Autonomic control in preterm infants - what we can learn from mathematical descriptions of vital signs

Background: Preterm birth is a major burden, affecting approximately 15 million infants each year. Recent advances in reproductive medicine increases that number even more. The population of preterm infants in particular suffers from autonomic dysregulation that manifests as temperature instability and poor control of heart rate and breathing. Thermal care, monitoring of vital signs in a neonatal intensive care unit, pharmacotherapy, and respiratory support over weeks to months is necessary. Improvements in neonatal care in the past years lead to a decrease in mortality, especially in very preterm infants. However, former preterm infants still are a high-risk population for acute and chronic sequelae as a result of the interruption of the physiological development. A better understanding of the pathophysiology of the autonomic dysregulation in that population would be very useful. Unfortunately, accurate diagnostic tools that objectively assess and quantify the immature autonomic control in neonates are lacking. Methods: In this PhD thesis we examined different effects of the immature autonomic control in very preterm infants under clinically relevant conditions. We conducted a prospective single center observational study, where we assessed fluctuations in body temperature, sleep behavior, and heart rate variability in very preterm infants. We described the different regulatory systems using distinct mathematical expressions, such as detrended fluctuation analysis and sample entropy. We assessed associations between these outcome parameters and relevant factors of the infant’s history, such as demographic parameters and co-morbidities. Besides that, we analyzed lung function measurements of preterm infants and healthy term controls at a comparable postconceptional age, to describe respiratory control. Results: This study is systematically assessing different physiological signals of autonomic dysregulation in preterm infants during their first days of life. We found associations between parameters describing the complexity of time series analysis and maturity or relevant co-morbidities of the infants. In the analysis of heart rate variability we even found that parameters derived from time series analysis, assessed during the infants first days of life, improve our ability to predict future evolution of the infants’ autonomic stability. Lastly, several weeks after the expected due date, tidal breathing pattern of preterm infants showed a different reaction in response to a sigh when compared to term born controls at equivalent postmenstrual age indicating that autonomic dysregulation in preterm infants is still present well beyond the expected due date. Conclusion: A better understanding about the resolution of autonomic dysregulation in this population is not only important for the infant and its family but has the potential to support resource allocation and identification of patients with elevated risk for future deterioration. We thus think that the insights about the immature autonomic control in preterm infants, gained through this PhD work, are of substantial scientific and clinical relevance

Advanced analyses of physiological signals and their role in Neonatal Intensive Care

Preterm infants admitted to the neonatal intensive care unit (NICU) face an array of life-threatening diseases requiring procedures such as resuscitation and invasive monitoring, and other risks related to exposure to the hospital environment, all of which may have lifelong implications. This thesis examined a range of applications for advanced signal analyses in the NICU, from identifying of physiological patterns associated with neonatal outcomes, to evaluating the impact of certain treatments on physiological variability. Firstly, the thesis examined the potential to identify infants at risk of developing intraventricular haemorrhage, often interrelated with factors leading to preterm birth, mechanical ventilation, hypoxia and prolonged apnoeas. This thesis