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DOI: 10.1055/s-2006-931552
Die Langzeitprognose von Frühgeborenen: Was sich hinter den Statistiken verbirgt
Long-Term Outcome of Preterm Neonates: The Message behind the StatisticsPublication History
Eingereicht: 19.12.2005
Angenommen nach Überarbeitung: 22.12.2005
Publication Date:
27 March 2006 (online)
Zusammenfassung
Wegen der Therapiefortschritte in der Neonatologie gibt die heute feststellbare Langzeitprognose ehemaliger Frühgeborener nicht zwingend das künftige Outcome heutiger Frühgeborener wieder. Unabhängig von dieser statistischen Unsicherheit lassen Langzeitstudien der vergangenen Jahre aber erkennen, dass sich die Folgen einer Frühgeburt weit über das Säuglingsalter hinaus erstrecken und sich in späteren Lebensphasen nicht selten in gewandelter Form manifestieren. Dementsprechend wird in dem vorliegenden Beitrag eine Chronologie der Folgeprobleme aufgezeigt, die sich angefangen von der perinatalen Mortalität und Frühmorbidität über das Kleinkindes-, Vorschul- und Adoleszentenalter bis hin zum Erwachsenenalter ergeben können. Dabei wird auch ein doppelter Paradigmenwechsel in der Neonatologie erkennbar, dem zufolge das Outcome von Frühgeborenen zum einen nicht von der Unreife allein abhängt, sondern wesentlich durch die Ursachen der Frühgeburtlichkeit (Infektion, intrauterine Mangelversorgung) mitbestimmt wird, und zum anderen auch nicht am Ende der Klinikaufenthaltes unveränderlich feststeht, sondern vielmehr im weiteren Verlauf erheblich von familiären Faktoren moduliert wird. Diese Erkenntnisse bilden, auch wenn die statistische Datenlage im Einzelnen noch im Fluss ist, die Grundlage für eine qualifizierte Langzeitbetreuung von Frühgeborenen, die nach der zunehmenden Etablierung der Akutbehandlungsstrategien eine immer wichtigere Zukunftsaufgabe der Neonatologie innerhalb der Pädiatrie darstellen wird.
Abstract
In view of the current progress in neonatal intensive care, the present outcome of former preterm neonates does not necessarily reflect the future outcome of today’s preterm neonates. In spite of this statistical uncertainty, long-term follow-up studies performed in the past few years point to the fact that the sequelae of prematurity may appear well beyond infancy and may be revealed in varying manners with increasing age. Therefore, a chronological account of the consequences of prematurity is given in this paper, ranging from perinatal mortality/morbidity to the problems to be observed during early childhood, preschool age, and adolescence right up to the long-term sequelae arising in later adulthood. Within this context, a two-fold paradigm shift in neonatology becomes apparent in that, first, the outcome of preterm neonates is not a result of immaturity per se, yet is significantly influenced by the factors leading to preterm birth (inflammation, intrauterine growth restriction), and, second, the sequelae of prematurity do not end with the end of neonatal intensive care, but are greatly modulated by familial conditions in their further course. Even though the statistical data are still subject to changes, these insights form the basis of a structured long-term follow-up of preterm neonates which, after the progressive establishment of acute treatment strategies, will become an increasingly important challenge to neonatology within the framework of paediatrics.
