M, Orfeo L, Ottaviano C, Paganin P, Palamides S, Palatta S, Paolillo P, Pappalardo MG, Pasta E, Patti L, Paviotti G, Perniola R, Perotti G, Perrone S, Petrillo F, Piazza MS, Piccirillo A, Pierro M, Piga E, Pingitore GA, Pisu S, Pittini C, Pontiggia F, Pontrelli G, Primavera A, Proto A, Quartulli L, Raimondi F, Ramenghi L, Rapsomaniki M, Ricotti A, Rigotti C, Rinaldi M, Risso FM, Roma E, Romanini E, Romano V, Rosati E, Rosella V, Rulli I, Salvo V, Sanfilippo C, Sannia A, Saporito A, Sauna A, Scapillati E, Schettini F, Scorrano A, Mantelli SS, Sepporta V, Sindico P, Solinas A, Sorrentino E, Spaggiari E, Staffler A, Stella M, Termini D, Terrin G, Testa A, Tina G, Tirantello M, Tomasini B, Tormena F, Travan L, Trevisanuto D, Tuling G, Tulino V, Valenzano L, Vedovato S, Vendramin S, Villani PE, Viola S, Viola V, Vitaliti G, Vitaliti M, Wanker P, Yang Y, Zanetta S, and Zannin E more...
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- Female, Humans, Infant, Newborn, Airway Extubation adverse effects, Bronchopulmonary Dysplasia therapy, Continuous Positive Airway Pressure, Gestational Age, Intubation, Intratracheal, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Time Factors, Treatment Outcome, Infant, Premature, Pulmonary Surfactants administration & dosage, Respiratory Distress Syndrome, Newborn therapy, Respiratory Distress Syndrome, Newborn mortality
- Abstract
Background: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration., Methods: In this study, 382 infants born at 24
+0 -27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR)., Discussion: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0 -27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life., Trial Registration: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023., (© 2024. The Author(s).) more...- Published
- 2024
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8. Safe and efficient practice of parenteral nutrition in neonates and children aged 0-18 years - The role of licensed multi-chamber bags.
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Senterre T, van den Akker CHP, Domellof M, Saenz de Pipaon M, Arnell H, Tabbers M, Valla FV, Tomlin S, Paulsson M, Wackernagel D, Haiden N, Luukkainen P, Orfeo L, Carnielli VP, and Rigo J
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- Humans, Infant, Newborn, Infant, Child, Child, Preschool, Adolescent, Parenteral Nutrition Solutions standards, Infant, Premature, Practice Guidelines as Topic, Infant, Very Low Birth Weight, Parenteral Nutrition standards, Parenteral Nutrition methods
- Abstract
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.) more...
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- 2024
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9. Evolution of Ultrasound-Assessed Lung Aeration and Gas Exchange in Respiratory Distress Syndrome and Transient Tachypnea of the Neonate.
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Pezza L, Sartorius V, Loi B, Regiroli G, Centorrino R, Lanciotti L, Carnielli VP, and De Luca D
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- Humans, Infant, Newborn, Tachypnea, Ultrasonography, Prospective Studies, Cohort Studies, Lung diagnostic imaging, Lung physiology, Respiratory Distress Syndrome, Newborn diagnosis, Respiratory Distress Syndrome, Newborn diagnostic imaging, Transient Tachypnea of the Newborn diagnostic imaging
- Abstract
Objective: To use clinical, lung ultrasound, and gas exchange data to clarify the evolution of lung aeration and function in neonates with respiratory distress syndrome (RDS) and transient tachypnea of the neonate (TTN), the most common types of neonatal respiratory failure., Study Design: In this prospective observational cohort study, lung aeration and function were measured with a semiquantitative lung ultrasound score (LUS) and transcutaneous blood gas measurement performed at 1 hour (time point 0), 6 hours (time point 1), 12 hours (time point 2), 24 hours (time point 3) and 72 hours (time point 4) of life. Endogenous surfactant was estimated using lamellar body count (LBC). LUS, oxygenation index (OI), oxygen saturation index (OSI), and transcutaneous pressure of carbon dioxide (PtcCO
2 ) were the primary outcomes. All results were adjusted for gestational age., Results: Sixty-nine neonates were enrolled in the RDS cohort, and 58 neonates were enrolled in the TTN cohort. LUS improved over time (within-subjects, P < .001) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001). Oxygenation improved over time (within-subjects, P = .011 for OI, P < .001 for OSI) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001 for OI and OSI). PtcCO2 improved over time (within-subjects, P < .001) and was similar in the RDS and TTN cohorts at all time points. Results were unchanged after adjustment for gestational age. LBC was associated with RDS (β = -0.2 [95% CI, -0.004 to -0.0001]; P = .037) and LUS (β = -3 [95% CI, -5.5 to -0.5]; P = .019)., Conclusions: For the first 72 hours of life, the RDS cohort had worse lung aeration and oxygenation compared with the TTN cohort at all time points. CO2 clearance did not differ between the cohorts, whereas both lung aeration and function improved in the first 72 hours of life., (Copyright © 2022 Elsevier Inc. All rights reserved.) more...- Published
- 2023
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10. Which birth weight threshold to start parenteral nutrition? A single center experience.
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Biagetti C, Correani A, Antognoli L, Burattini I, D'Ascenzo R, Bellagamba MP, Andresciani E, Garzone AMF, Cogo P, and Carnielli VP
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- Infant, Newborn, Infant, Humans, Birth Weight, Retrospective Studies, Infant, Low Birth Weight, Infant, Very Low Birth Weight, Infant, Premature, Parenteral Nutrition
- Abstract
Objectives: To analyze the need for parenteral nutrition (PN) in infants with a birth weight (BW) between 1250 and 1499 g., Methods: Retrospective evaluation of clinical, nutritional, growth and neurodevelopmental data of infants with a BW between 1250 and 1499 g consecutively admitted to our institution between 2004 and 2020., Results: Of the 503 infants admitted during the study period, 130 (26%) received PN: in 97 (19%) PN was medically indicated, while in 33 (7%) there was no clear indication. Patients who received medically indicated PN were younger, smaller, and sicker than the 373 infants who were managed with enteral nutrition, and their weight gain was lower (14.6 ± 4.1 vs 16.9 ± 4.2 g∙kg
-1 ∙ d-1 , p = 0.000). Body size at 36 weeks and 2-year anthropometry and neurodevelopment of the infants managed with enteral nutrition were not different from our reference values., Conclusions: After lowering the BW threshold for bridging PN from 1500 to 1250 g, we found that PN was started in only 20% of infants with a BW between 1250 and 1500 g. Withholding PN if not medically indicated did not result neither in growth faltering nor in reduced neurodevelopment., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.) more...- Published
- 2023
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11. UPDATE - 2022 Italian guidelines on the management of bronchiolitis in infants.
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Manti S, Staiano A, Orfeo L, Midulla F, Marseglia GL, Ghizzi C, Zampogna S, Carnielli VP, Favilli S, Ruggieri M, Perri D, Di Mauro G, Gattinara GC, D'Avino A, Becherucci P, Prete A, Zampino G, Lanari M, Biban P, Manzoni P, Esposito S, Corsello G, and Baraldi E more...
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- Infant, Newborn, Child, Infant, Humans, Child, Preschool, Hospitalization, Risk Factors, Albuterol therapeutic use, Bronchiolitis therapy, Bronchiolitis drug therapy, Respiratory Syncytial Virus Infections
- Abstract
Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis., (© 2023. The Author(s).) more...
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- 2023
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12. European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update.
