This study was undertaken primarily to investigate the plasma protein system in infants with IRDS, as compared with healthy premature infants, as it had previously been reported that the plasma protein concentration in affected infants was abnormally low. It was attempted further to establish biochemical and/or immunological criteria for diagnosis of the disease and to discover reasons for the low IgG concentrations and raised α-fetoprotein concentrations found in the sera of these infants. Maternal serum proteins were also studied during pregnancy and at and after delivery of the infant. Interrelationships between α-fetoprotein, Human Growth Hormone and other proteins, in immunochemical systems were investigated. In summary, the main conclusions reached were as follows: (i) The total serum-protein concentration in affected infants is much reduced, as compared with healthy premature infants of the same gestational age. (ii) In IRDS infants, the relative and absolute concentration, of IgG is extremely low, whereas concentrations of other immune globulins, as far as could be determined, are within normal limits. (iii) Mothers of affected infants have significantly lower concentrations both of serum IgG and of IgM, than mothers of healthy premature infants. These changes in the serum-proteins are present throughout pregnancy. By six weeks post-partum, the IgG level has returned to normal, but the IgM level remains low. Concentrations of IgA and total serum-protein are normal at all times. (iv) Examination of oedema fluid, urine, faeces and amniotic fluid for γ-globulin content, has excluded the possibility that IgG is being lost from the circulation by these routes. (v) IRDS infants have, in their serum, agglutinins of the IgM type directed against the intact maternal IgG molecule. Similar agglutinins are present in a minority of healthy premature infants. Both IRDS and healthy infants have agglutinins against IgG fragments, in approximately 50% of cases. Agglutinin titres against these are similar in the two groups, but the incidence of agglutinins against Bence Jones protein type Lis raised in IRDS. (vi) Affected infants have an elevated serum concentration of α-fetoprotein, which disappears from the serum during the: first week of post-natal life. (vii) The majority of pregnant women examined have been observed to have serum agglutinins directed against α-fetoprotein. These cross-react with albumin prepared from sera of healthy adult males α-fetoprotein has been found in the serum of many pregnant women, especially during the second trimester. (viii) Immunological interrelationships between α-fetoprotein human serum albumin, Human Growth Hormone and human IgG have been demonstrated. (ix) Infants suffering from Rh-isoimmunization exhibit a serum- protein pattern similar to that seen in IRDS. Biochemical and immunological criteria for the diagnosis of IRDS have thus been established. The data to be presented indicate the presence of an immunological factor in the aetiology of the disease.

Background: Hemolytic disease of the fetus and newborn (HDFN) attributable to anti-M is rare, although case reports implicate anti-M in varying severities of HDFN, including fetal hydrops and intrauterine death. Case Description: We describe the case of a newborn with HDFN associated with an atypical immunoglobulin (Ig) G anti-M that reacted best at cold temperatures. The maternal antibody detected in pregnancy was not reactive at 37°C, and a direct antiglobulin test (DAT) on red blood cells (RBCs) from the newborn was negative, suggesting an anti-M that should not have been clinically relevant. However, the infant developed hyperbilirubinemia (bilirubin level, 17.6 mg/dL), hemolytic anemia (hemoglobin nadir, 5.5 g/dL), and reticulocytopenia. Laboratory testing demonstrated the presence of an IgG anti-M in maternal and neonatal samples reacting best at 4°C. This passively acquired IgG anti-M provoked hemolytic anemia in the infant and likely suppressed erythropoiesis, resulting in reticulocytopenia with prolonged anemia. He was treated for IgG anti-M HDFN with 10 intravenous Ig infusions and 10 days of oral prednisone followed by a taper. He required seven transfusions with M− RBCs. His hemoglobin level normalized at 3 months of age. Follow-up at 2 years revealed no hematologic or neuro-developmental concerns. Conclusion: To our knowledge, this is the second report of HDFN attributable to an IgG anti-M reacting preferentially at cold temperature with no 37°C reactivity. Clinically relevant IgG anti-M may elude standard testing. Early recognition and testing for cold-reacting IgG anti-M should be considered for newborns with hemolysis, a negative DAT, and prolonged anemia.