Schlüsselwörter
Frühgeburt - Ursachen - Prognose - Nachsorge
Key words
Prematurity - causes - outcome - follow-up
Literatur
- 1 Hentschel J, Arlettaz R, Bührer C. Überlebenschancen und Langzeitprognose bei Geburt in der Grauzone der Lebensfähigkeit. Gynäkologe. 2001; 34 697-707
- 2 Bauer K, Zemlin M, Bartsch M, Versmold H. Mortalität und neonatale Morbidität von extrem unreifen Frühgeborenen (Gestationsalter ≤ 25 Wochen, Geburtsgewicht < 750g). Pädiat Prax. 2001/02; 60 231-242
- 3 Sauve R S, Robertson C, Etches P, Byrne P J, Dayer-Zamora V. Before viability: a geographically based outcome study of infants weighing 500 grams or less at birth. Pediatrics. 1998; 101 438-445
- 4 Evans D J, Levene M I. Evidence of selection bias in preterm survival studies: a systematic review. Arch Dis Child Fetal Neonatal Ed.. 2001; 84 F79-84
-
5 Harms K. Erstversorgung von sehr unreifen Frühgeborenen. In: Friese K, Plath C, Briese V (eds)
Frühgeburt und Frühgeborenes - eine interdisziplinäre Aufgabe . Berlin; Springer 2000 - 6 Rettwitz-Volk W. Mortalität und Morbidität von Frühgeborenen - eine Zusammenfassung der deutschen Neonatalerhebungen 2001. Z Geburtsh Neonatol. 2003; 207 143-147
- 7 Rapp M, Thyen U, Müller-Steinhardt K, Kohl M. Morbidität und Mortalität extrem frühgeborener Kinder in Schleswig-Holstein. Nachuntersuchung von extrem frühgeborenen Kindern unter 27 + 0 Schwangerschaftswochen im korrigierten Alter von drei bis sechs Jahren in Schleswig-Holstein. Z Geburtsh Neonatol. 2005; 209 35-143
- 8 Jo B. Bayerische Arbeitsgemeinschaft für Qualitätssicherung: Bayerische Neonatalerhebung 2004. München; BAQ 2005 (www.baq-bayern.de)
- 9 Pohlandt F. Frühgeburt an der Grenze der Lebensfähigkeit des Kindes. Perinatalmedizin. 1998; 10 99-101
-
10 Pohlandt F (Koordination). Frühgeburt an der Grenze der Lebensfähigkeit des Kindes (B16). In: Deutsche Gesellschaft für Kinderheilkunde und Jugendmedizin (ed)
Leitlinien Kinderheilkunde und Jugendmedizin . München; Urban und Fischer 1999 - 11 Rieger-Fackeldey E, Schulze A, Pohlandt F, Schwarze R, Dinger J, Lindner W. Short-term outcome in infants with a birthweight less than 501 grams. Acta Paediatr. 2005; 94 211-216
- 12 Berger T M, Büttiker V, Fauchère J -C, Holzgreve W, Kind C H, Largo R, Moessinger A, Zimmermann R. Empfehlungen zur Betreuung von Frühgeborenen an der Grenze der Lebensfähigkeit (Gestationsalter 22 - 26 SSW). Schweizerische Gesellschaft für Neonatologie 2002
- 13 Sauer P J. Ethical dilemmas in neonatology: recommendations of the Ethics Working Group of the CESP (Confederation of European Specialists in Paediatrics). Eur J Pediatr.. 2001; 160 364-368
- 14 Schollin J. Views on neonatal care of newborns weighing less than 500 grams. Acta Paediatr.. 2005; 94 140-142
- 15 Stewart A L, Reynolds E OR, Lipscomb A P. Outcome for infants of very low birthweight: Survey of world literature. Lancet. 1981; 1 1038-1040
- 16 Blackman J A. Neonatal intensive care: Is it worth it? Developmental sequelae of very low birthweight. Pediatr Clin North Am. 1991; 38 1497-1511
- 17 Costeloe K, Hennessy E, Gibson A T, Marlow N, Wilkinson A R. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics. 2000; 106 659-671
- 18 Wood N S, Marlow N, Costeloe K, Gibson A T, Wilkinson A R. Neurologic and developmental disability after extremely preterm birth. N Engl J Med. 2000; 343 378-384
- 19 Marlow N, Wolke D, Bracewell M A, Samara, for the EPICure Study Group M. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med. 2005; 352 9-19
- 20 Vanhaesebrouck P, Allegaert K, Bottu J, Debauche C, Devlieger H, Docx M, Francois A, Haumont D, Lombet J, Rigo J, Smets K, Vanherreweghe I, Van Overmeire B, Van Reempts (Extremely Preterm Infants in Belgium Study Group) P. The EPIBEL study: outcomes to discharge from hospital for extremely preterm infants in Belgium. Pediatrics. 2004; 114 663-675
- 21 Bancalari E, Claure N, Sosenko I R. Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. Semin Neonatol. 2003; 8 63-71
- 22 Thomas W, Speer C P. Bronchopulmonale Dysplasie Frühgeborener. Epidemiologie, Pathogenese und Therapie. Monatsschr Kinderheilkd. 2005; 153 211-219
- 23 Tin W. Optimal oxygen saturation for preterm babies. Do we really know?. Biol Neonate. 2004; 85 319-325