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Sweet DG, Carnielli VP, Greisen G, Hallman M, Klebermass-Schrehof K, Ozek E, Te Pas A, Plavka R, Roehr CC, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GHA, and Halliday HL
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- Pregnancy, Infant, Infant, Newborn, Child, Female, Humans, Anti-Bacterial Agents, Cognition, Consensus, Respiratory Distress Syndrome, Respiratory Distress Syndrome, Newborn therapy
- Abstract
Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of "European Guidelines for the Management of RDS" by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12, 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS)., (© 2023 S. Karger AG, Basel.) more...
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- 2023
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13. A novel deuterium-based model for measurement of exogenous surfactant using deuterium-depleted water.
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Simonato M, Ricci F, Catozzi C, Storti M, Correani A, Salomone F, Cogo P, and Carnielli VP
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- Animals, Deuterium analysis, Palmitic Acid, Phosphatidylcholines, Rabbits, Water, Pulmonary Surfactants analysis, Surface-Active Agents
- Abstract
Stable isotope tracers, like
13 C, can be used for the measurement of the partition between the endogenous and exogenous pulmonary disaturated-phosphatidylcholine (DSPC). Deuterium labeling methods are still not fully explored. Our aim was to investigate the feasibility of using deuterium-depleted water (DDW) and deuterium-enriched water (DEW) to measure endogenous and exogenous pulmonary DSPC in a rabbit model of surfactant depletion. Data obtained from the13 C dilution method were used as a reference. We studied 9 adult rabbits: 4 drank DDW and 5 DEW for 5 days. Lung surfactant depletion was induced at Day 5 by repeated saline bronchoalveolar lavages (BAL), which were stored as a pool (BAL pool). After endogenous surfactant depletion, rabbits received exogenous surfactant followed by a second BAL depletion procedure (End-Experiment Pool). DSPC quantity, and palmitic acid (PA)-DSPC2 H/1 H (δ2 H) and13 C/12 C ratios (δ13 C) of exogenous surfactant batches and of BAL pools were measured by High-Resolution Mass Spectrometry. The amount of exogenous surfactant recovered from the lungs ranged from 45% to 81% and, it was highly correlated with those obtained with the use of the13 C (r = 0.9844, p < 0.0001). We demonstrated that commercially available purified DDW and even low doses of DEW can be used to modify the deuterium background of endogenous surfactants with the purpose of measuring the contribution of exogenous surfactants to the endogenous alveolar surfactant pool., (© 2022 Wiley Periodicals LLC.) more...- Published
- 2022
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14. Respiratory distress syndrome in preterm infants of less than 32 weeks: What difference does giving 100 or 200 mg/kg of exogenous surfactant make?
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Lanciotti L, Correani A, Pasqualini M, Antognoli L, Dell'Orto VG, Giorgetti C, Colombo S, Palazzi ML, Rondina C, Burattini I, and Carnielli VP
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- Cohort Studies, Continuous Positive Airway Pressure methods, Humans, Infant, Infant, Newborn, Infant, Premature, Retrospective Studies, Surface-Active Agents, Bronchopulmonary Dysplasia drug therapy, Pulmonary Surfactants therapeutic use, Respiratory Distress Syndrome, Newborn drug therapy
- Abstract
Background: Surfactant dosing and effective delivery could affect continuous positive airways pressure (CPAP)-failure. Nevertheless, information on exogenous surfactant dosing with current administration methods is limited., Objective: To describe the effect of 100 or 200 mg/kg of surfactant as first-line treatment of respiratory distress syndrome in preterm infants of less than 32 weeks gestation., Study Design: A retrospective single-center cohort study comparing two epochs, before and after switching from 100 to 200 mg/kg surfactant therapy., Results: Six hundred and fifty-eight of the 1615 infants of less than 32 weeks were treated with surfactant: 282 received 100 mg/kg (S-100) and 376 received 200 mg/kg (S-200). There were no differences between S-100 and S-200 in perinatal data including prenatal corticosteroids, medication use, age at first surfactant administration and respiratory severity before surfactant. The S-200 vs. S-100 had fewer retreatments (17.0% vs. 47.2%, p < 0.001) and a shorter duration of oxygen therapy and mechanical ventilation (315 vs. 339 h, p = 0.018; 37 vs. 118 h, p = 0.000, respectively). There was no difference in postnatal corticosteroid use (S-200 10.0% vs. S-100 11.0%, p = 0.361). Bronchopulmonary dysplasia (BPD) was significantly lower in S-200 vs. S-100 when comparing either the 4 and 6-year periods before and after the dose switch (29.4% vs. 15.7%, p = 0.003, and 18.7% vs. 27.3%, p = 0.024, respectively) CONCLUSIONS: The switch from 100 to 200 mg/kg was associated with a marked reduction in the need for surfactant redosing, respiratory support, and BPD. This information could be important when designing a study in the modern era of less invasive administration as surfactant dosing and its effective delivery may affect the outcome., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.) more...
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- 2022
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15. Efficacy and Safety of Enteral Recombinant Human Insulin in Preterm Infants: A Randomized Clinical Trial.
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Mank E, Sáenz de Pipaón M, Lapillonne A, Carnielli VP, Senterre T, Shamir R, van Toledo L, and van Goudoever JB
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- Birth Weight, Enteral Nutrition methods, Female, Humans, Infant, Infant, Newborn, Insulin, Male, Milk, Human, Enterocolitis, Necrotizing, Infant, Premature
- Abstract
Importance: Feeding intolerance is a common condition among preterm infants owing to immaturity of the gastrointestinal tract. Enteral insulin appears to promote intestinal maturation. The insulin concentration in human milk declines rapidly post partum and insulin is absent in formula; therefore, recombinant human (rh) insulin for enteral administration as a supplement to human milk and formula may reduce feeding intolerance in preterm infants., Objective: To assess the efficacy and safety of 2 different dosages of rh insulin as a supplement to both human milk and preterm formula., Design, Setting, and Participants: The FIT-04 multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 46 neonatal intensive care units throughout Europe, Israel, and the US. Preterm infants with a gestational age (GA) of 26 to 32 weeks and a birth weight of 500 g or more were enrolled between October 9, 2016, and April 25, 2018. Data were analyzed in January 2020., Interventions: Preterm infants were randomly assigned to receive low-dose rh insulin (400-μIU/mL milk), high-dose rh insulin (2000-μIU/mL milk), or placebo for 28 days., Main Outcomes and Measures: The primary outcome was time to achieve full enteral feeding (FEF) defined as an enteral intake of 150 mL/kg per day or more for 3 consecutive days., Results: The final intention-to-treat analysis included 303 preterm infants (low-dose group: median [IQR] GA, 29.1 [28.1-30.4] weeks; 65 boys [59%]; median [IQR] birth weight, 1200 [976-1425] g; high-dose group: median [IQR] GA, 29.0 [27.7-30.5] weeks; 52 boys [55%]; median [IQR] birth weight, 1250 [1020-1445] g; placebo group: median [IQR] GA, 28.8 [27.6-30.4] weeks; 54 boys [55%]; median [IQR] birth weight, 1208 [1021-1430] g). The data safety monitoring board advised to discontinue the study early based on interim futility analysis (including the first 225 randomized infants), as the conditional power did not reach the prespecified threshold of 35% for both rh-insulin dosages. The study continued while the data safety monitoring board analyzed and discussed the data. In the final intention-to-treat analysis, the median (IQR) time to achieve FEF was significantly reduced in 94 infants receiving low-dose rh insulin (10.0 [7.0-21.8] days; P = .03) and in 82 infants receiving high-dose rh insulin (10.0 [6.0-15.0] days; P = .001) compared with 85 infants receiving placebo (14.0 [8.0-28.0] days). Compared with placebo, the difference in median (95% CI) time to FEF was 4.0 (1.0-8.0) days for the low-dose group and 4.0 (1.0-7.0) days for the high-dose group. Weight gain rates did not differ significantly between groups. Necrotizing enterocolitis (Bell stage 2 or 3) occurred in 7 of 108 infants (6%) in the low-dose group, 4 of 88 infants (5%) in the high-dose group, and 10 of 97 infants (10%) in the placebo group. None of the infants developed serum insulin antibodies., Conclusions and Relevance: Results of this randomized clinical trial revealed that enteral administration of 2 different rh-insulin dosages was safe and compared with placebo, significantly reduced time to FEF in preterm infants with a GA of 26 to 32 weeks. These findings support the use of rh insulin as a supplement to human milk and preterm formula., Trial Registration: ClinicalTrials.gov Identifier: NCT02510560. more...
