Hintergrund Ein rascher enteraler Nahrungsaufbau bei Frühgeborenen verkürzt die Zeit der parenteralen Ernährung. Somit lassen sich bestimmte Risikofaktoren beeinflussen, die evt. die Morbiditätshäufigkeit der Kinder senken könnten. Mehrere Kohortenstudien zeigten, dass ein standardisierter Nahrungsaufbau mit einer geringeren Komplikationsrate und einem schnelleren Nahrungsaufbau assoziiert ist. Ziel der Studie ist zu überprüfen, ob ein standardisiertes Ernährungsprogramm einen rascheren und komplikationsärmeren enteralen Nahrungsaufbau bei Frühgeborenen ermöglicht. Patienten und Methode In die vorliegende randomisierte, kontrollierte Studie wurden 99 Frühgeborene mit einem Geburtsgewicht von ≤1750 g aufgenommen. In der Gruppe mit standardisierter Ernährung (ST) wurde der enterale Nahrungsaufbau mit Muttermilch oder gespendeter Frauenmilch nach einem speziell ausgearbeiteten Protokoll durchgeführt. In der Gruppe mit der individuellen Ernährungsform (IN) wurde je nach Bedarf und Zustand des Kindes auch semi-elementare Nahrung (Pregomin®) gefüttert. Über die Steigerungsdynamik und Nahrungspausen wurde hier individuell entschieden. Primäres Zielkriterium war die Dauer bis zum Erreichen der vollenteralen Ernährung. Ergebnisse In der ST-Gruppe war die vollständig enterale Ernährung nach 14,93 ± 9,95 (Median 12) Tagen, in der IN-Gruppe nach 16,23 ± 10,86 (Median 14) Tagen möglich. Es konnte kein signifikanter Unterschied gefunden werden. Nur bei hypotrophen Frühgeborenen erwiesen sich die Unterschiede bei der ST-Gruppe gegenüber der IN-Gruppe als statistisch signifikant: 10,20 ± 4,78 (Median 8,5) vs. 16,73 ± 8,57 (Median 15) Tage (p = 0,045). Die Gewichtsentwicklung verlief in beiden Studiengruppen nicht different. Die Kinder in der ST-Gruppe konnten bei einem Gewicht von 116% des Geburtsgewichtes vollständig enteral ernährt werden, in der IN-Gruppe bei einem Gewicht von 122% des Geburtsgewichtes. Die Inzidenz der nekrotisierenden Enterokolitis (4%) und anderer Komplikationen blieb in beiden Studiengruppen niedrig. Die Diagnose „Ernährungsschwierigkeiten“ wurde mit klaren Symptomen definiert und in der IN-Gruppe doppelt so oft gestellt, wie in der ST-Gruppe (14 vs. 7) Schlussfolgerung Das Standardisieren führte unter den Studienbedingungen nicht zu einer Beschleunigung des Nahrungsaufbaus. Anhand unserer Ergebnisse ist es möglich, dass die hypotrophen Frühgeborenen von der standardisierten Ernährung entsprechend des Ernährungsprotokolls profitieren. Diese Hypothese muss in einer neuen Studie überprüft werden. Diese Kinder konnten schneller vollständig enteral ernährt werden, als Frühgeborene, mit individuellem enteralem Nahrungsaufbau. Ein standardisiertes Nahrungsprotokoll ist im klinischen Alltag durchsetzbar, und darauf aufbauend ein enteraler Nahrungsaufbau unter strenger klinischer Beobachtung ohne Komplikationen erfolgreich durchführbar.

