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Z Geburtshilfe Neonatol 2001; 205(5): 174-188
DOI: 10.1055/s-2001-18503
ORIGINALARBEIT

Georg Thieme Verlag Stuttgart · New York

Fetale Chirurgie für schwere kongenitale Fehlbildungen[1]

Fetal surgical therapy for severe congenital malformationsE. Danzer1, 2 , F. Schier1 , B. Paek2 , M.  R. Harrison2 , C.  T. Albanese2
  • 1 Abteilung für Kinderchirurgie, Friedrich Schiller Universität Jena
  • 2 The Fetal Treatment Center, Department of Surgery, Division of Pediatric Surgery, University of California, San Francisco
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Publication History

Publication Date:
19 November 2001 (online)

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Zusammenfassung

Hintergrund und Fragestellung Mit Hilfe modernster Diagnosetechniken, der molekularen Zytogenetik und der Verbesserungen der bildgebenden Verfahren während der letzten 20 Jahre ist es immer öfter möglich geworden, Fehlbildungen und Anomalien des Feten bereits im Mutterleib zu diagnostizieren. Eine frühe Diagnose und fundiertes Wissen über den natürlichen Verlauf einer Fehlbildung gestatten dem Perinatalmediziner eine realistische Einschätzung der kindlichen Prognose und die Definition geeigneter therapeutischer Strategien. Die fetale Chirurgie ist eine logische Konsequenz der Entwicklungen in der pränatalen Diagnostik. Ziel dieser Arbeit ist es, einen Überblick über die aktuellen Entwicklungen und Möglichkeiten in der pränatalen chirurgischen Therapie zu geben sowie die Risiken und ethischen Probleme zu diskutieren.Material und Methodik Die gegenwärtig zur Verfügung stehende Literatur sowie die zur Zeit laufenden experimentellen und klinischen Studien wurden wissenschaftlich aufgearbeitet und die Ergebnisse zusammengetragen.Ergebnisse Wenn auch die meisten in utero festgestellten Fehlbildungen am besten nach der Geburt medikamentös und/oder chirurgisch behandelt werden, führen einige Anomalien bereits während der Schwangerschaft zu einer nicht mit dem postnatalen Leben des Fetus zu vereinbarenden Organschädigung. Insbesondere diese Feten profitieren von einer intrauterinen Korrektur. Um einen pränatalen Eingriff mit entsprechenden Risiken zu rechtfertigen, müssen verschiedene Selektionskriterien formuliert werden: die Diagnose muss in utero sicher zu stellen sein, assoziierte Anomalien müssen ausgeschlossen werden, die intrauterine Organschädigung muss nach dem Eingriff reversibel sein und die fetale Operation muss die Prognose des Feten signifikant verbessern.Es wurden drei Zugangswege zum Feten entwickelt: perkutan, fetoskopisch und die offene fetale Chirurgie. Derzeit werden folgende Eingriffe durchgeführt: temporäre Trachealokklusion bei der kongenitalen Zwerchfellhernie, Dekompression der abführenden Harnwege bei der obstruktiven Uropathie, intrauterine Lasertherapie bei dem Zwillings-Transfusion-Syndrom, Tumorresektion bei der zystisch-adenomatoiden Lungenmalformation und dem Steißbeinteratom, sowie die intrauterine Deckung einer Myelomeningocele. Die Hauptkomplikationen eines intrauterinen Eingriffes sind vorzeitige Wehen und vorzeitiger Blasensprung. Um die mütterliche Morbidität und das Risiko der Frühgeburtlichkeit zu senken, wurde die endoskopische fetale Chirurgie entwickelt (FETENDO).Schlussfolgerung Bei ausgewählten Patientinnen kann durch einen fetalchirurgischen Eingriff die Mortalität und die postnatale Morbidität des Feten bzw. des Neugeborenen verringert werden. Durch den Erfolg der minimal-invasiven fetalen Chirurgie wird die offene fetale Chirurgie mit all ihren Komplikationen in Zukunft nur eine untergeordnete Rolle einnehmen.

