Update in Fetal Surgery
Jimmy Espinoza, MD, MSc, FACOG Associate Professor Baylor College of Medicine and Texas Children’s Pavilion for Women Houston, Texas Texas Children’s Pavilion for Women Disclosures
Ø I have no conflict of interests with the contents of this lecture Objectives
Ø What is fetal surgery?
Ø Why do fetal surgery?
Ø Who needs fetal surgery?
Ø Who should do fetal surgery and how should we monitor what is being done?
Ø Some examples of fetal surgery What is Fetal Surgery? • Application of established surgical techniques to the unborn baby – During gestation – At end of gestation Why do Fetal Surgery? • To improve outcome in cases of congenital malformation.
• To prevent fetal death
• To prevent postnatal death and/or reduce significant long-term morbidity Principles of fetal surgery
Ø Correct and precise prenatal diagnosis Ø Absence of associated anomaly Ø Knowledge of the natural history Ø High perinatal morbidity/mortality Ø Absence of effective neonatal therapy Ø Animal studies showing favorable results Ø Performed in specialized centers - multi-D approach Ø Not compromise the reproductive future Ø Should not increase maternal mortality
Harrison et al 2001 Level I evidence - RCT ØTTTS (Laser ablation)
ØCDH (fetoscopic tracheal occlusion)
ØMMC (Open in-utero closure)
ØLUTO (vesico amniotic shunting) Candidates for Fetal Surgery
Established Benefit Probable Benefit
• TTTS, TRAP Sequence • Selective IUGR • Thoracic: lung mass or • Congenital diaphragmatic hydrothorax with hydrops hernia • Teratoma: sacrococcygeal or • Bladder outlet obstruction cervical teratoma with hydrops • Aortic or pulmonary outflow • Airway obstruction: Neck obstruction masses or laryngeal atresia • Gene/ stem cell therapy for (CHAOS) metabolic-cellular defects/ stem • EXIT procedure for predictable cell-enzyme defects cardiorespiratory compromise • Myelomeningocele • Amniotic band release
Monochorionic
The hidden mortality of monochorionic Dichorionic twin pregnancies
Sebire et al 1997.
Level I evidence - RCT
ØTTTS (Laser ablation)
ØCDH (fetoscopic tracheal occlusion)
ØMMC (Open in-utero closure)
ØLUTO (vesico amniotic shunting) Twin –Twin Transfusion Syndrome (TTTS) Twin –Twin Transfusion Syndrome (TTTS) Recipient Donor AVRD Territory Territory A-A Twin-to-Twin Transfusion S. Laser vs. Amnioreduction Laser Amnioreduction Survival of one fetus 40% 26%
Survival of both fetuses 36% 60 - 70% 26%
Survival of at least 76% 75 - 90% 51% one fetus GA at delivery 33.3 29.0
Alive w/o neurologic 52% 31% problems Senat et al. N Eng J Med 2004; 351:136-44 Laser Photocoagulation Laser Photocoagulation of Placental Anastomoses
“Solomonization” - connect the dots and decrease the chance of persistent anastamoses Selective Solomon Technique
Lancet. 2014; 383: 2144-51 Lancet. 2014; 383: 2144-51 Am J Obstet Gynecol. 2014; 211: 285
Am J Obstet Gynecol. 2014; 211: 285 Anterior Placenta-Challenges
ØUse of curve scopes and lateral access if there is a “window” to place the fetoscope ØIf no “window”: laparoscopic-assisted procedure
Laparoscopic-assisted laser surgery for TTTS 33
Preterm PROM Twin Anemia Polycythemia Sequence (TAPS)
Level I evidence - RCT
ØTTTS (Laser ablation)
ØCDH (fetoscopic tracheal occlusion)
ØMMC (Open in-utero closure)
ØLUTO (vesico amniotic shunting) Congenital Diaphragmatic Hernia Failure of closure of pleuroperitoneal folds during Weeks 4 – 10 post fertilization 1:2200 – 1:5000
Left sided 85% and right sided 10-15% Bilateral is rare Bowel Lung ...... 50% isolated and 50% have other anomalies 15% aneuploidy, 10% syndromic Liver Survival According to the Severity of CDH
Ruano et al 2012 Congenital Diaphragmatic Hernia
• 3 major issues: • lung hypoplasia • pulmonary hypertension • cardiac compression Normal
Hypoplasia CDH: Fetal MRI CDH: 2 Predictors of Outcome
• Lung Volume • LHR: Lung-to-head ratio • >1.2 = 79% survival (30/38) • 0.9-1.2 = 59% survival (13/24) • < 0.9 = 4% survival (1/24) • MRI volumetric assessment
• Liver herniation: • No: 79% survival • Yes: 41% survival
Metkus AP, et al. J Pediatr Surg 31:148, 1996 Walsh DS, et al. Am J Obstet Gynecol 18:1067, 2000 Lung-Head Ratio
(Long axis x Short axis)/HC
LHR 0.67 Heart
Liver ST LUNG Bowel Fetoscopic Tracheal Occlusion (FETO)
Deprest, et al. Ultrasound Obstet Gyn 24:121, 2004 TRACHEAL OCCLUSION Fetoscopic endotracheal balloon Fetal ET Occlusion (FETO) SEVERE CONGENITAL DIAPHRAGMATIC HERNIA 20 days Post - FETO
LHR 0.67 LHR 2.5 When to un-PLUG the lung?
