Early Human Development
Volume 88, Issue 1 , Pages 15-19, January 2012

Best practice guidelines: Fetal surgery

  • Nada Sudhakaran

      Affiliations

    • St Georges Hospital, London, United Kingdom
    • ,
  • Uma Sothinathan

      Affiliations

    • Medway Maritime Hospital, Kent, United Kingdom
    • ,
  • Shailesh Patel

      Affiliations

    • King's College Hospital, London, United Kingdom
    • Corresponding Author InformationCorresponding author at: Department of Paediatric Surgery, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom. Tel.: +44 203 299 3350; fax: +44 203 299 4021.

Article Outline

Abstract 

Fetal intervention encompasses a range of procedures on the fetus with congenital structural anomalies, whilst still on the placental circulation. The concept of fetal surgery was conceived in order to prevent fetal or early postnatal death, or to prevent permanent irreversible organ damage. The benefit of these procedures has to be balanced with risks to both the mother and the fetus. Open fetal surgery, more commonly conducted in North American centres, involves open surgery to the uterus in order to operate on the fetus. Fetal intervention centres in Europe more commonly use minimally invasive fetoscopic surgery. This paper elaborates on the various strategies used in dealing with anomalies of different organ systems of the fetus.

Keywords: Fetal intervention, Antenatal, Fetoscopic, Twin to twin transfusion syndrome, Congenital diaphragmatic hernia, Spina bifida, Congenital lung lesions

 

Back to Article Outline

1. Introduction 

Antenatally detected anomalies, in most cases can wait for treatment after birth. However, fetuses may rarely require intervention whilst still in the womb. This is to save the life of the fetus or to prevent permanent organ damage [1]. The intervention may be to correct the malformation, arrest disease progression, or to treat the immediately life-threatening situation, thus allowing the fetus to mature and delaying definitive procedure until after birth [2].

Michael Harrison from the University of California, San Francisco, was the first to use animal models to develop fetal surgery in 1980. The following year his group performed the world's first open human fetal surgery [1]. He conducted a drain vesicostomy for a fetus with marked hydronephrosis, who then went on to have definitive surgery postnatally. There has been significant advancement in human fetal interventions since this first procedure. With development of instrumentations and techniques, fetal surgery has now become more minimally invasive [3].

Fetal surgery carries a risk to the pregnancy and has a risk of failure. The claimed benefits of the intervention therefore must be weighed against the inherent risk of complications to the fetus or mother. Rupture of the amniotic sac and preterm labour remain the main concern postoperatively following fetal interventions. Here we will discuss the common procedures undertaken in fetal intervention centres worldwide.

Back to Article Outline

2. Criteria for fetal interventions [1], [2] 


1.Accurate diagnosis and staging is possible, with exclusion of associated anomalies.

2.Natural history of the disease is documented, and prognosis established.

3.Currently no effective postnatal therapy.

4.In-utero surgery proven feasible in animal models, reversing deleterious effects of the condition.

5.Interventions performed in specialised multidisciplinary fetal treatment centres within strict protocols and approval of the local ethics committee, with informed consent of the mother or parents.

Back to Article Outline

3. Open fetal surgery 

Open fetal surgery involves a caesarean section approach to access the fetus. A uterine stapler (US Surgical Corporation, Norwalk, CT, USA) with absorbable staples is used to anchor the amniotic membrane to the uterus and create a haemostatic opening to the uterus [4]. The fetus will remain on the placental circulation whilst surgery is done on it. Upon completion of the surgery, the fetus is put back inside the uterus and the uterus and abdominal wall are closed up. The amniotic fluid is replaced prior to complete closure of the uterus. The mother remains in the hospital for 3–7days for monitoring. The baby will be delivered by planned caesarean section. However, they are often born pre-maturely [5].

