Introduction: High levels of bilirubin in newborns can cause permanent neurodevelopmental disabilities, and it is crucial to keep the incidence low. However, the Swedish Neonatal Register revealed a high incidence of extreme neonatal hyperbilirubinemia (bilirubin ≥425 umol/L) in Region Örebro County during 2014-2019, and the reason behind this is unknown. Aim: This study aimed to review cases of extreme neonatal hyperbilirubinemia regarding the compliance to the local guidelines, and to explore potential benefits of an alternative method considering bilirubin’s rate of rise, the ruler method. Method: In this case series, a retrospective medical record review was performed on 63 newborns who were delivered at ≥35 gestational weeks and developed extreme hyperbilirubinemia before or during an admission to a hospital in Region Örebro County within the first 14 days of life (2014-2020). Results: The incidence was 2.7 cases per 1000 live births during 2014-2020. Forty-three (68.3%) cases were related to failed detection/treatment initiation and 20 (31.7%) to failed treatment. Out of the newborns classified as failed detection/treatment initiation, 27 individual newborns (62.8%) could potentially have been prevented from developing extreme hyperbilirubinemia if there were no cases of non-compliance (30.2%), if a pre-discharge screening had been performed (14.0%) and if the ruler method had been applied (19/31 investigated). Conclusion: The local guidelines used in Region Örebro County might not be sufficient in preventing the development of extreme neonatal hyperbilirubinemia. However, mandatory pre-discharge screening and a consideration of bilirubin’s current rate of rise when scheduling follow-ups could potentially lower the incidence further.

Made available in DSpace on 2014-02-26T19:13:30Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 56122.pdf: 943164 bytes, checksum: 31ab7a412fa0e24ec2743d0b364e47f6 (MD5) Previous issue date: 2013-07-22 / Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Ensino. Programa de Pós-Graduação em Saúde da Criança e da Mulher. Rio de Janeiro, RJ, Brasil. / Introdução: a Doença Hemolítica Perinatal pelo fator Rh é causada pela incompatibilidade entre o sangue da mãe e do recém-nascido, levando a destruição de hemácias fetais e, sem tratamento os fetos mais severamente afetados podem morrer intra-útero. No recém-nascido, a doença pode resultar em icterícia,anemia, dano cerebral, falência cardíaca e morte.Desde introdução da profilaxia anti-Rh D o número de recém-nascidos com doença hemolítica tem caído drasticamente em países desenvolvidos, porém essa não é a realidade nacional. Objetivo Geral:descrever as práticas usadas para tratar os pacientes com doença hemolítica perinatal pelo fator Rh, nascidos no Instituto Fernandes Figueira nos últimos 10 anos e apresentar dados clínicos,laboratoriais, o tipo de abordagem terapêutica oferecida e o perfil imunohematológico de suas mães. Material e métodos:Foi realizada uma cohort de 300 recém-nascidos de gestantes Aloimunizadas Rh, nascidos no Instituto Fernandes Figueira no período de janeiro de1995 a dezembro de 2004. Foram coletados dados do pré-natal,nascimento e acompanhamento do Follow-up até 1 ano de idade. Resultados: a maioria de nossas gestantes possuía um anticorpo que foi o anti-D, sendo que a gravidade da doença hemolítica não teve relação com o tipo de anticorpo. O início do pré-natal em nossa unidade é tardio, mas mesmo assim a maioria dos recém-nascidos nasce bem. Nosso índice de óbitos e hidropisialmente está em torno de 7%. Foi evidenciada uma queda de 66 para 35,8% do número de pacientes submetidos à exsangüineotransfusão após o ano 2000 coincidindo com a introdução biliberço e uso da imunoglobulina humana inespecífica, sem comprometimento do prognóstico. Nosso índice de mortalidade relacionado à exsangüineotransfusão foi de 0,7% e de eventos adversos foi de 61%, sendo os mais comuns a plaquetopenia (mais ou menos 50.000) e distúrbios hidroeletrolíticos (hipocalcemia).Os eventos mais graves foram os distúrbios cardiológicos e de sangramento foram estatisticamente maiores nos pacientes cujas condições clínicas eram mais instáveis antes do procedimento. Fatores como níveis críticos de bilirrubina(mais ou menos 20 mg/dl), a prematuridade, hidropisia e asfixia pioram o prognóstico tardio (surdez e encefalopatia bilirrubínica)apesar de intervenção terapêutica precoce. Conclusões: Novas terapias têm sido desenvolvidas para abordagem do recém-nascido com Doença Hemolítica Perinatal como as fototerapias de alta intensidade e a imunoglobulina humana inespecífica, levando a uma diminuição no uso da exsangüineotransfusão, porém esta ainda é uma técnica usada em casos graves de hiperbilirrubinemia.Vários eventos adversos são descritos em conseqüência deste procedimento e são na maioria das vezes assintomáticos e passiveis de correção, mas não podemos deixar de levar em consideração a gravidade do recém-nascido antes do procedimento,além da experiência clínica do profissional que realizará o procedimento. Apesar da intervenção terapêutica precoce os pacientes com fatores de risco(Bt máx mais ou menos 20mg/dl,asfixia,hipoproteinemia e prematuridade) tiveram um prognóstico neurológico pior. / Introduction: The hemolytic disease secondary to rhesus alloimmunization is caused by the incompatib ility between the mother's and the newborn’s blood, leading to the destruction of fetal r ed blood cells and without treatment the fetuses more severely affected can di e intra-uterus. Afte r the delivery the newborn’s disease can result in j aundice, anemia, cerebral damage, heart failure and death. Since the introducti on of the prophylaxis anti-Rh D the number of newborn with hemolytic dis ease has been falling drastically in developed countries, however that is not the Brazilian reality. Objective : Describe the practices used to tr eat the patients with the hemolytic disease secondary to rhesus alloimmunizati on, who were born at IFF in the last 10 years. Describing clinical data, lab abnormalities, therapeutic approach and immunohematologic characteristic of their mothers. Material and methods: Its was done a cohort of 300 newborns of pregnant women’s with alloimmunization by Rh ant ibody, with babies Instituto Fernandes Figueira in the period of January 1995 to