then characterised the cardiovascular impact of caffeine therapy which is often administered to prevent and treat apnoea of prematurity, finding greater pulse pressure variability and enhanced responsiveness of the autonomic nervous system. Cerebral autoregulation maintains cerebral blood flow despite fluctuations in arterial blood pressure and is an important consideration for preterm infants who are especially vulnerable to brain injury. Using various time and frequency domain correlation techniques, the thesis found acute changes in cerebral autoregulation of preterm infants following caffeine therapy. Nutrition in early life may also affect neurodevelopment and morbidity in later life. This thesis developed models for identifying malnutrition risk using anthropometry and near-infrared interactance features. This thesis has presented a range of ways in which advanced analyses including time series analysis, feature selection and model development can be applied to neonatal intensive care. There is a clear role for such analyses in early detection of clinical outcomes, characterising the effects of relevant treatments or pathologies and identifying infants at risk of later morbidity

Prediction of short-term health outcomes in preterm neonates from heart-rate variability and blood pressure using boosted decision trees

Background and Objective: Efficient management of low blood pressure (BP) in preterm neonates remains challenging with considerable variability in clinical practice. There is currently no clear consensus on what constitutes a limit for low BP that is a risk to the preterm brain. It is argued that a personalised approach rather than a population based threshold is more appropriate. This work aims to assist healthcare professionals in assessing preterm wellbeing during episodes of low BP in order to decide when and whether hypotension treatment should be initiated. In particular, the study investigates the relationship between heart rate variability (HRV) and BP in preterm infants and its relevance to a short-term health outcome. Methods: The study is performed on a large clinically collected dataset of 831 h from 23 preterm infants of less than 32 weeks gestational age. The statistical predictive power of common HRV features is first assessed with respect to the outcome. A decision support system, based on boosted decision trees (XGboost), was developed to continuously estimate the probability of neonatal morbidity based on the feature vector of HRV characteristics and the mean arterial blood pressure. Results: It is shown that the predictive power of the extracted features improves when observed during episodes of hypotension. A single best HRV feature achieves an AUC of 0.87. Combining multiple HRV features extracted during hypotensive episodes with the classifier achieves an AUC of 0.97, using a leave-one-patient-out performance assessment. Finally it is shown that good performance can even be achieved using continuous HRV recordings, rather than only focusing on hypotensive events – this had the benefit of not requiring invasive BP monitoring. Conclusions: The work presents a promising step towards the use of multimodal data in providing objective decision support for the prediction of short-term outcome in preterm infants with hypotensive episodes

Heart beat variability analysis in perinatal brain injury and infection

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica) Universidade de Lisboa, Faculdade de Ciências, 2018Todos os anos, mais de 95 mil recém-nascidos são admitidos nas Unidades de Cuidados Intensivos Neonatais (UCIN) do Reino Unido, devido principalmente a partos prematuros ou outras complicações que pudessem ter ocorrido, como é o caso da encefalopatia hipóxico-isquémica (EHI), que assume 3% de todas as admissões nas unidades referidas. EHI é o termo que define uma complicação inesperada durante o parto, que resulta em lesões neurológicas a longo prazo e até em morte neonatal, devido à privação de oxigénio e fluxo sanguíneo ao recém-nascido durante o nascimento. Estima-se que tenha uma incidência de