Fetal Interventions Performed at Tertiary Care Centers

 

Editorial advice and videos courtesy:  Rodrigo Ruano, M.D., Ph.D., Senior Associate Consultant, Chair, Division of Maternal-Fetal Medicine, Professor of Obstetrics and Gynecology and Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota.

Acknowledgements:  Nasrin Benion, RDMS, Supervisor, Maternal Fetal Center Imaging. Texas Children’s Pavilion for Women, Houston, Texas.

 

Fetal Interventions for Congenital Diaphragmatic Hernia (CDH), Lower Urinary Tract Obstruction (LUTO), and Twin-Twin Transfusion Syndrome (TTTS)

In this chapter, a summary is presented for the treatment of severe congenital diaphragmatic hernia (CDH) by the introduction of fetal endoscopic tracheal occlusion (FETO); the treatment of severe lower urinary tract obstruction (LUTO) by the introduction of vesico-amniotic shunt; and the treatment of twin-twin transfusion syndrome (TTTS) with photocoagulation of placental vessels (Solomon technique).

These fetal interventions are performed in certain specialized tertiary care centers.  Each procedure represents an advance in the care of the prenatal patient, and in each, preliminary data suggest increased survival and quality survival.  These approaches represent innovations in maternal-fetal therapy.  For guidelines and suggestions, see a recent article by Luks, et.al. [1] In addition, randomized controlled trials are recommended or ongoing for these procedures.  A review of closed and open surgical therapies is presented at the end of this chapter.

 

Congenital Diaphragmatic Hernia (CDH)

Congenital Diaphragmatic Hernia (CDH)

Congenital diaphragmatic hernia (CDH) is a defect in the diaphragm permitting herniation of abdominal viscera into the fetal thorax.  High mortality and morbidity occur in severe cases due to pulmonary hypoplasia and pulmonary hypertension.  Fetal endoscopic tracheal occlusion (FETO) is a technique whereby an inflatable balloon is passed within the fetal trachea to assist in the management of severe CDH since fetal tracheal occlusion accelerates lung growth in both animal and human models and promotes contralateral pulmonary vascularity. [2] FETO is feasible and safe in specialized tertiary care units, and patients undergoing FETO are more likely to survive than those who do not since a subset of fetuses with severe CDH are likely to die without intervention. [3] In a number of studies, the most frequent procedural complication is premature rupture of the membranes (PROM).

Fetal Interventions Lung-to-Head Ratio

*Note:  For Lung-to-head ratio, see “Imaging Considerations” in the  Congenital Diaphragmatic Hernia Chapter.

Above.  In 2004, preliminary results were published, and a lung-to-head ratio of < 1.0 and the presence of fetal liver within the chest and no other malformations were established as the initial inclusion criteria. [4] Successful placement of the endotracheal balloon was possible in all initial cases.  PROM occurred in 52.4% of patients and survival was 30% in the first group of 10 fetuses and 63.6% in the second group of 11 fetuses.

Fetal membrane rupture

Above.  In a follow-up study, membrane rupture occurred in 35% of patients at < 32 weeks and a decrease in the occurrence of PROM was noted over time.  Survival to discharge was 50% and long term survival quality was encouraging. [5] Retrospective analysis found the position of the liver and LHR correlates to survival.  The combination of liver up in the chest and an LHR < 1.0 resulted in a survival rate of only 9%, and when the LHR was less than 0.6, there were no survivors irrespective of fetal liver position.

Fetal CDH fetuses with an extremely severe form

Ruano et al demonstrated that FETO is possible using a smaller 1 mm fetoscope. [6] Ruano’s group performed a randomized controlled trial of FETO with similar criteria (lung-to-head ratio < 1.0) with tracheal balloon placement at 26 to 30 weeks and demonstrated increased survival in the FETO group (50%) versus (4.8%) in the non-intervention group. [7] Improved survival was further observed when FETO was performed at 22 to 24 weeks in CDH fetuses with an extremely severe form (LHR < 0.7), liver herniation into the thoracic cavity, and no other detectable anomalies. [8]

These authors recommended balloon removal after 6 weeks in early FETO patients since maximal benefit and minimal risk may be achieved with that interval.  Finally 4-D ultrasound may improve guidance in FETO procedures. [9] With respect to FETO, other randomized clinical trials in Europe and North America are ongoing, but it is now acknowledged that the gestational age at birth, the pre-existing lung size, the ability to remove the balloon prior to birth, and the lung response are predictive of outcome. [10]

congenital diaphragmatic hernia and fetal MRI

Above.  Overall, survival for patients undergoing FETO has improved from 15% to approximately 50%. [11],[12] Survival rates increased for right-sided diaphragmatic hernias from 0% to 35.3%. [13]

Complimentary support for the effects of FETO is suggested by intrapulmonary arterial Doppler, which predicts increased survival among treated patients [14], and MRI demonstration of increased lung volume in FETO patients compared to controls. [15]

Changes in the trachea such as tracheal widening are potential complications, which will require long-term follow-up. [16],[17],[18]

Ongoing clinical trials can be followed at:  ClinicalTrials.gov Inentifier: NCT00881660.

