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Z Geburtshilfe Neonatol 2000; 204(6): 203-209
DOI: 10.1055/s-2000-9579
ÜBERSICHT

Georg Thieme Verlag Stuttgart ·New York

Lungenreifetherapie mit Glukokortikoiden bei drohender Frühgeburt[1]

Überlegungen zur Nutzen-Risiko-Abwägung im Sinne der Evidence-based medicineAntenatal glucocorticoids in prematurityAxel Sauerwald, Werner Rath
  • Universitätsklinik für Gynäkologie und Geburtshilfe der Rheinisch-Westfälisch Technischen Hochschule (RWTH) Aachen
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Publication History

Publication Date:
31 December 2000 (online)

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Zusammenfassung

Frühgeburtlichkeit ist häufige Ursache für perinatale Morbidität und Mortalität. Zu deren Senkung hat die Lungenreifebehandlung mit Glukokortikoiden maßgeblich beigetragen. 1994 wurden von den NIH Empfehlungen zur Durchführung der Lungenreifeinduktion publiziert und die Wirksamkeit wurde 1999 von der Cochrane Collaboration erneut evaluiert. Danach reduziert die antenatale Glukokortikoidapplikation signifikant die perinatale Morbidität und die Rate an RDS und Hirnblutungen bei Frühgeborenen zwischen der 24. und 34. SSW.

Der Wert der repetitiven Glukokortikoidgabe ist nicht hinreichend geklärt; insbesondere deren Einfluss auf die Geburtsgewichte der Kinder und auf die Entwicklung von Infektionen bei vorzeitigem Blasensprung sowie die Festlegung des optimalen Wiederholungsintervalls. Nach Glukokortikoidgabe muss passager mit einer Verminderung der Kindsbewegungen und der fetalen Herzfrequenzvariabilität gerechnet werden; nicht geklärt sind die Auswirkungen auf das intrauterine Wachstum, das maternale und fetale Immunsystem und spätere Erkrankungen einschließlich Atopien.

Bei vorzeitiger, nicht muttermundswirksamer Wehentätigkeit wird daher die Indikation zur antenatalen Gabe von Glukokortikoiden zunehmend kritischer beurteilt. Bei vorzeitigem Blasensprung senkt die antenatale Glukokortikoidgabe nicht die Rate an RDS, jedoch signifikant die an Hirnblutungen und an nekrotisierenden Enterokolitiden. Für die Lungenreifebehandlung mit Glukokortikoiden bei Diabetes mellitus und bei intrauteriner Wachstumsretardierung liegen bisher keine prospektivrandomisierten Studien vor. Bei schwerer Präeklampsie vermindert Betamethason die RDS-Häufigkeit und die neonatale Mortalität signifikant.

Ungeachtet des lückenhaftes Wissens und der potenziellen (Langzeit-) Auswirkungen auf Mutter und Kind bleibt die antenatale Glukokortikoidmedikation nach den Empfehlungen der NIH von 1994 gemeinsam mit der Behandlung dieser Schwangeren in einem Perinatalzentrum entscheidender Eckpfeiler im Vorgehen bei Frühgeburtlichkeit. Die Indikation zur repetitiven Gabe von Glukokortikoiden sollte allerdings sorgfältig geprüft werden.