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- 2022
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16. DHA turnover in pregnant women using the natural abundance variation of 13 C: a pilot study.
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Simonato M, Visentin S, Verlato G, Cosmi E, Correani A, Cogo P, and Carnielli VP
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The importance of DHA intake to support fetal development and maternal health is well established. In this pilot study we applied the natural abundance approach to determine the contribution of 200 mg/day of DHA supplement to the plasma DHA pool in 19 healthy pregnant women on a free diet.Women received DHA, from pregnancy week 20 until delivery, from an algal source (N=13, Algae group) or from fish oil (N=6, Fish group) with slightly different content of 13C.We measured plasma phospholipids DHA 13C:12C ratio (reported as δ13C) prior to supplementation (T0), after 10 (T1) and 90 days (T2) and prior to delivery (T3).The δ13C of DHA in algae and fish supplements were -15.8±0.2 mUr and -25.3±0.2 mUr (p<0.001).DHA δ13C in the Algae group increased from -27.7±1.6 mUr (T0) to -21.9±2.2 mUr (T3) (p<0.001), whereas there were not significant changes in the Fish group (-27.8±0.9 mUr at T0 and -27.3±1.1 mUr at T3, p=0.09).In the Algae group 200 mg/day of DHA contributed to the plasma phospholipid pool by a median value of 53% (31-75% minimum and maximum). This estimation was not possible in the fish group.Our results demonstrate the feasibility of assessing the contribution of DHA from an algal source to the plasma DHA pool in pregnant women by the natural abundance approach. Plasma δ13C DHA did not change when consuming DHA of fish origin, with almost the same δ13C value of that of the pre-supplementation plasma δ13C DHA. more...
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- 2022
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17. [Práctica de la nutrición parenteral en lactantes prematuros].
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Carnielli VP, Correani A, Giretti I, D'Ascenzo R, Bellagamba MP, Burattini I, and Biagetti C
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- 2022
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18. Neonatal Lung Ultrasound and Surfactant Administration: A Pragmatic, Multicenter Study.
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Raimondi F, Migliaro F, Corsini I, Meneghin F, Pierri L, Salomè S, Perri A, Aversa S, Nobile S, Lama S, Varano S, Savoia M, Gatto S, Leonardi V, Capasso L, Carnielli VP, Mosca F, Dani C, Vento G, Dolce P, and Lista G more...
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- Female, Humans, Infant, Newborn, Male, Oxygen Saturation, Infant, Premature, Pulmonary Surfactants administration & dosage, Respiratory Distress Syndrome, Newborn diagnostic imaging, Respiratory Distress Syndrome, Newborn drug therapy, Ultrasonography methods
- Abstract
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, Fio2 , and Silverman score for surfactant administration were evaluated using receiver operating characteristic curves. The simultaneous prognostic values of LUS and oxygen saturation to Fio2 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 Fio2 , oxygen saturation to Fio2 ratio, LUS, and Silverman scores as criteria for surfactant administration, only the latter showed a significantly poorer performance. The combination of oxygen saturation to Fio2 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 Fio2 ratio significantly improves the prediction power for surfactant need., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2021
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19. Early nasal continuous positive airway pressure failure prediction in preterm infants less than 32 weeks gestational age suffering from respiratory distress syndrome.
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Dell'Orto V, Nobile S, Correani A, Marchionni P, Giretti I, Rondina C, Burattini I, Palazzi ML, and Carnielli VP
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- Continuous Positive Airway Pressure, Female, Gestational Age, Humans, Infant, Infant, Newborn, Infant, Premature, Pregnancy, Retrospective Studies, Respiratory Distress Syndrome, Respiratory Distress Syndrome, Newborn epidemiology, Respiratory Distress Syndrome, Newborn therapy
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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 (FiO2 180-240 min) was the strongest factor associated with CPAP-F (odds ratio: 16.01 [95% confidence interval: 10.34-24.81])., Conclusion: FiO2 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.) more...- Published
- 2021
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20. Chorioamnionitis alters lung surfactant lipidome in newborns with respiratory distress syndrome.
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Giambelluca S, Verlato G, Simonato M, Vedovelli L, Bonadies L, Najdekr L, Dunn WB, Carnielli VP, and Cogo P
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- Female, Humans, Infant, Newborn, Infant, Premature, Male, Pregnancy, Respiratory Distress Syndrome, Newborn complications, Chorioamnionitis metabolism, Lipidomics, Pulmonary Surfactants metabolism, Respiratory Distress Syndrome, Newborn metabolism
- Abstract
Background: Chorioamnionitis is associated with preterm delivery and morbidities; its role in lung disease is controversial. The aim of this study is to assess the effect of chorioamnionitis on metabolite and lipid profiles of epithelial lining fluid in preterm newborns with respiratory distress syndrome (RDS)., Methods: The study involved 30 newborns with RDS, born from mothers with or without histological chorioamnionitis (HCA): HCA+, N = 10; HCA-, N = 20. Patients had a gestational age ≤30 weeks; the groups were matched for age and birth weights. Tracheal aspirates were collected within 24 h after birth and analyzed using liquid chromatography/mass spectrometry-based untargeted lipidomics., Results: According to Mann-Whitney U tests, 570 metabolite features had statistically significantly higher or lower concentrations (p < 0.05) in tracheal aspirates of HCA+ compared to HCA-, and 241 metabolite features were putatively annotated and classified. The most relevant changes involved higher levels of glycerophospholipids (fold change 2.42-17.69) and sphingolipids, with lower concentration of all annotated sphingomyelins in HCA+ (fold change 0.01-0.50)., Conclusions: Untargeted lipidomics of tracheal aspirates suggested the production of lipid mediators in the context of an ongoing inflammatory status in HCA+ babies. However, the effect of chorioamnionitis on epithelial lining fluid composition deserves further investigations on a larger group of infants., Impact: Our lipidomics investigation on tracheal aspirates of preterm newborns at birth suggested that exposure to maternal histological chorioamnionitis may cause changes in epithelial lining fluid composition. This is the first description of epithelial lining fluid lipidomic profiles in preterm infants with and without exposition to chorioamnionitis. These results could provide novel link between placental membrane inflammation and newborns' respiratory outcome., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.) more...
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- 2021
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21. Hypertriglyceridemia and lipid tolerance in preterm infants with a birth weight of less than 1250 g on routine parenteral nutrition.
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Giretti I, D'Ascenzo R, Correani A, Antognoli L, Monachesi C, Biagetti C, Pompilio A, Marinelli L, Burattini I, Cogo P, and Carnielli VP
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- Birth Weight, Female, Gestational Age, Humans, Incidence, Infant, Newborn, Infant, Premature, Male, Retrospective Studies, Fat Emulsions, Intravenous administration & dosage, Hypertriglyceridemia epidemiology, Infant, Premature, Diseases epidemiology, Infant, Very Low Birth Weight, Parenteral Nutrition, Triglycerides blood
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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.) more...- Published
- 2021
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22. Lung Ultrasound to Monitor Extremely Preterm Infants and Predict Bronchopulmonary Dysplasia. A Multicenter Longitudinal Cohort Study.
