Academic literature on the topic 'Prematurity'

Violation of the regulation of congenital immune reactions plays an important role in the etiology of common and serious neonatal complications in prematurely born children such as bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity and others. This review is devoted to the study of one of the indicators of cellular immunity - T-regulatory cells CD4 + CD25 + FoxP3 + CD127low in prematury infants. Further studies of immunity and in particular T-regulatory cells in premature infants in various diseases, including retinopathy of prematurity, will further develop pathogenetically substantiated correction of immunological disorders to prevent their occurrence and progression.

Introduction: Retinopathy of Prematurity (ROP) is almost exclusively in premature infants. With advanced care and technology, the prevalence of retinopathy of prematurity in babies is increasing, which means the incidence of preventable blindness in ROP is increasing. Objectives: To evaluate the effects of protein, glucose, lipids, and total calories from Aggressive Parenteral Nutrition (APN) in improving neovascularisation of ROP in premature infants. Methods: We searched PubMed, Ophthalmology Advance, Scientific Reports, and Science Direct using the terms "Retinopathy of Prematurity", "Aggressive Parenteral Nutrition", "Prevalence of Retinopathy of Prematurity in Indonesia", "Protein", "Lipid", "Carbohydrate", "Glucose", "Total Calories", "Neovascularization", and "Prematurity" in various combinations. Results: We found three pieces of literature stating a positive association between APN and improvement of ROP, while one literature states that there is no significant change of prevalence of ROP by administering APN. Keywords: Aggressive Parenteral Nutrition, glucose, lipid, protein, Retinopathy of Prematurity Pendahuluan: Retinopathy of Prematurity (ROP) adalah penyakit yang hampir secara eksklusif terjadi pada bayi prematur. Dengan perawatan dan teknologi yang canggih, prevalensi retinopati pada bayi prematur meningkat dan ini berarti kejadian kebutaan yang dapat dicegah pada ROP meningkat. Tujuan: Untuk mengevaluasi efek protein, glukosa, lipid, dan kalori total dari Nutrisi Parenteral Agresif (APN) dalam meningkatkan neovaskularisasi ROP pada bayi prematur. Metode: Kami mencari PubMed, Ophthalmology Advance, Scientific Reports dan Science Direct menggunakan istilah “Retinopathy of Prematurity”, “Aggressive Parenteral Nutrition”, “Prevalence of Retinopathy of Prematurity in Indonesia”, “Protein”, “Lipid”, “Carbohydrate” , "Glukosa", "Kalori Total", "Neovaskularisasi", dan "Prematuritas" dalam berbagai kombinasi. Hasil: Ditemukan tiga literatur yang menyatakan terdapat hubungan positif antara APN dengan peningkatan ROP sedangkan satu literatur menyatakan tidak ada perubahan signifikan prevalensi ROP dengan pemberian APN. Kata Kunci: Nutrisi Parenteral Agresif, glukosa, lipid, protein, Retinopati Prematuritas

Aim. The objective of the present study was to identify the main stages of the organization and the results of the ophthalmological care for the children presenting with retinopathy of prematurity (ROP) in the Republic of Crimea. Material and methods. This retrospective analysis of the results of ophthalmological screening of 2105 prematurely born children, monitoring of 281 children with the early stages of ROP, the laser-assisted treatment of 64 babies undergoing the progression of the disease to its threshold stages and the follow up of the children with ROP in the Crimea during the period from 1999 to 2016 years. All the above patients were nursed and treated in the clinical hospital over the territory of the Crimea and in the perinatal centre of Simferopol. Results. ROP was diagnosed in 281 (26%) of the 2105 prematurely born children. The progression of the disease to the threshold stage was documented in 64 (22.8%) patients within 1 to 12 (mean 3-4) weeks after the identification of the initial stages of active ROP. ROP of the posterior aggressive type developed in 15 children. The duly-timed laser-assisted treatment permitted to prevent the appearance of blindness among the prematurely born children attributable to retinopathy of prematurity. As a results of the implementation of the program for the modernization of the ophthalmological care for the retinopathy of prematurity in the Republic of Crimea it is currently organized and provided in conformity with the relevant normative acts of the Ministry of Health of the Russian Federation. The ophthalmological Department of the Republic of Crimea Children’s Clinical Hospital is equipped with the necessary modern medical and diagnostic instruments and techniques; training of the Crimean ophthalmologists in retinopathy of prematurity and laser-assisted treatment of active retinopathy of prematurity.

In recent years there is an increasing topicality of the problem of prematurity because of the growing incidence of premature births in spite of the treatment of pregnant women and application of modern technologies of pregnancy prolongation. According to the WHO report (2015), 15 million children are born prematurely every year and this number is increasing. The article analyzes the risk factors for miscarriage depending on the degree of prematurity and also studies the pathology of the perinatal period, physical and psychomotor development in the first year of life of premature infants. Some distant outcomes of prematurity related to disturbances of physical development, motor and neurological disorders, and premature infant`s intellectual malfunction have been analyzed.

Term infants with hypertrophic pyloric stenosis (HPS) typically present between 4 and 6 weeks. There is limited consensus, however, regarding age of presentation of premature infants. We aim to determine if there is an association between the degree of prematurity and chronological age of presentation of HPS. A total of 2988 infants who had undergone a pyloromyotomy for HPS were identified from the 2012 and 2013 NSQIP-P Participant Use Files. Two hundred seventeen infants (7.3%) were born prematurely. A greater degree of prematurity was associated with an older chronological age of presentation ( P < .0001). Prematurity was significantly associated with an increase in overall postoperative morbidity, reintubation, readmission, and postoperative length of stay. When clinicians evaluate an infant with nonbilious emesis with a history of prematurity, they should consider pyloric stenosis if the calculated postconceptional age is between 44 and 50 weeks. When counseling families of premature infants, surgeons should discuss the increased incidence of postpyloromyotomy morbidity.