December 2004. The program EPI 6 made the statistical analyses. Results: The mostly found antibody in the pregnant women was the anti-D, and the severity of the hemolytic diseas e didn't have relationship with the types of antibodies. The beginning of the prenatal in our unit is late, but even so most are healthy. Deaths or hydrops ar e around 7%. It was evidenced a newborns fall of 50% in patients undergoing the exchange transfusion after the year 2000, coinciding with the introduction of the Biliberço® and use of the intravenous immunoglobulin, without affecting their prognos tic. Our mortality rate related to the exchange transfusion was of 0,7% and the one related to adverse events was of 61% , being the most co mmon thrombocytopenia (< 50.000) and hypocalcemia. The most serious events were bradycardia or heart arrhythmia and bleeding. These disturbances were mo re prevalent in the patients whose clinical conditions were unstable bef ore exchange transfusion. Factors as critical levels of bilirubin ( ≥ 20 mg/dl), prematurity, hydrops fetalis and asphyxia, worsen the neurological prognostic (deafness and bilirubin encephalopathy). Conclusions: New therapies have been developed for the approach of the newborns with hemolytic disease as the phototherapy of high intensity and the intravenous immunoglobulin, leading to a dec rease in the use of the exchange transfusions, but this is still a saving life technique in the serious cases of hiperbilirrubinemia. Several adverse ev ents are described as a consequence of this procedure and most of the ti me they show no symptoms and are susceptible to correction, but we have consider the severity of the patient’s clinical conditions and the professional's skill. Besides the early therapeutic intervention in patients with risk factors (BT máx ≥ 20 mg/dl, the preterm infants, hydrops fetalis and asphyxia) it had a worse neurological prognostic.

A icterícia por hiperbilirrubinemia indireta afeta mais de 60% dos recém-nascidos a termo. O tratamento, quando necessário, é realizado através da fototerapia. Não existem estudos na literatura avaliando os efeitos da fototerapia na função dos neutrófilos de recém-nascidos. O melhor entendimento da função dos neutrófilos nos recém-nascidos antes e após a fototerapia seria importante para avaliar as possíveis repercussões na expressão dos neutrófilos desencadeadas pelo tratamento fototerápico. O objetivo deste estudo foi avaliar e comparar a função dos neutrófilos, através da mensuração pela citometria de fluxo da expressão dos principais marcadores de superfície em recémnascidos ictéricos, antes e após 24 horas de fototerapia. Metodologia: Foram incluídos recém-nascidos com idade gestacional ≥ 35 semanas e peso de nascimento ≥ 2000g, que possuiam critérios da Academia Americana de Pediatria para tratamento fototerápico. Os critérios de exclusão foram: mal-formações congênitas, síndromes com alterações cromossômicas, erro inato do metabolismo, infecções do grupo STORCH, asfixia neonatal, sepse ou suspeita de sepse, exsanguineotransfusão, transfusão de hemocomponentes e uso de imunoglobulina. Foi realizada a avaliação de expressão da intensidade média de fluorescência (IMF) de CD10, CD11b, CD11c, CD15, CD16, CD18, CD62L, CD64 e CD66, antes do início e após 24 horas do início da fototerapia. Foram utilizados o teste T de Student para análise dos dados. Resultados: Foram incluídos 25 recém-nascidos no estudo, com idade mediana de 53 (27.5-75.5) horas de vida e bilirrubina média de 13.6±2.85 mg/dL. Não houve diferença estatística na expressão de CD11b, CD15, CD18, CD62L, CD64 e percentual de neutrófilos antes e após 24 horas de fototerapia. Ocorreu aumento da expressão de CD10 8 (p=0.038) e CD16 (p=0.017) e redução da expressão de CD11c (p=0.023) e CD66acde (p=0.004) após 24 horas de fototerapia. Conclusão: Os recém-nascidos submetidos ao tratamento fototerápico apresentaram aumento da expressão de CD10 e de CD16 e diminuição da expressão de CD11c e de CD66acde após 24 horas de exposição, que pode estar relacionado a um efeito antiinflamatório da fototerapia nos recém-nascidos expostos a este tratamento. / Jaundice due to indirect hyperbilirubinemia affects more than 60% of term neonates. The treatment when necessary is carried out using phototherapy. There are no studies in the literature evaluating the effect of phototherapy on the function of neonates' neutrophils. A better understanding of the function of neutrophils in neonates before and after phototherapy would be important in order to assess potential effects on the expression of neutrofils triggered by the phototherapy treatment. The aim of this study was to assess and compare the function of neutrophils by measuring the expression of the main surface markers in icteric neonates, using flow cytometry, before and after 24 hours of phototherapy. Methodology: Neonates at a gestational age ≥ 35 weeks and at a birth weight ≥ 2000g who met the criteria of the American Academy of Pediatrics for phototherapy were included. The exclusion criteria were: congenital malformations, syndromes with chromosomal alterations, inborn errors of metabolism, infections of the STORCH group, neonatal asphyxia, sepsis or suspicion of sepsis, exchange transfusion, transfusion of blood components, and use of immunoglobulin. The evaluation of the MFI expression of CD10, CD11b, CD11c, CD15, CD16, CD18, CD62L, CD64 and CD66 was performed before and 24 hours after the initiation of phototherapy. The chi-square and Student T tests were used for data analysis. Results: Twenty-five neonates were included in the study at the mean age of 53 (27.5- 75.5) hours of life and with a mean bilirubin level of 13.6±2.85 mg/dL. There was no statistical difference in the expression of CD11b, CD15, CD18, CD62L, CD64 and percentage of neutrophils before and after 24 hours of phototherapy. There was an increase in the expression of CD10 (p=0.038) and CD16 (p=0.017) and a reduction in 10 the expression of CD11c (p=0.023) and CD66acde (p=0.004) after 24 hours of phototherapy. Conclusion: The newborns submitted to phototherapy had increased expression of CD10 and CD16 and decreased expression of CD11c and CD66acde after 24 hours of exposure, which may be related to an anti-inflammatory effect of phototherapy on the neonates exposed to this treatment.

