Orientador: Leandro Gustavo de Oliveira / Resumo: Introdução: O Lúpus Eritematoso Sistêmico (LES) é uma doença sistêmica de caráter autoimune, que acomete mulheres em idade reprodutiva, sendo que a inter-relação entre a doença e a gestação determina importantes desfechos maternos e perinatais. Objetivos: Descrever os desfechos maternos e perinatais em gestações de pacientes portadoras de LES e avaliar o impacto da nefrite lúpica sobre os resultados encontrados. Métodos: Este é um estudo observacional descritivo desenvolvido para avaliar as inter-relações entre gestação e lúpus eritematoso sistêmico em pacientes atendidas na Maternidade do Hospital das Clínicas da Faculdade de Medicina de Botucatu – HCFMB. O período de estudo foi de janeiro de 2010 a agosto de 2019. Resultados: Foram avaliadas 38 gestações em 31 pacientes com LES. A média das idades foi de 27,4 + 6 anos. A média das idades gestacionais ao nascimento foi de 36 + 3 semanas. As principais intercorrências observadas foram: anemia (39,4%), nefrite lúpica (29%) e hipertensão arterial crônica (10,5%). Hidroxicloroquina foi utilizada em 47,4% das gestações. Em 51,4% das pacientes houve necessidade de antecipação do parto e em 13,1% houve piora da função renal. A incidência de pré-eclâmpsia foi de 19,4%. Prematuridade ocorreu em 20% dos casos e restrição de crescimento fetal, em 19,4%. Nefrite lúpica determinou maior ocorrência de flare (p<0,05) e maior necessidade de antecipação do parto (p< 0,05). Conclusão: O presente estudo permitiu avaliar a inter-relação entre L... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Systemic Lupus Erythematosus is an autoimmune systemic disease that affects women of reproductive age, and the interrelation between disease and pregnancy determines important maternal and perinatal outcomes. Objectives: To describe maternal and perinatal outcomes in pregnancies of patients with SLE and to evaluate the impact of lupus nephritis on the results found. Methods: Descriptive observational study developed to assess the interrelation between pregnancy and systemic lupus erythematosus in patients attended at the Maternity of the Clinics Hospital from Botucatu Medical School – HCFMB. The study period corresponded to January 2010 until August 2019. Results: Thirty-eight pregnancies were evaluated in 31 patients with SLE. Their average age was 27.4 + 6.0 years. The average gestational age at birth was 36 + 3 weeks. The main clinical complications observed were anemia (39.4%), lupus nephritis (29%) and chronic hypertension (10.5%). In 51,4% of the patients, it was necessary to anticipate delivery and in 13.1%, there was worsening of the renal function. Prematurity occurred in 20% of cases and FGR in 19,4%. Hydroxicloroquine was used in 47,4% of the pregnancies. Lupus nephritis determined a higher occurrence of flare (p<0.05) and a greater need to anticipate delivery (p<0.05). Conclusion: The present study made it possible to relate the main clinical characteristics and the maternal and perinatal outcomes from the pregnant women with SLE treated at the prena... (Complete abstract click electronic access below) / Mestre

Proteomics is the global study of proteins in an organism or a tissue/fluid and is clinically relevant since most disease states are accompanied by specific alterations in an organism's proteome. This review focuses on the application of proteomics to neonatology with particular emphasis on retinopathy of prematurity (ROP), which is a disease in which oxidative stress plays a key pathophysiological role. Oxidative stress is a physiologically relevant redox imbalance caused by an excess of reactive oxygen (ROS) or reactive nitrogen oxide species (RNOS). A major conclusion of this review is that proteomics may be the optimal technology for studying neonatal diseases such as ROP, particularly in the setting of a neonatal intensive care unit (NICU). Proteomics has already identified a number of ROP serum biomarkers. This review will also suggest novel therapeutic approaches to ROP and other neonatal oxidative stress diseases (NOSDs) based on a systems medicine approach.