Back to Article Outline

4. Minimally invasive fetal surgery (MIFS) 

Minimally invasive fetoscopic surgery (Fetendo) uses real-time video imagery from fetoscopy and possible ultrasonography to guide very small surgical instruments into the uterus to perform surgery in the fetus. In contrast to open fetal surgery, the minimally invasive fetoscopic approach poses a lower risk of maternal and fetal morbidity. Fetal surgeries can also be done percutaneously, such as insertion of vesico-amniotic shunts for fetal bladder outflow obstruction. These minimally invasive procedures are often conducted under local anaesthetic, hence improving the mother's postoperative recovery. However, despite the use of small-calibre trocars and instruments, complications such as bleeding from vascular or placental injuries, separation of chorioamniotic membranes, amniotic fluid leakage, chorioamnionitis, or preterm delivery are common [2], [3].

Back to Article Outline

5. Twin to twin transfusion syndrome 

The twin–twin transfusion syndrome (TTTS) is the most common serious complication of monochorionic twin pregnancies, affecting about 9% of such pregnancies each year [6]. The natural history of severe TTTS is well established, with mortality approaching 100% if left untreated when it presents at less than 20weeks of gestation. Numerous treatments have been proposed including selective feticide, cord coagulation, sectio parva, placental bloodletting, maternal digitalis, maternal indomethacin, serial amnioreduction, microseptostomy of the inter-twin membrane, and nonselective or selective fetoscopic laser photocoagulation [6], [7], [8], [9].

Many studies and a meta-analysis have shown laser therapy to be a superior procedure compared to amnioreduction [11]. However, since the publication of the Eurofetus randomised trial comparing amnioreduction with selective laser photocoagulation, there has been no doubt that laser therapy is superior to amnioreduction, hence its recognition as the best therapy for severe TTTS that develop before 26weeks of gestation [10]. At St George's Hospital, London this is done by identifying the common villous district of the placenta using ultrasound technique and photocoagulating any vessels that cross the vascular equator. This technique is efficient, associated with a short operating time, low likelihood of TTTS recurrence or fetal anaemia, and with survival results that are comparable to previously reported techniques [12]. Fig. 1.

Back to Article Outline

6. Congenital diaphragmatic hernia 

Early antenatal diagnosis of congenital diaphragmatic hernia (CDH) when left untreated is associated with a significant number of fetal demise and postnatal mortality rate of around 30%. This is due to other major congenital defects, and a combination of pulmonary hypoplasia and persistent pulmonary hypertension. Measurement of the lung head ratio (LHR), comparing the size of the contralateral lung to the side of the diaphragmatic hernia with the size of the head, was first described by Metkus et al. [13]. An observed over expected LHR (O/E LHR) helps predict the degree of lung hypoplasia independent of the fetal gestational age [14]. O/E LHR of <15% predicts ‘no chance’ of survival due to extreme pulmonary hypoplasia. If the O/E LHR is between 15 and 25%, the fetus has severe pulmonary hypoplasia and the chance of survival is around 15%. With an O/E LHR of >25%, survival of the fetus increases to above 60% [2].

The fetal lungs secrete fluid into the airway, which is interchanged with amniotic fluid during fetal breathing movements. Fetal tracheal occlusion prevents escape of the fluid, which then induces lung tissue stretch. This in turn triggers lung growth in the form of airways and vessels [15]. Fetoscopic Endoluminal Tracheal Occlusion (FETO) has largely replaced other techniques of fetal tracheal occlusion [16], [17].

A randomised controlled trial conducted by Harrison et al., from North America, suggested that the risk of premature delivery outweighed the benefits of fetal tracheal occlusion. However this result was biased by the patient cohort which included fetuses with O/E LHR >25% [18].

The European FETO consortium offered FETO to the severe O/E LHR group with a predicted survival rate of 15%. Their published series of 210 fetuses revealed FETO intervention was conducted at a median gestational age of 27weeks. Premature delivery before 37weeks of gestation occurred in 47.1% of cases at a median of 30days post FETO. 97.1% from this cohort were live born and 48.0% were discharged from the hospital alive. This study helped define the predictors of outcome as O/E LHR pre FETO, premature rupture of membranes and gestational age at delivery [19], [20], [21]. Previous publication by the same group had shown that the increase in lung area post FETO is a good predictor of survival [22]. Conducting FETO at a later gestation will decrease the risk of early delivery but this will be at the cost of poorer lung growth [23].

