It is known that the birth process and initial life exposures, such as feeding, may have an important impact on the acquisition of bacterial communities throughout the human body, including the gut. Preterm infants usually have special dietary needs and undergo increased oxidative stress related to intensive care, which can ultimately impair their gastrointestinal microbial colonization and microbial diversity in the bowel. Using molecular techniques, we analyzed the fecal microbiome of 20 preterm infants and tested the association between bacterial communities and feeding type, as well as levels of F2-isoprostanes. We found that feeding influences the fecal microbiome of preterm infants, however more research is needed to clarify the role of human milk fortifiers in this process. We also observed preliminary evidence of an association between microbial composition and oxidative stress, indicating that future studies in this area should be conducted. / February 2017

One in every 10 infants is born premature, with premature being defined as being born before 37 weeks gestation. The immediate concerns of premature birth are fairly well understood, but the long-term consequences are much less known. Previous studies have shown pulmonary insufficiencies in adulthood, but less have looked at hemodynamic variables. None have investigated exercise and hypoxia intolerance in adults who survived prematurity. The goals of this study were to determine exercise capacity and hemodynamic response during exercise and hypoxia in prematurely born adults, as well as deriving pulse wave velocity in normoxia and hypoxia. Preterm (N=10) and term-born, age-matched subjects (N=12) performed incremental exercise in normoxia (21% O2) or hypoxia (12% O2) until volitional maximum was reached. Subjects had arterial and venous catheters collecting blood gas concentration and blood pressure, and breath-by-breath metabolics gathering ventilation data. Preterm and term-born subjects were well matched for anthropometrics, pulmonary, and exercise capacity values. The preterm adults had elevated heart rates, systolic blood pressure, pulse pressure throughout the exercise protocol in normoxia and hypoxia. The preterm group experienced an increased diastolic blood pressure and mean arterial pressure during normoxic exercise, but had a transient decrease in diastolic blood pressure and mean arterial pressure in hypoxia. Additionally, adults born prematurely had an increase aortic pulse wave velocity (aPWV). With these findings, we aimed to determine if aortic stiffness was increased in premature infants at birth with the neonatal intensive care unit (NICU), or if there was a phenotype of premature aging in this population. Prior to beginning the study with the NICU, the effects of simulation on clinicians and researchers was investigated. Simulation is often used for noninvasive teaching or practicing procedures. No one has looked into the effect simulation has on research being done in an intensive care unit setting. Bay 1 and 2 nurses (n=23) in the NICU were surveyed to rate their thoughts of clinical research, comfort with new research, comfort with simulation, and comfort with researchers not from the NICU. Nurses did not know what aspects of the NICU were overwhelming to researchers nor did they agree that researchers could identify infants stress cue. Nurses also reported discomfort communicating with parents about novel research technology. But overall, nurses support research in the NICU and are comfortable with new research knowing the research team participated in a NICU-specific simulation. A questionnaire was also filled out by researchers (n=3), neonatal intensive care unit physicians (n=3) and nurses (n=3) prior to and after completing a research study simulation. Prior to simulation, scientists showed more unfamiliarity with the infants, the NICU setting, and simulation than did the physicians or nurses. Physicians and nurses, however, were not familiar with the technology the researchers used. The simulation alleviated the differences found among the groups. Simulation improves nurses’ opinions of new technology and researchers coming into the NICU and working with patients. Simulation helps researchers familiarize themselves with the NICU and infants, while also improving the clinicians’ comfort with the technology and methods being used.

Prematurity is associated with poor neurodevelopmental outcomes, and laws mandate the provision of early intervention services to those infants with disability. However, it is often difficult to identify early which infants would benefit most from these services. The Neurobiologic Risk Score (NBRS) and the Neurodevelopmental Risk Exam (NRE) are instruments used to assess infants at near-term corrected age. These instruments have been shown to correlate with later developmental outcomes. However, the environment of the neonatal intensive care unit (NICU) has changed since the NBRS and NRE were first validated, and it is not known whether they are still able to accurately predict future developmental outcomes. The objective of this study was therefore to examine the ability of the NBRS and NRE, both alone and in combination with socio-economic variables, to predict future developmental outcomes in the contemporary NICU. The subjects were 219 neonates of less than 32 weeks' gestational age discharged from the NICU between November 2001 and December 2006 who had undergone both the NBRS and NRE. Infants were assessed at chronological age 6, 12 and 24 months, with developmental quotients being assigned at these ages. Parental socio-economic data were also collected and analysed. The hypothesis was that the NBRS and NRE would be less effective at predicting neurodevelopmental outcomes in the contemporary NICU. The best measure of future developmental outcome is likely to need to include both neurobiological and socio-economic risk factors.