Fetal surgical therapy for severe congenital malformations

Background Over the past two decades the diagnosis of life threatening congenital malformations has evolved rapidly. Sophisticated and powerful new imaging and sampling techniques have stripped the veil of mystery from the once secretive fetus. Early detection and close follow-up of the fetus with congenital malformations have allowed us to define their natural history, determine the clinical features that affect clinical outcome, and plan management approaches to improve prognosis. Fetal surgical intervention is the logical culmination of the progress in fetal diagnosis. The purpose of this article is to describe the current techniques and recent advances in prenatal diagnosis and fetal intervention of severe congenital malformation.Material and Methods A complete review of the literature and our own experience concerning fetal surgery was performed.Results Although most prenatally diagnosed malformations are best managed by appropriate medical and surgical therapy after maternal transport and planned delivery at a tertiary care center, an expanding number of simple anatomical abnormalities with predictable, lethal consequences have been successfully corrected before birth. A malformation amenable to prenatal surgical intervention must fulfill a number of conditions. It must be severe enough to warrant the risks associated with in utero treatment and must be reliably detectable before birth. Additionally, the pathophysiology must be reversible by fetal surgery, significantly improving the prognosis over postnatal treatment.Many technical intricacies of open fetal surgery have been solved, but pre-term labor and premature rupture of membranes remain a omnipresent risks to both the mother and the fetus. To reduce maternal morbidity and the risk of prematurity we developed minimally invasive techniques to treat the fetus prenatally. Current indications of fetal surgery include the treatment of congenital diaphragmatic hernia, cystic adenomatoid malformation of the lung, sacrococcygeal teratoma, obstructive uropathy, twin-to-twin-transfusion-syndrome and myelomeningocele. Minimally invasive surgical techniques (FETENDO) have significantly lessened the incidence of preterm labor and promise to extend the indications for fetal surgical intervention.Conclusions Fetal surgical therapy for severe congenital malformations may improve the outcome of selected patients. The development of FETENDO will in all probability reduce the importance of open fetal surgery in the future.

Schlüsselwörter

Pränatale Diagnose - angeborene Fehlbildungen - Fetus - fetale Chirurgie

Key words

Prenatal diagnosis - Congenital malformation - Fetus - Fetal surgical intervention