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Loi B, Vigo G, Baraldi E, Raimondi F, Carnielli VP, Mosca F, and De Luca D
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- Bronchopulmonary Dysplasia physiopathology, Female, Gestational Age, Humans, Infant, Extremely Premature, Infant, Newborn, Longitudinal Studies, Male, Predictive Value of Tests, Prospective Studies, ROC Curve, Reproducibility of Results, Respiratory Function Tests, Bronchopulmonary Dysplasia diagnostic imaging, Ultrasonography
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Rationale: Lung ultrasound is useful in critically ill patients with acute respiratory failure. Given its characteristics, it could also be useful in extremely preterm infants with evolving chronic respiratory failure, as we lack accurate imaging tools to monitor them. Objectives: To verify if lung ultrasound can monitor lung aeration and function and has good reliability to predict bronchopulmonary dysplasia in extremely preterm neonates. Methods: A multicenter, international, prospective, longitudinal, cohort, diagnostic accuracy study consecutively enrolling inborn neonates with gestational age 30
+6 weeks or younger. Lung ultrasound was performed on the 1, 7, 14, and 28 days of life, and lung ultrasound scores were calculated and correlated with simultaneous blood gases and work of breathing score. Gestational age-adjusted lung ultrasound scores were created, verified in multivariate models, and subjected to receiver operator characteristics (ROC) analyses to predict bronchopulmonary dysplasia at 36 weeks postmenstrual age. Measurements and Main Results: Mean lung ultrasound scores are different between infants developing ( n = 72) or not developing ( n = 75) bronchopulmonary dysplasia ( P < 0.001 at any time point). Lung ultrasound scores significantly correlate with oxygenation metrics and work of breathing at any time point ( P always < 0.0001). Gestational age-adjusted lung ultrasound scores significantly predict bronchopulmonary dysplasia at 7 (area under ROC curve, 0.826-0.833; P < 0.0001) and 14 (area under ROC curve, 0.834-0.858; P < 0.0001) days of life. Bronchopulmonary dysplasia severity and gestational age-adjusted lung ultrasound scores are significantly correlated at 7 and 14 days ( P always < 0.0001). Conclusions: Lung ultrasound scores allow monitoring of lung aeration and function in extremely preterm infants. Gestational age-adjusted scores significantly predict the occurrence of bronchopulmonary dysplasia, starting from the seventh day of life. more...- Published
- 2021
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23. Is intravenous fish oil associated with the neurodevelopment of extremely low birth weight preterm infants on parenteral nutrition?
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Biagetti C, Correani A, D'Ascenzo R, Ferretti E, Proietti C, Antognoli L, Giretti I, Pompilio A, Cogo P, and Carnielli VP
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- Central Nervous System drug effects, Humans, Infant, Newborn, Retrospective Studies, Central Nervous System growth & development, Child Development drug effects, Fish Oils administration & dosage, Infant, Extremely Low Birth Weight, Infant, Premature, Parenteral Nutrition
- Abstract
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.) more...- Published
- 2021
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24. Lung Ultrasound Score Progress in Neonatal Respiratory Distress Syndrome.
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Raimondi F, Migliaro F, Corsini I, Meneghin F, Dolce P, Pierri L, Perri A, Aversa S, Nobile S, Lama S, Varano S, Savoia M, Gatto S, Leonardi V, Capasso L, Carnielli VP, Mosca F, Dani C, Vento G, and Lista G more...
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- Female, Gestational Age, Humans, Infant, Infant, Newborn, Infant, Premature, Intensive Care Units, Neonatal, Male, Oxygen blood, Predictive Value of Tests, Prospective Studies, Respiratory Distress Syndrome, Newborn complications, Sensitivity and Specificity, Bronchopulmonary Dysplasia etiology, Lung diagnostic imaging, Point-of-Care Systems, Respiratory Distress Syndrome, Newborn diagnostic imaging, Ultrasonography
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Background and Objectives: The utility of a lung ultrasound score (LUS) has been described in the early phases of neonatal respiratory distress syndrome (RDS). We investigated lung ultrasound as a tool to monitor respiratory status in preterm neonates throughout the course of RDS., Methods: Preterm neonates, stratified in 3 gestational age cohorts (25-27, 28-30, and 31-33 weeks), underwent lung ultrasound at weekly intervals from birth. Clinical data, respiratory support variables, and major complications (sepsis, patent ductus arteriosus, pneumothorax, and persistent pulmonary hypertension of the neonate) were also recorded., Results: We enrolled 240 infants in total. The 3 gestational age intervals had significantly different LUS patterns. There was a significant correlation between LUS and the ratio of oxygen saturation to inspired oxygen throughout the admission, increasing with gestational age (b = -0.002 [ P < .001] at 25-27 weeks; b = -0.006 [ P < .001] at 28-30 weeks; b = -0.012 [ P < .001] at 31-33 weeks). Infants with complications had a higher LUS already at birth (12 interquartile range 13-8 vs 8 interquartile range 12-4 control group; P = .001). In infants 25 to 30 weeks' gestation, the LUS at 7 days of life predicted bronchopulmonary dysplasia with an area under the curve of 0.82 (95% confidence interval 0.71 to 93)., Conclusions: In preterm neonates affected by RDS, the LUS trajectory is gestational age dependent, significantly correlates with the oxygenation status, and predicts bronchopulmonary dysplasia. In this population, LUS is a useful, bedside, noninvasive tool to monitor the respiratory status., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.) more...
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- 2021
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25. Response to therapy among neonates with gastro-esophageal reflux is associated with esophageal clearance.
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Nobile S, Meneghin F, Marchionni P, Noviello C, Salvatore S, Lista G, Carnielli VP, and Vento G
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- Electric Impedance, Humans, Infant, Infant, Newborn, Proton Pump Inhibitors therapeutic use, Retrospective Studies, Esophageal pH Monitoring, Gastroesophageal Reflux drug therapy, Gastroesophageal Reflux epidemiology
- Abstract
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.) more...
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- 2021
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26. Blood urea in preterm infants on routine parenteral nutrition: A multiple linear regression analysis.
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Giretti I, Correani A, Antognoli L, Monachesi C, Marchionni P, Biagetti C, Bellagamba MP, Cogo P, D'Ascenzo R, Burattini I, and Carnielli VP
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- Amino Acids analysis, Birth Weight, Creatinine blood, Ductus Arteriosus, Patent physiopathology, Female, Gestational Age, Humans, Infant, Newborn, Infant, Small for Gestational Age blood, Linear Models, Male, Multivariate Analysis, Respiratory Distress Syndrome, Newborn physiopathology, Eating physiology, Infant Nutritional Physiological Phenomena, Infant, Premature blood, Parenteral Nutrition, Urea blood
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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.) more...
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- 2021
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27. Personalized Medicine for the Management of RDS in Preterm Neonates.