A icterícia por hiperbilirrubinemia indireta afeta mais de 60% dos recém-nascidos a termo. O tratamento, quando necessário, é realizado através da fototerapia. Não existem estudos na literatura avaliando os efeitos da fototerapia na função dos neutrófilos de recém-nascidos. O melhor entendimento da função dos neutrófilos nos recém-nascidos antes e após a fototerapia seria importante para avaliar as possíveis repercussões na expressão dos neutrófilos desencadeadas pelo tratamento fototerápico. O objetivo deste estudo foi avaliar e comparar a função dos neutrófilos, através da mensuração pela citometria de fluxo da expressão dos principais marcadores de superfície em recémnascidos ictéricos, antes e após 24 horas de fototerapia. Metodologia: Foram incluídos recém-nascidos com idade gestacional ≥ 35 semanas e peso de nascimento ≥ 2000g, que possuiam critérios da Academia Americana de Pediatria para tratamento fototerápico. Os critérios de exclusão foram: mal-formações congênitas, síndromes com alterações cromossômicas, erro inato do metabolismo, infecções do grupo STORCH, asfixia neonatal, sepse ou suspeita de sepse, exsanguineotransfusão, transfusão de hemocomponentes e uso de imunoglobulina. Foi realizada a avaliação de expressão da intensidade média de fluorescência (IMF) de CD10, CD11b, CD11c, CD15, CD16, CD18, CD62L, CD64 e CD66, antes do início e após 24 horas do início da fototerapia. Foram utilizados o teste T de Student para análise dos dados. Resultados: Foram incluídos 25 recém-nascidos no estudo, com idade mediana de 53 (27.5-75.5) horas de vida e bilirrubina média de 13.6±2.85 mg/dL. Não houve diferença estatística na expressão de CD11b, CD15, CD18, CD62L, CD64 e percentual de neutrófilos antes e após 24 horas de fototerapia. Ocorreu aumento da expressão de CD10 8 (p=0.038) e CD16 (p=0.017) e redução da expressão de CD11c (p=0.023) e CD66acde (p=0.004) após 24 horas de fototerapia. Conclusão: Os recém-nascidos submetidos ao tratamento fototerápico apresentaram aumento da expressão de CD10 e de CD16 e diminuição da expressão de CD11c e de CD66acde após 24 horas de exposição, que pode estar relacionado a um efeito antiinflamatório da fototerapia nos recém-nascidos expostos a este tratamento. / Jaundice due to indirect hyperbilirubinemia affects more than 60% of term neonates. The treatment when necessary is carried out using phototherapy. There are no studies in the literature evaluating the effect of phototherapy on the function of neonates' neutrophils. A better understanding of the function of neutrophils in neonates before and after phototherapy would be important in order to assess potential effects on the expression of neutrofils triggered by the phototherapy treatment. The aim of this study was to assess and compare the function of neutrophils by measuring the expression of the main surface markers in icteric neonates, using flow cytometry, before and after 24 hours of phototherapy. Methodology: Neonates at a gestational age ≥ 35 weeks and at a birth weight ≥ 2000g who met the criteria of the American Academy of Pediatrics for phototherapy were included. The exclusion criteria were: congenital malformations, syndromes with chromosomal alterations, inborn errors of metabolism, infections of the STORCH group, neonatal asphyxia, sepsis or suspicion of sepsis, exchange transfusion, transfusion of blood components, and use of immunoglobulin. The evaluation of the MFI expression of CD10, CD11b, CD11c, CD15, CD16, CD18, CD62L, CD64 and CD66 was performed before and 24 hours after the initiation of phototherapy. The chi-square and Student T tests were used for data analysis. Results: Twenty-five neonates were included in the study at the mean age of 53 (27.5- 75.5) hours of life and with a mean bilirubin level of 13.6±2.85 mg/dL. There was no statistical difference in the expression of CD11b, CD15, CD18, CD62L, CD64 and percentage of neutrophils before and after 24 hours of phototherapy. There was an increase in the expression of CD10 (p=0.038) and CD16 (p=0.017) and a reduction in 10 the expression of CD11c (p=0.023) and CD66acde (p=0.004) after 24 hours of phototherapy. Conclusion: The newborns submitted to phototherapy had increased expression of CD10 and CD16 and decreased expression of CD11c and CD66acde after 24 hours of exposure, which may be related to an anti-inflammatory effect of phototherapy on the neonates exposed to this treatment.