1 Eingang: 18. 8. 2000
Angenommen nach Revision: 13. 11. 2000

Literatur

1 Eingang: 18. 8. 2000
Angenommen nach Revision: 13. 11. 2000

  • 001 Harrison  M R, Golbus  M S, Filly  R A. Management of the fetus with correctable congenital defects.  JAMA. 1981;;  246 774-777
    Google Scholar
  • 002 Harrison  M R, Adzick  N S. Fetal surgical techniques.  Sem Pediatr Surg. 1993;;  2 136-142
    Google Scholar
  • 003 Harrison  M R, Golbus  M, Filly  R A (eds). The Unborn Patient. WB Saunders, Philadelphia; 1991:
    Google Scholar
  • 004 Harrison  M R, Adzick  N S. The fetus as a patient: Surgical considerations.  Ann Surg. 1990;;  213 279-291
    Google Scholar
  • 005 Adzick  N S, Flake  A W, Harrison  M R. Recent advances in prenatal diagnosis and treatment.  Pediatr Clinics North Am. 1985;;  32 1103-1116
    Google Scholar
  • 006 Harrison  M R, Anderson  J, Rosen  M A, Ross  N A, Hendrickx  A F. Fetal surgery in the primate. I. Anesthetic, surgical, and tocolytic management to maximize fetal-neonatal survival.  J Pediatr Surg. 1982;;  17 115-122
    Google Scholar
  • 007 Harrison  M R, Mychaliska  G B, Albanese  C T, Jennings  R W, Farrell  J A, Hawgood  S, Sandberg  P, Levine  A H, Lobo  E, Filly  R A. Correction of congenital diaphragmatic hernia in utero IX: Fetuses with poor prognosis (Liver herniation and low Lung-to-Head ratio) can be saved by fetoscopic temorary tracheal occlusion.  J Pediatr Surg. 1998;;  33 1017-1023
    Google Scholar
  • 008 Adzick  N S, Harrison  M R, Flake  A W. Automatic uterine stapling devices in fetal operation: Experience in a primate model.  Surg Forum. 1985;;  36 479-480
    Google Scholar
  • 009 Bond  S J, Harrison  M R, Slotnick  R N. Cesarean delivery and hysterotomy using an absorbable stapling device.  Obstet Gynecol. 1989;;  74 25-28
    Google Scholar
  • 010 Jennings  R W, Adzick  N S, Longaker  M T, Lorenz  H P, Harrison  M R. Radiotelemetric fetal monitoring during and after open fetal operation.  Surg Gynecol Obstet. 1993;;  176 59-64
    Google Scholar
  • 011 Albanese  C T, Harrison  M R. Surgical treatment for fetal disease. The state of the art.  Ann N Y Acad Sci. 1998;;  847 74-85
    Google Scholar
  • 012 VanderWall  K J, Bruch  S W, Meuli  M, Kohl  T, Szabo  Z, Adzick  N S, Harrison  M R. Fetal endoscopic (FETENDO) tracheal clip.  J Pediatr Surg. 1996;;  31 1101-1104
    Google Scholar
  • 013 Harrison  M R. Fetal surgery.  Am J Obstet Gynecol. 1996;;  174 1255-1263
    Google Scholar
  • 014 Harrison  M R. Fetal surgery.  West J Med. 1993;;  159 341-349
    Google Scholar
  • 015 Sabik  J F, Assad  R S, Hanley  F L. Halothane as an anesthetic for fetal surgery.  J Pediatr Surg. 1993;;  28 543-546
    Google Scholar
  • 016 Jennings  R W, GacGillivray  T E, Harrison  M R. Nirtic oxide inhibits preterm labor in the rhesus monkey.  J Maternal-Fetal Med. 1993;;  2 170-175
    Google Scholar
  • 017 Bealer  J F, Rice  H E, Adzick  N S, Harrison  M R. Acute non-cardiac pulmonary edema complicating nitroglycerin tocolysis following open fetal surgery. Obstet Gynecol (in press) :
    Google Scholar
  • 018 Harrison  M R, VanderWall  K J, Bealer  J F, Metkus  A P, Adzick  N S, Rose  M A, Auer  I K, Heymann  M A. Nitroglycerin suppresses preterm labor after hysterotomy and fetal surgery. Am J Obstet Gynecol (in press) :
    Google Scholar
  • 019 Longaker  M T, Golbus  M S, Filly  R A, Rosen  M A, Chang  S W, Harrison  M R. Maternal outcome after open fetal surgery.  JAMA. 1991;;  265 737-741
    Google Scholar
  • 020 Farrell  J A, Albanese  C T, Jennings  R W, Kilpatrick  S J, Bratton  B J, Harrison  M R. Maternal fertility is not affected by fetal surgery.  Fetal Diagn Ther. 1999;;  14 190-192
    Google Scholar