The purpose of the study was to identify factors associated with the delay in the initiation of breastfeeding to premature infants before discharge from hospital. The need for this research is evident in the current practice of feeding premature infants after a nasogastric tube is removed. The study sought to provide answers to delayed initiation of breastfeeding to premature infants before discharge from hospital. Fifty members of staff in the Sick Neonate Unit and 50 mothers of premature infants participated in the study. Self-administered data collection instruments were used to collect data from mothers of premature infants and staff of a Sick Neonate Unit in the hospital. The results showed that sociodemographic factors of staff 15 (f=30%) were 31-40 years old, and young nursing staff have decreased knowledge of breastfeeding as compared to senior and older staff members. Maternal demographic factors 36 (f=73.5%) were single and 13 (f=26.5) were married. Married mothers were more likely to breastfeed with the support of the partner than unmarried mothers. Health service factors staff views towards breastfeeding were 11(f=22.0% staff members were neutral about breastfeeding, and Eighteen (f=36.0%) staff members strongly disagreed to other methods of infant feeding. Maternal breastfeeding knowledge was one of the factors under maternal breastfeeding factors because it showed that 48 mothers (f=98.0%) did not have breastfeeding knowledge. Descriptive statistics were used to analyse data. / Health Studies / M.A. (Health Studies)

Prematurity is a worldwide problem. Every year, 15 million babies are born prematurely, and 1 million of those babies die because of related complications. The surviving premature babies are struggling to hold on to their lives, and even when they do live, most of them end up having various complications to survive and get stronger. There are physical complications faced on their journey such as having underdeveloped lungs, pneumonia, obesity, sepsis, retinopathy of prematurity, respiratory distress syndrome, bronchopulmonary dysplasia, asthma, wheezing, bronchiolitis, cerebral palsy, and motor impairment. They can also develop mental and behavioral health complications such as depression, seizures developmental delay, schizophrenia, autism spectrum disorder, psychological development disorders, behavioral problems, attention problems, and ADHD later in life. The purpose of this systemic review is to understand the impact of long-term complications of premature birth on individual life and society. We hypothesized that based on data from primary research, nearly one half of the infants will have either physical and/or cognitive/developmental health complications. We hypothesized that infants born premature have more physical complications than cognitive complications and infants born prematurely have more cognitive complications than physical complications. This research was carried out by finding cohort study design studies through Medline, Academic Search Premier, and APA PsychINFO, where the studies will be compiled from 2003 – 2020.

Au cours des trois dernières décennies, l’amélioration des soins périnataux a permis une meilleure survie des nouveau-nés nés prématurément (<37 semaines de gestation), et en particulier ceux extrêmement prématurés (<28 semaines). Plusieurs études ont montré une vulnérabilité accrue des individus prématurés aux maladies chroniques. En effet, la naissance prématurée est associée à des modifications au niveau des systèmes cardiovasculaire, pulmonaire, métabolique ou encore osseux. On retrouve également une réduction de la capacité à l’exercice, souvent attribuée à l’atteinte cardio-pulmonaire. Cependant, l’impact de la naissance prématurée sur le développement et la fonction des muscles squelettiques, un acteur essentiel de la capacité d’exercice et de la santé cardiorespiratoire, reste à élucider. Afin de faire état de la littérature concernant l'impact de la naissance prématurée sur les muscles squelettiques, nous avons réalisé une revue systématique et méta-analyse. Dans l’ensemble, les résultats indiquaient une altération de la masse et de la fonction des muscles squelettiques chez les individus nés prématurément comparés à ceux nés à terme. Cette étude a également mis en évidence un manque évident de connaissances des mécanismes liant les impacts de la naissance prématurée et le développement et la fonction des muscles squelettiques depuis l’enfance jusqu’à l’âge adulte. L’objectif de cette thèse est donc d’identifier comment les conditions associées à une naissance prématurée en début de vie ont un impact sur la santé des muscles squelettiques plus tard dans la vie. Dans un premier article, utilisant un modèle animal mimant les conditions délétères liées à la naissance prématurée, nous avons rapporté un stress oxydatif et une inflammation tissulaire des muscles aux stades néonatal, juvéniles et adultes. Ces modifications étaient associées à un changement des types de