1.- FETOSCOPY. intra-tracheal ballon(PLUG).
2nd FETOSCOPY. Balloon retrieval (UN-PLUG).
2.- Planned delivery or emergency (PPROM) E.X.I.T. strategy
3.- NEONATAL SURGERY (Defect Repair)
0 26 w 34 w 36 w
1 2 3
TRACHEAL OCCLUSION Fetoscopic Endotracheal Balloon Experience at TCH/BCM
• To evaluate the feasibility and initial outcomes of a comprehensive FETO program
• To investigate whether there is an independent additive benefit to FETO by having immediate ECMO availability and capacity Methods and Materials • Prospective cohort: January 2012 – June 2015 • IRB and FDA approved protocol • FETO offered between 22-0/7 - 29-6/7 weeks: – severe left-sided CDH (LHR < 1.0) and liver herniation – no chromosomal/structural anomalies/latex allergy – ability to relocate to live within 30 minutes of hospital • Obstetrical and postnatal outcomes: – Feasibility and safety of FETO – Compared with similar cases at TCH without FETO Subject Cohort • Evaluation with US and MRI at 24 +/- 3 wks – US: LHR = 0.82+/ 0.09 o/e LHR = 0.26+/- 0.04 – MRI: o/e TLV = 0.24 +/- 0.06 % liver herniation = 0.36 +/- 0.09
• FETO attempted in 11 patients at 28 +/- 1 wks – Successful in 10/11 (91%) Demonstrable Surgical Feasibility • FETO balloon retrieval: – Retrieved in 6/10 at 34 +/- 1 wks – Placement/removal interval = 5.9 +/- 1.5 wks
• Removal of tracheal balloon by: – Fetoscopy: balloon removal (n = 6), no balloon (n = 1) – Ultrasound-guided puncture of the balloon (n = 2) – EXIT procedure with balloon removal (n = 1)
• No abruption, chorioamnionitis or fetal demise PPROM Occurrence
• Spontaneous PPROM (< 35 weeks) in 3/11 (27%) – 31.7 weeks, 31.3 weeks, and 34.9 weeks
• Spontaneous PROM did not occur in any of the 7 patients who had 2 fetoscopy procedures: – 3 of these 7 patients (43%) had a vaginal delivery Significantly Improved in utero Measures with FETO Largely Late Preterm & Stable Delivery
• Interval from balloon removal/birth: 7 days [0-35] • GA at birth (FETO, n=10) was 35.5 [32.6 - 40.0] wks • 4/11 (36%) had vaginal delivery, and 7/11 (64%) CS • No acidosis at delivery: – Median Apgar score at 5 minutes was 7 [4-9] – Median UA pH was 7.30 [7.26 to 7.35] • Postnatal surgical repair on day 2-4 of life – All had very large defects and all required a patch at repair FETO Survival • Overall survival rate: – To 6 months = 80% (8/10) – To 1 year = 67% (6/9) – To date = 70% (7/10)
• Survival to 6 months for our historical cohort of non-FETO patients = 47% Improved Outcomes with FETO
• 1/10 died from pulmonary hypertension after 4 months (pulmonary capillary hemangiomatosis)
• 3/10 required ECMO (30%) - 1/3 (33%) survived –70% of our historical cohort of non-FETO patients received ECMO
• 2/7 surviving FETO patients (29%) continue to require supplemental oxygen Conclusions FETO:
1.Feasible without adding significant complications
2.Significant increases in fetal lung volume
3.Improved postnatal outcomes: - Increased 6 month survival (47% to 80%) - Decreased need for ECMO (70% to 30%) Level I evidence - RCT ØTTTS (Laser ablation)
ØCDH (fetoscopic tracheal occlusion)