  • 021 DiFiderico  E M, Burlingame  J M, Kilptrick  S J, Harrison  M R, Matthay  M A. Pulmonary edema in obstetric patients is rapidely resolved except in the precence of infection or of nitroglycerin tocolysis after open fetal surgery.  Am J Obstet Gynecol. 1998;;  179 925-933
    Google Scholar
  • 022 DiFiderico  E M, Harrison  M R, Matthay  M A. Pulmonary edema in a woman following fetal surgery.  Chest. 1996;;  109 1114-1117
    Google Scholar
  • 023 Skandalis  J E, Gray  S W, Ricketts  R R. The Diaphragm. In: Skandalis JE, Gray SW (eds). Embryology for Surgeons, 2nd edition. Williams & Wilkins, Baltimore; 1999: 491-539
    Google Scholar
  • 024 Harrison  M R, Bressak  M A, Churg  A M, de Lorimier  A A. Correction of congenital diaphragmatic hernia in utero. II. Simulated correction permits fetal lung growth with survival at birth.  Surgery. 1980;;  2 260-268
    Google Scholar
  • 025 Harrison  M R, Adzick  N S, Flake  A W. Congenital diaphragmatic hernia: an unsolved problem.  Sem Pediatr Surg. 1993;;  2 109-112
    Google Scholar
  • 026 Clark  R H, Hardin  W D Jr, Hirschl  R B, et al. Current surgical management of congenital diaphragmatic hernia: A report from the congenital diaphragmatic study group.  J Pediatr Surg. 1998;;  33 1004-1009
    Google Scholar
  • 027 Harrison  M R, Jester  J A, Ross  N A. Corresotion of congenital diaphragmatic hernia in utero. I. The model: inthrathoracic ballon produces fatal pulmonary hypoplasia.  Surgery. 1980;;  88 174-182
    Google Scholar
  • 028 Adzick  N S, Harrison  M R, Glick  P L, Nakayama  D K, Manning  F A, de Lorimier  A A. Diaphragmatic hernia in the fetus: prenatal diagnosis and outcome in 94 cases.  J Pediatr Surg. 1985;;  20 357-361
    Google Scholar
  • 029 Sharland  G K, Lockhart  S M, Heward  A J, Allan  L D. Prognosis in fetal diaphragmatic hernia.  Am J Obstet Gynecol. 1992;;  166 9-13
    Google Scholar
  • 030 Lipshutz  G S, Albanese  C T, Feldstein  V A, Jennings  R W, Housley  H AT, Beech  R, Farrell  J A, Harrison  M R. Prospective anaylsis of lung-to-head ratio predicts survival for patients with prenatally diagnosed congenital diaphragmatic hernia.  J Pediatr Surg. 1997;;  32 1634-1636
    Google Scholar
  • 031 Harrison  M R, Langer  J C, Adzick  N S. Correction of congenital diaphragmatic hernia in utero. V. Initial clinical experience.  J Pediatr Surg. 1990;;  25 47-55
    Google Scholar
  • 032 Harrison  M R, Adzick  N S, Flake  A W, Jennings  R W, Estes  J M, MacGillivary  T E, Chueh  J T, Goldberg  J D, Filly  R A, Goldstein  R B, Rosen  M A, Cauldwell  C, Levine  A H, Howell  L J. Correction of congenital diaphragmatic hernia in utero. VI. Hard-earned lessons.  J Pediatr Surg. 1993;;  28 1411-1418
    Google Scholar
  • 033 Harrison  M R, Adzick  N S, Bullard  K M, et al. Correction of congenital diaphragmatic hernia in utero. VII. a proscpective trail.  J Pediatr Surg. 1997;;  32 1637-1642
    Google Scholar
  • 034 Hedrick  M H, Estes  J M, Sullvian  K M, Bealer  J F, Kitterman  J A, Flake  A W, Adzick  N S, Harrison  M R. Plug the lung until it grows (PLUG): a new method to treat congenital diaphragmatic hernia in utero.  J Pediatr Surg. 1994;;  29 612-617
    Google Scholar
  • 035 Bealer  J F, Skarsgard  E D, Hedrick  M H, et al. The „PLUG” odessey: adventures in experimental fetal tracheal occlusion.  J Pediatr Surg. 1995;;  30 361-364
    Google Scholar
  • 036 DiFiore  J W, Fauza  D O, Slavin  D, Peters  C A, Fackler  J C, Wilson  J M. Eperimental fetal tracheal ligation reverse the structural and physiologic effects of pulmonary hypoplasia in congenital diaphragmatic hernia.  J Pediatr Surg. 1994;;  29 258-257
    Google Scholar