fibres, une fibrose et à des altérations fonctionnelles suggérant un phénotype de vieillissement prématuré. Dans un deuxième article nous avons mis en évidence chez les adultes nés prématurément une réduction de l’aire musculaire et de la force (préhension et extenseur de la jambe) associées à une rigidité musculaire accrue comparées aux individus nés à terme. Dans un troisième article nous avons approfondi les mécanismes physiopathologiques et nous avons mis en évidence que ce phénotype observé en modèle expérimental et chez l’humain serait en partie expliqué par une atteinte de la capacité myogénique des cellules souches musculaires, cruciales pour le développement et la réparation musculaire tout au long de la vie. En effet, nous avons démontré qu’une exposition aux conditions délétères liées à la naissance prématurée induit une inflammation chronique de faible intensité caractérisée par une régulation positive de la voie TNF-α/NF-κB dans le muscle squelettique. Cette inflammation est responsable d’une altération de la capacité myogénique des cellules souches musculaires et de la capacité régénérative du muscle. Ces altérations peuvent entraîner une modification de la santé musculaire et un phénotype de vieillissement/faiblesse musculaire à l’âge adulte. Dans l’ensemble, les travaux présentés dans cette thèse ouvrent une nouvelle voie de recherche dans notre compréhension des conséquences de la naissance prématurée sur la santé à long terme. Ils apportent plusieurs éléments déterminants concernant les mécanismes sous-jacents expliquant l’atteinte musculaire suite à une naissance prématurée. Ces travaux permettent de souligner l’importance de déterminer des stratégies visant à améliorer la santé des muscles squelettiques, avec le postulat que ces interventions peuvent représenter une nouvelle voie pour prévenir les maladies chroniques suite à une naissance prématurée. / Over the last three decades, improved perinatal care allow the survival of the vast majority of infants born preterm (<37 weeks of gestation), especially those extremely prematurely (<28 weeks). Several studies have shown an increased vulnerability of individuals born preterm to chronic diseases. Indeed, premature birth is associated with changes in cardiovascular, pulmonary, metabolic and bone systems. Preterm birth is associated with reduce exercise capacity explained by the cardiopulmonary impairment. However, the impact of preterm birth on the development and function of skeletal muscles, critical player of exercise capacity and cardiorespiratory health, remains to be exam. To report the literature regarding the impact of premature birth on skeletal muscles, we conducted a systematic review and meta-analysis. Overall, the results indicated impaired skeletal muscle mass and function in individuals born prematurely compared to those born at term. This study also highlighted a clear lack of knowledge of the mechanisms linking the impacts of premature birth and the development and function of skeletal muscles from childhood to adulthood. The objective of this thesis is therefore to identify how conditions associated with premature birth early in life impact skeletal muscle health later in life. In a first article, using an animal model mimicking the deleterious conditions associated to premature birth, we reported oxidative stress and muscle tissue inflammation. These modifications were associated with fiber typing changing, fibrosis and functional alterations suggesting a premature aging phenotype. In a second article we demonstrated in adults born preterm a reduction of muscle area and strength (grip and leg extensor) associated with increased stiffness of the tissue compared to individuals born at term. Thus, individuals born preterm appear to show signs of premature muscle aging, as observed in the animal model. In a third article, we demonstrated that this phenotype observe could be explained by an impairment of the myogenic capacity of muscle stem cells, crucial for muscle development and repair throughout the life. Indeed, we reported that exposure to deleterious conditions linked to premature birth induces low-grade inflammation characterized by an upregulation of the TNF-α/NF-κB pathway in skeletal muscle. This inflammation is responsible for an alteration of the myogenic capacity of muscle stem cells and of the regenerative capacity of muscle. These modifications could lead to altered muscle health and an aging/weakened muscle phenotype in adulthood. Overall, the work presented in this thesis opens a new avenue of research to enhance our understanding of the consequences of preterm birth on long-term health. We provide several determining elements concerning the underlying mechanisms explaining muscle damage following preterm birth. This work highlights the importance of determining strategies aimed at improving skeletal muscle health, with the postulate that these interventions may represent a new avenue for preventing chronic diseases following premature birth.