ØMMC (Open in-utero closure)
ØLUTO (vesico amniotic shunting) Chiari II Malformation Incidence
• 3.4 per 10,000 live births in US • Folic acid supplementation • Improved prenatal screening
• 1,400 to 1,500 infants born with MMC per year in the US MMC: Fetal Surgery Two-Hit Hypothesis
• 2 Hit Hypothesis: The final neurologic deficit results from • A combination of failure of neural tube formation • Injury from prolonged exposure of the neural elements to the intrauterine environment Methods
• Randomized control trial • Recruitment done at 3 MFM surgery centers • All other centers in USA agreed to not perform the surgery for the duration of the trial • Prenatal repair: • Standardized technique and perioperative management • Participants stayed near by until CD at 37 weeks • Postnatal repair • Delivered by CD at 37 weeks • Postnatal repair done by the same surgical team Inclusion Criteria: • singleton pregnancy • MMC with upper boundary between T1 and S1 • Evidence of hindbrain herniation • GA 19-25.9 weeks at randomization • Normal karyotype • US residency • At least 18 years old
Exclusion Criteria: • Fetal anomaly • Severe kyphosis • Risk of PTB • Placental abruption • BMI≥ 35kg/m2 • Contraindication to surgery (ie previous classical hysterotomy) Methods
• All children were evaluated at 12 and 30 months with physical and neurological exams
• Primary outcomes: • 12 months: • composite of fetal or neonatal death • Need for a cerebrospinal fluid shunt • 30 months: • composite score of the Mental Development Index of the Bayley Scales of Infant Development II and the child’s motor function (adjusted for lesion level) Methods
• Secondary outcomes: • Maternal/fetal/neonatal • Pregnancy complications • Surgical complications • Neonatal morbidity and mortality • Infant • Radiographic appearance of components of the Chiari II malformation • Time to first shunt placement • Locomotion • Psychomotor Development Index of the Bayley Scales • Scores on the Peabody Developmental Motor Scales • Degree of functional impairment • Degree of disability (measured by Functional Independence Measure for Children)
MOMs Trial Results Primary Outcome: Death or hydrocephalus at 12 months Met criteria for Decreased the Actually had risk of primary a shunt hydrocephalus by outcome placed 30-50% Prenatal-Surgery Group 68% 40%
Postnatal-Surgery Group 98% 82%
2/2003-12/2010 Maternal and pregnancy complications were more common with prenatal surgery
1/3 of subjects had a dehiscence or very thin hysterotomy site at time of delivery Conclusions
• Despite having more severe lesions and a nearly 13% incidence of preterm delivery before 30 weeks, the prenatal surgery group had significantly better outcomes than the postnatal surgery group
• Benefits must be balanced against the risks of prematurity and maternal/ fetal morbidity Case Report Fetoscopic Repair of Meningomyelocele Michael A. Belfort, MD, PhD, William E. Whitehead, MD, Alireza A. Shamshirsaz, MD, Rodrigo Ruano, MD, PhD, Darrell L. Cass, MD, and Oluyinka O. Olutoya, MD