<p>Retinopati prematuritas (ROP) adalah kelainan proliferatif progresif pembuluh darah retina bayi prematur yang dapat menyebabkan kebutaan. International Classification of Retinopathy of Prematurity (ICROP) membagi ROP berdasarkan tingkat keparahan, perluasan, lokasi, adanya penyakit lain, dan adanya ROP posterior yang agresif. ROP dimulai dari penundaan vaskularisasi retina akibat keadaan hiperoksia relatif dan dilanjutkan dengan fase vasoproliferasi. Skrining adekuat dengan oftalmoskop indirek dan tatalaksana sesuai pedoman The Early Treatment for Retinopathy of Prematurity (ETROP) menjadi modalitas penanganan ROP saat ini. Tatalaksana dengan modalitas lain masih diteliti.</p><p>Retinopathy of prematurity (ROP) is a proliferative, progressive vascularization in premature infants which can lead to blindness. International Classification of Retinopathy of Prematurity (ICROP) classified the ROP based on severity, extent, zone, the existence of other diseases, and the existence of aggressive posterior ROP. ROP starts with the delay of retinal vascularization from relative hyperoxia state and develops to vasoproliferation phase. Adequate screening by indirect ophthalmoscope and The Early Treatment for Retinopathy of Prematurity (ETROP) treatment guideline become the current modality for ROP therapy. Treatment with other modalities are still under investigation.</p>

Retinopathy of prematurity (RP) is a complex pathology among prematurely born children, which requires a comprehensive approach, including both prevention of the development of more severe stages of the disease, leading to poor vision and irreversible loss of visual functions, and the organization of dispensary observation and rehabilitation. Modern organization of dispensary observation, which is based on a detailed study of the etiology, pathogenesis, as well as the interaction of local and systemic factors on visual functions, can significantly reduce the visual disability of children as a result of this disease.

The evolution of perinatology and the progress of advanced methods of prenatal diagnosis have contributed to the rise of frequency of birth and survival of newborns with very low birth weight, born before 32 weeks of pregnancy. A three-tier perinatology care system in Poland, an increasingly outstanding knowledge of neonatologists, and newer and more advanced equipment for critical care therapy, all provide growingly safer conditions for the life and development of prematurely born children. Prematurity is not only a problem of the preterm baby, but poses a challenge for the family, notably the mother, who must face the challenges of care of the preterm baby. In this article, selected problems of prematurity and care of a preterm baby are presented. The most common causes of preterm birth incidence are reported. The mother’s situation after a preterm birth is defined. Based on the current literature, the profile of preterm babies and the EBM (Evidence-Based Medicine) paradigm, the rules for treatment and care for a preterm baby are presented.

Aim. To study the effectiveness and safety of pentahydroxyethylnaphtoquinone (Hystochrome) in patients with active and fibrous stages of retinopathy of prematurity. Methods. 281 prematurely born babies: first group - 63 patients with retinopathy of prematurity stages I-II and vast non-vascular area; second group - 201 baby with stage III retinopathy of prematurity and posterior aggressive form of retinopathy after the performed retinal laser photocoagulation; third group - 17 babies with subtotal intraocular hemorrhage - were followed up. In addition, 29 children with fibrous stage of retinopathy of prematurity were observed. Pentahydroxyethylnaphtoquinone (Hystochrome) was used as epibulbar instillations and peribulbar injections. To assess the treatment results, examination using the «RETCAM-120» system, B-scan ultrasonography using the «AVISO» scanner and visual evoked potentials examination with flash light stimulus using the «Neuro-MVP» device were performed. Results. In babies from the first group the improvement of electrophysiological parameters was observed in 20% of cases after treatment with pentahydroxyethylnaphtoquinone, compared to 4% in control group. In the second group pentahydroxyethylnaphtoquinone improved the electrophysiological parameters in 39% of cases. In the third group (17 babies with subtotal intraocular hemorrhage) the hemorrhage degradation was twice more rapid compared to controls. There was no effect from pentahydroxyethylnaphtoquinone treatment at the late stages of the disease. No adverse effects were registered. Conclusion. Pentahydroxyethylnaphtoquinone (Hystochrome) has shown good effectiveness and safety while treating patients with non-proliferative stages of retinopathy of prematurity and vitreous hemorrhage.

Apnoea remains an important problem in the prematurely born infant. Apnoeas can be divided into central, obstructed and mixed apnoea. Apnoeas frequently occur in association with periodic breathing, as well as isolated events. It remains unclear whether there is a common mechanism for all these types of disturbance in normal respiratory activity or whether there are additional factors which determine the type of apnoea. HYPOTHESES The hypotheses explored in this thesis were that isolated central apnoea was due to reduced chemoreceptor sensitivity, in mixed apnoea there was additional activation of the costophrenic inhibitory reflex and apnoea associated with periodic respiration was due to instability of respiratory control, with periods of over ventilation leading to apnoea. METHODS Polygraphic techniques were used to identify the frequency, type and length of apnoeic periods in infants born at/or less than 33 weeks gestation who were otherwise healthy sequential studies were undertaken to determine the pattern of apnoea and how it changed with time. Chemoreceptor sensitivity was assessed by measuring the ventilatory response to an added respiratory dead space of twice the anatomical dead space. The rate of response to the added dead space was assessed to determine if it related to the apnoea types and in particular was reduced in periodic respiration. The respiratory response to an imposed airway obstruction was used to determine the strength of the Hering Breuer and costophrenic inhibitory reflex, as respiratory efforts against an obstruction would induce chest wall distortion. RESULTS Twenty-eight infants with a mean gestation of 29+4 weeks and birth weight was of 1.39kg, were studied on 71 occasions. The prevalence of apnoea in this preterm population was nearly 100%, with the more immature infants at greater risk. Ninety percent of apnoeas (>5secs) were central, 9% mixed and 1 % obstructive; however, 50% of apnoeas over 14s had an obstructive component. Thirty-three percent of apnoeas were associated with a desaturation, the longer the apnoea the greater degree of desaturation. Apnoea associated with periodic respiration accounted for 72.3% of all apnoeas and periodic respiration increased with postmentrual age. In ninety-three percent of the studies there was at least one episode of periodic breathing. This relationship was not related to postmentrual age. A significant relationship was found between the rate of periodic central apnoeas and chemoreceptor sensitivity, as examined by the response to added dead space, related to a increased reliance on chemoreceptors in this group of infants The rate of response to the added dead space however shortened with increasing post menstrual age and that there was a significant inverse relationship between this and the rate of central periodic apnoeas. No significant relationship was found between the response to external obstruction and the rate of apnoea. Although an active Hering Breuer reflex was found in all infants, this was related to both to the gestational and postmenstrual age of the infants. CONCLUSIONS Apnoeas associated with periodic respiration are the commonest form of apnoea. As demonstrated in this thesis these occur most frequently in infants with the most rapidly responding chemoreceptors, these data support the hypothesis that this pattern of respiration is due to an underdamping of the chemoreceptor response. No evidence was found to support the hypothesis that mixed apnoea was associated with activation of the costophrenic inhibitory reflex.