Prematurity is a major cause of perinatal morbidity and mortality. Antenatal administration of glucocorticoids improves the neonatal outcome of preterm born infants. 1994 the NIH published recommendations for the use of glucocorticoids for women at risk of preterm delivery. A recent evaluation by the Cochrane Collaboration in 1999 showed that antenatal administration of glucocorticoids significantly reduced the rate of RDS and IVH in the gestational age between 24 and 34 weeks. Consequences of repeated courses of antenatal glucocorticoids are not sufficiently studied. The effectivity and safety regarding birth weights, infectious diseases, and the best timing remains unknown. Administration of glucocorticoids lowers fetal activity and heart rate variability. Effects on fetal growth, maternal and fetal immunosystem, and the development of atopic diseases are controversely discussed. Thus preterm labour not leading to a cervical ripening is not necessarily a reason for antenatal glucocorticoids. Antenatal glucocorticoids with PROM do not lower the rate of RDS but of IVH. No prospective randomized trial evaluated the effectivity of antenatal glucocorticoids in diabetes mellitus and IUGR. In preeclampsia betamethason could improve the rate of RDS and the neonatal outcome. Still our knowledge of antenatal glucocorticoid administration is not sufficient. But despite possible (longtime-) risks for mother and child the administration of glucocorticoids according to the guidelines of the NIH is a major part in the treatment of prematurity and improves the outcome of premature infants. The indication for multiple courses of glucocorticoids should be considered carefully.