um a seis casos por 1000 nascimentos. Nos países desenvolvidos, a hipotermia é utilizada como método preventivo-terapêutico para esta condição. No entanto, existem dois grandes obstáculos para a obtenção da neuroprotecção pretendida e totalmente benéfica, na prática clínica. Em primeiro lugar, esta técnica é eficaz se for iniciada dentro de seis horas após o parto. Visto que o estado clínico da encefalopatia neonatal evolui nos dias posteriores ao nascimento, a sua deteção precoce é um grande desafio. Tal situação pode levar a diversos erros nas UCIN, tal como indivíduos sujeitos à terapia de hipotermia desnecessariamente, ou ainda mais grave, casos em que recém-nascidos foram inicialmente considerados como saudáveis, não tendo sido submetidos à terapia referida, apresentarem sinais de EHI após seis horas de vida. A segunda questão prende-se com o facto de a neuroprotecção poder ser perdida se o bebé estiver stressado durante o tratamento. Para além disso, não existe nenhuma ferramenta válida para a avaliação da dor dos recém-nascidos submetidos a esta terapia. Os obstáculos frisados anteriormente demonstram duas necessidades ainda não correspondidas: a carência de um método não invasivo e largamente adaptável a diferentes cenários para uma correta identificação de recém-nascidos com maior probabilidade de HIE, dentro de uma margem de seis horas após o parto, mas também um método preciso de stress em tempo real, não invasivo, que possa orientar tanto pessoal médico, como pais, de modo a oferecer um tratamento mais responsável, célere e individualizado. Deste modo, a análise do ritmo cardíaco demostra um enorme potencial para ser um biomarcador de encefalopatia neonatal, bem como um medidor de stress, através da eletrocardiografia (ECG), visto que é um importante indicador de homeostase, mas também de possíveis condições que podem afetar o sistema nervoso autónomo e, consequentemente, o equilíbrio do corpo humano. É extremamente difícil a obtenção de um parâmetro fisiológico, sem a presença de artefactos, especialmente no caso de recém-nascidos admitidos nas UCIN. Tanto no caso da aquisição de ECGs, como de outros parâmetros, existe uma maior probabilidade de o sinal ser corrompido por artefactos, visto que são longas aquisições, normalmente dias, onde o bebé é submetido a diversas examinações médicas, está rodeado de equipamentos eletrónicos, entre outros. Artefactos são definidos como uma distorção do sinal, podendo ser causados por diversas fontes, fisiológicas ou não. A sua presença nos dados adquiridos influencia e dissimula as informações corretas e reais, podendo mesmo levar a diagnósticos e opções terapêuticas erradas e perigosas para o paciente. Apesar de existirem diversos algoritmos de identificação de artefactos adequados para o sinal cardíaco adulto, são poucos os que funcionam corretamente para o de recém-nascido. Para além disso, é necessário bastante tempo tanto para o staff clínico, como para os investigadores, para o processo de visualização e identificação de artefactos no eletrocardiograma manualmente. Deste modo, o projeto desenvolvido na presente dissertação propõe um novo algoritmo de identificação e marcação de artefactos no sinal cardíaco de recém-nascidos. Para tal, foi criado um modelo híbrido de um método que tem em consideração todas as relações matemáticas de batimento para batimento cardíaco, com outro que tem como objetivo a remoção de spikes no mesmo sinal. O algoritmo final para além de cumprir com o objetivo descrito acima, é também adaptável a diferentes tipos de artefactos presentes no sinal, permitindo ao utilizador, de uma forma bastante intuitiva, escolher o tipo de parâmetros e passos a aplicar, podendo ser facilmente utilizado por profissionais de diferentes áreas. Deste modo, este algoritmo é uma mais-valia quando aplicado no processamento de sinal pretendido, evitando assim uma avaliação visual demorada de todo o sinal. Para obter a melhor performance possível, durante o desenvolvimento do algoritmo foram sempre considerados os resultados de validação, tais como exatidão, sensibilidade, entre