Preterm infants are at increased risk of cardiometabolic and neurodevelopmental disorders in later life. The typical postnatal growth pattern of failure to achieve the equivalent of a normal fetal growth rate, followed up by catch-up growth, altered adiposity and altered hypothalamic-pituitary-adrenal axis (HPA) activity may be predisposing factors. Potential mechanisms that may mediate such programmed effects include altered DNA methylation and faster telomere attrition. A prospective cohort of 46 very preterm (25+2 to 31+5 weeks’ gestation, mean 28.6) and 40 full term (38+3 to 42+2 weeks’ gestation, mean 40.2) infants was established to investigate potential mechanisms. Infants were studied at birth, term equivalent age, 3 months and 1 year corrected for prematurity. At all time points, linear growth and body composition (by densitometry) were measured and buccal (epithelial) cells was collected for measurement of DNA methylation (5mC) and relative telomere length. Compared with full term infants, preterm infants were lighter (p < 0.001) and had a smaller head circumference (p < 0.05) at all time-points and were shorter at term equivalent (p < 0.001) and 3 months corrected age (p = 0.002). Preterm infants also had greater percentage body fat at term equivalent age (mean difference = 5.5%, p < 0.001), which normalised by 3 months corrected (mean difference = 0.9%, p = 0.4). Preterm infants had a blunted salivary cortisol response (mean difference 0.4 μg/dL, p = 0.02) to a stressor (physical examination) at 3 months compared to term infants at this age, suggesting altered activity of the HPA axis. 5mC is fundamental in the control of expression of imprinted genes involved in fetal growth. Notably, a number of studies in humans exposed to an adverse environment in early life have demonstrated altered 5mC at the differentially methylated regions (DMRs) controlling the expression of the key fetal growth factor insulin like growth factor 2 (IGF2) and at the linked H19 imprinting control region (H19 ICR). At birth, preterm infants had a significant decrease in 5mC at DMR2 compared with term infants at birth (β = –11.5, p < 0.001) and compared with preterm infants at term equivalent age (mean difference = -7.4, p = 0.01). By term equivalent age, preterm infants had decreased 5mC at both DMR2 (β = –2.8, p = 0.01) and the H19 ICR (β = –2.3, p = 0.048) compared with term infants at birth, although this difference disappeared at 1 year corrected. Although research has suggested that catch up growth may confer an unfavourable metabolic phenotype, poor initial weight gain can associate with worse cognitive outcome. A pathway was established for obtaining advanced magnetic resonance images of the preterm brain. 5mC at H19 ICR and DMR2 in buccal DNA showed no association with measures of white matter microstructure or whole brain volumes. Term infants demonstrated telomere lengthening over the first year of life (mean difference = -0.3, p = 0.02). There was no significant change in telomere length over the first year of life in preterm infants (mean difference = 0.2, p = 0.34). However, as preterm infants at term equivalent age had longer telomeres compared to term infants at birth (β = 0.6, p < 0.001), ultimately there were no differences between the term and the preterm groups at 1 year corrected age (β = 0.3, p = 0.07). The DNA modification 5-hydroxymethylcytosine (5hmC) is a stable modification in its own right and is also thought to be an intermediate step in DNA demethylation. 5hmC is abundant in the placenta but has not been studied in the context of fetal programming. Additionally, previous research using methods such as bisulphite conversion would not have discriminated between 5mC and 5hmC and therefore the role of 5mC may not have been accurately measured. To study the relationship between 5mC, 5hmC and fetal growth, gene expression of candidate imprinted and non-imprinted genes in full term placental samples from the Edinburgh Reproductive Tissue BioBank was analysed. 5mC and 5hmC within the IGF2/H19 and KvDMR (controlling CDKN1C) loci was estimated using chemical capture and immunoprecipitation techniques that discriminate between modifications. Relationships between the expression of IGF2 (r = 0.3, p = 0.02) and CDKN1C (r = -0.3, p = 0.01) and birth weight across the normal range were found and in keeping with the known action of these genes. 5mC at IGF2 DMR0 (β = 0.3, p = 0.02) and KvDMR (β = 0.3, p = 0.02) and 5hmC at H19 gene body (β = 0.2, p = 0.04) associated with birth weight. Thus, DNA modifications at imprinted DMRs may modulate environmental influences on fetal growth across the normal range. DNA methylation at IGF2/H19 can be influenced by early life events. It remains to be seen whether any changes are present later in childhood and whether they associate with risk factors for the metabolic syndrome.