Currently there is a multi centre randomised trial in Europe looking at FETO in fetuses with moderate lung hypoplasia.

Back to Article Outline

7. Lower urinary tract obstruction (LUTO) 

Lower urinary tract obstruction is most commonly due to posterior urethral valves (PUVs) and urethral atresia. This accounts for one third of renal tract anomalies at autopsy following termination of pregnancy for antenatally detected fetal anomaly. PUV accounts for about half of the cases presenting with ultrasonic features of LUTO. The perinatal mortality rate if left untreated is up to 95%. This is predominantly due to lung hypoplasia, secondary to severe oligohydramnios [24], [25], [26].

Percutaneous vesicoamniotic shunting is the most commonly used method to relieve urinary tract obstruction. A double pig tailed catheter (either Rodeck/Rocket or Harrison shunts) is placed under ultrasound guidance and local anaesthesia. The distal end of the shunt is positioned in the fetal bladder and the proximal end in the amniotic cavity. This allows for drainage of the fetal urine into the amniotic cavity. Amnio infusion may be needed, if there is severe oligohydramnios, to allow space for insertion of the shunt [27], [28].

A systematic review and meta-analysis was conducted by Clark et al. in 2003. He estimated the effect of prenatal bladder drainage procedures on perinatal survival of fetuses with LUTO. The procedures included in the analysis were vesicocentesis, vesico-amniotic shunting, and open fetal bladder surgery for LUTO. The meta-analysis showed that in-utero vesico-amniotic drainage improved overall perinatal survival when compared to the non-drainage group (P<0.03), albeit predominantly in fetuses with a ‘poor prognosis’ (defined on ultrasound appearance and/or fetal urinalysis) [29].

To date, there have been many reported observational series. However, these lack control data and the methodological quality were deemed relatively poor. For these reasons the outcome of PLUTO study is awaited with much anticipation. PLUTO is a randomised, controlled trial investigating the role of fetal vesicoamniotic shunting in moderate/severe LUTO. This is a multi centre trial based at Birmingham University, UK. The primary outcome measures looked at are perinatal mortality and serum creatinine, and the secondary outcome measures include the degree of reflux, bladder wall thickness and renal pelvic dilatation on postnatal ultrasound [27]. Fig. 2.

Back to Article Outline

8. Lung anomalies 

Congenital parenchymal lung lesions typically arise from disorganised development during embryogenesis. These include congenital cystic adenomatoid malformation (CCAM), bronchopulmonary sequestration (BPS) and congenital lobar/segmental emphysema. It is likely that all except bronchogenic cysts share the same abnormal spectrum of developmental malformation [30], [31]. Possible symptoms include polyhydramnious, mediastinal shift and ultimately, hydrops fetalis (i.e. skin oedema, pleural effusion or ascites). The development of hydrops is probably the only specific adverse indicator of postnatal outcome.

Some authors have attempted to define measurement of antenally-detected CCAM volume in relation to head circumference, and used this as the basis for prognostication. This remains controversial and not widely used [32].

The first reported thoracoamniotic shunt placement was by Clark in 1987 [33]. The main indications for the placement of a shunt are symptomatic macrocystic CCAM or pleural effusion [34], [35], [36], [37] Fig. 3. Reports that are more recent have shown good results, with up to 70% survival at birth.

Solid lung lesions that are causing mechanical compression, mediastinal shift and caval obstruction may be treated by antenatal laser coagulation of the feeding vessels, as for BPS. Laser coagulation may shrink the size of the lesion and in some cases result in complete resolution of the lesion. However, for large multicystic or predominantly solid lesion the treatment option may be limited to fetal lung resection if there is associated hydrops. The postnatal survival rate following fetal lung resection is about 50% [38], [39].