A icterícia por hiperbilirrubinemia indireta afeta mais de 60% dos recém-nascidos a termo. O tratamento, quando necessário, é realizado através da fototerapia. Não existem estudos na literatura avaliando os efeitos da fototerapia na função dos neutrófilos de recém-nascidos. O melhor entendimento da função dos neutrófilos nos recém-nascidos antes e após a fototerapia seria importante para avaliar as possíveis repercussões na expressão dos neutrófilos desencadeadas pelo tratamento fototerápico. O objetivo deste estudo foi avaliar e comparar a função dos neutrófilos, através da mensuração pela citometria de fluxo da expressão dos principais marcadores de superfície em recémnascidos ictéricos, antes e após 24 horas de fototerapia. Metodologia: Foram incluídos recém-nascidos com idade gestacional ≥ 35 semanas e peso de nascimento ≥ 2000g, que possuiam critérios da Academia Americana de Pediatria para tratamento fototerápico. Os critérios de exclusão foram: mal-formações congênitas, síndromes com alterações cromossômicas, erro inato do metabolismo, infecções do grupo STORCH, asfixia neonatal, sepse ou suspeita de sepse, exsanguineotransfusão, transfusão de hemocomponentes e uso de imunoglobulina. Foi realizada a avaliação de expressão da intensidade média de fluorescência (IMF) de CD10, CD11b, CD11c, CD15, CD16, CD18, CD62L, CD64 e CD66, antes do início e após 24 horas do início da fototerapia. Foram utilizados o teste T de Student para análise dos dados. Resultados: Foram incluídos 25 recém-nascidos no estudo, com idade mediana de 53 (27.5-75.5) horas de vida e bilirrubina média de 13.6±2.85 mg/dL. Não houve diferença estatística na expressão de CD11b, CD15, CD18, CD62L, CD64 e percentual de neutrófilos antes e após 24 horas de fototerapia. Ocorreu aumento da expressão de CD10 8 (p=0.038) e CD16 (p=0.017) e redução da expressão de CD11c (p=0.023) e CD66acde (p=0.004) após 24 horas de fototerapia. Conclusão: Os recém-nascidos submetidos ao tratamento fototerápico apresentaram aumento da expressão de CD10 e de CD16 e diminuição da expressão de CD11c e de CD66acde após 24 horas de exposição, que pode estar relacionado a um efeito antiinflamatório da fototerapia nos recém-nascidos expostos a este tratamento. / Jaundice due to indirect hyperbilirubinemia affects more than 60% of term neonates. The treatment when necessary is carried out using phototherapy. There are no studies in the literature evaluating the effect of phototherapy on the function of neonates' neutrophils. A better understanding of the function of neutrophils in neonates before and after phototherapy would be important in order to assess potential effects on the expression of neutrofils triggered by the phototherapy treatment. The aim of this study was to assess and compare the function of neutrophils by measuring the expression of the main surface markers in icteric neonates, using flow cytometry, before and after 24 hours of phototherapy. Methodology: Neonates at a gestational age ≥ 35 weeks and at a birth weight ≥ 2000g who met the criteria of the American Academy of Pediatrics for phototherapy were included. The exclusion criteria were: congenital malformations, syndromes with chromosomal alterations, inborn errors of metabolism, infections of the STORCH group, neonatal asphyxia, sepsis or suspicion of sepsis, exchange transfusion, transfusion of blood components, and use of immunoglobulin. The evaluation of the MFI expression of CD10, CD11b, CD11c, CD15, CD16, CD18, CD62L, CD64 and CD66 was performed before and 24 hours after the initiation of phototherapy. The chi-square and Student T tests were used for data analysis. Results: Twenty-five neonates were included in the study at the mean age of 53 (27.5- 75.5) hours of life and with a mean bilirubin level of 13.6±2.85 mg/dL. There was no statistical difference in the expression of CD11b, CD15, CD18, CD62L, CD64 and percentage of neutrophils before and after 24 hours of phototherapy. There was an increase in the expression of CD10 (p=0.038) and CD16 (p=0.017) and a reduction in 10 the expression of CD11c (p=0.023) and CD66acde (p=0.004) after 24 hours of phototherapy. Conclusion: The newborns submitted to phototherapy had increased expression of CD10 and CD16 and decreased expression of CD11c and CD66acde after 24 hours of exposure, which may be related to an anti-inflammatory effect of phototherapy on the neonates exposed to this treatment.