  • 037 Harrison  M R, Mychaliska  G B, Albanese  C T, et al. Correction of congenital diaphragmatic hernia in utero IX. fetus with poor prognosis (liver herniation and low lung-to-head ratio) can be saved by fetoscopic temorary tracheal occlusion.  J Pediatr Surg. 1998;;  33 1017-1022
    Google Scholar
  • 038 Mychaliska  G B, Bealer  J F, Graf  J L, Rosen  M A, Adzick  N S, Harrison  M R. Operating on placental support: the ex utero intrapartum treatment procedure.  J Pediatr Surg. 1997;;  32 227-230
    Google Scholar
  • 039 Adzick  N S. Fetal thoracic lesions.  Sem Pediatr Surg. 1993;;  2 103-108
    Google Scholar
  • 040 Adzick  N S, Harrison  M R, Glick  P L, et al. Fetal cystic adenomatoid malformation: prenatal diagnosis and natural history.  J Pediatr Surg. 1985;;  20 483-488
    Google Scholar
  • 041 Westerburg  B, Albanese  C T, Hasbergen  U, Hepp  H, Harrison  M R. Prognose von Feten mit zystisch-adenomatoider Lungenmalformation. 6. Kongress der Deutschen Gesellschaft für Pränatal- und Geburtsmedizin, Nürnberg; 1998:
    Google Scholar
  • 042 Rice  H E, Estes  J M, Hedrick  M H, Bealer  J F, Harrison  M R, Adzick  N S. Congenital cystic adenomatoid malformation: a sheep model of fetal hydrops.  J Pediatr Surg. 1994;;  29 692-696
    Google Scholar
  • 043 Stocker  T J, Manewll  J E, Drake  R M. Congenital cystic adenomatoid malformation of the lung: classification and morphologic spectrum.  Hum Pathol. 1977;;  8 155-167
    Google Scholar
  • 044 Oster  A G, Fortune  D W. Congenital cystic adenomatoid malformation of the lung.  Am J Clin Pathol. 1979;;  70 595-603
    Google Scholar
  • 045 Nicolaides  K H, Azar  G B. Thoraco-amniotic shunting.  Fetal Diagn Ther. 1990;;  5 153-164
    Google Scholar
  • 046 Blott  M, Nicolaides  K H, Greenough  A. Postnatal respiratory function after chronic drainage of fetal pulmonary cyst.  Am J Obstet Gynecol. 1988;;  159 858-859
    Google Scholar
  • 047 Harrison  M R, Adzick  N S, Jennings  R W, et al. Antenatal intervention for congenital cystic malformation ofthe lung.  Lancet. 1990;;  336 965-967
    Google Scholar
  • 048 Adzick  N S, Harrison  M R, Flake  A W, et al. Fetal surgery for cystic adenomatoid malformation of the lung.  J Pediatr Surg. 1993;;  28 806-812
    Google Scholar
  • 049 Milner  R, Kitano  Y, Olutoye  O, Flake  A W, Adzick  N S. Radiofrequency thermal ablation: A potential treatment for hydropic fetuses with a large chest mass.  J Pediatr Surg. 2000;;  35 386-389
    Google Scholar
  • 050 Estes  J M, Harrison  M R. Fetal obstructive uropathy.  Sem Pediatr Surg. 1993;;  2 129-135
    Google Scholar
  • 051 Harrison  M R, Filly  R A, Parer  J T, Faer  M J, Jacobson  J B, de Lorimier  A A. Management of the fetus with a urinary tract malformation.  JAMA. 1981;;  246 635-639
    Google Scholar
  • 052 Adzick  N S, Harrison  M R, Glick  P L, et al. Fetal urinary tract obstruction: experimental pathophysiology.  Semin Perinatol. 1985;;  9 79-90
    Google Scholar
  • 053 Harrison  M R, Ross  N, Noall  R, de Lorimier  A A. Correction of congenital hydronephrosis in utero. I. The model: fetal urethral obstruction produces hydronephrosis and pulmonary hypoplasia in fetal lambs.  J Pediatr Surg. 1983;;  18 247-256
    Google Scholar
  • 054 Harrison  M R, Nakayama  D K, Noall  R, de Lorimier  A A. Correction of congenital hydronephrosis in utero. II. Decompression reverses the effects of obstruction on the fetal lung and urinary tract.  J Pediatr Surg. 1983;;  17 965-974
    Google Scholar
  • 055 Lawson  T L, Foley  W D, Berland  L L, et al. Ultrasonographic evaluation of the kidneys: anlysis of normal size and frequency of visualization as related to stage of pregnancy.  Radiol. 1981;;  138 153-156
    Google Scholar