INTRODUCTION Preterm birth, defined as the birth of a baby of less than 37 weeks gestational age, has a number of consequences at social, ethical, economic and health care level. These consequences affect both hospital health care programs, local programs and prevention plans. The rapid and remarkable innovation of assistance methods and of equipment in the Neonatal Intensive Care Unit has allowed a gradual increase of survival rates of extremely low weight and low gestational age premature infants. Several studies have demonstrated that premature and extremely premature infants show severe short, medium and long-term clinical outcomes, in particular neurological and neurosensorial outcomes. However, long-term follow-ups of infants cohorts selected by area-based surveillance are not available. AIM The aim of this study is to analyse the clinical outcomes of preterm infants in the Veneto Region by means of a follow-up assessment of short, medium and long-term health outcomes according to gestational age, in particular for extremely low weight and extremely low gestational age premature infants. MATERIALS AND METHODS The study has been divided into different phases. In the first preliminary phase a stratification sampling of population has been carried out on the basis of the gestational age of all infants born in the Veneto Region from 2003 to 2009. For this phase the current flow of the Certificate of Delivery Care (CEDAP) has been used. This flow has been mandatory since 2001 and records all newborns of the Region, it contains information on the infant (gender, weight, length, head circumference, gestational age, major resuscitation care in case of assisted intubation and ventilation and medical cardiac resuscitation, minor resuscitation care in case of aspiration and cardiac massage, infant’s admission in neonatal intensive care unit, possible malformations and possible cause of infant mortality), on the delivery (single or multiple, natural or cesarean, possible type of pain relief and type of anesthetic, maternal complications), on pregnancy (number of tests and ultrasound scans, prenatal diagnosis, course of pregnancy: physiological or pathological, threatened abortion, threatened preterm labour, infectious diseases, infections of the genitourinary tract, diabetes and gestosis) and on the mother and the father (age, education, job, marital status, exposure to risk factors such as smoke). Stratification sampling has been carried out according to the gestational week (GW) from 20 GW to 42 GW. In particular, all newborns ≤ 28 gestational weeks in the above mentioned period have been considered. Patients cohorts have thus been arranged and the cohorts of infants born in 2005 and from 2007 to 2009 have been studied. In the next phase, starting from current statistics, patients’ natural history has been reconstructed, when possible, by means of death certificates (ISTAT) in order to assess survival, hospital discharge records for recoveries, intercurrent acute pathologies and chronic pathologies, information flow on the rehabilitation activity ex art. 26 L 833/1978 of the Veneto Region in order to assess the admission to rehabilitative services and the flow Rare Diseases Registry. In particular, the “chronic” patients have been identified, defined as subjects with at least 2 hospitalizations within 12 months, both characterized by the same pathology code of hospital discharge records. Eventually the results have been analysed: mortality, survival rate, patients affected by chronic pathologies, patients affected by rare diseases and patients who have undergone rehabilitation cycles. The patients not included in the categories described above will be sampled and assessed in follow-up after this study according to the following protocol: qualitative assessment of spontaneous motor function, qualitative assessment by means of classification systems (ABC, Gross Motor Function Measure, and, for the most severe cases, Besta scale and QUEST scale), cognitive assessment (Griffiths, WIPPSI, WISC-IV), neurosensorial assessment by means of the analysis of the Multimodal Evoked Potentials (PEV, BAEPs, SEP), assessment of neuroimaging (standard protocol and 3D brain NMRI with DTI and resting state for tractographic assessment). RESULTS During the analysed period from 2003 to 2009 in the Veneto Region 322.598 neonates have been recorded, approximately 46.000 neonates/year. 91,71% of these were born at term (>37 GW), 7,63% were born premature (<37 GW). If we consider preterm neonates, 2,13% were born before 32 GW and 0,55% are ≤ 28 GW. The recorded premature neonates ≤ 28 GW, who are 0,55% of the total amount, are approximately 1785, on average 255/year. Birth mortality total rate in neonates between 2003 and 2009 is 2,9 x 1000 in single deliveries and 8,7 x 1000 in multiple deliveries; the rate grows along with the decrease of gestational age, in particular rates of 8,3 at 36 GW for single deliveries vs 1,1 for multiple deliveries are recorded, 17,8 for single deliveries (35 GW) vs 6,0 for multiple deliveries and 117,6 for single deliveries vs 57,7 for multiple deliveries in neonates born before 28 GW. Premature babies <28 GW increased from 201 in 2003 (0,48% of neonates in 2003) to 301 in 2009 (0,63% of neonates in 2009). Multiple deliveries of neonates < 28 GW are 24% (20% twins, 3% multiple twins) in comparison to 1,2 % of babies born at term (2,7% twins and 0,1% multiple twins) and 3% in comparison to the total amount of deliveries. The percentage of extremely low weight and gestational age neonates and their survival are thus growing rapidly in the Veneto Region. This is due to the growing innovation of care methods and of equipment in the Neonatal Intensive Care Units: even babies born at 20 GW are resuscitated and survive (1 baby born in 2007 recorded, 1 at 19 GW and 1 at 20 GW; in 2008 7 babies born at 21 GW, only two neonatal deaths). Our analysis shows that apparently some factors are implied in preterm birth: one factor is the mother’s age, in particular the percentage of neonates <28 GW decreases from 1,2% for mothers <24 years old to 0,8% between 25 and 29 years and 1,5% if >40 years old (relative risk RR is of 2,3). Another factor is the mother’s ethnic group: among African women and Eastern European women the percentage of preterm neonates is twice as high as among Italian women. If we analyse the women who have delivered preterm babies, 55% are primiparas (RR 1.2), 30% report a spontaneous abortion in their anamnesis before the delivery (RR 1.8), 4% report a stillbirth before the delivery (RR 3.1) and 12% report a voluntary interruption of pregnancy (RR 2.1). 7% are smokers (RR 1.1) and 2,6% undergo medically assisted procreation or MAP (RR 2.03). With regard to MAP, 1.8% babies are born every year; 11% of the neonates ≤28 GW were born by means of MAP vs 1% of babies born at term by means of MAP. If we now analyse the results of neonates born < 28 GW in 2005 and 2007-2009 cohorts, in 2005 the babies who died during the first year of life are 65 (29%); the survivors are 160 (71%). 11 survivors out of the total amount are chronic patients (6.8%); 9 have been rehabilitated (5.6%); 1 affected with a rare disease has been registered (0.6%). Although they were not mentioned in the considered sources, 105 show diagnosis of complications at birth and/or during the first year of life (66%). The percentage of premature babies with severe outcomes is thus 79%. 37 are not mentioned in any source and have had no complications (23%). From 2007 to 2009 dead babies during the first year of life are 250 (31%); survivors are 545 (69%). 61 patients out of the total amount are chronic patients (11%), 1 of them is affected by a rare disease and registered in the Rare Disease Registry, 13 have been rehabilitated (2.3%) and 3 (0.5%) report rare diseases diagnosis on the hospital discharge record; 63 are rehabilitated (12%), 15 out of these are chronic; 11 are affected by rare diseases (2.7%), only two of which are registered in the Rare Disease Registry. Although they were not mentioned in the considered sources, 360 report diagnosis of complications at birth and/or during the first year of life (66%). The percentage of premature babies with severe outcomes is approximately 91%. 72 are not mentioned in any source and have had no complications (13%). CONCLUSIONS The percentage of neonates with severe prematurity is rising remarkably in the Veneto Region due to the growth of the survival rate of babies born between 22 and 28 GW. By means of preliminary analyses, several factors related to the mother’s history, to the reproductive history and to the pregnancy course, as well as to the neonate, can apparently determine a preterm birth. In light of these preliminary data, considering the above mentioned survival and disability rates, it is particularly important to know the babies’ natural history and to verify the short and long-term clinical outcomes in terms of impact on the health care and rehabilitation planning.