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De Luca D, Autilio C, Pezza L, Shankar-Aguilera S, Tingay DG, and Carnielli VP
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- Continuous Positive Airway Pressure, Humans, Infant, Newborn, Infant, Premature, Precision Medicine, Reproducibility of Results, Pulmonary Surfactants therapeutic use, Respiratory Distress Syndrome, Newborn therapy
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Continuous positive airway pressure and surfactant represent the first- and second-line treatment for respiratory distress syndrome in preterm neonates, as European and American guidelines, since 2013 and 2014, respectively, started to recommend surfactant replacement only when continuous positive airway pressure fails. These recommendations, however, are not personalized to the individual physiopathology. Simple clinical algorithms may have improved the diffusion of neonatal care, but complex medical issues can hardly be addressed with simple solutions. The treatment of respiratory distress syndrome is a complex matter and can be only optimized with personalization. We performed a review of tools to individualize the management of respiratory distress syndrome based on physiopathology and actual patients' need, according to precision medicine principles. Advanced oxygenation metrics, lung ultrasound, electrical impedance tomography, and both quantitative and qualitative surfactant assays were examined. When these techniques were investigated with diagnostic accuracy studies, reliability measures have been meta-analysed. Amongst all these tools, quantitative lung ultrasound seems the more developed for the widespread use and has a higher diagnostic accuracy (meta-analytical AUC = 0.952 [95% CI: 0.951-0.953]). Surfactant adsorption (AUC = 0.840 [95% CI: 0.824-0.856]) and stable microbubble test (AUC = 0.800 [95% CI: 0.788-0.812]) also have good reliability, but need further industrial development. We advocate for a more accurate characterization and a personalized approach of respiratory distress syndrome. With the above-described currently available tools, it should be possible to personalize the treatment of respiratory distress syndrome according to physiopathol-ogy., (© 2021 S. Karger AG, Basel.) more...
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- 2021
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28. Practice of Parenteral Nutrition in Preterm Infants.
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Carnielli VP, Correani A, Giretti I, D Apos Ascenzo R, Bellagamba MP, Burattini I, and Biagetti C
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- Humans, Infant, Infant, Newborn, Parenteral Nutrition, Total, Infant, Premature, Parenteral Nutrition
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- 2021
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29. Meckel's diverticulum perforation in a newborn positive to Sars-Cov-2.
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Bindi E, Cruccetti A, Ilari M, Mariscoli F, Carnielli VP, Simonini A, and Cobellis G
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The health emergency linked to the Sars-Cov-2 infection represented an absolutely new problem for all health professionals. In particular, the information regarding the spread of the virus in the pediatric field and its manifestations are still incomplete. In this paper we present a case of neonatal infection which, as far as we know, represents one of the few published cases and which occurred in a patient who came to our attention for acute abdomen from intestinal perforation. The perforation was caused by Meckel's diverticulum, an event considered infrequent in the first year of life and almost exceptional in the neonatal period. This case required particular management, putting pediatric surgeons in front of new and difficult to solve problems. New onset clinical events, such as this one described, represent an opportunity for sharing useful data for the creation of universal protocols for the management of patients with problems that are becoming common and of which little is known., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.) more...
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- 2020
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30. Factors affecting early-life intestinal microbiota development.
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Vandenplas Y, Carnielli VP, Ksiazyk J, Luna MS, Migacheva N, Mosselmans JM, Picaud JC, Possner M, Singhal A, and Wabitsch M
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- Adult, Breast Feeding, Female, Humans, Infant, Infant Formula, Milk, Human, Oligosaccharides, Pregnancy, Gastrointestinal Microbiome, Microbiota
- Abstract
Objectives: This paper reviews the published evidence on early-life intestinal microbiota development, as well as the different factors influencing its development before, at, and after birth. A literature search was done using PubMed, Cochrane and EMBASE databases. A growing body of evidence indicates that the intrauterine environment is not sterile as once presumed, but that maternal-fetal transmission of microbiota occurs during pregnancy. The consecutive order of bacteria with which the gastrointestinal tract is colonized will influence the outcome of community assembly and the ecological success of individual colonizers. The genetic background of the infant may also strongly influence microbial colonization of the gastrointestinal tract. The composition and development of infant gut microbiota can be influenced by many prenatal factors, such as maternal diet, obesity, smoking status, and use of antibiotic agents during pregnancy. Mode of delivery is generally accepted as a major factor determining the initial colonization. Breast milk stimulates the most balanced microbiome development for the infant, mainly because of its high content of unique oligosaccharides. Feeding is another important factor to determine intestinal colonization. Compared with breastfed infants, formula-fed infants have an increased richness of species. Initial clinical studies show that infant formulas supplemented with specific human milk oligosaccharides (HMOs) -2´-fucosyllactose alone or in combination with lacto-n-neotetraose are structurally identical to those in breast milk. HMOs increase the proportion of infants with a high bifidobacterial-dominated gut microbiota typical of that observed in breastfed infants, lead to plasma immune marker profiles similar to those of breast-fed infants and to lower morbidity and antibiotics use. Further clinical studies with the same, others or more HMOs are needed to confirm these clinical effects. A growing number of studies have reported on how the composition and development of the microbiota during early life will affect risk factors related to health up to and during adulthood. If exclusive breastfeeding is not possible, the composition of infant formula should be adapted to stimulate the development of a bifidobacterial-dominated gut microbiota typical of that observed in breastfed infants. The main components in breast milk that stimulate the growth of specific bifidobacteria are HMOs., (Copyright © 2020 Elsevier Inc. All rights reserved.) more...
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- 2020
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31. The babyPose dataset.
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Migliorelli L, Moccia S, Pietrini R, Carnielli VP, and Frontoni E
- Abstract
The database here described contains data relevant to preterm infants' movement acquired in neonatal intensive care units (NICUs). The data consists of 16 depth videos recorded during the actual clinical practice. Each video consists of 1000 frames (i.e., 100s). The dataset was acquired at the NICU of the Salesi Hospital, Ancona (Italy). Each frame was annotated with the limb-joint location. Twelve joints were annotated, i.e., left and right shoul- der, elbow, wrist, hip, knee and ankle. The database is freely accessible at http://doi.org/10.5281/zenodo.3891404. This dataset represents a unique resource for artificial intelligence researchers that want to develop algorithms to provide healthcare professionals working in NICUs with decision support. Hence, the babyPose dataset is the first annotated dataset of depth images relevant to preterm infants' movement analysis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).) more...
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- 2020
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32. Inhaled nitric oxide (iNO) for preventing prematurity-related bronchopulmonary dysplasia (BPD): 7-year follow-up of the European Union Nitric Oxide (EUNO) trial.
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Greenough A, Decobert F, Field D, Hallman M, Hummler HD, Jonsson B, Sánchez Luna M, Van Overmeire B, Carnielli VP, Potenziano JL, and Mercier JC
- Subjects
- Administration, Inhalation, Bronchodilator Agents pharmacology, Bronchopulmonary Dysplasia mortality, Child, Europe epidemiology, Female, Follow-Up Studies, Health Status, Humans, Infant, Newborn, Infant, Premature, Male, Nitric Oxide pharmacology, Bronchodilator Agents therapeutic use, Bronchopulmonary Dysplasia prevention & control, Child Development drug effects, Hospitalization statistics & numerical data, Nitric Oxide therapeutic use
- Abstract
Objectives: Most studies of inhaled nitric oxide (iNO) for prevention of bronchopulmonary dysplasia (BPD) in premature infants have focused on short-term mortality and morbidity. Our aim was to determine the long-term effects of iNO., Methods: A 7-year follow-up was undertaken of infants entered into a multicenter, double-blind, randomized, placebo-controlled trial of iNO for prevention of BPD in premature infants born between 24 and 28 weeks plus six days of gestation. At 7 years, survival and hospital admissions since the 2-year follow-up, home oxygen therapy in the past year, therapies used in the previous month and growth assessments were determined. Questionnaires were used to compare general health, well-being, and quality of life., Results: A total of 305 children were assessed. No deaths were reported. Rates of hospitalization for respiratory problems (6.6 vs. 10.5%, iNO and placebo group, respectively) and use of respiratory medications (6.6 vs. 9.2%) were similar. Two patients who received iNO and one who received placebo had received home oxygen therapy. There were no significant differences in any questionnaire-documented health outcomes., Conclusions: iNO for prevention of BPD in very premature infants with respiratory distress did not result in long-term benefits or adverse long-term sequelae. In the light of current evidence, routine use of iNO cannot be recommended for prevention of BPD in preterm infants. more...