Indiana University-Purdue University Indianapolis (IUPUI) / Objectives: To determine (1) whether prescribed and delivered energy and protein intakes during the first two weeks of life met Ziegler’s estimated requirements for Very Low Birth Weight (VLBW) infants, (2) if actual energy during the first week of life correlated with time to regain birth weight and reach full enteral nutrition (EN) defined as 100 kcal/kg/day, (3) if growth velocity from time to reach full EN to 36 weeks’ postmenstrual age (PMA) met Ziegler’s estimated fetal growth velocity (16 g/kg/day), and (4) growth outcomes at 36 weeks’ PMA. Study design: Observational study of feeding, early nutrition and early growth of 40 VLBW infants ≤ 30 weeks GA at birth in three newborn intensive care units NICUs. Results: During the first week of life, the percentages of prescribed and delivered energy (69% [65 kcal/kg/day]) and protein (89% [3.1 g/kg/day]) were significantly less than theoretical estimated requirements. Delivered intakes were 15% less than prescribed because of numerous interruptions in delivery and medical complications. During the second week, the delivered intakes of energy (90% [86 kcal/kg/day]) and protein (102% [3.5 g/kg/day]) improved although the differences between prescribed and delivered were consistently 15%. Energy but not protein intake during the first week was significantly related to time to reach full EN. Neither energy nor protein intake significantly correlated with days to return to birth weight. The average growth velocity from the age that full EN was attained to 36 weeks’ PMA (15 g/kg/day) was significantly less than the theoretical estimated fetal growth velocity (16 g/kg/day) (p<0.03). A difference of 1 g/kg/day represents a total deficit of 42 - 54 grams over the course of a month. At 36 weeks’ PMA, 53% of the VLBW infants had extrauterine growth restriction, or EUGR (<10th percentile) on the Fenton growth grid and 34% had EUGR on the Lubchenco growth grid. Conclusions: The delivered nutrient intakes were consistently less than 15% of the prescribed intakes. Growth velocity between the age when full EN was achieved and 36 weeks’ PMA was 6.7% lower than Ziegler’s estimate. One-third to one-half of the infants have EUGR at 36 weeks’ PMA.

In der vorliegenden Arbeit wurde anhand der im Rahmen des Vermont-Oxford-Neonatal-Networks erhobenen Daten an der Berliner Klinik für Neonatologie der Charité Campus Mitte und der Abteilung für neonatologische Intensivmedizin der Universitätskinderklinik in Innsbruck ein Benchmarking-Projekt für die Jahre 1997 bis 2001 durchgeführt. Nach der Analyse des Outcomes wurde eine Analyse der externen Evidenz anhand von Literatursuche in PubMed und der Cochrane Datenbank für systematische Reviews durchgeführt. Danach wurde ein Fragebogen entworfen, der gezielt Handlungsstrategien und -richtlinien bezüglich der relevanten Outcome-Parameter erfragt. Für das Benchmarking-Projekt wurden das Atemnotsyndrom, die nekrotisierende Enterokolitis und die bakteriellen Infektionen ausgewählt. Die Analyse der Handlungsstrategien durch den Fragebogen zeigte, dass in den drei Bereichen respiratorische Interventionen, Nahrung und Ernährung sowie im Infektionsmanagement Unterschiede vorlagen. In der Diskussion zeigte sich, dass in vielen Bereichen noch Bedarf nach guter externer Evidenz und weiterer Forschung besteht. / This dissertation presents the results of a 1997 - 2001 benchmark project in co-operation with the "Berliner Klinik für Neonatologie der Charité Campus Mitte" and the "Abteilung für neonatologische Intensivmedizin der Universitätskinderklinik" in Innsbruck. The study is based on the Vermont-Oxford-Neonatal-Network''s data. After analysing the results, further evidence was analysed by way of literary research in PubMed and the Cochrane Database of Systematic Reviews. Afterwards, a questionnaire was created, lining out the clinical guidelines of the relevant outcome parameters. The respiratory distress syndrom, the necrotising enterocolitis and the bacterial infections were selected for the benchmark. The internal guidelines'' analysis showed that there were differences between the two clinics'' results in respiratory interventions, feeding and the management of infections. The discussion made clear that research based on further evidence is necessary in many fields.