INTRODUZIONE La nascita pretermine, definita come nascita che avviene prima di 37 settimane complete di gravidanza, comporta una serie di implicazioni sociali, etiche, economiche e sanitarie che impattano sui programmi assistenziali ospedalieri e territoriali e sui programmi preventivi di salute. La rapida e cospicua innovazione dell’assistenza e delle strumentazioni nelle Unità di Terapia Intensiva Neonatale ha prodotto negli ultimi anni un progressivo aumento della sopravvivenza dei gravi prematuri di basso peso e di bassa età gestazionale. Numerosi studi hanno dimostrato che i bambini nati prematuri ed estremamente prematuri presentano severi esiti clinici a breve e medio termine, in particolare neurologici e neurosensoriali. Non sono tuttavia disponibili follow-up a lungo termine di coorti di bambini selezionate da sorveglianze area-based. SCOPO Lo scopo di questo studio è analizzare gli esiti clinici dei nati prematuri in Regione Veneto, valutando in follow-up gli esiti di salute a breve, medio e lungo termine per età gestazionale, in particolare per i gravi prematuri di basso peso e di bassa età gestazionale. MATERIALI E METODI Lo studio è stato suddiviso in diverse fasi. In una prima fase preliminare è stata condotta una stratificazione per età gestazionale della popolazione di tutti i nati in Regione Veneto nel periodo 2003-2009. Per questa fase è stato utilizzato il flusso corrente del Certificato di Assistenza al Parto (CEDAP). Tale flusso è mandatorio dal 2001 e registra tutti i nati della Regione, contiene informazioni relative al nato (sesso, peso, lunghezza, circonferenza cranica, età gestazionale, necessità di rianimazione maggiori se intubazione e ventilazione assistita e rianimazione cardiologica con farmaci, necessità di rianimazione minore se aspirazione e massaggio, necessità di ricovero del nato in reparto di cure intensive neonatali, eventuale presenza di malformazione ed eventuale causa di nati-mortalità), al parto (genere del parto: semplice o plurimo, modalità parto se spontaneo o cesareo, eventuale tipo di controllo del dolore e tipo di anestesia, complicanze materne legate al parto), alla gravidanza (numero di accertamenti eseguiti in gravidanza, numero di ecografie, indagini prenatali, decorso gravidanza se fisiologico o patologico, se patologico il tipo di condizione morbosa insorta durante la gravidanza: minacce di aborto, minaccia di parto prematuro, malattie infettive, infezioni tratto genito-urinario, diabete e gestosi) e informazioni riguardanti il padre e la madre (tra cui età, scolarità, professione, parità, stato civile, esposizione a fattori di rischio quali il fumo). La stratificazione è stata fatta per settimana gestazionale dalla 20 sg alla 42 sg. In particolare sono stati considerati tutti i nati < 28 settimane gestazionali nel periodo sovra descritto. Sono state pertanto create delle coorti di pazienti e sono state analizzate le coorti dei nati nel 2005 e nel triennio 2007-2009. Nella fase successiva, a partire dalle statistiche correnti, sono state ricostruite le storie naturali di ciascun paziente, quando possibile, utilizzando le schede di morte (ISTAT) per valutare la sopravvivenza, le schede di dimissione ospedaliera (SDO) per le ospedalizzazioni, le patologie acute intercorrenti e patologie croniche, flusso informativo sull’attività di riabilitazione dei centri ex art.26 L 833/1978 per valutare l’accesso a servizi riabilitativi e il flusso Registro Malattie Rare. In particolare sono stati identificati i soggetti “cronici” definiti come i soggetti con almeno 2 ospedalizzazioni nell’arco di 12 mesi caratterizzate entrambe dallo stesso codice di patologia SDO. ,Alla fine sono stati analizzati gli esiti: mortalità, sopravvivenza, soggetti affetti da patologie croniche, soggetti affetti da malattie rare e soggetti che hanno necessitato di cicli di riabilitazione. I soggetti non inclusi nella categorie sovradescritte verranno in un tempo successivo a questo studio campionati e valutati in follow up secondo il protocollo seguente: valutazione qualitativa della motricità spontanea, valutazione quantitativa mediante l’utilizzo di scale di valutazione (ABC, Gross Motor Function Measure, e, per i casi con esiti più gravi, Scala Besta e scala QUEST), valutazione cognitiva (Griffiths, WIPPSI, WISC-IV), valutazione neurosensoriale mediante studio del Potenziali Evocati Multimodali (PEV, BAEPs, SEP), valutazione di neuroimaging (RMN cerebrale con protocollo standard e 3D con DTI e resting state per la valutazione trattografica) trattografica). RISULTATI Nel periodo considerato 2003-2009 in Regione Veneto sono stati registrati 322.598 nati, in media circa 46.000 nati/anno. Di questi 91,71% sono nati a termine (>37 sg), 7,63% nascono prematuri (<37 sg). Se consideriamo i nati pretermine, 2,13% sono nati prima delle 32 sg e 0,55% sono <28 sg. I nati prematuri <28 sg registrati, che rappresentano lo 0,55%, sono 1785 circa, in media 255/anno. Il quoziente di natimortalità totale dei nati dal 2003 al 2009 è 2,9 x 1000 per i parti singoli e 8,7 x 1000 per i parti plurimi; tale quoziente aumenta con il decrescere dell’età gestazionale in particolare si registrano quozienti di 8,3 alla 36 sg per i parti singoli vs 1,1 per i parti plurimi , 17,8 per i parti singoli (35 sg) vs 6,0 per i parti plurimi e 117,6 per i parti singoli vs 57,7 per i parti plurimi nei nati prima delle 28 sg. I nati prematuri <28 sg sono passati da 201 nel 2003 (0,48% dei nati nel 2003) a 301 nel 2009 (0,63% dei nati nel 2009). I parti plurimi dei neonati < 28 sg sono il 24% (20% gemellari e 3% plurigemellari) rispetto al 1,2 % dei nati a termine (2,7% gemellari e 0,1% trigemellari) e il 3% rispetto al totale del parti. La percentuale di nati con prematurità grave e la loro sopravvivenza sono dunque in grande aumento nella Regione Veneto. Questo fenomeno è dovuto alla crescente innovazione dell’assistenza e delle strumentazioni nelle Unità di Terapia Intensiva Neonatale: vengono rianimati e sopravvivono anche nati dalle 20 sg (registrati 1 nati nel 2007 uno alla 19 sg e 1 alla 20 sg; nel 2008 7 nati alla 21 sg di cui solo due decessi alla nascita). Dalle nostre analisi alcuni fattori sembrano implicati nella nascita pretermine: l’età della madre è uno di questi in particolare la percentuale dei nati <28 sg passa da 1,2% per madri <24 aa allo 0,8% tra i 25 e i 29 anni e 1,5% se >40 aa (rischio relativo RR di 2,3). Un altro fattore è la cittadinanza materna: le donne africane e le donne dell’Europa dell’Est hanno una percentuale di nati pretermine doppia rispetto alle donne italiane. Se analizziamo le donne che hanno partorito dei neonati prematuri, il 55% sono primipare (RR 1,2), il 30% segnala in anamnesi un aborto spontaneo precedente al parto (RR pari a 1,8), il 4% un nato morto precedente al parto (RR 3,1) e il 12% una interruzione volontaria di gravidanza precedente (RR 2,1). Il 7% fuma (RR 1,1) e il 2,6% ricorre a una Procreazione Medicalmente Assistita o PMA (RR 2.03). Per quanto riguarda la PMA i nati sono 1,8% all’anno; 11% dei nati <28 sg sono nati da PMA vs 1% dei nati a termine da PMA. Se analizziamo ora gli esiti dei nati < 28 sg nelle coorti 2005 e 2007-2009, nel 2005 i morti entro il primo anno di vita sono 65 (29%); i sopravissuti sono 160 (71%). Dei sopravissuti 11 sono pazienti cronici (6,8%); 9 sono stati riabilitati (5,6%); 1 affetto da malattia rara certificato (0,6%). 105 pur non essendo presenti nelle fonti considerate presentano diagnosi di complicazione alla nascita e/o dentro l’anno (66%). La percentuale di nati prematuri con esiti maggiori è pertanto di 79%. 37 non sono presenti in alcuna fonte né hanno avuto delle complicazioni (23%). Nel triennio 2007-2009 i morti entro il primo anno di vita sono 250 (31%); i sopravissuti sono 545 (69%). Dei sopravissuti 61 sono pazienti cronici (11%) di cui 1 con malattia rare e certificato verificato nel flusso malattie rare, 13 riabilitati (2,3%) e 3 (0,5%) presentano diagnosi di malattie rare alla SDO; 63 sono riabilitati (12%) di questi 13 sono cronici ; 15 affetti da malattia rara (2,7%) di cui solo due con certificato di patologia rara. 360 pur non essendo presenti nelle fonti considerate presentano diagnosi di complicazione alla nascita e/o dentro l’anno (66%). La percentuale di nati prematuri con esiti maggiori è circa 91%. 72 non sono presenti in alcuna fonte né hanno avuto delle complicazioni (13%). CONCLUSIONI La percentuale di nati con prematurità grave è in grande aumento nella Regione Veneto per l’incremento della sopravvivenza dei nati tra le 22 e le 28 sg da analisi preliminari sembra che numerosi fattori relativi alla storia materna, alla storia riproduttiva e al decorso della gravidanza nonché fattori relativi al neonato possano determinare una nascita pretermine. Alla luce di questi dati preliminari, risulta particolarmente rilevante, soprattutto per le ricadute programmatorie dei servizi di assistenza e di riabilitazione, conoscere la storia naturale di questi bambini e verificarne gli esiti in termini di disabilità complesse che ne possono derivare viste le percentuali di sopravvivenza e di disabilità sovra riportate.