Eine Erhöhung des Bilirubins über 2 mg/dl betrifft 90 % aller Neugeborenen. Sie ist meist physiologisch und tritt optisch sichtbar bei 60-70 % dieses Kollektivs auf. In der pathologischen, exzessiv erhöhten Form ist sie der häufigste Grund für eine stationäre Wiederaufnahme während der ersten sieben Lebenstage. Ihre schwerste Komplikation, der Kernikterus, scheint - trotz allgemein verfügbarer, preiswerter und sicherer Therapiemöglichkeiten - wieder vermehrt aufzutreten. Die Gründe liegen im Überwachungsdefizit bei früher Entlassung von schlecht aufgeklärten Eltern, Nichtbeachtung der Besonderheiten der Neugeborenen ≤ 38 Schwangerschaftswochen und der zunehmenden Tendenz zum Stillen bei häufig unzureichender Anleitung. Ferner werden ikterische Kinder nur zu oft lediglich visuell bezüglich des Grades der Bilirubinämie eingeschätzt und die Therapie somit erheblich verzögert. Gegenstand dieser Arbeit ist die Frage, ob aus der Dynamik des Serumbilirubinspiegels von der Geburt bis zum 3. Lebenstag die Wahrscheinlichkeit des Auftretens einer phototherapiepflichtigen Hyperbilirubinämie abgeschätzt werden kann. Dazu wurde der Serumbilirubinspiegel direkt postnatal aus dem Nabelschnurblut, bzw. am 3. Lebenstag gleichzeitig mit dem Stoffwechselscreening ermittelt und der Phototherapiebedarf im Verlauf festgehalten. Um die Aussage zu präzisieren, wurde die Studienpopulation aus 2573 Kindern weiter unterteilt in 2180 reife tAGA- (hier Eu- und Hypertrophe), 267 reife tSGA-Kinder (Hypotrophe) und 126 FG (Frühgeborene). In allen 3 Gruppen korrelierten das Nabelschnurbilirubin und der Serumbilirubinwert vom 3. Lebenstag positiv mit der Entwicklung einer Hyperbilirubinämie. Anhand dieser Ausgangswerte konnten Grenzen für Hoch-, Mittelhoch-, Mittelniedrig- und Niedrigrisikogruppen definiert werden, welche die Entwicklung einer Hyperbilirubinämie mit einer Wahrscheinlichkeit von ≥ 20 %, 5-20 %, 0 < x <5 % und 0 % voraussagen. Damit kann man bereits früh eine Vorabselektion entsprechend dem Gefährdungspotential treffen und die Verlaufskontrollen entsprechend terminieren. Als Risikofaktoren einer therapiepflichtigen Hyperbilirubinämie wurden außerdem Frühgeburtlichkeit, seltener tSGA, geringes Geburtsgewicht und niedriges Gestationsalter (in der vorliegenden FG-Gruppe nicht signifikant) gefunden. Im Falle einer Sectiogeburt und bei Zuhilfenahme von Hilfsmitteln im Rahmen einer vaginalen Entbindung nahm der Bedarf an Phototherapie in der tAGA- und tSGA-Gruppe zu.:Bibliographische Beschreibung……………………………………………………………………….1 Abkürzungsverzeichnis………………………………………………………………………………..2 1. Einleitung…………………………………………………………………………………...3 1.1. Geschichtliche Entwicklung……………………………………………………………………...3 1.2. Wandel der Anschauungen zu den Therapiegrenzen…..…………………………….................4 1.3. Hyperbilirubinämie……………………………………………………………………………….7 1.4. Kernikterusregister………………………………………………………………………………..8 1.5. Problemstellung…………………………………………………………………………………...9 2. Patienten und Methoden………………………………………………………………..11 2.1. Patientenkollektiv………………………………………………………………………………...11 2.2. Ausschlusskriterien………………………………………………………………………………11 2.3. Datenerfassung………………………………………………………………………………...…11 2.4. Phototherapie (PT)………………………………………………………………………………12 2.5. statistische Analyse………………………………………………………………………………13 2.5.1. konkrete Fragestellung………………………………………………………………………………...…13 2.6. Signifikanzniveau……………………………………………………..………………………….13 3. Ergebnisse………………………………………………………………………………..14 3.1. Gesamtpopulation…………………………………………………………….………………….14 3.2. Charakteristika der Studienpopulation…………………………….…………………………..14 3.3. tAGA (reife eu- und hypertrophe Neugeborene)………………………………………………16 3.4. tSGA (reife hypotrophe Neugeborene).……….……………………………………………….18 3.5. Frühgeborene (FG)………………………………..…………………………….……………….20 3.6. direkter Vergleich der 3 Untergruppen (tAGA, tSGA und FG)…………………………...…22 3.7. Charakteristika der Population der zweiten Studienphase…………………………………...28 3.8. tAGA-Kinder in der zweiten Studienphase (TSB3-tAGA)……………………………………30 3.9. tSGA in der zweiten Studienphase (TSB3-tSGA)….…………………………………………..32 3.10. Frühgeborene in der zweiten Studienphase (TSB3-FG)……………….…………………….35 3.11. direkter Vergleich der drei Untergruppen der zweiten Studienphase…………….………..37 3.12. Vergleich der retro- und prospektiven Teile der Studie…….……………………………….43 3.13. Die Phototherapiegruppe………………………………………………………………………45 3.13.5. Zusammenhang zwischen Phototherapie und Geburtsmodus………………………………………..47 3.13.6. Zusammenhang zwischen Phototherapie und Nabelschnurbilirubin………………………………..48 3.13.7. Zusammenhang zwischen Phototherapie und Serumbilirubin vom 3.LT (TSB3)…………………..51 3.14. Vorhersage der therapiepflichtigen Hyperbilirubinämie anhand der Nabelschnurbilirubin-Werte…..………………………………………………….…………………………………….……..54 3.14.1. statistische Begriffe………………………………………………………………………………………54 3.14.2. Vorhersage der therapiepflichtigen Hyperbilirubinämie anhand der Nabelschurbilirubin-Werte.54 3.15. Vorhersage der therapiepflichtigen Hyperbilirubinämie anhand TSB3 (Serumbilirubin vom 3. Lebenstag)……………………...………………………………………..……………………56 3.16. Zusammenhang zwischen NS-Bili und TSB3(Serumbilirubin vom 3. Lebenstag)…………58 3.17. Regressionsanalyse…………………………………...…………………………………………59 3.17.1. univariate Regressionsanalyse………………………………………………………………………….59 3.17.2. multivariate Regressionsanalyse………………………………………………………………………..59 3.18. Odds Ratio einer therapiepflichtigen Hyperbilirubinämie………………………………….61 3.19. Beginn und Dauer der Phototherapie…………………………………………………………62 4. Diskussion……………………………………….