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- 2020
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33. Oxygen saturation to fraction of inspired oxygen ratio in preterm infants on routine parenteral nutrition with conventional or fish oil containing lipid emulsions.
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Correani A, Dell'Orto V, Nobile S, Antognoli L, Marchionni P, Giretti I, Monachesi C, Rondina C, Palazzi ML, Biagetti C, D'Ascenzo R, Pompilio A, Simonato M, Cogo P, Burattini I, and Carnielli VP
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- Female, Humans, Infant, Newborn, Lung growth & development, Male, Retrospective Studies, Fat Emulsions, Intravenous, Fish Oils administration & dosage, Infant, Premature growth & development, Oxygen administration & dosage, Parenteral Nutrition
- Abstract
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 (FiO2 ) 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 SpO2 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.) more...- Published
- 2020
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34. Surfactant-secreted phospholipase A 2 interplay and respiratory outcome in preterm neonates.
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De Luca D, Shankar-Aguilera S, Autilio C, Raschetti R, Vedovelli L, Fitting C, Payré C, Jeammet L, Perez-Gil J, Cogo PE, Carnielli VP, Lambeau G, and Touqui L
- Subjects
- Bronchoalveolar Lavage Fluid, Epithelial Cells metabolism, Female, Humans, Infant, Newborn, Male, Phospholipases A2, Secretory antagonists & inhibitors, Phospholipids, Infant, Premature physiology, Phospholipases A2, Secretory metabolism, Pulmonary Surfactants metabolism, Respiration
- Abstract
Secreted phospholipase A
2 hydrolyzes surfactant phospholipids and is crucial for the inflammatory cascade; preterm neonates are treated with exogenous surfactant, but the interaction between surfactant and phospholipase is unknown. We hypothesize that this interplay is complex and the enzyme plays a relevant role in neonates needing surfactant replacement. We aimed to: 1 ) identify phospholipases A2 isoforms expressed in preterm lung; 2 ) study the enzyme role on surfactant retreatment and function and the effect of exogenous surfactant on the enzyme system; and 3 ) verify whether phospholipase A2 is linked to respiratory outcomes. In bronchoalveolar lavages of preterm neonates, we measured enzyme activity (alone or with inhibitors), enzyme subtypes, surfactant protein-A, and inflammatory mediators. Surfactant function and phospholipid profile were also tested. Urea ratio was used to obtain epithelial lining fluid concentrations. Follow-up data were prospectively collected. Subtype-IIA is the main phospholipase isoform in preterm lung, although subtype-IB may be significantly expressed. Neonates needing surfactant retreatment have higher enzyme activity ( P = 0.021) and inflammatory mediators ( P always ≤ 0.001) and lower amounts of phospholipids ( P always < 0.05). Enzyme activity was inversely correlated to surfactant adsorption (ρ = -0.6; P = 0.008; adjusted P = 0.009), total phospholipids (ρ = -0.475; P = 0.05), and phosphatidylcholine (ρ = -0.622; P = 0.017). Exogenous surfactant significantly reduced global phospholipase activity ( P < 0.001) and subtype-IIA ( P = 0.005) and increased dioleoylphosphatidylglycerol ( P < 0.001) and surfactant adsorption ( P < 0.001). Enzyme activity correlated with duration of ventilation (ρ = 0.679, P = 0.005; adjusted P = 0.04) and respiratory morbidity score at 12 mo postnatal age (τ-b = 0.349, P = 0.037; adjusted P = 0.043) but was not associated with mortality, bronchopulmonary dysplasia, or other long-term respiratory outcomes. more...- Published
- 2020
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35. Obstetric network reorganization during the COVID-19 pandemic: Suggestions from an Italian regional model.
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Giannubilo SR, Giannella L, Delli Carpini G, Carnielli VP, and Ciavattini A
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- COVID-19, Female, Humans, Italy, Pregnancy, SARS-CoV-2, Triage, Betacoronavirus, Coronavirus Infections epidemiology, Pandemics, Pneumonia, Viral epidemiology, Postnatal Care organization & administration, Prenatal Care organization & administration
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. more...
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- 2020
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36. Less-invasive surfactant administration in sub-Saharan Africa - Authors' reply.
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De Luca D, Shankar-Aguilera S, Centorrino R, Fortas F, Yousef N, and Carnielli VP
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- Africa South of the Sahara, Humans, Surface-Active Agents
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- 2020
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37. Less invasive surfactant administration: a word of caution.
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De Luca D, Shankar-Aguilera S, Centorrino R, Fortas F, Yousef N, and Carnielli VP
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- Airway Resistance, Humans, Infant, Newborn, Intubation, Intratracheal adverse effects, Intubation, Intratracheal methods, Laryngoscopy adverse effects, Meta-Analysis as Topic, Pulmonary Surfactants therapeutic use, Randomized Controlled Trials as Topic, Respiration, Artificial adverse effects, Respiration, Artificial methods, Respiratory Distress Syndrome, Newborn epidemiology, Respiratory Distress Syndrome, Newborn therapy, Intensive Care, Neonatal methods, Lung Diseases, Interstitial complications, Pulmonary Surfactants administration & dosage, Respiratory Distress Syndrome, Newborn physiopathology
- Abstract
Surfactant is a cornerstone of neonatal critical care, and the presumed less (or minimally) invasive techniques for its administration have been proposed to reduce invasiveness of neonatal critical care interventions. These techniques are generally known as less invasive surfactant administration (LISA) and have quickly gained popularity in some neonatal intensive care units. Despite the increase in the use of LISA, we believe that the pathobiological background supporting its possible clinical benefits is unclear. Similarly, it is unclear whether there are any ignored drawbacks, as LISA has been tested in only a few trials and some physiopathological issues seem to have gone unnoticed. Active research is warranted to fill these knowledge gaps before LISA can be firmly recommended. In this Viewpoint, we provide an in-depth analysis of LISA techniques, based on physiological and pathobiological factors, followed by a critical appraisal of available clinical data, and highlight some possible future research directions., (Copyright © 2020 Elsevier Ltd. All rights reserved.) more...
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- 2020
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38. Hypertriglyceridemia and Intravenous Lipid Titration During Routine Parenteral Nutrition in Small Preterm Infants.
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Correani A, Giretti I, Antognoli L, Monachesi C, Cogo P, D'Ascenzo R, Biagetti C, and Carnielli VP
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- Case-Control Studies, Energy Intake, Female, Humans, Infant Nutritional Physiological Phenomena, Infant, Newborn, Infusions, Intravenous, Male, Retrospective Studies, Hypertriglyceridemia therapy, Infant, Low Birth Weight, Infant, Premature, Parenteral Nutrition, Total
- Abstract
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. more...
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- 2019
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39. Urinary metabolomics reveals kynurenine pathway perturbation in newborns with transposition of great arteries after surgical repair.