Preterm birth may lead to complications during the neonatal period that can cause visual dysfunctions. Retinopathy of prematurity (ROP) and neurological complications are well known reasons for visual dysfunctions, but preterm children with no or only mild ROP and no evident neurological problems may also be affected visually when they grow up. Retinal development starts early after gestation and continues long after birth. Major processes are underway during the second half of pregnancy when preterm children are born, and a preterm birth could possibly have a negative effect on normal retinal development. The aims of the studies were to evaluate retinal morphology and function in former preterm children and compare the results with children born at term. Former preterm children aged 5 to 17 years and born in a gestational age (GA) of 32 weeks or less were included in the different study groups. Children of similar ages who were born at term and with normal visual acuity (VA) acted as controls. Best corrected VA and refraction in cycloplegia were assessed in all children. Macular thickness and retinal nerve fiber layer (RNFL) thickness were measured with optical coherent tomography (OCT). Total retinal function was assessed with fullfield electroretinography (ffERG) and central macular function was assessed with multifocal electroretinography (mfERG). Preterm children had thicker central maculae than controls. There was a positive correlation between central macular thickness and GA at birth. RNFL thickness was reduced in the preterm children with severe ROP and treated ROP, but children with mild or no ROP did not differ from the fullterm children. The photoreceptor function measured with ffERG and the macular function measured with mfERG were reduced in the preterm group compared to controls. Preterm birth affects the retina both morphologically and functionally, and ROP has been suggested to be a reason for retinal changes. However, the results of this thesis indicate that children with no ROP also have retinal changes, suggesting an effect of prematurity itself. There were no correlations between any retinal changes and VA, but it is possible that larger studies using improved techniques may elucidate this further.

No description available.

No description available.

Respiratory Syncytial Virus (RSV) infects the lower respiratory tract in children under the age of two years and is spread through droplet and contact with infected persons. An estimated 200,000 children suffer from complications of RSV annually worldwide. Palivizumab is a monoclonal antibody used to immunize children from RSV and has been on the market since 1988. In 2014, the American Academy of Pediatrics (AAP) updated its policy for recommendation of RSV in premature infants. The objective of this capstone is to propose an evaluation framework with an example of how it could have been applied to assess the impact of the AAP policy change on RSV vaccination use and RSV outcomes among premature infants. The proposed evaluation framework would be a unique link between birth certificate records and surveys of parents/guardians of 32 week gestation premature infants or less in the metropolitan Atlanta area. The birth certificate data would identify “at risk” infants and would allow for selection of a sample of parents/guardians, both pre-policy change (August 1, 2013 to July 30, 2014) and post-policy change (August 1, 2014 to July 30, 2015). The primary endpoints would be: initiation and completion of the RSV vaccine series and RSV infection rates. Moderating variables would be obtained from birth certificate data (e.g. mother’s education and race) and survey data (e.g. attitudes toward vaccine acceptance). The evaluation framework proposed in this Capstone can be used in future analyses of RSV vaccination policy changes. It can also be generalized to other geographic areas in the US and used for routine surveillance of RSV vaccination use and RSV outcomes.

No description available.