…………………………………..…….64 Nabelschnurbilirubin und Phototherapie………………………………………………….……….64 Serumbilirubin vom 3. Lebenstag und Phototherapie….………………………………………….67 Kombination aus Nabelschnurbilirubin und Serumbilirubin vom 3.Lebenstag…………………71 Phototherapiegruppe…………………………………………………………………………………73 Schlussfolgerung…………………………...…………………………………………………………76 5. Zusammenfassung der Arbeit……………………………………………………………78 6. Literaturverzeichnis………………………………………………………………………82 7. Abbildungsverzeichnis……………………………………………………………………98 8. Tabellenverzeichnis……………………………………………………………………….99 Erklärung über die eigenständige Abfassung der Arbeit…………………………..……101 Danksagung…………………...…………………………………………………..………..102 Lebenslauf……………………………………………………………………………………………103

<p>Ormarsdóttir, S. 2001. Osteoporosis in Chronic Liver Disease. Acta Universitatis Upsaliensis. <i>Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine</i> 1037. 60 pp. Uppsala. ISBN 91-554-5021-0. </p><p>Osteoporosis is a well-known and frequently reported complication of chronic liver disease (CLD) with a high fracture rate contributing to significant morbidity after liver transplantation. The pathogenesis is unknown and controversy exists about many risk factors for osteoporosis in CLD. </p><p>In the present thesis, bone mineral density (BMD) was found to be significantly lower at the lumbar spine (<i>p</i><0.01) in a cohort of patients with CLD compared with age- and gender -matched individuals. Osteoporosis was found in 30% of the patients and 15% of the controls, respectively. Low body mass index (BMI), corticosteroid treatment, prothrombin time, age and female gender were independent risk factors for osteoporosis in the patients. </p><p>In a follow-up study, 43 of 72 patients were available for a second BMD measurement 25 months (median) after the first. Bone loss at the femoral neck was 1.5 ± 2.4% in females and 2.9 ± 2.0% in males with a significant decrease in BMD Z-score over time (<i>p</i>=0.005 and <i>p</i>=0.02 for females and males, respectively), indicating increased bone loss at this site. Hyperbilirubinaemia and low circulating levels of 25-hydroxy vitamin D₃ predicted increased bone loss at the femoral neck. These findings suggest that cortical bone, in addition to trabecular bone, may be affected in CLD and bilirubin and vitamin D₃ may be involved in the pathophysiology of osteoporosis in CLD. </p><p>In order to elucidate the suggested role of insulin-like growth factors (IGFs) and leptin in the pathophysiology of osteoporosis in CLD, we studied the relationship between these factors and BMD. Levels of IGFs were extremely low (<i>p</i><0.0001 compared with the controls) and related to liver function but no correlation was found between the IGFs and BMD. Serum leptin adjusted for BMI correlated negatively with BMD in female patients (<i>p</i>=0.003 and <i>p</i>=0.04 at the lumbar spine and the femoral neck, respectively) and in male patients at the femoral neck (<i>p</i>=0.04). Thus, the IGFs appear not to be involved in the pathophysiology of osteoporosis in CLD but a role of circulating leptin is possible. </p>

Ormarsdóttir, S. 2001. Osteoporosis in Chronic Liver Disease. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1037. 60 pp. Uppsala. ISBN 91-554-5021-0. Osteoporosis is a well-known and frequently reported complication of chronic liver disease (CLD) with a high fracture rate contributing to significant morbidity after liver transplantation. The pathogenesis is unknown and controversy exists about many risk factors for osteoporosis in CLD. In the present thesis, bone mineral density (BMD) was found to be significantly lower at the lumbar spine (p&lt;0.01) in a cohort of patients with CLD compared with age- and gender -matched individuals. Osteoporosis was found in 30% of the patients and 15% of the controls, respectively. Low body mass index (BMI), corticosteroid treatment, prothrombin time, age and female gender were independent risk factors for osteoporosis in the patients. In a follow-up study, 43 of 72 patients were available for a second BMD measurement 25 months (median) after the first. Bone loss at the femoral neck was 1.5 ± 2.4% in females and 2.9 ± 2.0% in males with a significant decrease in BMD Z-score over time (p=0.005 and p=0.02 for females and males, respectively), indicating increased bone loss at this site. Hyperbilirubinaemia and low circulating levels of 25-hydroxy vitamin D3 predicted increased bone loss at the femoral neck. These findings suggest that cortical bone, in addition to trabecular bone, may be affected in CLD and bilirubin and vitamin D3 may be involved in the pathophysiology of osteoporosis in CLD. In order to elucidate the suggested role of insulin-like growth factors (IGFs) and leptin in the pathophysiology of osteoporosis in CLD, we studied the relationship between these factors and BMD. Levels of IGFs were extremely low (p&lt;0.0001 compared with the controls) and related to liver function but no correlation was found between the IGFs and BMD. Serum leptin adjusted for BMI correlated negatively with BMD in female patients (p=0.003 and p=0.04 at the lumbar spine and the femoral neck, respectively) and in male patients at the femoral neck (p=0.04). Thus, the IGFs appear not to be involved in the pathophysiology of osteoporosis in CLD but a role of circulating leptin is possible.