Back to Article Outline

9. Spina bifida 

Open spina bifida or myelomeningocele (MMC) is a congenital defect of the central nervous system with protrusion of the meninges and spinal cord through open vertebral arches. It is a disabling condition that causes paralysis of the lower limbs, affects bowel and bladder functions and is associated with variable degree of learning difficulties [40], [41].

The damage in MMC may be directly due to defective development of the central nervous system or secondary to damage by amniotic fluid exposure, direct trauma, hydrodynamic pressure, or a combination of these factors [42], [43]. Early fetal surgical repair helps avoid or minimise the secondary damage.

Adzick, a doyen in this field, suggested that the timing for fetal surgical procedure is ideally between 19 and 25weeks of gestation to minimise the length of time secondary damage can occur. Prior to this age, fetal tissues are gelatinous, making the procedure technically difficult. Early repair has the benefit of limiting progression of hydrocephalus [43]. Postnatal requirement of ventriculoperitoneal (VP) shunt rate was 46%, compared to the predicted untreated rate of 84%. These treated patients also had better lower limb function than predicted, 66% being independent walkers [46], [47].

Adzick's group reported their early series of 58 patients treated with fetal surgery. There was resolution of hindbrain herniation in nearly all patients with ascent of hindbrain structures on MRI scans 3weeks post surgery [44]. In addition, the smaller overall head size in myelomeningocele patients is shown to increase towards normal after fetal surgery due to normalisation of extra-axial CSF spaces [45].

Currently, a multi centre Management of Myelomeningocele Study (MOMS) is being conducted in North America. It is a randomised control trial looking at postnatal versus intrauterine repair of MMC. This study seeks to explore primary outcome measures of mortality and the need for VP shunt at 1year of age. Secondary outcome explored are improvement of Chiari II malformation, cognitive function, neurodevelopmental status at 12 and 30months and neuromotor function [43].

Back to Article Outline

10. EXIT 

The ex-utero intrapartum therapy (EXIT) procedure was first used for the delivery of fetuses with tracheal occlusion for severe CDH [48]. The EXIT procedure uses high concentrations of maternal inhalational anaesthetics and tocolytics, maintenance of uteroplacental blood flow, or placental bypass to provide uterine relaxation and to preserve placental perfusion. The head and upper torso of the fetus is delivered via a caesarean section opening and amniotic fluid volume is replaced by amnioinfusion. This preserves uterine volume and prevents uterine contraction, hence maintaining placental blood flow. Pulse oximetry and echocardiography is used to monitor the fetus. EXIT is used in delivering babies with airway obstructions, neck masses, congenital high airway obstruction syndrome and thoracic masses [49], [50], [51] Fig. 4.

Back to Article Outline

11. Discussion 

There are many fetal surgical procedures, some of which have not been discussed in this article, such as fetal valvuloplasty or cardiac septostomy, amniotic band release (around extremities) and fetal transfusion. Intra uterine interventions not involving the fetus directly such as chorioangioma ablation and release of amniotic band adhesions on cord are important for fetal survival and growth.

The introduction of real-time, three-dimensional, ultra-high-resolution imaging has enabled fetal specialists to view them as if being seen directly. As technology in imaging and instrumentations continues to improve, antenatal detection rate of structural abnormalities is increasing and more of these are presenting to fetal surgical centres. A balance between technological advancement and alternative approach needs to be struck. Absence of guidelines for most fetal interventions means patient safety and outcome data need to be carefully audited. The results should factor in the learning curve for most innovations in medicine, allowing sufficient room to progress without causing further harm. For more established fetal procedures like TTTS laser therapy, good standards should be set for service and for training, so that provision for such interventions can expand to local units.

Apart from fetal surgery, there has been great interest in non-surgical management of congenital anomalies. It is believed that the future innovations would focus on tissue engineering, using stem cells or even gene therapy.

Back to Article Outline

12. Conclusion 

Fetal surgery has come a long way and it is now practiced in many centres around the world. As the number of fetuses requiring therapy remains relatively low, strict protocol for intervention and centralisation of this practice in centres with skilled multidisciplinary team would best benefit the mother and the fetus. As fetal surgery is being more recognised and accepted, there are more multi centre randomised trials being conducted. There should however be more collaborative work and research by centres in both Europe and North America.

