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1. Intersociety policy statement on the use of whole-exome sequencing in the critically ill newborn infant

Author

Borghesi, A, Mencarelli, Ma, Memo, L, Ferrero, Gb, Bartuli, A, Genuardi, M, Stronati, M, Villani, A, Renieri, A, Corsello, G, Their Respective Scientific Societies, Agostiniani, R, Staiano, A, Del Vecchio, A, Banderali, G, Peroni, D, Piazzolla, R, Turra, R, Bozzola, E, Vecchio, D, Rosati, Gv, Macrì, F, Romagnoli, C, De Curtis, M, Orfeo, L, Mangili, G, Mosca, F, Fanos, V, Paolillo, P, Raimondi, F, Rizzo, A, Chirico, G, Corvaglia, Lt, Cacace, Concetta, Poggiani, C, Zuppa, Aa, Pisano, D, Melis, D, Giuffrè, M, Carbone, Mt, Macchiaiolo, M, Tarani, L, Selicorni, A, Andria, G, Coviello, D, Gentile, M, Ghiorzo, P, Novelli, A, Ragusa, A, Scarano, G, Giardino, D., Borghesi A, Mencarelli MA, Memo L, Ferrero GB, Bartuli A, Genuardi M, Stronati M, Villani A, Renieri A, Corsello G, Borghesi, Alessandro, Mencarelli, Maria Antonietta, Memo, Luigi, Ferrero, Giovanni Battista, Bartuli, Andrea, Genuardi, Maurizio, Stronati, Mauro, Villani, Alberto, Renieri, Alessandra, Corsello, Giovanni, and Agostiniani R, Staiano A, Del Vecchio A, Banderali G, Peroni D, Piazzolla R, Turra R, Bozzola E, Vecchio D, Rosati GV, Macrì F, Romagnoli C, De Curtis M, Orfeo L, Mangili G, Mosca F, Fanos V, Paolillo P, Raimondi F, Rizzo A, Chirico G, Corvaglia LT, Cacace C, Poggiani C, Zuppa AA, Pisano D, Melis D, Giuffrè M, Carbone MT, Macchiaiolo M, Tarani L, Selicorni A, Andria G, Coviello D, Gentile M, Ghiorzo P, Novelli A, Ragusa A, Scarano G, Giardino D.

Subjects
0301 basic medicine, Male, Neonatal intensive care unit, Disease, Review, 030105 genetics & heredity, Pediatrics, Whole Exome Sequencing, Neonate, Neonatal, Outcome Assessment, Health Care, Diagnosis, Policy Making, Exome sequencing, Sanger sequencing, Genome, lcsh:RJ1-570, Perinatology and Child Health, Settore MED/38, Intensive Care Units, Italy, Whole-exome sequencing, Practice Guidelines as Topic, symbols, WES, Female, Human, Diagnosi, NICU, medicine.medical_specialty, Mendelian, 03 medical and health sciences, symbols.namesake, Outcome Assessment (Health Care), Neonatal Screening, Genetic, Intensive Care Units, Neonatal, Exome Sequencing, medicine, WGS, Pediatrics, Perinatology and Child Health, Humans, Genetic Testing, Intensive care medicine, Settore MED/06 - ONCOLOGIA MEDICA, Genetic heterogeneity, Critically ill, business.industry, Genome, Human, Infant, Newborn, Infant, lcsh:Pediatrics, Newborn, Infant newborn, 030104 developmental biology, Differential diagnosis, business
Abstract

The rapid advancement of next-generation sequencing (NGS) technology and the decrease in costs for whole-exome sequencing (WES) and whole-genome sequening (WGS), has prompted its clinical application in several fields of medicine. Currently, there are no specific guidelines for the use of NGS in the field of neonatal medicine and in the diagnosis of genetic diseases in critically ill newborn infants. As a consequence, NGS may be underused with reduced diagnostic success rate, or overused, with increased costs for the healthcare system. Most genetic diseases may be already expressed during the neonatal age, but their identification may be complicated by nonspecific presentation, especially in the setting of critical clinical conditions. The differential diagnosis process in the neonatal intensive care unit (NICU) may be time-consuming, uncomfortable for the patient due to repeated sampling, and ineffective in reaching a molecular diagnosis during NICU stay. Serial gene sequencing (Sanger sequencing) may be successful only for conditions for which the clinical phenotype strongly suggests a diagnostic hypothesis and for genetically homogeneous diseases. Newborn screenings with Guthrie cards, which vary from country to country, are designed to only test for a few dozen genetic diseases out of the more than 6000 diseases for which a genetic characterization is available. The use of WES in selected cases in the NICU may overcome these issues. We present an intersociety document that aims to define the best indications for the use of WES in different clinical scenarios in the NICU. We propose that WES is used in the NICU for critically ill newborn infants when an early diagnosis is desirable to guide the clinical management during NICU stay, when a strong hypothesis cannot be formulated based on the clinical phenotype or the disease is genetically heterogeneous, and when specific non-genetic laboratory tests are not available. The use of WES may reduce the time for diagnosis in infants during NICU stay and may eventually result in cost-effectiveness.