O Brasil é um dos países do mundo onde mais se realiza cesarianas, muitas delas são realizadas de forma eletiva em idades gestacionais diversas entre 37 e 41 semanas. Cesarianas eletivas realizada em idades gestacionais muito precoces aumentam a o risco de eventos neonatais adversos. Objetivo: Avaliar a relação entre a idade gestacional em que a cesariana eletiva foi realizada e os resultados neonatais em mulheres atendidas no setor privado de saúde. Metodologia: Estudo de coorte retrospectivo entre mulheres assistidas no setor privado de saúde do sul do Brasil, avaliando desfechos neonatais em cesarianas eletivas. No período de janeiro de 2015 a dezembro de 2016. Utilizaram-se os seguintes critérios de elegibilidade: foram incluíram gestantes primíparas e secundíparas com uma cesariana prévia, com idade gestacional entre 37 e 39 semanas (grupo I) ou ≥39 semanas (grupo II) submetidas à cesariana eletiva. Mulheres com indicações médicas para cesariana e gestantes que apresentavam comorbidades associadas foram excluídas, assim como menores de 18 anos, gestações com fetos malformados e gestantes que apresentavam rupreme. Os desfechos neonatais foram comparados entre os dois grupos de idade gestacional. Resultados: Ocorreram 8480 nascimentos de fetos vivos no Hospital Moinhos de Vento durante o período do estudo. Destes, 6542 cesarianas foram excluídos e 1938 cesarianas foram elegíveis para o presente estudo: 625 no grupo I e 1313 no grupo II. A mediana de gestações e abortamentos anteriores foram maiores 14 no grupo I (p≤0,0001 para ambos). A média de idade das mulheres nos dois grupos foi de 34 anos. Não houve variação significativa em relação à etnia, onde a média das mulheres estudadas foi de 97,8% de brancos nos dois grupos. Cerca de 72% das mulheres eram casadas ou moravam com companheiros e 26,1% do total de mulheres eram solteiras ou moravam sem companheiro em ambos os grupos. O índice de massa corporal médio em ambos os grupos foi de 28,7kg / m2. A internação na Unidade de Tratamento Intensivo (UTI) neonatal e a hiperbilirrubinemia foram positivamente associadas ao grupo I em relação ao grupo II (Teste Qui-quadrado com análise residual ajustada, p≤0,0001 e p = 0,049, respectivamente). Nas análises de Spearman observamos que a cesariana realizada ≥39+0 semanas gestacionais (grupo II) foi negativamente relacionada à admissão na UTI Neonatal (rS=-0,091, p≤0,001), à hipoglicemia com necessidade de intervenção terapêutica (rS=-0,047, p=0,039) e eventos de hiperbilirrubinemia (rS=-0,051, p=0,023). Conclusão: A cesariana eletiva realizada antes de 39 semanas completas aumenta o risco de desfechos neonatais adversos. / Brazil is one of the countries in the world where caesarean sections are most frequently performed, many of which are performed electively at different gestational ages between 37 and 41 weeks. Elective cesarean sections performed at very early gestational ages increase the risk of adverse neonatal events. Objective: To evaluate the relationship between the gestational age at which elective cesarean section was performed and the perinatal outcomes in women treated in the private health sector. Methodology: Retrospective cohort study among women assisted in the private health sector of southern Brazil, evaluating neonatal outcomes in elective cesarean sections. From January 2015 to December 2016. The following eligibility criteria were used: primiparous and secondary infants with a previous cesarean section, gestational age between 37 and 39 weeks (group I) or ≥39 weeks (group II) submitted to elective caesarean section. Women with medical indications for cesarean section and pregnant women with associated comorbidities were excluded, as well women under 18 years old and those who presented amoniorexe. Neonatal outcomes were compared between the two gestational age groups. Results: There were 8480 births of live fetuses at Hospital Moinhos de Vento during the study period. Of those, 6542 cesareans were excluded and 1938 cesareans were eligible for the present study: 625 in group I and 1313 in group II. The median of previous pregnancies and abortions were higher in group I (p≤0,0001 for both). The mean age of women in both groups was 34 years. There was no significant variation in relation to ethnicity, where the average of the 16 studied women was 97.8% whites in both groups. About 72% of the women were married or lived with partners and 26,1% of the total women were single or lived without a partner in both groups. The mean body mass index in both groups was 28.7 kg / m2. Neonatal Intensive Care Unit (ICU) and hyperbilirubinemia were positively associated with group I in relation to group II (Chi-square test with adjusted residual analysis, p≤0,0001 and p = 0.049, respectively). In the Spearman analyzes, we observed that cesarean section performed ≥39 + 0 gestational weeks (group II) was negatively related to admission to the neonatal ICU (rS = -0.091, p≤0.001), to hypoglycemia requiring therapeutic intervention (rS = -0.047, p = 0.039) and hyperbilirubinemia events (rS = -0.051, p = 0.023). Conclusion: Elective caesarean section performed before 39 completed weeks increases the risk of adverse neonatal outcomes.