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Simonato M, Fochi I, Vedovelli L, Giambelluca S, Carollo C, Padalino M, Carnielli VP, and Cogo P
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- Cardiac Surgical Procedures, Humans, Infant, Newborn, Kynurenine urine, Mass Spectrometry, Transposition of Great Vessels surgery, Kynurenine metabolism, Metabolomics, Transposition of Great Vessels metabolism
- Abstract
Introduction: Transposition of the great arteries (TGA) is a cyanotic congenital heart defect that requires surgical correction, with the use of cardiopulmonary-bypass (CPB), usually within 3 weeks of life. The use of CPB in open heart surgery results in brain hypoperfusion and in a powerful systemic inflammatory response and oxidative stress., Objective: We aimed to develop a novel untargeted metabolomics approach to detect early postoperative changes in metabolic profile following neonatal cardiac surgery., Methods: We studied 14 TGA newborns with intact ventricular septum undergoing arterial switch operation with the use of CPB. Urine samples were collected preoperatively and at the end of the surgery and were analyzed using an untargeted metabolomics approach based on UHPLC-high resolution mass spectrometry., Results: Since post surgery metabolic spectra were heavily contaminated by metabolites derived from administered drugs, we constructed a list of drugs used during surgery and their related metabolites retrieved from urine samples. This library was applied to our samples and 1255 drugs and drug metabolites were excluded from the analysis. Afterward, we detected over 39,000 unique compounds and 371 putatively annotated metabolites were different between pre and post-surgery samples. Among these metabolites, 13 were correctly annotated or identified. Metabolites linked to kynurenine pathway of tryptophan degradation displayed the highest fold change., Conclusions: This is the first report on metabolic response to cardiac surgery in TGA newborns. We developed an experimental design that allowed the identification of perturbed metabolic pathways and potential biomarkers of brain damage, limiting drugs interference in the analysis. more...
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- 2019
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40. Does intravenous fish oil affect the growth of extremely low birth weight preterm infants on parenteral nutrition?
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Biagetti C, Correani A, D'Ascenzo R, Bellagamba MP, Marchionni P, Antognoli L, Pompilio A, Cogo P, and Carnielli VP
- Subjects
- Birth Weight physiology, Energy Intake physiology, Fat Emulsions, Intravenous administration & dosage, Fatty Acids, Omega-3, Female, Humans, Infant, Newborn, Infant, Newborn, Diseases epidemiology, Male, Retrospective Studies, Fish Oils administration & dosage, Infant, Extremely Low Birth Weight growth & development, Infant, Premature growth & development, Parenteral Nutrition methods
- Abstract
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.) more...- Published
- 2019
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41. Pre-surgery urine metabolomics may predict late neurodevelopmental outcome in children with congenital heart disease.
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Vedovelli L, Cogo P, Cainelli E, Suppiej A, Padalino M, Tassini M, Simonato M, Stellin G, Carnielli VP, Buonocore G, and Longini M
- Abstract
Background: From fetal life until cardiac surgery, complex congenital heart diseases (CHD) exhibit different hemodynamic and oxygenation patterns that can lead to alteration of the metabolic profile. We used a metabolomic approach to identify urine metabolic markers before cardiac surgery, aiming to define the physiology of patients with complex CHD and to contribute to predict their neurodevelopmental outcome., Methods: In a prospective, observational, single-center study we enrolled 28 patients with complex biventricular and univentricular CHD aged less than 5 years, on stable hemodynamic conditions, and with no genetic anomalies. We analyzed urine samples, collected at the induction of anesthesia, by 1H NMR spectroscopy. Profiles of 1H NMR spectra were submitted to unsupervised (principal component) and supervised (partial least squares-discriminant) multivariate analysis. Neurodevelopment was assessed by neuropsychological and adaptive functioning testing., Results: Principal components analysis divided CHD patients metabolic profiles in two distinct clusters (RED and BLACK). Metabolic profiles belonging to the RED cluster showed higher levels of accumulation of citric acid cycle intermediates and glucose compared to the profiles in the BLACK cluster, indicating a possible switching to anaerobic metabolism. Patients belonging to the RED cluster were significantly more prone to show an adverse neurodevelopment pattern (p = 0.01)., Conclusions: The application of metabolomic analysis to CHD children permitted a deeper insight on their metabolic status that could help to obtain a better understanding of the physiological implications and to predict long-term neurodevelopmental outcome., (© 2019 The Authors. Published by Elsevier Ltd.) more...
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- 2019
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42. Tracing exogenous surfactant in vivo in rabbits by the natural variation of 13 C.
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Giambelluca S, Ricci F, Simonato M, Vedovelli L, Traldi U, Correani A, Casiraghi C, Storti M, Mersanne A, Cogo P, Salomone F, and Carnielli VP
- Subjects
- Animals, Biological Products administration & dosage, Carbon Isotopes administration & dosage, Dose-Response Relationship, Drug, Lung drug effects, Male, Phospholipids administration & dosage, Pulmonary Surfactants administration & dosage, Rabbits, Surface-Active Agents administration & dosage, Surface-Active Agents metabolism, Biological Products metabolism, Carbon Isotopes metabolism, Lung metabolism, Phospholipids metabolism, Pulmonary Surfactants metabolism
- Abstract
Background: Respiratory Distress Syndrome (RDS) is a prematurity-related breathing disorder caused by a quantitative deficiency of pulmonary surfactant. Surfactant replacement therapy is effective for RDS newborns, although treatment failure has been reported. The aim of this study is to trace exogenous surfactant by
13 C variation and estimate the amount reaching the lungs at different doses of the drug., Methods: Forty-four surfactant-depleted rabbits were obtained by serial bronchoalveolar lavages (BALs), that were merged into a pool (BAL pool) for each animal. Rabbits were in nasal continuous positive airway pressure and treated with 0, 25, 50, 100 or 200 mg/kg of poractant alfa by InSurE. After 90 min, rabbits were depleted again and a new pool (BAL end experiment) was collected. Disaturated-phosphatidylcholine (DSPC) was measured by gas chromatography. DSPC-Palmitic acid (PA)13 C/12 C was analyzed by isotope ratio mass spectrometry. One-way non-parametric ANOVA and post-hoc Dunn's multiple comparison were used to assess differences among experimental groups., Results: Based on DSPC-PA13 C/12 C in BAL pool and BAL end experiment, the estimated amount of exogenous surfactant ranged from 61 to 87% in dose-dependent way (p < 0.0001) in animals treated with 25 up to 200 mg/kg. Surfactant administration stimulated endogenous surfactant secretion. The percentage of drug recovered from lungs did not depend on the administered dose and accounted for 31% [24-40] of dose., Conclusions: We reported a risk-free method to trace exogenous surfactant in vivo. It could be a valuable tool for assessing, alongside the physiological response, the delivery efficiency of surfactant administration techniques. more...- Published
- 2019
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43. Dataset from spirometer and sEMG wireless sensor for diaphragmatic respiratory activity monitoring.
- Author
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Biagetti G, Carnielli VP, Crippa P, Falaschetti L, Scacchia V, Scalise L, and Turchetti C
- Abstract
We introduce a dataset to provide insights into the relationship between the diaphragm surface electromyographic (sEMG) signal and the respiratory air flow. The data presented had been originally collected for a research project jointly developed by the Department of Information Engineering and the Department of Industrial Enginering and Mathematical Sciences, Polytechnic University of Marche, Ancona, Italy. This article describes data recorded from 8 subjects, and includes 8 air flow and 8 surface electromyographic (sEMG) signals for diaphragmatic respiratory activity monitoring, measured with a sampling frequency of 2 kHz. more...
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- 2019
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44. Correlation between cardiorespiratory events and gastro-esophageal reflux in preterm and term infants: Analysis of predisposing factors.
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Nobile S, Marchionni P, Noviello C, and Carnielli VP
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- Female, Heart Rate, Humans, Infant, Newborn, Male, Oxygen Consumption, Apnea epidemiology, Bradycardia epidemiology, Gastroesophageal Reflux epidemiology, Infant, Premature physiology
- Abstract
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.) more...- Published
- 2019
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45. Oxygen saturation/FIO2 ratio at 36 weeks' PMA in 1005 preterm infants: Effect of gestational age and early respiratory disease patterns.