Children born prematurely are at higher risk for medical, learning and developmental concerns than children born full term. This study analysed the files of 73 pre-term children who completed an Assessment and Monitoring programme in New Zealand between 1998 and 2007. The participants were 39 boys and 34 girls with gestational ages ranging from 23 weeks to 32 weeks at birth and who attended the programme until they were 4 years chronological age. Analysis of the reports sent to paediatricians following the children’s monitoring visits at 8 months, 12 months, 18 months, 24 months and 36 months (corrected age) and at 48 months, chronological age indicated delays in achieving the expected developmental milestones in expressive language, cognition and gross motor skills for up to half of the cohort. Moreover, the findings further suggest that a ‘sleeper effect’ or ‘invisible prematurity’ emerged for up to half of the cohort at age 36 months. This ‘invisible prematurity’ and the developmental delay in cognition, expressive language and gross motor skills have implications for early childhood teachers as teachers need to develop an awareness of, and skills to identify and work effectively with these young children and their families. Practical teaching and learning strategies are presented for teachers.

The ocular problems associated with premature birth have been with us ever since it was discovered that the application of high levels of inspired oxygen provided a reduction in mortality. The consequence of this reduction in mortality has been a rise in morbidity; these mortality and morbidity rates have oscillated during the attempt to find a reasonable balance. The use of contemporary technology during the attempt both to understand the premature baby's delicate physiology and to maintain life to younger and lighter babies has not yet produced stability. The incidence of typical retinal maldevelopment, retinopathy of prematurity (RCP), was analysed by serial weekly ophthalmoscopy examinations in a regional special care baby unit, 579 examinations being made on 138 babies. The best instrument for this examination was found to be a compact indirect ophthalmoscope incorporating an inverting eyepiece - the Reichert Jung monocular indirect ophthalmoscope. The optimum time for ocular examination to discover potential ocular morbidity was at 33 weeks post-conceptual age (PCA) with continued examinations to the age of 37 weeks PCA. The babies that were found to be at risk of a significant grade of RCP were found to be of a birth weight of less than 1251 grams or had an estimated gestational age at birth of 30 weeks or less. A refractive state of myopia was found to be the norm. The myopia reduced as life progressed to attain emmetropia around the age of 50 weeks PCA or 22 weeks survival. The reduction of the myopic state was found to be dependent on birth weight and gestational age at birth, the youngest and therefore the lightest being more predictable in attaining emmetropia. Refractive variations were found to be coincident with the timings of certain medical treatment regimes and a hypothesis is postulated as to the mechanism of this association.