Back to Article Outline

Conflict of interest 

The authors have no conflict of interest to disclose.

Back to Article Outline

Acknowledgement 

Professor Basky Tilaganathan from the Fetal Medicine Unit, St Georges Hospital, London, is acknowledged for the images.

Back to Article Outline

References 

  1. Harrison MR, Filly RA, Golbus MS, Berkowitz RL, Callen PW, Canty TG, et al Fetal treatment. N Engl J Med. 1982;307:1651–1652
  2. Deprest JA, Devlieger R, Srisupundit K, Beck V, Sandaite I, Rusconi S, et al Fetal surgery is a clinical reality. Seminars in fetal and neonatal medicine. 2010;15(1):58–67
  3. Kohl T. Minimally invasive fetoscopic interventions: an overview in 2010. Surg Endosc. 2010;24:2056–2067
  4. Bond SJ, Harrison MR, Slotnick RN, Anderson J, Flake AW, Adzick NS. Cesarean delivery and hysterotomy using an absorbable stapling device. Obstet Gynecol. 1989;74:25–28
  5. Adzick NS. Open fetal surgery for life-thretening fetal anomalies. Semin Fetal Neonatal Med. 2010;15(1):1–8
  6. Lewi L, Jani J, Blickstein I, Huber A, Gucciardo L, Van Mieghem T, et al. The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study. Am J Obstet Gynecol. 2008;199:514.e1–514.e8
  7. Lewi L, Jani J, Deprest J. Invasive interventions in complicated multiple pregnancies. Clin Obstet Gynecol North Am. 2005;32:105–126
  8. El Kateb A, Ville Y. Update on twin-to-twin transfusion syndrome. Best Pract Res Clin Obstet Gynaecol. 2008;22:63–75
  9. Bebbington Michael. Twin-to-twin transfusion syndrome: current understanding of pathophysiology, in-utero therapy and impact for future development. Semin Fetal Neonatal Med. 2010;15(1):15–20
  10. Senat MV, Deprest J, Boulvain M, Paupe A, Winer N, Ville Y. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome. N Engl J Med. 2004;351:136–144
  11. Rossi AC, D'Addario V. Comparison of donor and recipient outcomes following laser therapy performed for twin–twin transfusion syndrome: a meta-analysis and review of the literature. Am J Obstet Gynecol. 2008;198:147–152
  12. Ierullo AM, Papageorghiou AT, Bhide A, Fratelli N, Thilaganathan B. Severe twin–twin transfusion syndrome: outcome after fetoscopic laser ablation of the placental vascular equator. BJOG. 2007 Jun;114(6):689–693
  13. Metkus AP, Filly RA, Stringer MD, Harrison MR, Adzick NS. Sonographic predictors of survival in fetal diaphragmatic hernia. J Pediatr Surg. 1996;31:148–152
  14. Jani JC, Nicolaides KH, Keller RL, Benachi A, Peralta CF, Favre R, et al. Antenatal-CDH-Registry Group Observed to expected lung area-to-head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia. Ultrasound Obstet Gynecol. 2007;30:67–71
  15. Khan PA, Cloutier M, Piedboeuf B. Tracheal occlusion: a review of obstructing fetal lungs to make them grow and mature. Am J Med Genet C Semin Med Genet. 2007;145:125–138
  16. Deprest J, Gratacos E, Nicolaides KH, FETO task group . Fetoscopic tracheal occlusion (FETO) for severe congenital diaphragmatic hernia: evolution of a technique and preliminary results. Ultrasound Obstet Gynecol. 2004;24:121–126
  17. Gucciardo L, Deprest J, Done´ E, Van Mieghem T, Van de Velde M, Gratacos E, et al. Prediction of outcome in isolated congenital diaphragmatic hernia and its consequences for fetal therapy. Best Pract Res Clin Obstet Gynaecol. 2008;22:123–138