Die Frühgeborenenretinopathie (Retinopathia praematurorum (RPM)) ist eine Erkrankung der Netzhaut, die vor allem sehr unreife Frühgeborene betrifft und in ihrem Endstadium zur Erblindung führen kann. Ein gesicherter Risikofaktor für die Entwicklung einer RPM ist die Gabe von hohen Konzentrationen an Sauerstoff nach der Geburt. Gegenstand dieser Arbeit war die Frage, ob nach der Einführung eines Sauerstoffprotokolls 2007 das Auftreten höherer Stadien der RPM reduziert werden konnte. Das Sauerstoffprotokoll hatte zum Ziel die Gabe von inspiratorischem Sauerstoff nach Möglichkeit zu senken und übermäßige Fluktuationen zu vermeiden. Hierfür wurden 268 Frühgeborene mit einem Gestationsalter < 32Wochen bei Geburt, welche in den Jahren von 2005 bis 2006 (pre-Gruppe) und 2008 bis 2009 (post-Gruppe) in der Universitätsklinik Leipzig geboren und einem RPM-Screening unterzogen wurden, verglichen. Es konnte gezeigt werden, dass die Inzidenz der RPM nach 2007 signifikant niedriger war. So erkrankten in der pre-Gruppe 12 von 102 Kinder an einer höhergradigen RPM (>Stadium 3), wohingegen diese Stadien in der post-Gruppe nicht mehr beobachtet wurden. Demzufolge reduzierte sich auch die Notwendigkeit einer Therapie von 7,4 % auf 0 % (jeweils p = 0.0005). In Hinblick auf die Kerndaten wie Gestationsalter, Geburtsgewicht, Körpergröße, sowie dem Auftreten schwerer Begleiterkrankungen wie u.a. der nekrotisierenden Enterokolitis oder der bronchopulmonalen Dysplasie fanden sich keine Unterschiede zwischen den Gruppen. Allerdings wies die post-Gruppe eine höheren Anteil an männlichen Frühgeborenen auf. Die Mortalität zeigte keine signifikante Veränderung nach der Intervention und lag bei 7.8 % in der pre- bzw. 6.6 % in der post-Gruppe (p = 0.81). Die Auswertung der pulsoximetrisch gemessenen Sauerstoffsättigung (SpO2) und der inspiratorischen Sauerstofffraktion (FiO2) zeigte, dass der SpO2 leicht und der FiO2 deutlich reduziert werden konnte. Ein signifikanter Unterschied ergab sich hier jedoch lediglich für den FiO2, insbesondere in den ersten 14 Lebenstagen. Die logistische Regressionsanalyse legt nahe, dass hohe SpO2- und FiO2-Werte sowie das Auftreten von intrakraniellen Blutungen mit schwerwiegenden ROP-Stadien korrelieren. Ein bedachter Umgang in der Sauerstofftherapie Frühgeborenen könnte in der Lage sein das Auftreten der Frühgeborenenretinopathie zu reduzieren ohne eine Erhöhung der Mortalitätsrate zu riskieren.