In recent years, concern about a new epidemic of retinopathy of prematurity (ROP) has focused attention on the increasing incidence of the disease and the factors responsible for its most severe consequences. Two studies designed to address these issues were done using data from three sources: the B.C. Health Surveillance Registry (Registry), Physicians's Notices of Livebirth (PNOB), and the Vancouver General Hospital (VGH). In the first study, Registry and PNOB records were used to determine crude annual birth weight-specific incidence rates for ROP in infants liveborn in the Province of British Columbia (B.C.) in the period 1952-1983. These rates showed that, in B.C., the original epidemic of the disease ended in 1954. Linear regression lines fitted for each of four birth weight categories showed that, in the 29 year period after 1954, there was a significant increase in the incidence of ROP-induced blindness in infants weighing less than 1000 grams at birth. To refine this observation, the data were sub-divided: the 29 year period, to two smaller periods, 1955-1964 and 1965-1983; the less than 1000 gram birth weight category to two sub-categories, 500-749 and 750-999 grams. Since the inter-period incidence should have been similar if the birth weight-specific incidence had not changed since the end of the original epidemic, the crude weight-specific rates for ROP-induced blindness in the early period were used to calculate the expected number of cases in the later period. When weight-standardized incidence ratios (SIR's) and 95% confidence limits were calculated, the results showed that, in the 750-999 gram sub-category, the SIR was significantly increased. Infants born in the period 1965-1983 were 3.07 times more likely to be ROP: blind than their equal weight counterparts in the earlier period. In infants weighing 500-749 and 1000 grams or more, there was no evidence to suggest an increase in incidence after 1954. The second study was done to determine the cofactors that differentiate infants who are blinded by ROP from those who are not. Infants were included if (i) they were born in B.C. between 1955 and 1983, (ii) they were known to the Registry as being ROP: blind (cases) or not blind (controls), and (iii) they were born in or admitted to the VGH within 28 days of birth. When the data from all three data sources were dichotomized and analyzed using univariate techniques, two variables, respiratory distress syndrome (RDS) and neonatal weight loss, showed a significantly protective effect. The effect of RDS disappeared when the data were stratified by birth interval indicating that the observed association was confounded by time. When the variables were reanalyzed in continuous form, none were significantly associated with visual outcome. However, since the power of the cofactor study was extremely low, none of the variables that were included can be eliminated as potential cofactors for the induction of blindness in infants with ROP.
Medicine, Faculty of
Population and Public Health (SPPH), School of
Graduate

This thesis is an investigation into the effects of premature birth on the developing behaviour of both infant and caregiver. A neonatal assessment procedure sensitive to both the neurological and the interpersonal aspects of development and to obstetric complications was developed. This assessment was validated on a total sample of 62 premature and fullterm infants. In a further study utilising 30 infants from the first part of the thesis, the effects of a maternally-administered manual-based intervention for premature infant-mother dyads were evaluated as compared to fullterm and premature diary controls. This focussed on a variety of early interactional activities designed to enhance mutual parent-infant responsiveness in preterm dyads. The results of the study are discussed in terms of the possible clinical utility of such an approach in reducing the likelihood of dysfunctional parenting of the 'High-Risk' newborn. The thesis is set in the context of a review of the pertinent literature on the development of special care facilities for the premature infant, neonatal assessment procedures, mother-infant interaction and intervention research.