  • 056 Wilkins  I A, Chitkara  U, Lynch  L, et al. The nonpredictive valvue of fetal urinary electrolytes: Preliminary report of outcomes and correlations with pathologic diagnosis.  Am J Obstet Gynecol. 1987;;  157 694-698
    Google Scholar
  • 057 Mandelbrot  L, Dumez  Y, Muller  F, et al. Prenatal prdeiction of renal function in fetal obstructive uropathy.  J Perinat Med. 1991;;  19 283-287
    Google Scholar
  • 058 Nicolaides  K H, Cheng  H H, Snijders  R JM, et al. Fetal urine biochemistry in the assessment of obstructive uropathy.  Am J Obstet Gynecol. 1992;;  166 932-937
    Google Scholar
  • 059 Lipitz  S, Rayn  G, Samuell  C, et al. Fetal urine analysis for asessment of renal function in obstructive uropathy.  Am J Obstet Gynecol. 1993;;  168 174-179
    Google Scholar
  • 060 Manning  F A, Harrison  M R, Rodeck  C H, et al. Special report. Catheter shunts for fetal hydronephrosis and Hydrozephalus.  N Engl J Med. 1986;;  315 336-340
    Google Scholar
  • 061 Crombleholme  T M, Harrison  M R, Langer  J C, et al. Early experience with open fetal surgery for congenital hydronephrosis.  J Pediatr Surg. 1988;;  23 1114-1121
    Google Scholar
  • 062 MacMahan  R A, Renou  P M, Shekelton  P A, Paterson  R J. In utero cystostomy.  Lancet. 1992;;  340 1234
    Google Scholar
  • 063 Harrison  M R, Adzick  N S. The fetus as a patient. Surgical considerations.  Ann Surg. 1991;;  213 279-291
    Google Scholar
  • 064 Bale  P. Sacrococcygeal developmental abnormalities and tumors in children.  Perspect Pediatr Pathol. 1984;;  1 9-56
    Google Scholar
  • 065 Berry  C, Keeling  J, Hilton  C. Teratomata in infancy and childhood: a review of 91 cases.  J Pathol. 1969;;  98 241-250
    Google Scholar
  • 066 Grosfeld  J, Ballantine  T, Lowe  D, et al. Benign and malignant teratomas in children: Analysis of 85 patients.  Surgery. 1976;;  80 297-305
    Google Scholar
  • 067 Mahour  G, Wolley  M, Trivedi  S, et al. Teratomas in infancy and childhood: experience with 81 cases.  Surgery. 1974;;  76 309-319
    Google Scholar
  • 068 Flake  A W. Fetal sacrococygeal teratoma.  Sem Pediatr Surg. 1993;;  2 113-120
    Google Scholar
  • 069 Graf  J L, Housley  H AT, Albanese  C T, Adzick  N S, Harrison  M R. A surprising histological evolution of preterm sacrococcygeal teratoma.  J Pediatr Surg. 1998;;  33 177-179
    Google Scholar
  • 070 Bond  S J, Harrison  M R, Schmidt  K G, et al. Death due to high-output cardiac failure in fetal sacrococcygeal teratoma.  J Pediatr Surg. 1990;;  25 1287-1291
    Google Scholar
  • 071 Langer  J C, Harrison  M R, Schmidt  K G, et al. Fetal hydrops and death from sacrococoygeal teratoma: rationale for fetal surgery.  Am J Obstet Gynecol. 1989;;  160 1145-1150
    Google Scholar
  • 072 Kuhlmann  R S, Warsof  S L, Levy  D L, Flake  A W, Harrison  M R. Fetal sacrococcygeal teratoma.  J Pediatr Surg. 1986;;  21 563-566
    Google Scholar
  • 073 Evans  M J, Danielian  P J, Gray  E S. Sacrococcygeal teratoma: a case of mistaken identity.  Pediatr Radiol. 1994;;  24 52-53
    Google Scholar
  • 074 Lockwood  C, Chidini  A, Romero  R, Hobins  J C. Fetal Bowel perforation simulating sacrococcygeal teratoma.  J Ultrasound Med. 1988;;  7 227-229
    Google Scholar
  • 075 Bloechle  M, Bollmann  R, Wit  J, Buttenberg  S, Kursawe  R, Guski  H. Neuroectodermal cyst may be a rare differential diagnosis of fetal sacrococcygeal teratoma.  Ultrasound Obstet Gynecol. 1996;;  7 64-67
    Google Scholar
  • 076 Holzgreve  W, Mahony  B S, Glick  P L, Filly  R A, Harrison  M R, Delorimier  A A, Holzgreve  A C, Muller  K M, Callen  P W, Anderson  R L, et al. Sonographic demonstration of fetal sacrococcygeal teratoma.  Prenat Diag. 1985;;  5 245-257
    Google Scholar