Background Modern neonatal care has improved the survival rate of extremely preterm infants. These infants are at high risk of malnutrition and growth failure during 3-4 months of hospital care. The objectives of this study was to investigate nutritional intakes during hospitalization and explore associations between nutritional intakes, postnatal growth and retinopathy of prematurity (ROP). Perioperative nutrition in infants undergoing surgery for patent ductus arteriosus (PDA) was also investigated. Methods This is a population-based study of Swedish extremely preterm infants (&lt;27 weeks) born during 2004-2007 (n=602). Detailed data on nutritional supply and anthropometric measurements during hospitalization were retrospectively retrieved from hospital records. Comprehensive data on cohort characteristics, neonatal morbidity and infant mortality were obtained from the Extremely Preterm Infants in Sweden Study (EXPRESS). Results During the first 70 days of life, intakes of energy, protein and several micronutrients, with the exception of iron and some vitamins, were less than estimated requirements, and infants showed severe postnatal growth failure. Energy and protein intake predicted growth in all anthropometric outcomes even when adjusting for severity of illness, and fat intake was positively associated with head growth. Low folate intake was positively correlated with poor weight and length gain while high iron intake, mainly explained by blood transfusions, was negatively associated with poor length gain. Furthermore, a low energy intake was associated with severe ROP (stage 3-5). An increased energy intake of 10 kcal/kg/d was associated with 24% decrease in severe ROP (p=0.01). During the first month, 99% of the infants were exclusively fed human milk. Infants who underwent surgery for PDA (n=140) were malnourished, with energy and macronutrient intakes below minimum estimated requirements before, during and after surgery. Conclusions The severe postnatal growth failure observed in Swedish extremely preterm infants may be prevented by improved intakes of energy, protein, fat and folate and a reduction of the number of blood transfusions. Human milk is the main enteral food source and analyses of human milk macronutrient contents facilitates individualized fortification. Provision of adequate energy intakes during the first four weeks of life may be an effective way to reduce the risk of severe ROP. Perioperative nutrition in infants undergoing PDA surgery needs to be improved. The study results have important implications for nutritional regimens, postnatal growth and health outcome in this new generation of survivors.

Introduction : Les enfants prématurés ont la particularité de naître alors que leur développement est souvent incomplet et nécessite la mise en œuvre de soins intensifs visant à poursuivre leur croissance en dehors de l’environnement utérin. Souvent cependant, le stade développemental de l’enfant ne lui permet pas d’assimiler une alimentation entérale du fait de l’immaturité de son système digestif. Le recours à une voie centrale délivrant les nutriments assurant le développement devient alors une nécessité. Ce type de nutrition, appelée nutrition parentérale (NP, ou total parenteral nutrition TPN), permet l’administration de molécules simples, directement dans le sang du prématuré. Il n’est toutefois pas exempt de risques puisqu’exposée à la lumière, la NP peut s’oxyder et générer des molécules oxydantes telles que des hydroperoxydes lipidiques susceptibles de se fragmenter par la suite en hydroxy-alkénals. Ceci devient problématique au vu de l’immaturité des systèmes de défenses antioxydants du nouveau-né prématuré. L’utilisation prolongée de la NP est d’ailleurs à l’origine de maladie hépatiques dans lesquelles le stress oxydant et la nécro-inflammation sont des composantes majeures. Nous avons émis l’hypothèse que l’infusion chez les enfants prématurés, d’aldéhydes d’origine lipidique est en relation avec le développement du stress oxydant et de l’inflammation hépatique. Objectif : Notre étude a consisté à évaluer la relation entre les quantités d’hydroxy-alkénals dans la NP et les effets hépatiques engendrés sur les marqueurs de stress oxydant et les voies de signalisation responsables d’une induction de processus inflammatoire. Dans ce but, nous avons cherché à mesurer la peroxydation lipidique dans l’émulsion lipidique de la NP et la conséquence de l’infusion en continue d’hydroxy-alkénals sur les marqueurs de stress oxydant, sur la voie de signalisation médiée par le Nuclear Factor κB et sur le déclenchement du processus inflammatoire hépatique. A la suite de ce travail, nous avons également travaillé sur des alternatives à la photoprotection, qui est la seule méthode réellement optimale pour réduire la peroxydation des lipides de la NP, mais cliniquement difficilement praticable. Résultats : Nos résultats ont mis en évidence la génération de 4-hydroxynonenal in vitro dans la NP, ce phénomène est augmenté par une exposition lumineuse. Dans ce cadre, nous avons montré l’inefficacité de l’ajout de multivitamines dans l’émulsion lipidique comme alternative