Environmental conditions are considered an important factor influencing asphalt pavement performance. The addition of modifiers, both to the asphalt binder and the asphalt mixture, has attracted considerable attention in potentially alleviating environmentally induced pavement performance issues. Although many solutions have been developed, and some deployed, many asphalt pavements continue to prematurely fail due to environmental loading. The research reported herein investigates the synthetization and characterization of biobased Phase Change Materials (PCMs) and inclusion of Microencapsulated PCM (μPCM) in asphalt binders and mixtures to help reduce environmental damage to asphalt pavements. In general, PCM substances are formulated to absorb and release thermal energy as the material liquify and solidify, depending on pavement temperature. As a result, PCMs can provide asphalt pavements with thermal energy storage capacities to reduce the impacts of drastic ambient temperature scenarios and minimize the appearance of critical temperatures within the pavement structure. By modifying asphalt pavement materials with PCMs, it may be possible to "tune" the pavement to the environment.

The Mechanistic-Empirical Pavement Design Guide (MEPDG) has been employed for pavement design by the Indiana Department of Transportation (INDOT) since 2009 and has generated efficient pavement designs with a lower cost. It has been demonstrated that the success of MEPDG implementation depends largely on a high level of accuracy associated with the information supplied as design inputs. Vehicular traffic loading is one of the key factors that may cause not only pavement structural failures, such as fatigue cracking and rutting, but also functional surface distresses, including friction and smoothness. In particular, truck load spectra play a critical role in all aspects of the pavement structure design. Inaccurate traffic information will yield an incorrect estimate of pavement thickness, which can either make the pavement fail prematurely in the case of under-designed thickness or increase construction cost in the case of over-designed thickness. The primary objective of this study was to update the traffic design input module, and thus to improve the current INDOT pavement design procedures. Efforts were made to reclassify truck traffic categories to accurately account for the specific axle load spectra on two-lane roads with low truck traffic and interstate routes with very high truck traffic. The traffic input module was updated with the most recent data to better reflect the axle load spectra for pavement design. Vehicle platoons were analyzed to better understand the truck traffic characteristics. The unclassified vehicles by traffic recording devices were examined and analyzed to identify possible causes of the inaccurate data collection. Bus traffic in the Indiana urban areas was investigated to provide additional information for highway engineers with respect to city streets as well as highway sections passing through urban areas. New equivalent single axle load (ESAL) values were determined based on the updated traffic data. In addition, a truck traffic data repository and visualization model and a TABLEAU interactive visualization dashboard model were developed for easy access, view, storage, and analysis of MEPDG related traffic data.

Purpose/Background Overdose deaths in the U.S. from opioids have dramatically increased since the COVID-19 pandemic. Although medicated-assisted treatment (MAT) programs are widely available for sufferers of opiate addiction, many drop out of treatment prematurely. Twelve-step programs are considered a valuable part of treatment, but few studies have examined the effect of combining these approaches. We aimed to compare abstinence rates among patients receiving MAT who were referred to 12-step programs to those only receiving MAT. Methods In this prospective study, a cohort of participants from a MAT clinic agreeing to attend a 12-step program was compared to 15 controls selected from a database before project implementation. Eligible participants were diagnosed with OUD, receiving buprenorphine (opiate agonist), and at least 18. Participants were provided with temporary sponsors to attend Narcotics Anonymous, Alcoholics Anonymous, and Medication-Assisted Recovery meetings together. The primary endpoint was the change in positive opiate urine drug screens over 6 months between participants and controls. Results Between March 29, 2021, and April 16, 2021, 166 patients were scheduled at the clinic. Of those scheduled, 146 were established patients, and 123 were scheduled for face-to-face visits. Of these, 64 appeared for the appointment, 6 were screened, and 3 were enrolled. None of the participants attended a 12-step meeting. Enrollment barriers included excluding new patients and those attending virtual visits, the high percentage of patients who missed appointments, and lack of staff referrals. The low incidence of referrals was due to time constraints by both staff and patients. Implications for Nursing Practice Low enrollment limited our ability to determine whether combining medication management with a 12-step program improves abstinence. Failure to keep appointments is common among patients with OUD, and virtual meetings are becoming more prevalent post-COVID. Although these factors are unlikely to be controllable, developing strategies to expedite the enrollment process for staff and patients could hasten recruitment.

The “Novel streaming potential (SP) and thermal sensor techniques for monitoring water and nutrient fluxes in the vadose zone” project ended Oct. 30, 2015, after an extension to complete travel and intellectual exchange of ideas and sensors. A significant component of this project was the development and testing of the Penta-needle Heat Pulse Probe (PHPP) in addition to testing of the streaming potential concept, both aimed at soil water flux determination. The PHPP was successfully completed and shown to provide soil water flux estimates down to 1 cm day⁻¹ with altered heat input and timing as well as use of larger heater needles. The PHPP was developed by Scott B. Jones at Utah State University with a plan to share sensors with Shmulik P. Friedman, the ARO collaborator. Delays in completion of the PHPP resulted in limited testing at USU and a late delivery of sensors (Sept. 2015) to Dr. Friedman. Two key aspects of the subsurface water flux sensor development that delayed the availability of the PHPP sensors were the addition of integrated electrical conductivity measurements (available in February 2015) and resolution of bugs in the microcontroller firmware (problems resolved in April 2015). Furthermore, testing of the streaming potential method with a wide variety of non-polarizable electrodes at both institutions was not successful as a practical measurement tool for water flux due to numerous sources of interference and the M.S. student in Israel terminated his program prematurely for personal reasons. In spite of these challenges, the project funded several undergraduate students building sensors and several master’s students and postdocs participating in theory and sensor development and testing. Four peer-reviewed journal articles have been published or submitted to date and six oral/poster presentations were also delivered by various authors associated with this project. We intend to continue testing the "new generation" PHPP probes at both USU and at the ARO resulting in several additional publications coming from this follow-on research. Furthermore, Jones is presently awaiting word on an internal grant application for commercialization of the PHPP at USU.