- 24 Tin W. Oxygen therapy in preterm babies: Fifty years of uncertainty. Biol Neonate. 2005; 88 263-264 (Ext. Abs. 21)
- 25 Saugstad O D. Oxidative stress in the newborn - a 30-year perspective. Biol Neonate. 2005; 88 228-236
- 26 Smith L EH. IGF-1 and retinopathy of prematurity in the preterm infant. Biol Neonate. 2005; 88 237-244
- 27 Speer C P. New insights into the pathogenesis of pulmonary inflammation in preterm infants. Biol Neonate. 2001; 79 205-209
- 28 Kramer B W, Kramer S, Ikegami M, Jobe A H. Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin. Am J Physiol Lung Cell Mol Physiol. 2002; 283 L452-459
- 29 Dammann O. Inflammatory brain damage in the preterm newborn: Etiologic and pathogenetic aspects. Biol Neonate. 2005; 88 259-260 (Ext. Abs. 15)
- 30 Dammann O, Leviton A, Gappa M, Dammann C E. Lung and brain damage in preterm newborns, and their association with gestational age, prematurity subgroup, infection/inflammation and long term outcome. BJOG. 2005; 112 Suppl 1 4-9
- 31 Vaast P, Houfflin-Debarge V, Deruelle P, Subtil D, Storme L, Puech F. Could the consequences of premature delivery be further attenuated by means of new prenatal strategies?. Eur J Obstet Gynecol Reprod Biol. 2004; 117 Suppl 1 S21-24
- 32 Hagberg H, Jacobsson B. Brain injury in preterm infants - what can the obstetrician do?. Early Hum Dev. 2005; 81 231-235
- 33 Hack M, Taylor H G, Klein N, Eiben R, Schatschneider C, Mercuri-Minich N. School-age outcomes in children with birth weights under 750 g. N Engl J Med. 1994; 331 753-759
- 34 Hack M, Friedman H, Fanaroff A A. Outcomes of extremely low birth weight infants. Pediatrics. 1996; 98 931-937
- 35 Hack M, Flannery D J, Schluchter M, Cartar L, Borawski E, Klein N. Outcomes in young adulthood for very-low-birth-weight infants. N Engl J Med. 2002; 346 149-157
- 36 Hack M,Taylor H G, Drotar D, Schluchter M, Cartar L, Andreias L, Wilson-Costello D, Klein N. Chronic conditions, functional limitations, and special health care needs of school-aged children born with extremely low-birth-weight in the 1990s. JAMA. 2005; 294 318-325
- 37 Heller G, Schnell R, Richardson D K, Misselwitz B, Schmidt S. Hat die Größe der Geburtsklinik Einfluss auf das neonatale Überleben? Schätzung von „vermeidbaren” Todesfällen in Hessen 1990 - 2000. Dtsch Med Wochenschr. 2003; 128 657-662
- 38 Vohr B R, Wright L L, Dusick A M, Perritt R, Poole W K, Tyson J E, Steichen J J, Bauer C R, Wilson-Costello D E, Mayes L C. Center differences and outcomes of extremely low birth weight infants. Pediatrics. 2004; 113 781-789
- 39 Krageloh-Mann I, Toft P, Lunding J, Andresen J, Pryds O, Lou H C. Brain lesions in preterms: origin, consequences and compensation. Acta Paediatr. 1999; 88 897-908
- 40 Inder T E, Warfield S K, Wang H, Huppi P S, Volpe J J. Abnormal cerebral structure is present at term in premature infants. Pediatrics. 2005; 115 286-294
- 41 Cooke R WI, Foulder-Hughes L. Growth impairment in the very preterm and cognitive and motor performance at 7 years. Arch Dis Child. 2003; 88 482-487
- 42 Brandt I, Sticker E J, Lentze M J. Catch-up growth of head circumference of very low birth weight, small for gestational age preterm infants and mental development to adulthood. J Pediatr. 2003; 142 463-468
- 43 Wolke D, Meyer R. Cognitive status, language attainment, and prereading skills of 6-year-old very preterm children and their peers: the Bavarian Longitudinal Study. Dev Med Child Neurol. 1999; 41 94-109
- 44 Kilbride H W, Thorstad K, Daily D K. Preschool outcome of less than 801-gram preterm infants compared with full-term siblings. Pediatrics. 2004; 113 742-747
- 45 Hokken-Koelega A CS, de Ridder M AJ, Lemmen R J, den Hartog H, de Muinck Keizer-Schrama S MPF, Drop S LS. Children born small for gestational age: do they catch up?. Pediatr Res. 1995; 38 267-271
- 46 Karlberg J, Albertsson-Wikland K. Growth in full-term small-for-gestational-age infants: from birth to final height. Pediatr Res. 1995; 38 733-739
- 47 Wollmann H A. Zu klein bei Geburt (SGA). Wachstum und Langzeitkonsequenzen. Monatsschr Kinderheilkd. 2004; 152 528-535