MSc., Faculty of Science, University of the Witwatersrand, 2011 / Background: Due to the high cost and limited serotype coverage of pneumococcal conjugate vaccines (PCV), surface proteins of Streptococcus pneumoniae are being investigated for their role as potential vaccine candidates. There are limited data on natural antibody kinetics against pneumococcal surface proteins arising through exposure to pneumococcal nasopharyngeal (NP) colonization in African populations. Objectives: To characterize the natural antibody kinetics and sero-prevalence to 15 pneumococcal proteins with respect to age, PCV vaccination and HIV status as well as to explore the association between antibody titers and pneumococcal nasopharyngeal colonization in infants, older children and adults. Methods: We established a 15-plex Luminex assay for the following proteins: PspA, PspC, LytB, IgA1-proteinase, SP 0082, PdB, PcsB, PsaA, SP 0609, SP 0749, PpmA, SlrA, StkP, SP 2027 and SP 2194, and also validated the Luminex assay comparing it to a standard ELISA method for PspA, PspC, PsaA and PdB. We used the Luminex method to characterize the prevalence and dynamics of serum IgG antibodies against the pneumococcal proteins. The study involved 2 166 human subjects which included: i. A longitudinal cohort of children less than 2 years of age, who were vaccinated with the seven-valent pneumococcal conjugate vaccine (PCV-7) and were either a) HIV-exposed infected, b) HIV-exposed uninfected or c) HIV-unexposed uninfected. ii. A longitudinal cohort of PCV-7 unvaccinated children less than 2 years of age who were either: a) HIV-unexposed uninfected or b) HIV-exposed uninfected. The PCV-7 vaccinated and unvaccinated children were followed up from approximately 4 to 24 months of age. In addition, samples were also analyzed from HIV-uninfected and HIV-infected children Project ID: Pneumococcal protein antigens Student: Zanele Ditse Date: 04 October 2011 - 5 - aged between 4 to 7 years who received either a primary series of PCV-9 or placebo during infancy. Lastly, we analyzed cross-sectional samples from HIV-uninfected and HIV-infected women. Results: The multiplex Luminex assay correlated well with singleplex ELISAs for all four analyzed proteins with correlation coefficients of 0.86, 0.90, 0.87 and 0.96 for PspA, PspC, PdB and PsaA respectively. Antibody titers to PspC, PdB, LytB, SP 0082, PcsB and StkP showed increases in titer with respect to increasing age. Prevailing nasopharyngeal pneumococcal colonization in young children was associated with higher antibody titers to PspA, PspC, PdB, SP 0082, LytB, IgA1-proteinase, PpmA, PcsB and StkP. Conversely higher antibody titers to PspC, PdB, LytB, SP 0082, PcsB and StkP were associated with lower prevalence of pneumococcal colonization in older children and adults. In children under two years of age, PCV vaccination was associated with lower antibody titers to PspA, PspC, LytB, PdB, IgA1-proteinase, PcsB and StkP as well as higher antibody titers against SP 0082 and PpmA at multiple time-points. In PCV-vaccinated children under two years of age, those who were HIV-unexposed , -uninfected had higher antibody titers to PspA, PspC, SP 0082, IgA1-proteinase, PpmA and StkP compared to HIV-exposed, uninfected children. Conclusion: There was an age-related increase in antibody titers to PspA, PspC, PdB, SP 0082, LytB, IgA1-proteinase, PpmA, PcsB, and StkP in children under two years of age. PCV immunization was, however, associated with lower antibody titers to PspA, PspC, LytB, PdB, IgA1-proteinase, PcsB and StkP in young children which was not attributed to differences in the prevalence of nasopharyngeal colonization. Furthermore, HIV-infection status in young children was associated with higher antibody responses to PspA, PspC, PdB, SP 0082, LytB, IgA1-proteinase, PpmA, PcsB and StkP proteins in HIV-unexposed uninfected children compared to HIV-exposed uninfected and HIV-exposed infected children. Higher antibody concentrations to Project ID: Pneumococcal protein antigens Student: Zanele Ditse Date: 04 October 2011 - 6 - PspC, PdB, LytB, SP 0082, PcsB and StkP was negatively associated with nasopharyngeal pneumococcal colonization in older children and adults; indicating a protective role against colonization and a potential role as vaccine candidates.