outros. Para tal, foram analisados e comparados eletrocardiogramas de 4 recém-nascidos saudáveis e 4 recém-nascidos com encefalopatia. Todos possuíam aproximadamente 5 horas de sinal cardíaco adquirido após o nascimento, com diferentes níveis de presença de artefactos. O algoritmo final, obteve uma taxa de sensibilidade de 96.2% (±2.4%) e uma taxa de exatidão de 92.6% (±3.2%). Como se pode verificar pelos valores obtidos, o algoritmo obteve percentagens altas nos vários parâmetros de classificação, o que significa uma deteção correta. A taxa de exatidão apresenta um valor mais baixo, comparativamente ao parâmetro da sensibilidade, pois em diversas situações, normalmente perto de artefactos, os batimentos normais são considerados como artefactos, pelo algoritmo. Contudo, essa taxa não é alarmante, tendo sido considerada uma taxa reduzida, pelo pessoal médico. Após o processamento do sinal cardíaco dos grupos mencionados acima, um estudo comparativo, utilizando parâmetros da variabilidade do ritmo cardíaco, foi realizado. Diferenças significativas foram encontradas entre os dois grupos, onde o saudável assumiu sempre valores maiores. SDNN e baixa frequência foram os parâmetros que traduziram uma diferença maior entre os dois grupos, com um p-value <0.01. De modo a corresponder ao segundo obstáculo referido nesta dissertação, outro objetivo desta tese foi a criação de um algoritmo que pudesse identificar e diferenciar uma situação de stress nesta faixa etária, com recurso ao ritmo cardíaco. Um estudo multidimensional foi aplicado aos diferentes métodos de entropia utilizados nesta tese (approximate entropy, sample entropy, multiscales entopy e fuzzy entropy) de modo a estudar como os diferentes métodos de entropia interagem entre si e quais são os resultados dessa relação, especialmente na distinção de estados normais e stressantes. Para tal, a utilização de clusters foi essencial. Dado que para todos os ECGs de bebés saudáveis analisados neste projeto foram registados todas as possíveis situações de stress, como é o caso de choro, examinações médicas, mudança de posição, entre outros, foram escolhidos 10 minutos do sinal do ritmo cardíaco adquirido, antes da situação, para análise. Infelizmente, associado a um evento stressante, na maioria dos casos encontra-se uma percentagem bastante alta do sinal corrompida por artefactos. No entanto, em alguns casos foi possível observar uma clara distinção de grupos de clusters, indicando que naquele período de tempo, houve uma mudança de estado. Foi também realizado um estudo intensivo de diversos métodos de entropia aplicados ao grupo de sujeitos apresentados nesta dissertação, onde foi provado que o método mais adequado a nível de diferenciação é a Fuzzy Entropy (p=0.0078). Ainda é possível sugerir alguns aspetos e apontar algumas limitações, no âmbito de poderem ser ultrapassadas no futuro. Em primeiro lugar, é necessária a aquisição de mais eletrocardiogramas, quer de recém-nascidos saudáveis, quer com encefalopatia hipóxico-isquémica, de modo a aumentar o tamanho da amostra e, deste modo diminuir os valores do desvio-padrão em todos os parâmetros calculados. Relativamente ao estudo do stress, seria interessante, com uma amostra maior, a definição de clusters, de modo a ter uma identificação precisa de situações stressantes. Para além disso, a transformação do software atualmente escrito em MATLAB para GUI (interface gráfica do utilizador), a fim de tornar mais acessível a sua utilização por profissionais de diversas áreas.In Neonatal Intensive Care Unit (NICU), the heart rate (HR) offers significant insight into the autonomic function of sick newborns, especially with hypoxic ischemic encephalopathy condition (HIE). However, the intensity of clinical care and monitoring contributes to the electrocardiogram (ECG) to be often noisy and contaminated with artefacts from various sources. These artefacts, defined as any distortion of the signal caused by diverse sources, being physiological or non-physiological features, interfere with the characterization and subsequent evaluation of the heart rate, leading to