- 48 Sas T, de Waal W, Mulder P, Houdijk M, Jansen M, Reeser M, Hokken-Koelega A. Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial. J Clin Endocrinol Metab. 1999; 84 3064-3070
- 49 de Zegher F, Albertsson-Wikland K, Wollmann H A, Chatelain P, Chaussain J -L, Löfström A, Jonsson B, Rosenfeld R G. Growth hormone treatment of short children born small for gestational age: growth responses with continuous and discontinuous regimens over 6 years. J Clin Endocrinol Metab. 2000; 85 2816-2821
- 50 van Pareren Y, Mulder P, Houdijk M, Jansen M, Reeser M, Hokken-Koelega A. Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial. J Clin Endocrinol Metab. 2003; 88 3584-3590
- 51 Arends N JT, Boonstra V H, Hokken-Koelega A CS. Head circumference and body proportions before and during growth hormone treatment in short children who were born small for gestational age. Pediatrics. 2004; 114 683-690
- 52 Bannink E MN, van Pareren Y K, Theunissen N CM, Raat H, Mulder P GM, Hokken-Koelega A CS. Quality of life in adolescents born small for getational age: does growth hormone therapy make a difference?. Horm Res. 2005; 64 166-174
- 53 Hokken-Koelega A C, de Waal W J, Sas T C, van Pareren Y, Arends N J. Small for gestational age (SGA): endocrine and metabolic consequences and effects of growth hormone treatment. J Pediatr Endocrinol Metab. 2004; 17 Suppl 3 463-469
- 54 Hokken-Koelega A, van Pareren Y, Arends N, Boonstra V. Efficacy and safety of long-term continuous growth hormone treatment of children born small for gestational age. Horm Res. 2004; 62 Suppl 3 194-154
- 55 Walther F J, den Ouden A L, Verloove-Vanhorick S P. Looking back in time: outcome of a national cohort of very preterm infants born in The Netherlands in 1983. Early Hum Dev. 2000; 59 175-191
- 56 Cnattingius S, Hultman C M, Dahl M, Sparen P. Very preterm birth, birth trauma, and the risk of anorexia nervosa among girls. Arch Gen Psychiatry. 1999; 56 634-638
- 57 Smith G N, Flynn S W, McCarthy N, Meistrich B, Ehmann T S, MacEwan G W, Altman S, Kopala L C, Honer W G. Low birthweight in schizophreni prematurity or poor fetal growth. Schizophr Res. 2001; 47 177-184
- 58 Barker D J, Winter P D, Osmond C, Margetts B, Simmonds S J. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2 577-580
- 59 Godfrey K M, Barker D JP. Fetal nutrition and adult disease. Am J Clin Nutr. 2000; 71 S1344-1352
- 60 Barker D J, Hales C N, Fall C H, Osmond C, Phipps K, Clark P M. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia. 1993; 36 62-67
- 61 Singer D. Neonatal tolerance to hypoxia: A comparative-physiological approach. Comp Biochem Physiol A. 1999; 123 221-234
- 62 Singer D. Anpassung an Unreife und Sauerstoffmangel in der Neonatalperiode: Vergleichende kalorimetrische Untersuchungen (Habil.-Schr. Univ. Göttingen 1998). Shaker Aachen; 2001
- 63 Barker D JP. In utero programming of cardiovascular disease. Theriogenology. 2000; 53 555-574
- 64 Barker D JP. Fetal programming of coronary heart disease. Trends Endocrinol Metab. 2002; 13 364-368
- 65 Hofman P L, Cutfield W S, Robinson E M, Bergman R N, Menon R K, Sperling M A, Gluckman P D. Insulin resistance in short children with intrauterine growth retardation. J Clin Endocrinol Metab. 1997; 82 402-406
- 66 Metcalfe N B, Monaghan P. Compensation for a bad start: grow now, pay later. Trends Ecol Evol. 2001; 16 254-260
- 67 Drake A J, Walker B R. The intergenerational effects of fetal programming: non-genomic mechanisms for the inheritance of low birth weight and cardiovascular risk. J Endocrinol. 2004; 180 1-16
- 68 Gluckman P D, Hanson M A, Morton S M, Pinal C S. Life-long echoes - a critical analysis of the developmental origins of adult disease model. Biol Neonate. 2005; 87 127-139
- 69 Gluckman P D, Vickers M, Hofman P, Cutfield W. Life-long echoes - the developmental origins of health and disease in later life. Biol Neonate. 2005; 88 257 (Ext. Abs. 13)
- 70 Bhat A H, Sahn D J. Congenital heart disease never goes away, even when it has been "treated": the adult with congenital heart disease. Curr Opin Pediatr. 2004; 16 500-507
PD Dr. med. D. Singer
Perinatalzentrum
Universitäts-Kinderklinik
Josef-Schneider-Straße 2
97080 Würzburg
Phone: 0931/201-27484
Fax: 0931/201-61805
Email: d.singer@mail.uni-wuerzburg.de