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Fetoscopic NTD Repair Fetoscopic NTD Repair ENDO OPEN p (N = 18 ) (N = 31)
Maternal age (years) 29 5 28 6 0.55
White 9/18 (50) 23/31 (74) 0.16 Race or ethnic Black 1/18 (6) 3/31 (10) 0.61 groups, no. (%) Hispanic 8/18 (44) 5/31 (16) 0.07 Other 0/18 (0) 0/31 (0) - Nulliparity (%) 4/18 (31) 13/31 (42) 0.28 BMI at screening 27 4 28 5 0.47 Anterior placenta (%) 8/18 (44) 10/31 (32) 0.59 EGA at surgery (weeks) 24.7 2.0 24.4 1.3 0.53
Prior uterine surgery (%) 4/18 (22) 3/31 (10) 0.43
EFW < 10 % 1/18 (6) 4/31 (13) 0.74 Cervix (mm) 38 6.0 39 7.0 0.61 No Difference in Preterm PROM
ENDO OPEN p (N = 18) (N = 31 )
GA at PROM (weeks) 33.5 2.0 29.7 4.4 0.10
PPROM (%) 5/17 (29) 9/29 (31) 0.91
PPROM < 30 weeks (%) 0/17 (0) 5/29 (17) 0.19
PPROM 30-34 6/7 wks (%) 4/17 (24) 2/29 (7) 0.24
PPROM ≥ 35 weeks (%) 1/17 (6) 2/29 (7) 0.89 Higher Proportion of Vaginal Deliveries ENDO OPEN p (N = 18) (N = 31 ) GA at delivery (weeks) 35.4 3.4 34.1 4.0 0.27
Delivery < 30 weeks (%) 1/17 (6) 6/29 (21) 0.36
Delivery ≥ 37 weeks (%) 8/17 (47) 9/29 (31) 0.44
Vaginal Delivery (%) 7/17 (41) 0/29 (0) <0.01
Repair to delivery (wks) 10.7 3.6 9.9 4.2 0.52
PROM-delivery (days) 1.8 1.7 5.4 4.5 0.11 No Differences in Obstetrical Complications
ENDO OPEN P (N = 18) (N = 31 ) value
Placental abruption (%) 1/18 (6) 1/29 (3) 0.73 Membrane separation (%) 6/18 (33) 2/29 (7) 0.05 Oligohydramnios (%) 3/18 (19) 7/29 (25) 0.81 Pulmonary edema (%) 2/18 (11) 1/29 (4) 0.67 Chorioamnionitis (%) 0/18 (0) 2/29 (7) 0.69 Well healed scar (%) 10/ (100) 23/29 (79) 0.29 Partial dehiscence (%) 0/10 (0) 5/29 (17) 0.39 Any adhesions (%) 3/10 (30) 18/29 (62) 0.17
Adhesions to omentum (%) 3/10 (30) 12/29 (41) 0.79
Blood transfusion (%) 0/18 (0) 1/31 (3) 0.45 Maternal LOS 5 [3-8] 6 [2-23] 0.81 Similar Perinatal Outcomes ENDO OPEN P value (N = 18 ) (N = 31 )
Mean (g) 2444 694 2360 853 0.73 Birth weight <10% (%) 1/17 (6) 1/29 (4)* 0.7
Fetal demise (%) 0/17 (0) 0/29 (0)* - APGAR at 5 min < 7 (%) 1/17 (6) 3/29 (10)* 0.60 NICU ventilation (%) 1/17 (6) 4/29 (14)* 0.73 Early sepsis, (%) 0/17 (0) 4/29 (14)* 0.29
Retinopathy of prematurity (%) 0/17 (0) 3/29 (11)* 0.45
NICU LOS (days) 9.5 [2-38] 9.5 [2-76] - Perinatal death (%) 0/18 (0) 3/29 (10) 0.43 RDS (%) 2/17 (12) 9/29 (31) 0.26 Level I evidence - RCT
ØTTTS (Laser ablation)
ØCDH (fetoscopic tracheal occlusion)
ØMMC (Open in-utero closure)
ØLUTO (vesico amniotic shunting) Fetal Lower Urinary Tract Obstruction (LUTO)-Bladder Shunts Lancet 2013; 382: 1496–506 PLUTO trial
Lancet 2013; 382: 1496–506 PLUTO trial
Lancet 2013; 382: 1496–506 Complications of vesico-amniotic shunting
Lancet 2013; 382: 1496–506 Atrial Stent Placement Atrial Stent Placement Atrial Stent Placement Fetal Procedures offered at TCH
• Laser ablation for TTTS and SIUGR • Bipolar coagulation for Acardiac Twin • FETO for congenital diaphragmatic hernia • Intracardiac balloon valvuloplasty/shunt placement • Amniotic band release • Open fetal neural tube repair/Fetoscopic closure • Open fetal chest mass resection • EXIT for airway and SCT Thanks for your Attention