Newborn infants with differential patterns of fetal growth, as determined by their weight-for-length, typically display behaviors which have been conceptualized as reflecting the integrity of the infant's behavioral organization. The newborn infant's sucking is one behavior that has been hypothesized to both reflect the effects of previous experiences on behavioral organization and affect the infant's future behavioral development. In particular, the infant's pattern of sucking activity may not only reflect the integrity of the infant's nervous system, it may also alter the temporal organization of the infant's behavioral state and motor activity by increasing behavioral quiescence. The purpose of this study was to compare the sucking activity of underweight-for-length (N = 30) and average-weight-for-length (N = 30) infants and its effects on behavioral state and motor activity. Fifteen low-PI and 15 average-PI infants were randomly assigned to each of two experimental conditions. / Master of Science

No description available.

No description available.

The thesis begins by examining the history of the newborn screening (NBS) process in the United States and why it is the way it is today. The next section explores why certain genetic conditions, such as Long QT Syndrome (LQTS), do not fulfill requirements for the recommended uniform screening panel (RUSP). Lastly, ethical considerations of expanded NBS in the age of genomic technology are examined by highlighting the principles of autonomy, beneficence, equity, cost-effectiveness, privacy and trust. Overall, the NBS process benefits children by identifying serious rare diseases and intervening early to prevent harm; however, a deeper ethical analysis highlights some of the concerns with expanding mandatory, universal NBS in the age of precision medicine. The focus must be on educating the public and healthcare professionals about the NBS process and using evidence-based protocols for adding new conditions to the panel. / Urban Bioethics

published_or_final_version / Paediatrics / Master / Master of Philosophy

English Abstract This diploma thesis consists of nine chapters and focuses on the criminal law aspects of the crime - the murder of a newborn baby caused by mother. The first chapter contains an introduction to the topic, mainly the brief historical excursion and analysis of current legislation. The next chapter is devoted to the general discussion of the privileged state of facts. The following passage of my thesis deals with the characteristics of state of facts of newborn's murder crime. The characteristics specifically are: a subject, a subjective aspect, an object and an objective aspect. In the chapter about the subjective aspect (the psychological state of the mother character as a type of crime) I devote more attention to the theme of crime and the problematic term "distress after birth." I'm trying to define the duration of the distress caused by childbirth. In the chapter about the object of the crime, called Newborn's life as the object of a criminal offense, I mainly devote to the material object of an attack. I try to present the different views on the problems of determination of the human's life beginning. The sixth chapter (called Newborn's death as a result of mother's treatment) deals with various ways of murderous treatments, which are supplemented by the casuistry. In this section I also...