grave consequences, both in diagnostic and therapeutic decisions. Besides, its manual inspection in the ECG trace is highly time-consuming, which is not feasible in clinical monitoring, especially in NICU. In this dissertation, it is proposed an algorithm capable of automatically detect and mark artefacts in neonatal ECG data, mainly dealing with mathematical aspects of the heart rate, starting from the raw signal. Also, it is proposed an adjacent algorithm, using complexity science applied to HR data, with the objective of identifying stress scenarios. Periods of 10-minute ECG were considered from 8 newborns (4 healthy and 4 HIE) to the identification of stress situations, whereas for the artefacts removal algorithm small portions varying in time length according to the amount of noise present in the originally 5 hours long samples were utilised. In this report it is also present several comparisons utilising heart rate parameters between healthy and HIE groups. Fuzzy Entropy was considered the best method to differentiate both groups (p=0.00078). In this report, substantial differences in heart rate variability were found between healthy and HIE groups, especially in SDNN and low frequency (p<0.01), confirming results of previous literature. For the final artefact removal algorithm, it is illustrated significant differences between raw and post-processed ECG signals. This method had a Recall rate of 96.2% (±2.4%) and a Precision Rate of 92.6% (±3.2%), demonstrating high efficiency in ECG noise removal. Regarding stress measures, associated with a stressful event, in most cases there is a high percentage of the signal corrupted by artefacts. However, in some cases it was possible to see a clear distinction between groups of clusters, indicating that in that period, there was a change of state. Not all the time segments from subjects demonstrated differences in stress stages, indicating that there is still room for improvement in the method developed

A method to detect and represent temporal patterns from time series data and its application for analysis of physiological data streams

In critical care, complex systems and sensors continuously monitor patients??? physiological features such as heart rate, respiratory rate thus generating significant amounts of data every second. This results to more than 2 million records generated per patient in an hour. It???s an immense challenge for anyone trying to utilize this data when making critical decisions about patient care. Temporal abstraction and data mining are two research fields that have tried to synthesize time oriented data to detect hidden relationships that may exist in the data. Various researchers have looked at techniques for generating abstractions from clinical data. However, the variety and speed of data streams generated often overwhelms current systems which are not designed to handle such data. Other attempts have been to understand the complexity in time series data utilizing mining techniques, however, existing models are not designed to detect temporal relationships that might exist in time series data (Inibhunu & McGregor, 2016). To address this challenge, this thesis has proposed a method that extends the existing knowledge discovery frameworks to include components for detecting and representing temporal relationships in time series data. The developed method is instantiated within the knowledge discovery component of Artemis, a cloud based platform for processing physiological data streams. This is a unique approach that utilizes pattern recognition principles to facilitate functions for; (a) temporal representation of time series data with abstractions, (b) temporal pattern generation and quantification (c) frequent patterns identification and (d) building a classification system. This method is applied to a neonatal intensive care case study with a motivating problem that discovery of specific patterns from patient data could be crucial for making improved decisions within patient care. Another application is in chronic care to detect temporal relationships in ambulatory patient data before occurrence of an adverse event. The research premise is that discovery of hidden relationships and patterns in data would be valuable in building a classification system that automatically characterize physiological data streams. Such characterization could aid in detection of new normal and abnormal behaviors in patients who may have life threatening conditions