  18. Harrison MR, Keller RL, Hawgood SB, Kitterman JA, Sandberg PL, Farmer DL, et al. A randomized trial of fetal endoscopic tracheal occlusion for severe congenital diaphragmatic hernia. N Engl J Med. 2003;349:1887–1888
  19. Jani JC, Nicolaides KH, Gratacos E, Valencia CM, Done´ E, Martinez JM, et al. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol. 2009;34:304–310
  20. Deprest J, Jani J, Van Schoubroeck D, Cannie M, Gallot D, Dymarkowski S, et al. Current consequences of prenatal diagnosis of congenital diaphragmatic hernia. J Pediatr Surg. 2006;41:1345–1346
  21. Deprest JA, Flemmer AW, Gratacos E, Nicolaides K. Antenatal prediction of lung volume and in-utero treatment by fetal endoscopic tracheal occlusion in severe isolated congenital diaphragmatic hernia. Semin Fetal Neonatal Med. 2009;14:8–13
  22. Peralta CFA, Jani J, Van Schoubroeck D, Nicolaides KH, Deprest JA. Fetal lung volume after endoscopic tracheal occlusion in the prediction of postnatal outcome. Am J Obstet Gynecol. 2008;198:60.e1–60.e5
  23. Deprest J, Jani J, Gratacos E, Nicolaides KH, the FETO task group , Nelson S. Deliberately delayed and shortened fetoscopic tracheal occlusion — a different strategy after prenatal diagnosis of life threatening congenital diaphragmatic hernias. J Pediatr Surg. 2006;41:1345–1346
  24. Mahony BS, Callen PW, Filly RA. Fetal urethral obstruction: ultrasound evaluation. Radiology. 1985;157:221–224
  25. Mann S, Johnson MP, Wilson RD. Fetal thoracic and bladder shunts. 2010;15(1):28–33
  26. Housley HT, Harrison MR. Fetal urinary tract abnormalities. Natural history, pathophysiology, and treatment. Urol Clin North Am. 1998;25:63–73
  27. Lissauer D, Morris RK, Kilby MD. Fetal lower urinary tract obstruction. Semin Fetal Neonatal Med. 2007;12:464–470
  28. Harrison MR, Nakayama DK, Noall RA, de Lorimier AA. Correction of congenital hydronephrosis in utero. II: decompression reverses the effects of obstruction on the fetal lung and urinary tract. J Pediatr Surg. 1982;17:965–974
  29. Clark TJ, Martin WL, Divakaran TG, Whittle MJ, Kilby MD, Khan KS. Prenatal bladder drainage in the management of fetal lower urinary tract obstruction: a systematic review and meta-analysis. Obstet Gynecol. 2003;102(2):367–382
  30. van Leeuwen K, Teitelbaum DH, Hirschl RB, Austin E, Adelman SH, Polley TZ, et al. Prenatal diagnosis of congenital cystic adenomatoid malformation and its postnatal presentation, surgical indications, and natural history. J Pediatr Surg. 1999;34:794–799
  31. Adzick NS, Harrison MR, Glick PL, Golbus MS, Anderson RL, Mahony BS, et al. Fetal cystic adenomatoid malformation: prenatal diagnosis and natural history. J Pediatr Surg. 1985;20:483–488
  32. Crombleholme TM, Coleman B, Hedrick HL, Liechty K, Howell L, Flake AW, et al. Cystic adenomatoid malformation volume ratio predicts outcome in prenatally diagnosed cystic adenomatoid malformation of the lung. J Pediatr Surg. 2002;37:331–338
  33. Clark SL, Vitale DJ, Minton SC, Stoddard RA, Sabey PL. Successful fetal therapy for cystic adenomatoid malformation associated with second trimester hydrops. Am J Obstet Gynecol. 1987;157:294–297