Published
2017

2. Risk factors for bronchiolitis hospitalization during the first year of life in a multicenter Italian birth cohort

Author

Lanari M, Prinelli F, Adorni F, Di Santo S, Vandini S, Silvestri M, Musicco M, Faldella G, Spinelli M, Corsello G, Gabriele B, La Forgia N, Loprieno S, Boldrini A, Vuerich M, Del Vecchio A, Bertino E, Fabris C, Coscia A, Fanos V, Puddu M, Gargano G, Braibanti S, Corso G, Orfeo L, De Luca MG, Paolillo P, Fabiano A, Barberi I, Arco A, Barboni G, Molinari L, Bonomi A, Ladetto L, Carlucci A, Zorzi G, Dall’Agnola A, Girardi E, Di Fabio S, Faccia P, Bottau P, Macagno F, Ellero S, Magaldi R, Rinaldi M, Memo L, Nicolini G, Ngalikpima CJ, Nosari N, Sarnelli P, Parmigiani S, Agosti M, Negri C, Corona MF, Piano F, Scarcella A, Umbaldo A, De Curtis M, Natale F, Aurilia C, Romagnoli C, Lanari, Marcello, Prinelli, Federica, Adorni, Fulvio, Di Santo, Simona, Vandini, Silvia, Silvestri, Michela, Musicco, Massimo, and Lanari M, Prinelli F, Adorni F, Di Santo S, Vandini S, Silvestri M, Musicco M, Faldella G, Spinelli M, Corsello G, Gabriele B, La Forgia N, Loprieno S, Boldrini A, Vuerich M, Del Vecchio A, Bertino E, Fabris C, Coscia A, Fanos V, Puddu M, Gargano G, Braibanti S, Corso G, Orfeo L, De Luca MG, Paolillo P, Fabiano A, Barberi I, Arco A, Barboni G, Molinari L, Bonomi A, Ladetto L, Carlucci A, Zorzi G, Dall’Agnola A, Girardi E, Di Fabio S, Faccia P, Bottau P, Macagno F, Ellero S, Magaldi R, Rinaldi M, Memo L, Nicolini G, Ngalikpima CJ, Nosari N, Sarnelli P, Parmigiani S, Agosti M, Negri C, Corona MF, Piano F, Scarcella A, Umbaldo A, De Curtis M, Natale F, Aurilia C, Romagnoli C

Subjects
Palivizumab, Male, Pediatrics, medicine.medical_specialty, Multivariate analysis, Gestational Age, Respiratory Syncytial Virus Infections, Respiratory syncytial virus, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Risk Factors, 030225 pediatrics, medicine, Bronchiolitis, Viral, Humans, 030212 general & internal medicine, Bronchiolitis, Children, Hospitalization, Prophylaxis, Risk factor, Breast Feeding, Crowding, Female, Infant, Infant, Newborn, Italy, Multivariate Analysis, Pediatrics, Perinatology and Child Health, Viral, Bronchiolitis, Hospitalization, Risk factor, Respiratory syncytial virus, Prophylaxis, Palivizumab, Children, business.industry, Research, Gestational age, Perinatology and Child Health, medicine.disease, Newborn, 3. Good health, Gestation, business, Breast feeding, medicine.drug, Cohort study
Abstract

Background: Respiratory Syncytial Virus (RSV) is one of the main causes of respiratory infections during the first year of life. Very premature infants may contract more severe diseases and 'late preterm infants' may also be more susceptible to the infection. The aim of this study is to evaluate the risk factors for hospitalization during the first year of life in children born at different gestational ages in Italy. Methods: A cohort of 33-34 weeks gestational age (wGA) newborns matched by sex and age with two cohort of newborns born at 35-37 wGA and >37 wGA were enrolled in this study for a three-year period (2009-2012). Hospitalization for bronchiolitis (ICD-9 code 466.1) during the first year of life was assessed through phone interview at the end of the RSV season (November-March) and at the completion of the first year of life. Results: The study enrolled 2314 newborns, of which 2210 (95.5 %) had a one year follow-up and were included in the analysis; 120 (5.4 %) were hospitalized during the first year of life for bronchiolitis. Children born at 33-34 wGA had a higher hospitalization rate compared to the two other groups. The multivariate analysis carried out on the entire population associated the following factors with higher rates for bronchiolitis hospitalization: male gender; prenatal treatment with corticosteroids; prenatal exposure to maternal smoking; singleton delivery; respiratory diseases in neonatal period; surfactant therapy; lack of breastfeeding; siblings

Published
2015
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3. Prenatal tobacco smoke exposure increases hospitalizations for bronchiolitis in infants