à la photoprotection. Dans la validation biologique qui a suivi sur un modèle animal, nos résultats ont permis de démontrer que l’augmentation des adduits glutathion-hydroxynonenal était imputable à l’augmentation de 4-hydroxynonenal (4-HNE) dans la NP, et non à une peroxydation endogène. Nos données indiquent que la probable augmentation hépatique des niveaux de 4-HNE a conduit à une activation du NFκB responsable de l’activation de la transcription des gènes pro-inflammatoires du Tumour Necrosis Factor-α (TNF-α) et de l’interleukine-1 (IL-1). Nous avons alors évalué la capacité d’une émulsion lipidique enrichie en acides gras polyinsaturés (AGPI) n-3 à baisser les concentrations de 4-HNE dans la NP, mais également à moduler le stress oxydant et les marqueurs pro-inflammatoires. Enfin, nous avons démontré, en collaboration avec l’équipe du Dr Friel, que certains peptides isolés du lait humain (par un processus mimant la digestion) permettent également une modulation du stress oxydant et du processus inflammatoire. Conclusion : Le stress oxydant exogène issu de la NP a conduit par activation de facteurs de transcription intra-hépatiques au déclenchement d’un processus inflammatoire potentiellement responsable du développement de maladies hépatiques reliées à la NP telle que la cholestase. Dans ce sens, les AGPI n-3 et les peptides antioxydants peuvent se poser en tant qu’alternatives crédibles à la photoprotection. / Introduction: Premature infants usually born before full term require intensive care to continue to grow up outside the uterine environment. Premature newborns are born with gastrointestinal systems that are too immature to absorb nutrients safely. Therefore they receive their initial nutrients through intravenous feeding, called total parenteral nutrition which delivers simple nutrients directly into bloodstream. However, light exposed-TPN can generate oxidant molecules such as lipid hydroperoxides, which can potently break up into hydroxy-alkenals. Prolonged use of TPN is also a cause of liver disease in which oxidative stress and necro-inflammation are major components. Thus, we hypothesize that lipid aldehydes contained in TPN are associated with oxidative stress and hepatic inflammation developments. Objectives: The aim of our study is to assess the relationship between quantities of hydroxyl-alkenals generated in TPN and effects on oxidative stress biomarkers and cell-signalling pathways molecules implicated in hepatic inflammation induction. To this end, we measure lipid peroxidation in the TPN lipid emulsion in and the consequence of continuous infusion of hydroxy-alkenals on markers of oxidative stress, on cell-signaling pathway mediated by the NFkB, and on liver inflammation induction. Following these data, we also worked on alternatives of photoprotection, which is the only optimal method for preventing lipid peroxidation, but unfortunately clinically impractical. Results: In vitro studies have highlighted the generation of 4-HNE in the TPN, increased under light exposure. In this context, we have demonstrated that the addition of multivitamins in the lipid emulsion cannot be a valuable alternative to photoprotection. Concerning the biological validation in our guinea pig animal model, our results demonstrated that the increase of GS-HNE adducts was due to increased 4-HNE in the TPN, and does not provide from endogenous peroxidation. Our data also indicate that the increase of hepatic 4-HNE led to an activation of NFkB, responsible for the activation of the transcription of proinflammatory genes TNF-α, IL-1. In the next study, we have evaluated the ability of a lipid emulsion enriched with n-3 polyunsaturated fatty acids (PUFA) to reduce 4-HNE concentrations generated in TPN, and to modulate oxidative stress markers and pro-inflammatory process on the same animal model. We also have demonstrated, in collaboration with Dr Friel’s team, that two antioxidant peptides (derived from a process mimicking digestion process of human milk) allow also a modulation of oxidative stress and inflammatory process in the liver. Conclusion: This form of exogenous oxidative stress from the TPN led to an inflammatory process resulting from the activation of intrahepatic transcription, which is potentially responsible of liver disease development such as cholestasis. In this sense, the n-3 PUFA and antioxidant peptides may arise as a valuable alternative of photoprotection.