Schlüsselwörter

Frühgeburt - Lungenreife - Glukokortikoide - Evidence-based medicine

Key words

Prematurity - antenatal corticoids - evidence-based medicine

1 Eingang: 24. 5. 2000 Angenommen nach Revision: 27. 7. 2000

Literatur

1 Eingang: 24. 5. 2000 Angenommen nach Revision: 27. 7. 2000

  • 01 Ventura  S J, Martin  J A, Curtin  S C, Mathews  T J. Report of final natality statistics, 1996. Mon Vital Stat Rep 1998: 1-99
    Google Scholar
  • 02 Kramer  M S, Platt  R, Yang  H, et al. Secular trends in preterm birth: a hospital-based cohort study [published erratum appears in JAMA 1999 Feb 24; 281 (8): 705].  JAMA. 1998;  280 1849-1854
    Google Scholar
  • 03 Goldenberg  R L, Rouse  D J. Prevention of premature birth.  New Engl J Med. 1998;  339 313-320
    Google Scholar
  • 04 Towers  C V, Bonebrake  R, Padilla  G, Rumney  P. The effect of transport on the rate of severe intraventricular hemorrhage in very low birth weight infants.  Obstet Gynecol. 2000;  95 291-295
    Google Scholar
  • 05 Crowley  P A. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994.  Am J Obstet Gynecol. 1995;  83 483-494
    Google Scholar
  • 06 Effect of corticosteroids for fetal maturation on perinatal outcomes .Am J Obstet Gynecol. 1995 173: 246-252
    Google Scholar
  • 07 Gardner  M O, Papile  L A, Wright  L L. Antenatal corticosteroids in pregnancies complicated by preterm premature rupture of membranes.  Obstet Gynecol. 1997;  90 555-564
    Google Scholar
  • 08 Planer  B C, Ballard  R A, Ballard  P L, Cobum  C E, Boardman  C, Cnaan  A. Antenatal corticosteroid (ANCS) use in preterm labor in the USA [abstract].  Pediatr Res. 1996;  39 110A
    Google Scholar
  • 09 Pratt  L, Magness  R R, Phernetton  T, Hendricks  S K, Abbott  D H, Bird  I M. Repeated use of betamethasone in rabbits: Effects of treatment variation on adrenal suppression, pulmonary maturation, and pregnancy outcome.  Am J Obstet Gynecol. 1999;  180 995-1005
    Google Scholar
  • 10 Banks  B A, Cnaan  A, Morgan  M A, et al. Multiple courses of antenatal corticosteroids and outcome of premature neonates.  Am J Obstet Gynecol. 1999;  181 709-717
    PubMedGoogle Scholar
  • 11 French  N P, Hagan  R, Evans  S F, Godfrey  M, Newnham  J P. Repeated antenatal corticosteroids: Size at birth and subsequent development.  Am J Obstet Gynecol. 1999;  180 114-121
    PubMedGoogle Scholar
  • 12 Kohlmann  H. Mögliche endokrine und immunologische Folgen pränataler Glukokortikoidgabe zur Prophylaxe des Neugeborenen-Respiratory-Distress-Syndroms.  Frauenarzt. 1999;  40 1173-1178
    PubMedGoogle Scholar
  • 13 Seckl  J R, Chapman  K E. Medical and physiological aspects of the 11beta-hydroxysteroid dehydrogenase system.  Eur J Biochem. 1997;  249 361-364
    CrossrefPubMedGoogle Scholar
  • 14 Langley-Evans  S C, Phillips  G J, Bendiktsson  R, et al. Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension in the rat.  Placenta. 1996;  17 169-172
    PubMedGoogle Scholar
  • 15 Shams  M, Kilby  M D, Somerset  D A, et al. 11Beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction.  Hum Reprod. 1998;  13 799-804
    CrossrefPubMedGoogle Scholar
  • 16 McCalla  C O, Nacharaju  V L, Muneyyirci  D O, Glasgow  S, Feldman  J G. Placental 11 beta-hydroxysteroid dehydrogenase activity in normotensive and pre-eclamptic pregnancies.  Steroids. 1998;  63 511-515
    CrossrefPubMedGoogle Scholar
  • 17 Hardy  D B, Pereria  L E, Yang  K. Prostaglandins and leukotriene B4 are potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 2 activity in human choriocarcinoma JEG-3 cells.  Biol Reprod. 1999;  61 40-45
    PubMedGoogle Scholar
  • 18 Florio  P, Franchini  A, Reis  F M, Pezzani  I, Ottaviani  E, Petraglia  F. Human placenta, chorion, amnion and decidua express different variants of corticotropin-releasing factor receptor messenger RNA.  Placenta. 2000;  21 32-37