- Author
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Nobile S, Marchionni P, Gidiucci C, Correani A, Palazzi ML, Spagnoli C, Rondina C, and Carnielli VP
- Subjects
- Bronchopulmonary Dysplasia physiopathology, Bronchopulmonary Dysplasia therapy, Female, Humans, Infant, Infant, Newborn, Infant, Premature, Infant, Small for Gestational Age, Intensive Care Units, Neonatal, Lung physiopathology, Lung Diseases metabolism, Lung Diseases physiopathology, Lung Diseases therapy, Male, Milk, Human, Neonatal Sepsis, Oxygen Inhalation Therapy, Retrospective Studies, Severity of Illness Index, Bronchopulmonary Dysplasia metabolism, Gestational Age, Lung metabolism, Oxygen metabolism
- Abstract
Objective: To assess oxygen diffusion at 36 weeks' post-menstrual age in preterm infants by means of the non-invasive oxygen saturation/fraction of inspired oxygen ratio (36w-SFR) and to identify factors associated with 36w-SFR - ie, gestational age (GA) and early respiratory disease patterns (ERP)., Methods: Retrospective analysis of prospectively collected data., Setting: Neonatal Intensive Care Unit., Patients: 1005 preterm infants born below 32 weeks' GA., Interventions: 36w-SFR was the mean of SFR values over 24 h on the day infants reached 36 weeks' PMA., Main Outcome Measures: 36w-SFR., Statistics: descriptive statistics, univariate, and multivariate analysis to study associations of 36w-SFR, including GA and ERP., Results: 36w-SFR was significantly different between infants with and without bronchopulmonary dysplasia (BPD) (371 vs 467, P < 0.001), and according to ERP (LowFIO2 466, pulmonary improvement-PI 460, pulmonary deterioration-PD 405, early persistent pulmonary deterioration-EPPD 344, P < 0.001). Significant differences were found either in BPD and in non-BPD patients according to ERP (P < 0.001). Patients without BPD had significant differences in 36w-SFR according to GA (P < 0.001), while infants with BPD and increasing GA at birth had a non-significant trend for increased 36w-SFR (P = 0.621). Factors associated with 36w-SFR were GA, being small for GA, sepsis, human milk feeding, and ERP., Conclusions: Preterm infants without BPD had a spectrum of oxygen diffusion impairment that was inversely associated with GA at birth. Infants with different patterns of ERP had significant differences in 36w-SFR., (© 2019 Wiley Periodicals, Inc.) more...
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- 2019
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46. A rare mutation of retinoic acid receptor-β associated with lethal neonatal Matthew-Wood syndrome.
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Nobile S, Pisaneschi E, Novelli A, and Carnielli VP
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- Humans, Infant, Newborn, Male, Mutation, Receptors, Retinoic Acid physiology, Anophthalmos genetics, Lung Diseases genetics, Microphthalmos genetics, Receptors, Retinoic Acid genetics
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- 2019
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47. Effects of Arachidonic and Docosohexahenoic Acid Supplementation during Gestation in Rats. Implication of Placental Oxidative Stress.
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Reyes-Hernández CG, Ramiro-Cortijo D, Rodríguez-Rodríguez P, Giambelluca S, Simonato M, González MDC, López de Pablo AL, López-Giménez MDR, Cogo P, Sáenz de Pipaón M, Carnielli VP, and Arribas SM
- Subjects
- Animals, Arachidonic Acid blood, Diet, Docosahexaenoic Acids blood, Female, Fetal Development drug effects, Fetal Weight drug effects, Fetus anatomy & histology, Fetus drug effects, Lipid Peroxidation drug effects, Male, Organ Size drug effects, Oxidation-Reduction, Placenta drug effects, Pregnancy, Pregnancy Outcome, Rats, Arachidonic Acid pharmacology, Dietary Supplements, Docosahexaenoic Acids pharmacology, Oxidative Stress drug effects, Placenta pathology
- Abstract
Arachidonic and docosahexaenoic acids (ARA and DHA) are important during pregnancy. However, the effects of dietary supplementation on fetal growth and oxidative stress are inconclusive. We aimed to assess the effect of high ARA and DHA diet during rat gestation on: (1) ARA and DHA availability in plasma and placenta, (2) fetal growth, and (3) placental oxidative stress, analyzing the influence of sex. Experimental diet (ED) was prepared by substituting soybean oil in the control diet (CD) by a fungi/algae-based oil containing ARA and DHA (2:1). Rats were fed with CD or ED during gestation; plasma, placenta, and fetuses were obtained at gestational day 20. DHA, ARA, and their precursors were analyzed in maternal plasma and placenta by gas chromatography/mass spectrophotometry. Fetuses and placentas were weighed, the proportion of fetuses with intrauterine growth restriction (IUGR) determined, and placental lipid and protein oxidation analyzed. ED fetuses exhibited lower body weight compared to CD, being >40% IUGR; fetal weight negatively correlated with maternal plasma ARA, but not DHA. Only ED female placenta exhibited higher lipid and protein oxidation compared to its CD counterparts; lipid peroxidation is negatively associated with fetal weight. In conclusion, high ARA during gestation associates with IUGR, through placental oxidative stress, with females being more susceptible. more...
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- 2018
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48. The maternal-fetal gradient of free and esterified phytosterols at the time of delivery in humans.
- Author
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Correani A, Visentin S, Cosmi E, Ponchia E, D'Aronco S, Simonato M, Vedovelli L, Cogo P, and Carnielli VP
- Subjects
- Adult, Cohort Studies, Delivery, Obstetric, Female, Humans, Infant, Newborn, Male, Fetal Blood chemistry, Maternal-Fetal Exchange physiology, Phytosterols blood, Pregnancy blood, Pregnancy statistics & numerical data
- Abstract
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.) more...
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- 2018
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49. False positive screen test for mucopolysaccharidoses in healthy female newborns.
- Author
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Monachesi C, Zampini L, Padella L, Marchesiello RL, Galeazzi T, Santoro L, Catassi C, Gasparrini E, Carnielli VP, Volpi N, Fiumara A, Concolino D, Tomanin R, Coppa GV, and Gabrielli O
- Subjects
- Electrophoresis, False Positive Reactions, Female, Humans, Infant, Newborn, Male, Methylene Blue analogs & derivatives, Methylene Blue chemistry, Mucopolysaccharidoses diagnosis, Mucopolysaccharidoses urine
- Abstract
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.) more...
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- 2018
- Full Text
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50. Cardiopulmonary-Bypass Glial Fibrillary Acidic Protein Correlates With Neurocognitive Skills.
- Author
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Vedovelli L, Padalino M, Suppiej A, Sartori S, Falasco G, Simonato M, Carnielli VP, Stellin G, and Cogo P
- Subjects
- Academic Medical Centers, Biomarkers blood, Cardiopulmonary Bypass adverse effects, Child, Cognition Disorders etiology, Cognition Disorders physiopathology, Cohort Studies, Female, Follow-Up Studies, Heart Defects, Congenital diagnostic imaging, Humans, Hypothermia, Induced methods, Incidence, Infant, Infant, Newborn, Intellectual Disability blood, Intellectual Disability etiology, Italy, Male, Multivariate Analysis, Neurologic Examination methods, Prospective Studies, ROC Curve, Regression Analysis, Risk Assessment, Cardiopulmonary Bypass methods, Cognition Disorders epidemiology, Glial Fibrillary Acidic Protein blood, Heart Defects, Congenital surgery, Intellectual Disability epidemiology
- Abstract
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.) more...
- Published
- 2018
- Full Text
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