A asfixia perinatal e sua mais grave complicação, a encefalopatia hipóxicoisquêmica (EHI) são causas de elevada mortalidade e de sequelas neurológicas no recém-nascido (RN). Evidencias de comprometimento cerebral podem ser detectadas logo na primeira semana de vida e o diagnóstico precoce é de grande importância para o tratamento e seguimento. OBJETIVOS: Verificar a prevalência de asfixia perinatal e de EHI; analisar a utilidade de quatro marcadores sanguíneos: transaminase glutâmica oxalacética (TGO), transaminase glutâmica pirúvica (TGP), desidrogenasse láctica (DHL) e Creatina Quinase MB (CK-MB) coletados ao nascimento, com 24 e 72 horas de vida, como sinalizadores de lesões cerebrais nos RN asfixiados; identificar a presença de alterações neurológicas clínicas pelo Escore de Sarnat e Sarnat (1976) com 24 e 72 horas e com 28 dias de vida e identificar e descrever a presença de lesões cerebrais detectadas pela ultrassonografia de crânio com 24 e 72 horas e com 28 dias de vida. MÉTODO: Estudo de coorte prospectivo no qual foram incluídos RN de termo que apresentaram asfixia perinatal pelo critério de Buonocore (presença ao nascimento de pelo menos dois das seguintes condições clínico-laboratoriais: acidose metabólica com níveis de pH 7,20, Boletim de Apgar no quinto minuto de vida < 6, necessidade de fração inspirada de oxigênio 0,40 para manter uma saturação de oxigênio de 86%). Para realização do pH e dos marcadores bioquímicos foi coletado sangue logo ao nascimento, com 24 e 72 horas de vida. O exame clínico segundo critérios de Sarnat e Sarnat foi realizado com 24 e 72 horas e com 28 dias de vida e a ultrassonografia de crânio nos mesmos momentos. RESULTADOS: De 2.989 nascidos vivos durante o período do estudo, 28 recém-nascidos apresentaram asfixia perinatal (1% do total de nascimentos) e a EHI foi evidenciada em 21,42%. A enzima CK-MB se mostrou um bom marcador de asfixia, pois todos os valores foram superiores a 5,10 ng/ml, e se correlacionaram positivamente com as alterações apresentadas no exame clínico de Sarnat e com a ultrassonografia transfontanela. Os valores das outras enzimas como TGO (24h), TGO e TGP (72h) também se correlacionaram positivamente com as alterações ultrassonográficas as quais mostraram alteração em 3,5% dos pacientes com 24 horas de vida, 25% com 72 horas e 28,6% com 28 dias. A ultrassonografia de crânio com 28 dias mostrou aumento estatisticamente significante, no percentual de resultados anormais quando comparado com o observado com 24h (p=0,039), apesar dos estágios de Sarnat terem melhorado, com maior número de pacientes com estágio I no decorrer dos 28 dias. CONCLUSOES: A prevalência de asfixia perinatal e da EHI estão dentro da faixa citada na literatura. O melhor marcador bioquímico nesta casuística foi a isoenzima CK-MB e se correlacionou com as alterações apresentadas no exame clínico de Sarnat e na USG de crânio. A curva ROC mostrou: os valores de CK-MB de 24 horas em relação à USG de crânio de 72 horas Sensibilidade de 85,7%, Especificidade de 85,7% e Acurácia de 85,7%. O escore clínico de Sarnat não se alterou depois de 72 horas e apresentou correlação com as alterações na USG de crânio e este método de imagem foi adequado para detecção de lesões crebrais precoces e com 28 dias de vida / Perinatal asphyxia and its most serious complication, hypoxic-ischemic encephalopathy (HIE) are causes of high mortality and neurological sequelae in the newborn (NB). Evidence of cerebral impairment can be detected in the first week of life and early diagnosis is very important for the treatment and follow-up. OBJECTIVES: To assess the prevalence of perinatal asphyxia and HIE; consider the usefulness of four blood markers: glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) collected the birth, with 24 and 72 hours of life, as markers of brain damage in asphyxiated infants, to identify the presence of neurological clinical score by Sarnat and Sarnat (1976) with 24 and 72 hours and 28 days of life and describe the presence of brain lesions detected by cranial ultrasound with 24 and 72 hours and 28 days. METHOD: A prospective cohort study which included fullterm infants who had perinatal asphyxia by Buonocore criteria (presence at birth of at least two of the following clinical and laboratory conditions: metabolic acidosis with pH levels of the umbilical vein 7.20, Apgar score in the fifth minute of life <6, need for inspired oxygen fraction (FiO2) 0.40 to maintain an oxygen saturation of 86%). To perform the pH and biochemical markers of blood was collected at birth, 24 and 72 hours of life. Clinical examination according to criteria of Sarnat and Sarnat was performed with 24 and 72 hours and 28 days of life and cranial ultrasound was performed in the same time. RESULTS: Of 2989 live births during the study period, 28 had asphyxia (1% of total births) and HIE was found in 21.42%. The CK-MB showed that all above normal values (<5.10ng/ml) and correlated with the changes presented in the clinical examination of Sarnat and the USG transfontanelle. The values of other enzymes such as GOT (24h), GOT and GPT (72h) also correlated positively with the brain lesins detected by cranial ultrasound in 3.5% of patients with 24 hours of life, 25% at 72 hours and 28 6% after 28 days. Ultrasonography of brain at 28 days showed a statistically significant increase in the percentage of abnormal results when compared with that observed at 24h (p = 0.039), despite the Sarnat stages have improved, with larger numbers of patients with stage I during the 28 days. CONCLUSION: The prevalence of perinatal asphyxia and HIE is within the range cited in literature. The best biochemical marker in this series was the CK-MB and correlated with the changes presented in the clinical examination of Sarnat and ultrasound transfontanelle. The ROC curve showed: values of CK-MB of 24 hours and USG 72 hours sensitivity of 85.7%, specificity of 85.7% and accuracy of 85.7%. The clinical Sarnat score did not change after 72 hours and correlated with changes in ultrasound transfontanelle and this imaging method proved to be an appropiate study to detect brain lesions early and with 28 days of life