O Brasil é um dos países do mundo onde mais se realiza cesarianas, muitas delas são realizadas de forma eletiva em idades gestacionais diversas entre 37 e 41 semanas. Cesarianas eletivas realizada em idades gestacionais muito precoces aumentam a o risco de eventos neonatais adversos. Objetivo: Avaliar a relação entre a idade gestacional em que a cesariana eletiva foi realizada e os resultados neonatais em mulheres atendidas no setor privado de saúde. Metodologia: Estudo de coorte retrospectivo entre mulheres assistidas no setor privado de saúde do sul do Brasil, avaliando desfechos neonatais em cesarianas eletivas. No período de janeiro de 2015 a dezembro de 2016. Utilizaram-se os seguintes critérios de elegibilidade: foram incluíram gestantes primíparas e secundíparas com uma cesariana prévia, com idade gestacional entre 37 e 39 semanas (grupo I) ou ≥39 semanas (grupo II) submetidas à cesariana eletiva. Mulheres com indicações médicas para cesariana e gestantes que apresentavam comorbidades associadas foram excluídas, assim como menores de 18 anos, gestações com fetos malformados e gestantes que apresentavam rupreme. Os desfechos neonatais foram comparados entre os dois grupos de idade gestacional. Resultados: Ocorreram 8480 nascimentos de fetos vivos no Hospital Moinhos de Vento durante o período do estudo. Destes, 6542 cesarianas foram excluídos e 1938 cesarianas foram elegíveis para o presente estudo: 625 no grupo I e 1313 no grupo II. A mediana de gestações e abortamentos anteriores foram maiores 14 no grupo I (p≤0,0001 para ambos). A média de idade das mulheres nos dois grupos foi de 34 anos. Não houve variação significativa em relação à etnia, onde a média das mulheres estudadas foi de 97,8% de brancos nos dois grupos. Cerca de 72% das mulheres eram casadas ou moravam com companheiros e 26,1% do total de mulheres eram solteiras ou moravam sem companheiro em ambos os grupos. O índice de massa corporal médio em ambos os grupos foi de 28,7kg / m2. A internação na Unidade de Tratamento Intensivo (UTI) neonatal e a hiperbilirrubinemia foram positivamente associadas ao grupo I em relação ao grupo II (Teste Qui-quadrado com análise residual ajustada, p≤0,0001 e p = 0,049, respectivamente). Nas análises de Spearman observamos que a cesariana realizada ≥39+0 semanas gestacionais (grupo II) foi negativamente relacionada à admissão na UTI Neonatal (rS=-0,091, p≤0,001), à hipoglicemia com necessidade de intervenção terapêutica (rS=-0,047, p=0,039) e eventos de hiperbilirrubinemia (rS=-0,051, p=0,023). Conclusão: A cesariana eletiva realizada antes de 39 semanas completas aumenta o risco de desfechos neonatais adversos. / Brazil is one of the countries in the world where caesarean sections are most frequently performed, many of which are performed electively at different gestational ages between 37 and 41 weeks. Elective cesarean sections performed at very early gestational ages increase the risk of adverse neonatal events. Objective: To evaluate the relationship between the gestational age at which elective cesarean section was performed and the perinatal outcomes in women treated in the private health sector. Methodology: Retrospective cohort study among women assisted in the private health sector of southern Brazil, evaluating neonatal outcomes in elective cesarean sections. From January 2015 to December 2016. The following eligibility criteria were used: primiparous and secondary infants with a previous cesarean section, gestational age between 37 and 39 weeks (group I) or ≥39 weeks (group II) submitted to elective caesarean section. Women with medical indications for cesarean section and pregnant women with associated comorbidities were excluded, as well women under 18 years old and those who presented amoniorexe. Neonatal outcomes were compared between the two gestational age groups. Results: There were 8480 births of live fetuses at Hospital Moinhos de Vento during the study period. Of those, 6542 cesareans were excluded and 1938 cesareans were eligible for the present study: 625 in group I and 1313 in group II. The median of previous pregnancies and abortions were higher in group I (p≤0,0001 for both). The mean age of women in both groups was 34 years. There was no significant variation in relation to ethnicity, where the average of the 16 studied women was 97.8% whites in both groups. About 72% of the women were married or lived with partners and 26,1% of the total women were single or lived without a partner in both groups. The mean body mass index in both groups was 28.7 kg / m2. Neonatal Intensive Care Unit (ICU) and hyperbilirubinemia were positively associated with group I in relation to group II (Chi-square test with adjusted residual analysis, p≤0,0001 and p = 0.049, respectively). In the Spearman analyzes, we observed that cesarean section performed ≥39 + 0 gestational weeks (group II) was negatively related to admission to the neonatal ICU (rS = -0.091, p≤0.001), to hypoglycemia requiring therapeutic intervention (rS = -0.047, p = 0.039) and hyperbilirubinemia events (rS = -0.051, p = 0.023). Conclusion: Elective caesarean section performed before 39 completed weeks increases the risk of adverse neonatal outcomes.