Objetivo: Verificar a acurácia do Test of Infant Motor Performance (TIMP) e da ultrassonografia de crânio (USC) no diagnóstico neurológico precoce após os 10 meses de idade corrigida em recém-nascidos pré-termo (RNPT) Metodologia: Amostra não aleatória constituída por 59 RNPT (idade gestacional ao nascimento 32 semanas ou peso ao nascimento 1500 gramas) seguidos em média até os 12 meses de idade corrigida. Os resultados da USC foram agrupados em 3 intervalos: 1) de 0 a 15 dias, 2) de 16 a 30 dias e 3) de 31 a 45 dias. Os achados da USC foram classificados em normal e anormal (anormalidades moderada e grave). O TIMP foi aplicado mensalmente, do primeiro retorno após a alta hospitalar até o 4° mês de idade corrigida. As avaliações foram agrupadas em 5 intervalos, correspondentes às avaliações antes do termo, 1°, 2°, 3° e 4° meses de idade corrigida. Os resultados do TIMP foram classificados em normal (média e média baixa) ou anormal (abaixo da média e muito abaixo da média). A avaliação neurológica foi realizada em média aos 12 meses de idade corrigida, e usada como padrão-ouro. Foram calculados os valores de sensibilidade, especificidade e valores preditivos positivos (VPP) e negativos (VPN) para o TIMP e para a USC neonatal. Resultados: A paralisia cerebral foi diagnosticada em 6 crianças. Observamos que a USC apresentou alta sensibilidade (> 70%) assim como altos VPN (>88%) em todos os intervalos. Para a USC, especificidade e VPP foram baixos em todos os intervalos. A sensibilidade do TIMP foi baixa, exceto para o intervalo 0, e os VPP foram baixos em todas as idades. A escala TIMP apresentou alta especificidade (75%, 85%) no 3° e 4° meses e altos VPN (> 77%) em todos os intervalos. Conclusão: Concluímos que os RNPT com pontuação normal no 3° e 4° meses do TIMP tem grandes chances de não desenvolver PC enquanto que RNPT com anormalidades graves e persistentes à USC tem maiores chances de um prognóstico neurológico anormal / Objective: Calculate the accuracy of the Test of Infant Motor Performance (TIMP) and the cranial ultrasonography (CUS) in the neurological outcome after 10 months of corrected age of preterm infants. Methods: Non-random sample of 59 preterm newborn infants (gestational age 32weeks or birth weight1500g) were followed up to a mean of 12 months corrected age. CUS results were grouped into 3 periods: 1) from 0 to 15 days; 2) from 16 to 30 days, and 3) from 31 to 45 days of life. CUS findings were rated into two groups: normal and abnormal (moderate and severe abnormalities). TIMP was applied monthly, from the first outpatient visit after hospital discharge until four months corrected age. The evaluations were grouped into five intervals, corresponding to the assessments performed before term age, 1st, 2nd, 3rd and 4th month of corrected age. TIMP results were ranked as normal (average, low average) or abnormal (below average and far below average). A full neurological examination was performed at a mean of 12 months of corrected age, and used as gold standard. The sensitivity, specificity, positive predictive (PPV) and negative predictive (NPV) values for TIMP and CUS were calculated. Results: Cerebral palsy was diagnosed in six infants. We observed that CUS had a high sensitivity (> 70%) in all intervals as well as high NPV (>88%). For CUS, specificity and PPV were low in all intervals. TIMP sensitivity was low, except for interval 0, and PPV were low at all ages. TIMP scale showed high specificity in the 3rd and 4th month (75%, 85%) and high NPV (> 77%) at all ages. Conclusions: We conclude that preterm infants with normal score at the 3rd and 4th months of TIMP are likely to develop normally while infants with severe and persistent abnormalities in the CUS examinations are more likely to have an abnormal neurological outcome