Selected Lectures of the XXIV National Congress of the Italian Society of Neonatology (Società Italiana di Neonatologia, SIN); Rome (Italy); September 26-29, 2018

Selected Lectures of the XXIV National Congress of the Italian Society of Neonatology (Società Italiana di Neonatologia, SIN); Rome (Italy); September 26-29, 2018 Guest Editor: Mauro Stronati LECT 1. FEEDING INTOLERANCE IN PRETERM INFANTS • A. Aceti LECT 2. PREBIOTICS ARE ALL THE SAME • M. Agosti LECT 3. NURSE AND PAIN MANAGEMENT IN NEWBORN: THEORETICAL AND PRACTICAL ASPECTS • A. Allegro, I. Arenga, S. Lazzari LECT 4. THE “THINKING” NURSE: A RESOURCE OR A TROUBLESOME FIGURE? HOW TO INTERACT WITHIN A MULTIDISCIPLINARY TEAM • M. Altafini, D. Bolognini, P. Coscia LECT 5. COMPARISON OF PAIN MEASUREMENT PERFORMED BY NURSES AND PARENTS • G. Ancora, N. Simeone, E. Baudassi, T. Pesaresi, S. Grandi, F. Fabbri, S. Lazzari LECT 6. RED REFLEX AT BIRTH: AIM, EXECUTION AND IMPLEMENTATION • G. Araimo, S. Aversa, A. Baldascino, S. Frezza LECT 7. ERRORS IN THERAPY ADMINISTRATION IN THE NEONATAL INTENSIVE CARE UNIT: WHICH IS THE BEST STRATEGY TO PREVENT THEM? • M.C. Ariotti, F. Vignali, F. Logrippo, F. De Matteis, M. Luciano, A. Coscia, F. Cresi, E. Bertino LECT 8. KANGAROO MOTHER CARE AT THE HEART OF INDIVIDUALIZED FAMILY-CENTERED CARE: IMPLICATIONS FOR THE DEVELOPMENT OF PRETERM INFANTS • C. Artese, G. Calciolari LECT 9. KANGAROO MOTHER CARE IN ITALY: 2017 SURVEY • C. Artese, G. Paterlini; Neonatal Care Study Group LECT 10. NEWBORN OF MOTHERS AFFECTED BY THYROID DISEASE • G. Barera, M.C. Vigone, G. Vincenzi LECT 11. NURSING RECOMMENDATIONS ON THE SKIN MANAGEMENT OF TERM AND PRETERM INFANT • E. Bernabei, P. Coscia, M. Di Giuseppe, L. Guarinoni, S. Tuccio, V. Vanzi LECT 12. INTRAUTERINE GROWTH RESTRICTION: SHORT AND LONG TERM OUTCOME • E. Bertino, A. Coscia, E. Spada, M. Baricco, S. Sottemano, P. Di Nicola LECT 13. INTERSOCIETY POLICY STATEMENT ON THE USE OF WHOLE-EXOME SEQUENCING IN THE CRITICALLY ILL NEWBORN INFANT • A. Borghesi, M.A. Mencarelli, L. Memo, G.B. Ferrero, A. Bartuli, M. Genuardi, M. Stronati, A. Villani, A. Renieri, G. Corsello, on behalf of their respective Scientific Societies LECT 14. LET’S SHED SOME LIGHT ON DISCHARGE INSTRUCTIONS FOR NEWBORNS • K. Bressan, P. Paolillo LECT 15. STOP-IVH PROTOCOL IN VERY LOW BIRTH WEIGHT INFANTS: A QUALITY IMPROVEMENT APPROACH • L. Brombin, A. Galderisi, E. Baraldi, E. Lolli, D. Trevisanuto LECT 16. MINDFULNESS IN HELP FOR THE OPERATORS IN NICU: AN EXPERIMENTAL TRAINING PATH AT THE S. ANNA TURIN HOSPITAL • G. Cacciato, L. Ostacoli, M. Montanari LECT 17. KANGAROO MOTHER CARE: ITS BIRTH, WORLDWIDE DIFFUSION, SCIENTIFIC EVIDENCE • G. Calciolari LECT 18. USE OF BUNDLES TO PREVENT CENTRAL LINE ASSOCIATED BLOODSTREAM INFECTION IN NEONATAL INTENSIVE CARE UNITS • A. Capasso, D. Celentano, R. Mastroianni, N. Pozzi LECT 19. NEONATE OF MOTHER WITH AUTOIMMUNE DISEASE • L. Capasso, M. Palma, C. Coppola, C. Gagliardo, C. Parrella, S. Cioffi, C. Colinet, F. Raimondi LECT 20. RETINOPATHY OR PREMATURITY: DIAGNOSIS AND THERAPEUTIC APPROACHES BY THE OPHTHALMOLOGIST • S. Capobianco LECT 21. STRATEGIES FOR HUMAN MILK FORTIFICATION • M. Carta, G. Corsello LECT 22. NEONATAL ACUTE KIDNEY INJURY: DIAGNOSIS AND TREATMENT CHALLENGE • D. Cattarelli LECT 23. ROLE OF MILRINONE IN THE MANAGEMENT OF RIGHT VENTRICULAR DYSFUNCTION • R.M. Cerbo LECT 24. MULTIDISCIPLINARY EXPERIENCE WITH A CASE OF OMPHALOPAGUS TWINS • M. Cheli, A. Barletta, M. Colledan, B.G. Locatelli, P. Betalli, L. Migliazza, M. Colusso LECT 25. NEONATAL CRANIAL ULTRASOUND: HOW TO OPTIMIZE ITS PERFORMANCE • A. Chiara LECT 26. A CLINICAL AND DIAGNOSTIC APPROACH TO A NEWBORN WITH MULTIPLE CONGENITAL MALFORMATIONS • P. Cianci, A. D’Ambra, L. Memo