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Réalisé en cotutelle avec l'Université de Lorraine (France) / Ce projet traite de la programmation développementale de l’hypertension artérielle (HTA) à travers des influences néonatales précoces pouvant moduler le développement vasculaire. Les bébés prématurés présentent des défenses antioxydantes diminuées comparés aux nouveau-nés à terme et sont exposés à la naissance à des concentrations élevées en oxygène (O2) engendrant la production d’espèces réactives de l’O2 (ERO). Les conséquences vasculaires à long terme de dommages liés aux ERO en période néonatale et les mécanismes impliqués sont très partiellement compris. Les précédents résultats du laboratoire ont montré qu’un stress hyperoxique néonatal conduit chez le rat adulte à de l’HTA, une dysfonction endothéliale et une rigidité artérielle, éléments de vieillissement vasculaire. Nous émettons l'hypothèse qu'un stress hyperoxique néonatale conduit à long terme à l'altération de la structure vasculaire et à un vieillissement vasculaire précoce. Nous avons démontré une diminution de la prolifération cellulaire, une capacité angiogénique altérée, des dommages à l’ADN et une augmentation de l’expression de protéines de sénescences (des indices de sénescence cellulaire) au-delà de la période néonatale suite à une exposition brève à l’O2 au niveau vasculaire dans un modèle animal (ratons Sprague-Dawley exposés à 80 % d’O2 du 3ème au 10ème jour de vie comparés à des ratons restés à l’air ambiant) et cellulaire (cellules musculaires lisses d'aortes thoraciques d'embryon de rat exposées à 40% O2 pendant 24h ou 48h, puis remises en normoxie pendant 96h). De plus, des altérations des composants de la structure vasculaire indiquant un remodelage vasculaire aortique ont été mises en évidence. Ces changements précèdent tous l’HTA et la dysfonction vasculaire observées dans le modèle animal à l’âge adulte et pourraient y contribuer. L’étude de jeunes adultes nés < 29 semaines comparés à des jeunes adultes nés à terme indique une augmentation de marqueurs de rigidité artérielle (indices d’un vieillissement vasculaire précoce) chez la population prématurée. L’ensemble des résultats démontre un vieillissement vasculaire précoce après une exposition néonatale transitoire à un stress hyperoxique permettant une meilleure compréhension des mécanismes physiopathologiques impliqués dans la survenue des troubles vasculaires retrouvés chez l’adulte et contribue à la mise en place de moyens de prévention chez des patients prématurés. / The scope of this thesis is developmental programming of arterial high blood pressure (HBP) hypertension through early neonatal stimuli that may alter vascular development. Premature newborns have decreased antioxidant defenses compared to term babies and are exposed upon birth to high oxygen (O2) concentration, causing reactive oxygen species (ROS) production. Long term vascular consequences of ROS related damage during the neonatal period and the mechanisms involved remain unknown. Recent data from the laboratory show that neonatal hyperoxic stress leads in adult rat to HBP, endothelial dysfunction and arterial rigidity, characteristic features of vascular aging. We hypothesize that a neonatal hyperoxic stress leads to long term vascular structure alteration explained by an early aging of the vascular system. We showed a decreased proliferation rate, an altered angiogenic capacity, as well as long term DNA damage and increased expression of senescence proteins at a vascular level following O2 exposure in the animal (male Sprague-Dawley pups kept at 80% O2 from postnatal days 3 to 10 vs. rats remained in room air) and cellular models (embryonic vascular smooth muscle cells from rat thoracic aorta exposed to 40% O2 for 24h or 48h followed by 96h recovery in control conditions). In addition, alterations of vascular structure components indicating vascular remodeling was shown before the onset of the HBP at adult age. Those changes precede the HBP and vascular dysfunction observed in our animal model at adult age and could contribute to them. Study of young adults born before 29 weeks vs. young adults born at term showed that young adults born preterm present indices of arterial stiffness vs. term controls. Results of the present thesis demonstrate a major role of premature vascular aging in the surge of vascular diseases in adulthood and contribute to a better understanding of the patho-physiological mechanisms involved and could put into practice new prevention strategies among preterm patients.

The presented thesis deals with the topic of development of communication abilities in preterm infants from the perspective of special education. The thesis is for clarity divided into several parts. In the first part of the text the issue of incidence of premature births in the Czech Republic is discussed, following subsections are devoted to the definition and distribution of characteristics bonding with immaturity of child and approach selected health problems associated with postpartum adaptation and subsequent psychomotor development of child. The following chapter which analyzes the system of care for premature newborns in the Czech Republic focuses on two forms of care, acute care and followed-up. Next part has been devoted to issue of premature infants from logopedical perspective and describes the physiological process of development of communication abilities of child and based on current knowledge, especially foreign research, analyzes the peculiarities of speech development of preterm infants. The last and key part of the work, based on case studies, analyzes the specifics of development of communication abilities of four originally extremely and very preterm children of multiple pregnancies in the background of the their overall psychomotor development. KEYWORDS premature infant,...