    CrossrefPubMedGoogle Scholar
  • 19 Majjzoub  J A, McGregor  J A, Lockwood  C J, Smith  R, Snyder-Taggert  M, Schulkin  J. A central theory of preterm and term labour: putative role for corticotropin-releasing hormone.  Am J Obstet Gynecol. 1999;  180 232-242
    PubMedGoogle Scholar
  • 20 Robinson  B G, Emanuel  R L, Frim  D M, Majzoub  J A. Glucocorticoid stimulates expression of corticotropine-releasing hormone gene in human placenta.  Proc Natl Acad Sci USA. 1988;  85 5244-5248
    PubMedGoogle Scholar
  • 21 Phillips  D I, Barker  D J, Fall  C H, et al. Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome?.  J Clin Endocrinol Metab. 1998;  83 757-760
    CrossrefPubMedGoogle Scholar
  • 22 Reis  F M, Fadalti  M, Florio  P, Petraglia  F. Putative role of placental corticotropin-releasing factor in the mechanisms of human parturition.  J Soc Gynecol Investig. 1999;  6 109-119
    PubMedGoogle Scholar
  • 23 Blanford  A T, Murphy  B E. In vitro metabolism of prednisolone, dexamethasone, betamethasone and cortisol by human placenta.  Am J Obstet Gynecol. 1977;  127 164-267
    PubMedGoogle Scholar
  • 24 Ward  R M. Pharmacologic enhancement of fetal lung maturation.  Clin Perinatol. 1994;  21 523-542
    PubMedGoogle Scholar
  • 25 Muglia  L, Jacobson  L, Dikkes  P, Majzoub  J A. Corticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need.  Nature. 1995;  373 427-432
    CrossrefPubMedGoogle Scholar
  • 26 Economides  D L, Nicolaides  K H, Linton  E A, Perry  L A, Chard  T. Plasma cortisol and adrenocorticotropin in appropriate and small for gestational age fetuses.  Fetal Ther. 1988;  3 158-164
    PubMedGoogle Scholar
  • 27 White  E, Shy  K K, Benedetti  T J. Chronic fetal stress and the risk of infant respiratory distress syndrome.  Obstet Gynecol. 1986;  67 57-62
    PubMedGoogle Scholar
  • 28 Lieberman  E, Torday  J, Barbieri  R, Cohen  A, Van  V H, Weiss  S T. Association of intrauterine cigarette smoke exposure with indices of fetal lung maturation.  Obstet Gynecol. 1992;  79 564-570
    PubMedGoogle Scholar
  • 29 Curet  L B, Zachman  R D, Rao  A V, Poole  W K, Morrison  J, Burkett  G. Effect of mode of delivery on incidence of respiratory distress syndrome.  Int J Gynaecol Obstet. 1988;  27 165-170
    CrossrefPubMedGoogle Scholar
  • 30 Goldberg  J D, Cohen  W R, Friedman  E A. Cesarean section indication and the risk of respiratory distress syndrome.  Obstet Gynecol. 1981;  57 30-32
    PubMedGoogle Scholar
  • 31 Procianoy  R S, Garcia-Prats  J A, Adams  J M, Silvers  A, Rudolph  A J. Hyaline membrane disease and intraventricular hemorrhage in small for gestational age infants.  Arch Dis Child. 1980;  55 502-505
    PubMedGoogle Scholar
  • 32 Liggins  G C, Howie  R N. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants.  Pediatrics. 1972;  50 515-525
    PubMedGoogle Scholar
  • 33 Anwar  M A, Schwab  M, Poston  L, Nathanielsz  P W. Betamethasone-mediated vascular dysfunction and changes in hematological profile in the ovine fetus.  Am J Physiol. 1999;  H11 37-43
    PubMedGoogle Scholar
  • 34 Terrone  D A, Rinehart  B K, Rhodes  P G, Roberts  W E, Miller  R C, Martin  J N. Multiple courses of betamethasone to enhance fetal lung maturation do not suppress neonatal adrenal response.  Am J Obstet Gynecol. 1999;  180 1349-1353
    PubMedGoogle Scholar
  • 35 Derks  J B, Mulder  E JH, Visser  G HA. The effects of maternal betamethasone administration on the fetus.  Br J Obstet Gynaecol. 1995;  102 40-46
    PubMedGoogle Scholar
  • 36 Dawes  G S, Serra-Serra  V, Moulden  M, Redman  C WG. Dexamethasone and fetal heart rate variation.  Br J Obstet Gynaecol. 1994;  101 675-679
    PubMedGoogle Scholar