LECT 27. BASIC ECHOCARDIOGRAPHY COURSE FOR THE NEONATOLOGIST • I. Corsini, S. Fiocchi, K. Rossi, S. Salvadori, F. Schena, M. Savoia LECT 28. MANAGEMENT OF SHORT BOWEL SYNDROME IN THE NEONATAL POPULATION • L. Corvaglia, S. Martini LECT 29. STRATEGIES OF NUTRITION AND FORTIFICATION IN PRETERM SMALL-FOR-GESTATIONAL AGE OR GROWTH-RESTRICTED NEWBORNS • A. Coscia, M. Baricco LECT 30. THE MUCOPOLYSACCHARIDOSES • S. Costa, C. Cocca, G. Vento LECT 31. FEEDING INTOLERANCE AND GASTROESOPHAGEAL REFLUX • F. Cresi, E. Maggiora LECT 32. FAMILY-CENTERED CARE IN ITALIAN NEONATAL INTENSIVE CARE UNITS: PARENT EXPERIENCE AND SATISFACTION, A SYNTHESIS OF A MULTICENTER STUDY AND PRELIMINARY RESULTS • I. Dall’Oglio, A. Portanova, R. Mascolo, E. Tiozzo, A. Ragni, P. Amadio, O. Gawronski, M. Fiori, A. Dotta, C. Offidani, S. Piga, G. Rocco, R. Alvaro, J.M. Latour; the Italian NICUs Family-Centered Care Study Group LECT 33. RESPIRATORY SUPPORT AND PHARMACOLOGICAL TREATMENT OF BRONCHOPULMONARY DYSPLASIA: TOWARDS INDIVIDUALIZED CARE • C. Dani LECT 34. DECREASING THE POLLUTION OF HUMAN MILK, WHILE DEFENDING THE GOOD REPUTATION OF BREASTFEEDING • R. Davanzo, C. Di Lucca, A. Derosa, C. Mastrorilli, F. Forte, M. Delvecchio, P. Appio, V. Targiani, C. Figliuolo, T. Faillace LECT 35. CAN BLOOD GAS ANALYSIS BY UMBILICAL CORD ARTERY PREDICT CLINICAL OUTCOME IN NEWBORNS WITH APGAR SCORE ≥ 7 AT 5 MINUTES FROM BIRTH? • G. De Bernardo, R. Ippolito, M. Giordano, F. Beccagutti, D. Sordino, P. Villani LECT 36. ULTRASOUND FINDINGS IN NEONATAL MENINGITIS • A. Di Comite LECT 37. CONTAMINANTS IN INFANTS’ FOODS • S. Di Fabio, V. Nardi LECT 38. LEFT VENTRICULAR DYSFUNCTION: COULD BE FENOLDOPAM USEFUL? • D. Doni LECT 39. THE NEONATAL NETWORK OF THE ITALIAN SOCIETY OF NEONATOLOGY • A. Fabiano, D. Di Lallo, F. Franco, P. Paolillo LECT 40. VISUAL FUNCTION DEFICIT IN PRETERM NEWBORNS • E. Fazzi, L. Malerba, M. Gnesi, A. Rossi LECT 41. CASE REPORT: SEVERE ACUTE BRONCHIOLITIS • T. Fedeli, F. Cattaneo LECT 42. ACUTE KIDNEY INJURY: DEFINITION AND CLASSIFICATION • R. Galiano, P. Novellino LECT 43. HEALTH-RELATED QUALITY OF LIFE OF FORMERLY PRETERM INFANTS FROM CHILDHOOD TO ADULTHOOD • F. Gallini, D.U. De Rose, H. Hindocha, K. Del Vecchio, M. Coppola, L. Maggio LECT 44. COMPUTERIZED MANAGEMENT OF THE EMERGENCY: FROM THE REQUEST TO THE APPROPRIATE HOSPITALIZATION • M. Gente, F. Franco, D. Di Lallo LECT 45. SEX-RELATED DIFFERENCES IN THE OUTCOME OF PRETERM INFANTS: A REVIEW • P. Ghirri, M. Ciantelli LECT 46. GROWTH ASSESSMENT AND NUTRITION • M.L. Gianni, P. Roggero, F. Mosca LECT 47. BREASTFEEDING GUIDED BY NEWBORN • A. Giustardi, M. Stablum, A. Semjonova LECT 48. TEAMWORK AND ON THE JOB TRAINING IN NEONATAL INTENSIVE CARE UNIT • L. Guarinoni, E. Dioni LECT 49. THE ROLE OF THE NURSE IN THE PROMOTION OF THE KANGAROO MOTHER CARE IN THE NEONATAL INTENSIVE CARE UNIT • G. Ierardi, G. Cuomo, N. Bertoncelli, L. Lucaccioni, E. Garetti, L. Bedetti, F. Ferrari LECT 50. BREASTFEEDING PROMOTION IN NEONATAL INTENSIVE CARE UNIT • L. Ilardi LECT 51. PERINATAL PALLIATIVE CARE IN 2018: A NATIONAL SURVEY • P. Lago, M.E. Cavicchiolo, F. Benini LECT 52. METABOLIC ACIDOSIS IN CONGENITAL HEART DISEASES • S. La Placa LECT 53. RECENT ADVANCES IN BREASTFEEDING • S. Longo, M. Stronati LECT 54. CONJOINED TWINS: NEONATAL MANAGEMENT • G. Mangili, M. D’Angiò, C. Gilardi, M. Giozani, D. Martinelli LECT 55. INTRACAVITARY ECG FOR CENTRAL CATHETER’S TIP LOCATION IN INFANTS • R. Mastroianni, A. Capasso, N. Pozzi, D. Celentano LECT 56. RESPIRATORY VIRUS INFECTIONS IN CHILDREN: PREVENTION AND TREATMENT • P. Mastromarino, E. Schiavi LECT 57. COMMUNICATION, MEDIA, AND MASS-MEDIA: HOW CAN WE GET READY TO DEAL WITH ALL OF THIS? • A. Mattiola, B. Gigantesco, M. Del Pistoia, F. Lorenzoni, P. Ghirri, E. Sigali, S. Bardelli, S. Tognarelli, M. Ciantelli, R. Scaramuzzo, A. Cuttano LECT 58. GENETIC ASSOCIATION WITH CONGENITAL HEART DISEASE • I. Mauro LECT 59. EARLY STRESS AND EPIGENETIC EFFECTS IN PRETERM INFANTS • R. Montirosso, L. Provenzi LECT 60. FOLLOWING UP THE RESPIRATORY CONSEQUENCES OF PRETERM BIRTH • L. Moschino, M.E. Cavicchiolo, E. Baraldi