  34. Davenport M. Prognosis of antenatally diagnosed cystic adenomatoid malformation. J Pediatr Surg. 2002;37:1784
  35. Nicolaides K, Blott M, Greenough A. Chronic drainage of fetal pulmonary cyst. Lancet. 1987;(i):618
  36. Nicolaides KH, Azar GB. Thoraco-amniotic shunting. Fetal Diagn Ther. 1990;5:153–164
  37. Cavoretto P, Molina F, Poggi S, Davenport M, Nicolaides KH. Prenatal diagnosis and outcome of echogenic fetal lung lesions. Ultrasound Obstet Gynecol. 2008;32(6):769–783
  38. Adzick NS, Harrison MR, Flake AW, Jennings RW. Fetal surgery for cystic adenomatoid malformations of the lung. J Pediatr Surg. 1993;28:806–812
  39. Grethel EJ, Wagner A, Clifton M, Cortes R, Farmer D, Harrison M, et al. Fetal intervention for mass lesions and hydrops improves outcome: a 15-year experience. J Pediatr Surg. 2007;42:117–123
  40. Mitchell LE, Adzick NS, Melchionne J, Pasquariello PS, Sutton LN, Whitehead AS. Spina bifida. Lancet. 2004;364:1885–1895
  41. Hutchins GM, McGowan KD, Blakemore KJ. Spinal dysraphia: not a neural tube defect?. Am J Hum Genet. 1992;51:A319
  42. Hutchins GM, Meuli M, Meuli-Simmen C, Jordan MA, Heffez DS, Blakemore KJ. Acquired spinal cord injury in human fetuses with myelomeningocele. Pediatr Pathol Lab Med. 1996;16:701–712
  43. Adzick NS. Fetal myelomeningocele: natural history, pathophysiology and in utero intervention. Semin Fetal Neonatal Med. 2010;15(1):9–14
  44. Johnson MP, Sutton LN, Rintoul N, Crombleholme TM, Flake AW, Howell LJ, et al. Fetal myelomeningocele repair: short term clinical outcomes. Am J Obstet Gynecol. 2003;189:482–487
  45. Danzer E, Finkel RS, Rintoul NE, Bebbington MW, Schwartz ES, et al. Reversal of Hindbrain Herniation after Maternal-fetal Surgery for Myelomeningocele Subsequently Impacts on Brain Stem Function. Neuropediatrics. 2008;39(6):359–362
  46. Rintoul NE, Sutton LN, Hubbard AM, Cohen B, Melchionni J, Pasquariello PS, et al. A new look at myelomeningoceles: functional level, vertebral level, shunting, and the implications for fetal intervention. Pediatrics. 2002;109:409–413
  47. Danzer E, Gerdes M, Bebbington M, Sutton LN, Melchionni J, Adzick NS, et al. Lower extremity neuromotor function and short-term ambulatory potential following in utero myelomeningocele surgery. Fetal Diagn Ther. 2009;25:47–53
  48. Mychalishka GB, Bealor JF, Graf JL, Rosen MA, Adzick NS, Harrison MR. Operating on placental support: the exutero intrapartum treatment (EXIT) procedure. J Pediatr Surg. 1997;32:22–30
  49. Hedrick MH, Ferro MM, Filly RA, Flake AW, Harrison MR, ADzick NS. Congenital high airway obstruction syndrome (CHAOS): a potential for perinatal intervention. J Pediatr Surg. 1994;29:271–274
  50. Hedrick HL, Flake AW, Crombleholme TM, Howell LJ, Johnson MP, Wilson RD, et al. The ex utero intrapartum therapy for high-risk fetal lung lesions. J Pediatr Surg. 2005;40:1038–1044
  51. Kunisaki SM, Barnewolt CE, Estroff JA, Myers LB, Fauza DO, Wilkins-Haug LE, et al. Ex utero intrapartum treatment with extracorporeal membrane oxygenation for severe congenital diaphragmatic hernia. J Pediatr Surg. 2007;42:98–104

PII: S0378-3782(11)00352-5

doi:10.1016/j.earlhumdev.2011.11.006

Early Human Development
Volume 88, Issue 1 , Pages 15-19, January 2012

Article Tools

* Image Usage & Resolution