  • 077 Westerburg  B, Feldstein  V A, Sandberg  P L, Lopoo  J B, Harrison  M R, Albanese  C T. Sonographic prognostic factors in fetuses with sacrococcygeal teratoma.  J Pediatr Surg. 2000;;  35 322-326
    Google Scholar
  • 078 Bullard  K M, Harrison  M R. Before the horse is out of the barn: fetal surgery for hydrops.  Semin Perinatol. 1995;;  19 462-473
    Google Scholar
  • 079 Westerburg  B, Chiba  T, Gantert  W, Harrison  M R, Jennings  R W. Radiofrequency ablation of liver in fetal sheep - model for treatment of sacrococoygeal teratoma in the fetus. Surg Forum 1998;: 461-463
    Google Scholar
  • 080 Little  J, Elwood  J M. Geographic variation. In: Elwood JM, Little J, Elwood JH (eds). The Epidemiology and Control of neural tube defects. Oxford University Press, Oxford; 1992;: 96-145
    Google Scholar
  • 081 Adzick  N S, Sutton  L N, Crombleholme  T M, Flake  A W. Successful fetal surgery for spina bifida.  Lancet. 1998;;  352 1675-1676
    Google Scholar
  • 082 Tulipan  N, Bruner  J P. Myelomeningocele repair in utero: a report of three cases.  Pediatr Neurosurg. 1998;;  28 177
    Google Scholar
  • 083 180Bruner  J P, Richard  W O, Tulipan  N B, Arney  T L. Endoscopic coverage of fetal myelomeningocele in utero.  Am J Obstet Gynecol. 1999;;  180 153-158
    Google Scholar
  • 084 Simpson  J L. Fetal surgery for myelomeningocele - promise, progress, and problems.  JAMA. 1999;;  282 1873-1874
    Google Scholar
  • 085 MRC Vitamin research group .Prevention of neural tube defects: Results of the medical research council vitamin study. Lancet 1991; 338: 131-137
    Google Scholar
  • 086 Kirke  P N, Molloy  A M, Daly  L E, Burke  H, Weir  D G, Scott  J M. Maternal plasma folate and vitamin B 12 are independent risk factors for neural tube defects.  Q J Med. 1993;;  86 703-708
    Google Scholar
  • 087 Copp  A J. Prevention of neural tube defects: vitamins, enzymes and genes.  Curr Opin Neurol. 1998;;  11 97-102
    Google Scholar
  • 088 Lemire  R J. Neural tube defects.  JAMA. 1988;;  259 558-562
    Google Scholar
  • 089 Heffez  D S, Aryanpur  J, Hutchins  G M, et al. The paralysis associated with myelomeningocele: Experimental data implicating a preventable spin cord injury.  Neurosurg. 1990;;  26 987-992
    Google Scholar
  • 090 Heffez  D S, Aryanpur  J, Hutchins  G M, Freeman  J M. Intrauterine repair of experimental surgically created dysraphism.  Neurosurgery. 1993;;  32 1005-1010
    Google Scholar
  • 091 Meuli  M, Meuli-Simmen  C, Hutchins  G M, et al. In utero surgery rescues neurological function at birth in sheep with spina bifida.  Nat Med. 1995;;  1 342-347
    Google Scholar
  • 092 Michejda  M. Intrauterine treatment of spina bifida: primate Model.  Z Kinderchir. 1984;;  39 259-261
    Google Scholar
  • 093 Tulipan  N, Hernanz-Schulman  M, Bruner  J P. Reduced hindbrain herniation after intrauterine myelomeningocele repair: A report of four cases.  Pediatr Neurosurg. 1998;;  29 274-278
    Google Scholar
  • 094 Paek  P, Wilkinson  C, Farmer  D L, et al. Hindbrain herniation develops in surgically created myelomeningocele and is prevented by prenatal repair in fetal lambs. Abstract (Oral presentation) Society for Maternal-Fetal Medicine 20th Annual Meeting 1/2000
    Google Scholar
  • 095 Piatt  J H, D'Agostino  A. The Chiari II malformation: Lesions discovered within the fourth ventricle.  Pediatr Neurosurg. 1999;;  30 79-85
    Google Scholar
  • 096 Hoffman  H J. Syringomyelia in childhood. In: Batzdorf U (ed). Syringomyelia: Current concepts in diagnosis and treatment. Williams & Wilkins, Baltimore; 1991:
    Google Scholar
  • 097 McLone  D G, Naidich  T P. Myelomeningocele: Outcome and late complications. In: McLaurin, Schut, Venes, Epstein (eds). Pediatric Neurosurgery. 2nd ed. WB Saunders, Philadelphia; 1989:
    Google Scholar
  • 098 Brock  D JH, Sutcliffe  R G. Alpha-fetoprotein in antenatal diagnosis of anencephaly and spina bifida.  Lancet. 1972;;  2 197
    Google Scholar
  • 099 Nicolaides  K H, Campbell  S, Gabbe  S G, Guidetti  R. Ultrasound screening for spina bifida: cranial and cerebellar signs.  Lancet. 1986;;  2 72-74
    Google Scholar
  • 100 Bruner  J P, Tulipan  N, Paschall  R L, et al. Fetal surgery for myelomeningocele and the incidence of shunt-dependent Hydrozephalus.  JAMA. 1999;;  282 1819-1825
    CrossrefPubMedGoogle Scholar
  • 101 Sutton  L N, Adzick  N S, Bilaniuk  L T, et al. Improvement in Hindbrain herniation demonstrated by serial fetal magnetic resonance imaging following fetal surgery for myelomeningocele.  JAMA. 1999;;  282 1826-1831
    CrossrefPubMedGoogle Scholar
  • 102 Blickstein  I. The twin-twin transfusion syndrome.  Obstet Gynecol. 1990;;  76 714-722
    PubMedGoogle Scholar
  • 103 Bruner  J P, Rosemond  R L. Twin-to-twin transfusionsyndrome: A subset of the twin oligohydramnios-polyhadramnios sequence.  Am J Obstet Gynecol. 1993;;  169 925-930
    PubMedGoogle Scholar
  • 104 Machin  G, Still  K, Lanani  T. Correlations of placental vascular anatomy and clinical outcomes in 69 monochoroionic twin pregnancies.  Am J Med Genet. 1996;;  61 229-236
    CrossrefPubMedGoogle Scholar
  • 105 Mielke  G, Gonser  M. Pränatale Diagnostik und Therapie des feto-fetalen Transfusionssyndroms.  Z Geburth Neonatol. 1998;;  202 141-148
    PubMedGoogle Scholar
  • 106 Cinotta  R B, Fisk  N M. Current thoughts on twin-twin transfusion syndrome.  Clin Obstet Gynecol. 1997;;  40 290-302
    CrossrefPubMedGoogle Scholar
  • 107 Elliot  J P, Urig  M A, Clewell  W H. Agressive therapeutic amnioncentesis for treatment of twin-twin transfusion syndrome.  Obstet Gynecol. 1994;;  77 537-540
    PubMedGoogle Scholar
  • 108 De Lia  J E, Emery  M G, Sheafor  S A, Jennison  T A. Twin transfusion syndrome: successful in utero treatment with digoxin.  Int J Gynecol Obstet. 1985;;  23 197-201
    CrossrefPubMedGoogle Scholar
  • 109 De Lia  J E, Cruiksank  E DP, Keye  W R. Fetoscopic neodymium: YAG laser occlusion of placental vessels in severe twin-twin-transfusion syndrome.  Obstet Gynecol. 1990;;  75 1046-1053
    PubMedGoogle Scholar
  • 110 Hecher  K, Plath  H, Bregenzer  T, Hansmann  M, Hackeloer  B J. Endoscopic laser surgery versus serial amniocentesis in the treatment of severe twin-twin transfusion syndrome [In Progress Citation].  Am J Obstet Gynecol. 1999;;  180 717-724
    PubMedGoogle Scholar
  • 111 De Lia  J E, Kuhlman  R S, Harsted  T W, Cruikshank  D P. Fetoscopic laser ablation of placental vessels in severe previable twin-twin transfusion syndrome.  Am J Obstet Gynecol. 1995;;  172 1202-1208
    CrossrefPubMedGoogle Scholar
  • 112 Ginsberg  N A, Applebaum  A M, Rabin  S A, Caffarelli  M A, Muuspalu  M, Daskal  J L, Verlinsky  Y, Storm  C M, Barton  J J. Term birth after midtrimester hysterotomy and selective delivery of an acardiac twin.  Am J Obstet Gynecol. 1992;;  167 33-37
    PubMedGoogle Scholar
  • 113 Lees  C, Campbell  S, Jauniaux  E, et al. Arrest of preterm labor and prolongation of gestation with glyceryl trinitrate, a nitric oxide donor.  Lancet. 1994;;  343 1325-1326
    CrossrefPubMedGoogle Scholar
  • 114 Surbek  D V, Gratwohl  A, Holzgreve  W. In utero hematopoietic stem cell transfer: current status and future strategies.  Eur J Obstet Gynecol. 1999;;  85 109-115
    CrossrefPubMedGoogle Scholar

Dr. Enrico Danzer

Abteilung für Kinderchirurgie
Friedrich-Schiller-Universität

Bachstraße 18

07740 Jena

Phone: + + 49/36 41/93 31 65

Fax: + + 49/36 41/93 34 46

Email: edanzer@gmx.de