LECT 61. NEONATAL BLEEDING DISORDERS AND PLASMA TRANSFUSION • M. Motta, B. Guaragni, G. Chirico LECT 62. ASSESSMENT OF NURSING SKILLS: THE EXPERIENCE OF A NEONATAL INTENSIVE CARE UNIT • S. Muscolo, L. Plevani LECT 63. EMERGING BIOMARKERS AND METABOLOMICS FOR MANAGING NEONATAL SEPSIS • M. Mussap, V. Fanos LECT 64. ENTERAL FEEDING IN PRETERM INFANTS: NOT AS TRIVIAL AS IT IS SUPPOSED TO BE • A. Orsi, L. Ilardi, A. Coscia, G. Salvatori, F. Cresi LECT 65. KANGAROO MOTHER CARE AND PROMOTION OF BREASTFEEDING: THE BREASTFEEDING WHEEL • S. Perugi LECT 66. NEUROLOGICAL COMPLICATIONS DURING RESPIRATORY SYNCYTIAL VIRUS INFECTION • S. Picone, F. Di Palma, D. Roma, P. Paolillo LECT 67. SEDATION FOR NEUROIMAGING IN INFANTS • A. Pirelli, B. Garetti, G. Cristofori, I. Arenga, L. Iantorno, P. Lago LECT 68. PERINATAL STROKE: CLINICAL CLUES AND DIAGNOSIS • E. Piro, I.A.M. Schierz, I. Greco, V. Vanella, G. Corsello LECT 69. ULTRASOUND GUIDED CENTRAL VENOUS ACCESS IN CRITICALLY ILL NEONATES AND INFANT BABIES • N. Pozzi, D. Celentano, R. Mastroianni, A. Capasso LECT 70. NATIONAL NETWORK OF THE ITALIAN SOCIETY OF NEONATOLOGY: DATA SOURCE FOR SCIENTIFIC PAPERS • C. Protano, F. Franco, D. Di Lallo, M. De Curtis LECT 71. ANTIBIOTIC PROPHYLAXIS IN THE NEONATE? • L. Pugni, I. Bottino, A. Ronchi, C. Pietrasanta, B. Ghirardi, F. Mosca LECT 72. ETHICAL ISSUES AND NEONATAL RESUSCITATION • C. Romagnoli LECT 73. NUTRITIONAL PROBLEMS IN SURGICAL INFANTS: WHICH IS THE GOAL? • G. Salvatori, S. Foligno LECT 74. SYSTEMIC THROMBOEMBOLISM AND CEREBRAL SINOVENOUS THROMBOSIS IN NEONATAL AGE • P. Saracco, A. Viano, R. Bagna, S. Viola, M. Magarotto LECT 75. USE OF SUCROSE IN MINOR INVASIVE PROCEDURE: WHAT’S NEW? • P. Savant Levet LECT 76. CARDIOVASCULAR ABNORMALITIES IN BRONCHOPULMONARY DYSPLASIA (BPD). BPD IS NOT A MATTER OF PULMONARY HYPERTENSION ONLY • M. Savoia LECT 77. NEUROPROTECTION IN ADDITION TO HYPOTHERMIA • A. Scoppa LECT 78. STRATEGIES FOR STIMULATION OF ORAL FEEDING CAPACITY IN PRETERM • E. Stimoli, A. Maini, P. Servi LECT 79. EARLY, PROTECTED AND ASSISTED NEONATAL HOSPITAL DISCHARGE • I. Stolfi, L. Bristot, R. Pedicino, C. Fassi, G. Terrin LECT 80. NEONATAL PAROXYSMAL MOTOR PHENOMENA: FROM SEMIOLOGY TO CLINICAL DIAGNOSIS • A. Suppiej LECT 81. REIKI AND HEALTH: THE MEETING BETWEEN AN ANCIENT ORIENTAL DISCIPLINE AND SCIENCE • A. Tallone LECT 82. PREDICTIVE ROLE OF URINARY METABOLIC PROFILE FOR ABNORMAL MAGNETIC RESONANCE IMAGING SCORE IN PRETERM NEONATES • M.L. Tataranno, S. Perrone, M. Longini, C. Coviello, M. Tassini, A. Vivi, M. Calderisi, L. deVries, F. Groenendaal, G. Buonocore, M. Benders LECT 83. PARENTERAL NUTRITION IN PRETERM NEONATE • G. Terrin, V. Bozzetti, O. Amato, M. Di Chiara LECT 84. CARE IN LOW-INCOME COUNTRIES • B. Tomasini, S. Zani, M.J. Caldes, M. Usuelli LECT 85. MIGRANTS AND EMERGING INFECTIOUS DISEASES • C. Tzialla LECT 86. EVALUATION OF EFFICACY OF GLUCOSE GEL VS. GLUCOSE SOLUTION USED FOR PAIN RELIEF IN NEWBORN BABIES. A RANDOMIZED BLIND CLINICAL TRIAL • P.L. Vasarri, M. Dalla Ragione, S. Fligor LECT 87. PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN NOT RESPONSIVE TO NITRIC OXIDE THERAPY; TWO CASES REPORT AND REVIEW OF LITERATURE • G. Vellani, G. Morandi, F.P. Fusco, I. Lombardo, E. Agazzani, M. Zanzucchi, G. Calzetti, S. Boccacci, V. Fasolato LECT 88. RESPIRATORY PHENOTYPES IN NEONATAL CHRONIC LUNG DISEASE: WHAT IS BEHIND THE OXYGEN REQUIREMENT? • M.L. Ventura, C. Rigotti LECT 90. PHARMACOKINETICS IN THE NEONATAL PERIOD • M. Regazzi LECT 91. ORAL FEEDING: A TEAMWORK FOR THE PRETERM • A. Orsi, N. Liotto, P. Piemontese, P. Roggero, F. Mosca LECT 92. RESVERATROL PLUS CARBOXYMETHYL-β-GLUCAN IN INFANTS WITH COMMON COLD: A RANDOMIZED DOUBLE-BLIND TRIAL • M.E. Baldassarre, A. Di Mauro, M. Fanelli, G. Labellarte, C. Pignatelli, N. Laforgia LECT 93. PROPHYLAXIS AND TREATMENT OF ACUTE BRONCHIOLITIS: STATE OF THE ART • P. Biban, A. Serra, F. Sacco, L. Andaloro, G. Pagano, S. Spaggiari, P. Bonetti, M. Gaffuri, R. Frassoldati, P. Santuz LECT 94. NEONATES OF DIABETIC MOTHER: METABOLOMICS • A. Dessì, R. Pintus, M. Puddu, G. Ottonello, V. Fano