  • 37 Barker  D JP, Bull  A R, Osmond  C, Simmonds  S J. Fetal and placental size and risk of hypertension in adult life.  BMJ. 1990;  301 259-262
    CrossrefPubMedGoogle Scholar
  • 38 Nyirenda  M J, Seckl  J R. Intrauterine events and the programming of adulthood disease: The role of fetal glucocorticoid exposure (Review).  Int J Mol Med. 1998;  2 607-614
    PubMedGoogle Scholar
  • 39 Cunningham  D S, Evans  E E. The effects of betamethasone on maternal cellular resistance to infection.  Am J Obstet Gynecol. 1991;  165 610-615
    PubMedGoogle Scholar
  • 40 Vermillion  S T, Soper  D E, Chasedunn  R J. Neonatal sepsis after betamethasone administration to patients with preterm premature rupture of membranes.  Am J Obstet Gynecol. 1999;  181 320-327
    PubMedGoogle Scholar
  • 41 Dahlgren  J, Boguszewski  M, Rosberg  S, Albertsson  W K. Adrenal steroid hormones in short children born small for gestational age.  Clin Endocrinol (Oxf). 1998;  49 353-361
    CrossrefPubMedGoogle Scholar
  • 42 Terrone  D A, Smith  L J, Wolf  E J, Uzbay  L A, Sun  S, Miller  R C. Neonatal effects and serum cortisol levels after multiple courses of maternal corticosteroids [see comments].  Obstet Gynecol. 1997;  90 819-823
    CrossrefPubMedGoogle Scholar
  • 43 Bakker  J M, Schmidt  E D, Kroes  H, et al. Effects of short-term dexamethasone treatment during pregnancy on the development of the immune system and the hypothalamo-pituitary adrenal axis in the rat.  J Neuroimmunol. 1995;  63 183-191
    CrossrefPubMedGoogle Scholar
  • 44 Bakker  J M, Schmidt  E D, Kroes  H, et al. Effects of neonatal dexamethasone treatment on hypothalamo-pituitary adrenal axis and immune system of the rat.  J Neuroimmunol. 1997;  74 69-76
    CrossrefPubMedGoogle Scholar
  • 45 Bakker  J M, van den Dobbelsteen  G P, Kroes  H, et al. Long-term gender-specific effects of manipulation during pregnancy on immune and endocrine responsiveness in rat offspring.  J Neuroimmunol. 1998;  82 56-63
    CrossrefPubMedGoogle Scholar
  • 46 Kavelaars  A, van d Pompe  G, Bakker  J M, et al. Altered immune function in human newborns after prenatal administration of betamethasone: enhanced natural killer cell activity and decreased T cell proliferation in cord blood.  Pediatr Res. 1999;  45 306-312
    PubMedGoogle Scholar
  • 47 Baud  O, Foix-L'Helias  L, Kaminski  M, et al. Antenatal glucocorticoid treatment and cystic periventricular leukomacia in very premature infants.  N Engl J Med. 1999;  341 1190-1196
    CrossrefPubMedGoogle Scholar
  • 48 Mulder  E J, Derks  J B, Visser  G H. Antenatal corticosteroid therapy and fetal behaviour: a randomised study of the effects of betamethasone and dexamethasone [see comments].  Br J Obstet Gynaecol. 1997;  104 1239-1247
    CrossrefPubMedGoogle Scholar
  • 49 Crowley  P. Prophylactic corticosteroids for preterm birth (Cochrane Review). In: The Cochrane Library, Issue 1, 2000. Oxford: Update Software;
    Google Scholar
  • 50 Elimian  A, Verma  U, Visintainer  P, Nergesh  T. Effectiveness of multidose antenatal steroids.  Obstet Gynecol. 2000;  95 34-36
    CrossrefPubMedGoogle Scholar
  • 51 Abbassi  S, Hirsch  D, Davis  J, et al. Effect of single versus multiple courses of antenatal corticosteroids on maternal and neonatal outcome.  Am J Obstet Gynecol. 2000;  182 1243-1249
    CrossrefPubMedGoogle Scholar
  • 52 McNamara  M F, Bottoms  S F. The incidence of respiratory distress syndrome does not increase when preterm delivery occurs greater than 7 days after steroid administration.  Aust N Z J Obstet Gynaecol. 1998;  38 8-10
    PubMedGoogle Scholar
  • 53 Tucker  J M, Goldenberg  R L, Davis  R O, Copper  R L, Winkler  C L, Hauth  J C. Etiologies of preterm birth in an indigent population: is prevention a logical expectation?.  Obstet Gynecol. 1991;  77 343-347