Objetivo: Verificar a acurácia do Test of Infant Motor Performance (TIMP) e da ultrassonografia de crânio (USC) no diagnóstico neurológico precoce após os 10 meses de idade corrigida em recém-nascidos pré-termo (RNPT) Metodologia: Amostra não aleatória constituída por 59 RNPT (idade gestacional ao nascimento 32 semanas ou peso ao nascimento 1500 gramas) seguidos em média até os 12 meses de idade corrigida. Os resultados da USC foram agrupados em 3 intervalos: 1) de 0 a 15 dias, 2) de 16 a 30 dias e 3) de 31 a 45 dias. Os achados da USC foram classificados em normal e anormal (anormalidades moderada e grave). O TIMP foi aplicado mensalmente, do primeiro retorno após a alta hospitalar até o 4° mês de idade corrigida. As avaliações foram agrupadas em 5 intervalos, correspondentes às avaliações antes do termo, 1°, 2°, 3° e 4° meses de idade corrigida. Os resultados do TIMP foram classificados em normal (média e média baixa) ou anormal (abaixo da média e muito abaixo da média). A avaliação neurológica foi realizada em média aos 12 meses de idade corrigida, e usada como padrão-ouro. Foram calculados os valores de sensibilidade, especificidade e valores preditivos positivos (VPP) e negativos (VPN) para o TIMP e para a USC neonatal. Resultados: A paralisia cerebral foi diagnosticada em 6 crianças. Observamos que a USC apresentou alta sensibilidade (> 70%) assim como altos VPN (>88%) em todos os intervalos. Para a USC, especificidade e VPP foram baixos em todos os intervalos. A sensibilidade do TIMP foi baixa, exceto para o intervalo 0, e os VPP foram baixos em todas as idades. A escala TIMP apresentou alta especificidade (75%, 85%) no 3° e 4° meses e altos VPN (> 77%) em todos os intervalos. Conclusão: Concluímos que os RNPT com pontuação normal no 3° e 4° meses do TIMP tem grandes chances de não desenvolver PC enquanto que RNPT com anormalidades graves e persistentes à USC tem maiores chances de um prognóstico neurológico anormal / Objective: Calculate the accuracy of the Test of Infant Motor Performance (TIMP) and the cranial ultrasonography (CUS) in the neurological outcome after 10 months of corrected age of preterm infants. Methods: Non-random sample of 59 preterm newborn infants (gestational age 32weeks or birth weight1500g) were followed up to a mean of 12 months corrected age. CUS results were grouped into 3 periods: 1) from 0 to 15 days; 2) from 16 to 30 days, and 3) from 31 to 45 days of life. CUS findings were rated into two groups: normal and abnormal (moderate and severe abnormalities). TIMP was applied monthly, from the first outpatient visit after hospital discharge until four months corrected age. The evaluations were grouped into five intervals, corresponding to the assessments performed before term age, 1st, 2nd, 3rd and 4th month of corrected age. TIMP results were ranked as normal (average, low average) or abnormal (below average and far below average). A full neurological examination was performed at a mean of 12 months of corrected age, and used as gold standard. The sensitivity, specificity, positive predictive (PPV) and negative predictive (NPV) values for TIMP and CUS were calculated. Results: Cerebral palsy was diagnosed in six infants. We observed that CUS had a high sensitivity (> 70%) in all intervals as well as high NPV (>88%). For CUS, specificity and PPV were low in all intervals. TIMP sensitivity was low, except for interval 0, and PPV were low at all ages. TIMP scale showed high specificity in the 3rd and 4th month (75%, 85%) and high NPV (> 77%) at all ages. Conclusions: We conclude that preterm infants with normal score at the 3rd and 4th months of TIMP are likely to develop normally while infants with severe and persistent abnormalities in the CUS examinations are more likely to have an abnormal neurological outcome

There is no consensus about the hemodynamic significance and, therefore, the need to treat a persistent ductus arteriosus in preterm newborns. Since the diagnosis of a hemodynamically significant persistent ductus arteriosus (hsPDA) is made by a summary of non-uniform echo-criteria in combination with the clinical deterioration of the preterm neonate, standardized clinical and ultrasound scoring systems are needed. The objective of this study was the development of a clinical score for the detection and follow-up of hsPDA. In this observational cohort study of 154 preterm neonates (mean gestational age 28.1 weeks), clinical signs for the development of hsPDA were recorded in a standardized score and compared to echocardiography. Analyzing the significance of single score parameters compared to the diagnosis by echocardiography, we developed a short clinical score (calculated sensitivity 84% and specificity 80%). In conclusion, this clinical diagnostic PDA score is non-invasive and quickly to implement. The continuous assessment of defined clinical parameters allows for a more precise diagnosis of hemodynamic significance of PDA and, therefore, should help to detect preterm neonates needing PDA-treatment. The score, therefore, allows a more targeted use of echocardiography in these very fragile preterm neonates.