Management Options for CDH

fetal intervention Management Options

Above.  Summary of Management Options.

For more details, see “Management Options” in the Congenital Diaphragmatic Hernia Chapter.

 

Above.  This fetal video demonstrates placement of a small fetoscope within the trachea and placement of a detachable balloon to complete the fetal endoscopic tracheal occlusion.

 

Lower Urinary Tract Obstruction (LUTO)

final fetal lower urinary tract obstruction (LUTO)

Above.  Lower urinary tract obstruction (LUTO) is a potentially lethal fetal abnormality, which can result in ureteral dilation, hydronephrosis, anhydramnios, and neonatal death due to pulmonary hypoplasia or renal failure.  Prognosis is difficult to define among fetuses with lower urinary tract obstruction, but the best predictors of poor outcome are oligohydramnios and the presence of renal cortical cysts. [19] However, until recently, the prognosis for the severe variety of this disorder was dismal and few intervention techniques were successful.

posterior urethral valves (PUV)

Major etiologies for LUTO include posterior urethral valves (PUV) [63%], urethral atresia (absence of the urethra) [9.9%], urethral stenosis [7.0%], Prune Belly Syndrome [2.5%], unspecified [17.6%].  77.8% of LUTO cases were isolated. [20]

final fetal 2-D ultrasound

The “keyhole” sign, which is considered recognizable on 2-D ultrasound, is not specific for PUV but is commonly seen in a number of other non-PUV conditions such as vesicoureteral reflux, bilateral junction stenosis, and others. [21] However, the etiology cannot always be determined by ultrasound or MRI, while fetal cystoscopy is sometimes necessary to define the obstructive lesion. [22]

fetal cystoscopy

Above.  Options for fetal surgery include vesico-amniotic shunting and fetal cystoscopy.  Literature surveys indicate that survival and normal renal function occur in 40% to 50% after vesico-amniotic shunting and 65% to 75% after fetal cystoscopy. [23] Vesico-amniotic shunt placement using a double basket catheter is successful in a limited number of patients. [24] Fetal cystoscopy allows views of the upper urethra and may be successful, allowing guide wire passage or hydro-oblation. [25] In a study comparing fetal cystoscopy, vesicoamniotic shunting, and no intervention, cystoscopy and vesicoamniotic shunting improve the 6-month survival rate in cases of severe LUTO; and in fetuses with posterior urethral valves, fetal cystoscopy may prevent impairment of renal function.[26]

Further trials are ongoing.  See:  ClinicalTrials.gov Identifier: NCT02315521.

 

Above.  This video demonstrates a bladder to amniotic cavity shunt by the placement of a stent within the fetal bladder to decompress a lower urinary tract obstruction.

Long-term Outcome

antenatal diagnosis and early neonatal decompression of the urinary tract

The neonatal mortality for PUV has improved due to antenatal diagnosis and early neonatal decompression of the urinary tract. [27] Renal functional impairment correlates with poor bladder compliance, detrusor over-activity, vesicoureteral reflux, and renal dysplasia. [28]

Placental laser photocoagulation for twin-twin transfusion syndrome

 

Twin-Twin Transfusion Syndrome (TTTS)

Twin to twin transfusion syndrome is covered in detail elsewhere with information, imaging considerations, images, and video.  The purpose of this update is to discuss photocoagulation of the placental vessels using the Solomon technique for the treatment of TTTS.

fetal laser coagulation of connecting vessels in TTTS

Survival rates are greater with laser coagulation of connecting vessels in TTTS compared with other treatment options such as septostomy and amnioreduction.  Coagulation of the entire vascular equator (Solomon technique) may confer certain benefits compared to standard laser therapy, and may reduce postoperative fetal morbidity in severe twin-to-twin transfusion syndrome. [29], [30]

 

Above.  This video demonstrates fetoscopic laser photocoagulation of placental vessels in twin-twin transfusion syndrome utilizing the Solomon technique.

 

Review of Closed and Open Surgical Therapies

A review by Wenstrom and Carr updates the present status of fetal surgery.  An historical perspective is given and closed and open surgical therapies are discussed.  For details, please see their original article. [31] The following is a summary of significant findings.

“Closed Surgical Therapies”

Intrauterine fetal transfusion

Intravascular fetal transfusion through the umbilical vein is presently the standard of care for fetal anemia and following Mari’s work [32] suggesting that the peak systolic velocity of the middle cerebral is highly sensitive in determining fetal hemoglobin levels.  Amniocentesis is not employed to detect fetal anemia.

Lower urinary tract obstruction

Prognosis is difficult to define among fetuses with lower urinary tract obstruction, but the best predictors of poor outcome are oligohydramnios and the presence of renal cortical cysts. [33] Fetal urinary analytes are not predictors of poor outcome with the exception of elevated urinary calcium and elevated sodium. [34] While many issues require clarification, the efficacy for intervention in lower urinary tract obstruction is not clearly established.