Author

Lanari M, Vandini S, Adorni F, Prinelli F, Di Santo S, Silvestri M, Musicco M, ' Faldella G, Spinelli M, Corsello G, La Forgia N, Loprieno S, Boldrini A, Vuerich M, Del Vecchio A, Fabris C, Bertino E, Gaudino M, Coscia A, Fanos V, Puddu M, Gargano G, Braibanti S, Corso G, Orfeo L, De Luca MG, Paolillo P, Fabiano A, Barberi I, Barboni G, Molinari L, Bonomi A, Ladetto L, Carlucci A, Zorzi G, De Curtis M, Natale F, Di Fabio S, Faccia P, Bottau P, Macagno F, Ellero S, Magaldi R, Rinaldi M, Memo L, Nicolini G, Ngalikpima CJ, Nosari N, Sarnelli P, Parmigiani S, Agosti M, Negri C, Corona MF, Piano F, Umbaldo A, Dall’Agnola A, Girardi E, Gabriele B, Aurilia C, Romagnoli C, Lanari M, Vandini S, Adorni F, Prinelli F, Di Santo S, Silvestri M, Musicco M, ' Faldella G, Spinelli M, Corsello G, La Forgia N, Loprieno S, Boldrini A, Vuerich M, Del Vecchio A, Fabris C, Bertino E, Gaudino M, Coscia A, Fanos V, Puddu M, Gargano G, Braibanti S, Corso G, Orfeo L, De Luca MG, Paolillo P, Fabiano A, Barberi I, Barboni G, Molinari L, Bonomi A, Ladetto L, Carlucci A, Zorzi G, De Curtis M, Natale F, Di Fabio S, Faccia P, Bottau P, Macagno F, Ellero S, Magaldi R, Rinaldi M, Memo L, Nicolini G, Ngalikpima CJ, Nosari N, Sarnelli P, Parmigiani S, Agosti M, Negri C, Corona MF, Piano F, Umbaldo A, Dall’Agnola A, Girardi E, Gabriele B, Aurilia C, Romagnoli C, Lanari, Marcello, Vandini, Silvia, Adorni, Fulvio, Prinelli, Federica, Di Santo, Simona, Silvestri, Michela, and Musicco, Massimo

Subjects
Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Pediatrics, Time Factors, Time Factor, Offspring, Longitudinal Studie, Risk Assessment, Tobacco smoke exposure, Pregnancy, Infant, Bronchiolitis, Hospitalization, Risk factor, Bronchiolitis, Hospitalization, Infant, Pregnancy, Risk factor, Tobacco smoke exposure, Age Factors, Female, Humans, Infant, Newborn, Inhalation Exposure, Italy, Longitudinal Studies, Maternal Exposure, Risk Factors, Smoking, Tobacco Smoke Pollution, Prenatal Exposure Delayed Effects, medicine, Age Factor, Bronchioliti, Intensive care medicine, Inhalation exposure, business.industry, Research, Gestational age, Newborn, medicine.disease, Risk assessment, business, Human, Cohort study
Abstract

Background Tobacco smoke exposure (TSE) is a worldwide health problem and it is considered a risk factor for pregnant women’s and children’s health, particularly for respiratory morbidity during the first year of life. Few significant birth cohort studies on the effect of prenatal TSE via passive and active maternal smoking on the development of severe bronchiolitis in early childhood have been carried out worldwide. Methods From November 2009 to December 2012, newborns born at ≥33 weeks of gestational age (wGA) were recruited in a longitudinal multi-center cohort study in Italy to investigate the effects of prenatal and postnatal TSE, among other risk factors, on bronchiolitis hospitalization and/or death during the first year of life. Results Two thousand two hundred ten newborns enrolled at birth were followed-up during their first year of life. Of these, 120 (5.4 %) were hospitalized for bronchiolitis. No enrolled infants died during the study period. Prenatal passive TSE and maternal active smoking of more than 15 cigarettes/daily are associated to a significant increase of the risk of offspring children hospitalization for bronchiolitis, with an adjHR of 3.5 (CI 1.5–8.1) and of 1.7 (CI 1.1–2.6) respectively. Conclusions These results confirm the detrimental effects of passive TSE and active heavy smoke during pregnancy for infants’ respiratory health, since the exposure significantly increases the risk of hospitalization for bronchiolitis in the first year of life. Electronic supplementary material The online version of this article (doi:10.1186/s12931-015-0312-5) contains supplementary material, which is available to authorized users.

Published
2015
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4. [Phototherapy: recent acquisitions, indications and limits]

Author

Paludetto, R, Orfeo, L, DE CURTIS, Mario, and Manzi, F.

Subjects
Male, Exchange Transfusion, Whole Blood, Infant, Newborn, Infant, Jaundice, Phototherapy, Newborn, Jaundice, Neonatal, Neonatal, Humans, Female, Hyperbilirubinemia, Exchange Transfusion, Whole Blood
Published
1982

5. Prune Belly appearance in a Turner subject

Author

M Stabile, G. Esposito, S Iannuzzi, V Ventruto, U De Bellis, L. Orfeo, A. Savanelli, Savanelli, Antonio, Orfeo, L, Stabile, M, Iannuzzi, S, De Bellis, U, Esposito, G, and Ventruto, V.

Subjects
Genetics, Male, Turner Syndrome, Subject (documents), Karyotype, Anatomy, Biology, medicine.disease, Chromosome Banding, Phenotype, Prune belly syndrome, Prune belly, Turner syndrome, medicine, Humans, Prune Belly Syndrome, Female, Genetics (clinical), Research Article
Published
1986

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