O presente estudo teve por objetivo examinar os indicadores de temperamento e comportamento de crianças nascidas pré-termo em comparação a crianças nascidas a termo, assim como nos subgrupos de crianças nascidas pré-termo extremo, muito pré-termo, pré-termo moderado e tardio, na fase de 18 a 36 meses de idade cronológica. Além disso, examinou-se o efeito preditor da prematuridade, dos fatores do temperamento e das variáveis da criança e ambientais no comportamento das crianças. A amostra foi composta por 100 crianças, sendo 50 nascidas pré-termo (PT) que passaram por internação em Unidade de Tratamento Intensivo Neonatal e 50 nascidas a termo (AT), e suas mães. A amostra dos subgrupos de crianças nascidas pré-termo foi composta por 14 crianças nascidas pré-termo extremo (PTE) e 36 crianças nascidas muito pré-termo, pré-termo moderado e tardio (PTM/Mo/Ta). Em ambos os grupos as crianças estavam na faixa de 18-36 meses de idade cronológica. Os dados foram coletados em uma única sessão de entrevista face a face com as mães das crianças PT e de forma autoadministrada com as mães das crianças AT. Aplicou-se as versões brasileiras do Early Childhood Behavior Questionnaire (ECBQ), para avaliação do temperamento, e do Child Behavior Checklist (CBCL 1 ½ -5), para avaliação de problemas de comportamento das crianças. Além disso, foram aplicados questionários de caracterização da amostra e utilizado o Critério de Classificação Econômica Brasil da Associação Brasileira de Empresas e Pesquisa. Foram processadas as análises estatísticas descritivas e inferenciais. Para a comparação entre grupos (PTvs.AT e PTEvs.PTM/Mo/Ta) foram utilizados os testes t-independente de Student e Qui-quadrado. Utilizou-se os testes ANOVA e MANOVA para examinar as potenciais diferenças entre os grupos relacionadas ao temperamento e comportamento das crianças, controlando-se idade da criança, frequência à escola, sexo e nível socioeconômico. Foram realizadas análises de regressão linear múltiplas a fim de encontrar o melhor modelo explicativo das variáveis preditas (problemas de comportamento Totais, Externalizantes e Internalizantes). O nível de significância adotado no estudo foi de p <= 0,05. Em relação ao temperamento, o grupo PT apresentou maior escore nos fatores Afeto Negativo e Extroversão, assim como nas dimensões antecipação positiva, desconforto, sensibilidade perceptual, prazer de baixa intensidade e transferência de atenção, quando comparado ao grupo AT. O grupo PTE apresentou mais sensibilidade perceptual em comparação ao grupo PTM/Mo/Ta. Observou-se que, quanto maior a idade da criança, mais Controle com Esforço, assim como mais aconchego, controle inibitório, medo e antecipação positiva, e menos ativação motora. Quanto ao comportamento das crianças, o padrão de comportamento foi predominantemente normal, em ambos os grupos e subgrupos. Os problemas de comportamento Totais, Externalizantes e Internalizantes foram preditos por mais Afeto Negativo, moderado por menor idade gestacional, e menos Controle com Esforço. Esses achados contribuem para a compreensão do impacto dos riscos do nascimento prematuro nos indicadores disposicionais do temperamento e na constituição dos problemas de comportamento no desenvolvimento das crianças. É importante que programas de follow-up de prematuros considerem as intervenções preventivas de orientações de pais a fim de mediar os processos regulatórios ao longo do desenvolvimento das crianças. / The present study aimed to examine the temperament and behavior indicators of preterm toddlers compared to full-term counterparts, as well as in the subgroups of toddlers born extremely preterm and very preterm, moderate preterm and late preterm, in the phase of 18 to 36 months of chronological age. In addition, we examined the predictive effect of prematurity, temperament factors, and child and environmental variables on children\'s behavior. The sample consisted of 100 toddlers, of whom 50 were born preterm, who were hospitalized in a Neonatal Intensive Care Unit and 50 full-term (FT) counterparts enrolled in private schools. The sample of subgroups of preterm toddlers consisted of 14 toddlers born extremely preterm (PTE) and 36 toddlers born very preterm, moderate and late preterm (VPT/Mo/La). In both groups, the toddlers were in the range of 18-36 months of chronological age. Data were collected in a single face-to-face interview with the mothers of the PT toddlers and in a self-administered form with the mothers of the FT toddlers. The Brazilian versions of Early Childhood Behavior Questionnaire (ECBQ) and Achenbach\'s Child Behavior Checklist (CBCL 1 ½ -5) were used to assess children\'s temperament and behavioral problems. In addition, questionnaires were applied to characterize the sample and it used the Brazilian Economic Classification Criteria of the Brazilian Association of Companies and Research. Descriptive and inferential statistical analyzes were processed. For the comparison between groups of sociodemographic chacteristics (PTvs.FT and PTEvs.VPT/Mo/La), it was used the ANOVA and MANOVA tests to examine the potential differences between the groups related to temperament and behavior of the children controlling the child\'s age, school attendance, sex, and socioeconomic level. Multiple linear regression analyzes were calculated in order to find the best explanatory model of the predicted variables (Total, Externalizing, and Interalizing behaviors problem). The level of significance adopted in the study was p <= 0.05. Regarding temperament, the PT group presented a higher score in the Negative Affectivity and Surgency factors, as well as in the positive anticipation, discomfort, perceptual sensitivity, low intensity pleasure and attention shifting, than the FT group. The VPT group presented more perceptual sensitivity than the VPT/Mo/La group. It was observed that the greater the age of the child, the more Effortful Control, as well as more cuddliness, inhibitory control, fear and positive anticipation, and less motor activation. Regarding to the behavior of the children, the pattern of behavior was predominantly normal in both groups and subgroups. The Total, Externalizing, and Internalizing behavior problems were predicted by more Negative Affectivity, moderated by lower gestational age, and less Effortful Control. These findings contribute to the understanding of the impact of the risks of preterm birth on dispositional indicators of temperament and the constitution of behavioral problems throughout children´s development. It is important that follow-up programs for preterm infants consider preventive interventions in parental guidance in order to mediate regulatory processes throughout child development.