Placental laser photocoagulation for twin-twin transfusion syndrome (TTTS)

Survival rates are greater with laser coagulation of connecting vessels in TTTS (55% to 69% with neurologic abnormalities in 5% to 11% of survivors) compared with other treatment options such as septostomy and amnioreduction.  Coagulation of the entire vascular equator may confer certain benefits compared to standard laser therapy. [35]

Thoraco-Amniotic shunting

Pleural effusions are a complex group of abnormalities which may be isolated or primary (no association with other fetal conditions) or secondary (associated with fetal anomalies or conditions).  In addition, effusions can be due to lymph fluid or fetal hydrops.  Outcomes are unpredictable and some effusions undergo spontaneous regression. While there is no strong consensus for intervention, the following has been proposed [36]: Interventions may be warranted in the presence of fetal hydrops with pleural effusion as the etiology, isolated pleural effusion occupying over 50% of the thoracic cavity with mediastinal shift, rapid increase in pleural effusion associated with polyhydramnios, and isolated pleural effusion without anomaly.

“Open Surgical Therapies”

Myelomeningocele

A recent article about the treatment of Myelomenigocele by Adzick, et al. compared outcomes of fetuses undergoing prenatal surgery to a group undergoing postnatal repair.  The study results are numerous.  Please see the original report for details. [37] In summary, those undergoing prenatal surgery were less likely to experience fetal or neonatal death, and less likely to meet criteria to have a shunt placed or to have hindbrain herniation.  In addition, they were more likely to have motor function, to walk, and to have better neonatal psychomotor scores.  Tests of functional independence and cognitive scores were similar, while pregnancy complications were greater in the prenatal surgical group.  More children in the prenatal group required surgery for tethered cord (8% versus 1%).

Congenital diaphragmatic hernia (CDH)

Prenatal surgical intervention in CDH is typically offered to the most severe cases with the worst prognosis or life expectancy.  The results for prenatal tracheal occlusion (intended to accelerate fetal lung growth) are mixed and proof of efficacy is difficult to determine.  Poor prognostic fetuses (lung-to-head ratio of < 25% for left CDH and < 45% for right CDH) could potentially benefit from fetoscopic endotracheal occlusion. [38]

Fetal tumors

Fetal tumors are rare, but the tumors most likely to require consideration for antenatal surgery are sacrococcygeal teratomas (SCT) and thoracic masses such as cystic adenomatoid malformation and pulmonary sequestration.  In each, the presence of fetal hydrops is a prime determinant of outcome.  SCT can be associated with arterial-venous malformations leading to cardiomegaly and high output failure, and a variety of other associated malformations.  Numerous therapies have been reported for SCT (open fetal surgery, radiofrequency ablation, laser vessel ablation, alcohol sclerosis, and cyst drainage).  Since prognosis is poor in the presence of fetal hydrops, delivery is a viable treatment option.

 

References


 

    1
  1. Abstract: PMID: 25730229

    2
  2. Abstract: PMID: 22183216

    3
  3. Abstract: PMID: 21238635

    4
  4. Abstract: PMID: 15287047

    5
  5. Abstract: PMID: 16050527

    6
  6. Abstract: PMID: 20389048

    7
  7. Abstract: PMID: 22170862

    8
  8. Abstract: PMID: 23349059

    9
  9. Abstract: PMID: 17182715

    10
  10. Abstract: PMID: 21907109

    11
  11. Deprest J, Devlieger R, Rayyan M, Vanhole C, El handouni N, Claus F, Dymarkowski S, et al.  Treatment of congenital diaphragmatic hernia.  Fetal MRI (Medical Radiology).  2011;343-360.
     

  12. 12
  13. Abstract: PMID: 18634116

    13
  14. Abstract: PMID: 19658113

    14
  15. Abstract: PMID: 20178111

    15
  16. Abstract: PMID: 19508989

    16
  17. Abstract: PMID: 19894042

    17
  18. Abstract: PMID: 20713614

    18
  19. Abstract: PMID: 20385271

    19
  20. Abstract: PMID: 19438489

    20
  21. Abstract: PMID: 22925164

    21
  22. Abstract: PMID: 19642115

    22
  23. Abstract: PMID: 24375864

    23
  24. Abstract: PMID: 21413041

    24
  25. Abstract: PMID: 16817090

    25
  26. Abstract: PMID: 14691987

    26
  27. Abstract: PMID: 25157756

    27
  28. Abstract: PMID: 19838598

    28
  29. Abstract: PMID: 15126863

    29
  30. Abstract: PMID: 24613024

    30
  31. Abstract: PMID: 23616360

    31
  32. Abstract: PMID: 25198256

    32
  33. Abstract: PMID: 10620643

    33
  34. Abstract: PMID: 19438489

    34
  35. Abstract: PMID: 3900327

    35
  36. Abstract: PMID: 24613024

    36
  37. Abstract: PMID: 20069656

    37
  38. Abstract: PMID: 21306277

    38
  39. Abstract: PMID: 23444265