    PubMedGoogle Scholar
  • 54 Guzman  E R, Mellon  C, Vintzileos  A M, Ananth  C V, Walters  C, Gipson  K. Longitudinal assessment of endocervical canal length between 15 and 24 weeks' gestation in women at risk for pregnancy loss or preterm birth.  Obstet Gynecol. 1998;  92 31-37
    CrossrefPubMedGoogle Scholar
  • 55 Rozenberg  P. [New markers of the risk of preterm delivery].  Bull Acad Natl Med. 1998;  182 1455-1468
    PubMedGoogle Scholar
  • 56 Leitich  H, Brunbauer  M, Kaider  A, Egarter  C, Husslein  P. Cervical length and dilatation of the internal cervical os detected by vaginal ultrasonography as markers for preterm delivery: A systematic review.  Am J Obstet Gynecol. 1999;  181 1465-1472
    PubMedGoogle Scholar
  • 57 Jawny  J. Der vorzeitige Blasensprung.  Frauenarzt. 1999;  40 1165-1172
    PubMedGoogle Scholar
  • 58 Ragosch  V, Weitzel  H. Zum Beitrag von J. Jawny: „Der vorzeitige Blasensprung”.  Frauenarzt. 1999;  40 1548-1550
    PubMedGoogle Scholar
  • 59 Ragosch  V, Dudenhausen  W, Grauel  L, Schneider  K TM, Vetter  K, Weitzel  H. Empfehlungen zum Vorgehen beim vorzeitigen Blasensprung.  Frauenarzt. 2000;  41 271-272
    PubMedGoogle Scholar
  • 60 Morales  W J, Washington  S D, Lazar  A J. The effect of chorioamnionitis on perinatal outcome in preterm gestation.  J Perinatol. 1987;  7 105-110
    PubMedGoogle Scholar
  • 61 Lewis  D F, Brody  K, Edwards  M S, Brouillette  R M, Burlison  S, London  S N. Preterm premature ruptured membranes: a randomized trial of steroids after treatment with antibiotics.  Obstet Gynecol. 1996;  88 801-805
    CrossrefPubMedGoogle Scholar
  • 62 Mercer  B M. Management of preterm premature rupture of the membranes.  Clin Obstet Gynecol. 1998;  41 870-882
    CrossrefPubMedGoogle Scholar
  • 63 Imseis  H M, Iams  J D. Glucocorticoid use in patients with preterm premature rupture of the fetal membranes [published erratum appears in Semin Perinatol 1996 Dec; 20(6): 595].  Semin Perinatol. 1996;  20 439-450
    PubMedGoogle Scholar
  • 64 Bar  H I, Barnhard  Y, Scarpelli  S A, Orvieto  R, Ben  R, Divon  M Y. Gestational diabetes and preterm labour: is glycaemic control a contributing factor?.  Eur J Obstet Gynecol Reprod Biol. 1997;  73 111-114
    CrossrefPubMedGoogle Scholar
  • 65 Bourbon  J R, Farrell  P M. Fetal lung development in the diabetic pregnancy.  Pediatr Res. 1985;  19 253-267
    PubMedGoogle Scholar
  • 66 Matti  P, Pistoia  L, Fornale  M, Brunn  E, Zardini  E. [Prevalence of RDS in diabetic pregnancy].  Minerva Ginecol. 1996;  48 409-413
    PubMedGoogle Scholar
  • 67 Jacobs  H C, Bogue  C W, Pinter  E, Wilson  C M, Warshow  J B, Gross  I. Fetal lung mRNA levels of Hox genes are differentially altered by maternal diabetes and butyrate in rats.  Pediatric Res. 1998;  44 99-104
    PubMedGoogle Scholar
  • 68 Blank  A, Grave  G D, Metzger  B E. Effects of gestational diabetes on perinatal morbidity reassessed.  Diabetes Care. 1995;  18 127-129
    PubMedGoogle Scholar
  • 69 Pollack  R N, Divon  M Y. Intrauterine growth retardation: definition, classification and etiology.  Clin Obstet Gynecol. 1992;  35 99-107
    PubMedGoogle Scholar
  • 70 Elimian  A, Verma  U, Canterino  J, Shah  J, Visintainer  P, Tejani  N. Effectiveness of antenatal steroids in obstetric subgroups.  Obstet Gynecol. 1999;  93 174-179
    CrossrefPubMedGoogle Scholar
  • 71 Schiff  E, Friedman  S A, Mercer  B M, Sibai  B M. Fetal lung maturity is not accelerated in preeclamptic pregnancies.  Am J Obstet Gynecol. 1993;  169 1096-1101
    PubMedGoogle Scholar
  • 72 Amorim  M M, Santos  L C, Faundes  A. Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia.  Am J Obstet Gynecol. 1999;  180 1283-1288
    PubMedGoogle Scholar

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