Update in Fetal Surgery - Texas Children's Hospital...Principles of fetal surgery ØCorrect and...

Update in Fetal Surgery

Jimmy Espinoza, MD, MSc, FACOGAssociate Professor

Baylor College of Medicine and Texas Children’s Pavilion for WomenHouston, Texas

Texas Children’s Pavilion for Women

Disclosures

Ø I have no conflict of interests with the contents of this lecture

Objectives

ØWhat is fetal surgery?

ØWhy do fetal surgery?

ØWho needs fetal surgery?

ØWho should do fetal surgery and how should we monitor what is being done?

ØSome 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 deathand/or reduce significant long-term morbidity

Principles of fetal surgery

ØCorrect and precise prenatal diagnosisØAbsence of associated anomalyØKnowledge of the natural historyØHigh perinatal morbidity/mortalityØAbsence of effective neonatal therapyØAnimal studies showing favorable resultsØPerformed in specialized centers - multi-D approachØNot compromise the reproductive futureØShould not increase maternal mortality

Harrison et al 2001

Level I evidence - RCTØTTTS (Laser ablation)

ØCDH (fetoscopic tracheal occlusion)

ØMMC (Open in-utero closure)

ØLUTO (vesico amniotic shunting)

Candidates for Fetal Surgery

• TTTS, TRAP Sequence• Thoracic: lung mass or

hydrothorax with hydrops • Teratoma: sacrococcygeal or

cervical teratoma with hydrops• Airway obstruction: Neck

masses or laryngeal atresia (CHAOS)

• EXIT procedure for predictable cardiorespiratory compromise

• Myelomeningocele• Amniotic band release

• Selective IUGR• Congenital diaphragmatic

hernia• Bladder outlet obstruction• Aortic or pulmonary outflow

obstruction• Gene/ stem cell therapy for

metabolic-cellular defects/ stem cell-enzyme defects

Established Benefit Probable Benefit

The hidden mortality

of monochorionic

twin pregnancies

Sebire et al 1997.

Dichorionic

Monochorionic

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)

AVRDRecipientTerritory

DonorTerritory

A-A

Twin-to-Twin Transfusion S. Laser vs. Amnioreduction

Laser Amnioreduction

Survival of one fetus 40% 26%

Survival of both fetuses 36% 26%

Survival of at least one fetus

76% 51%

GA at delivery 33.3 29.0

Alive w/o neurologic problems

52% 31%

Senat et al. N Eng J Med 2004; 351:136-44

60 - 70%

75 - 90%

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)

Bowel

Liver

Lung ........

Congenital Diaphragmatic Hernia

Failure of closure of pleuroperitoneal folds during Weeks 4 – 10 post fertilization1:2200 – 1:5000

Left sided 85% and right sided 10-15%Bilateral is rare

50% isolated and 50% have other anomalies15% aneuploidy, 10% syndromic

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, 1996Walsh DS, et al. Am J Obstet Gynecol 18:1067, 2000

STLiver

BowelLUNG

Lung-Head Ratio

HeartLHR 0.67

(Long axis x Short axis)/HC

Fetoscopic Tracheal Occlusion (FETO)

Deprest, et al. Ultrasound Obstet Gyn 24:121, 2004

TRACHEAL OCCLUSIONFetoscopic endotracheal

balloon

Fetal ET Occlusion (FETO)

LHR 2.5

20 days Post - FETO

LHR 0.67

SEVERE CONGENITAL DIAPHRAGMATIC HERNIA

1.- FETOSCOPY. intra-tracheal ballon(PLUG).

2.- Planned delivery or emergency (PPROM)E.X.I.T. strategy

3.- NEONATAL SURGERY (Defect Repair)

0 26 w 36 w

1 2 3

2nd FETOSCOPY. Balloon retrieval (UN-PLUG).

34 w

When to un-PLUG the lung?

TRACHEAL OCCLUSIONFetoscopic 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+/ 0.09o/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

ConclusionsFETO:

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 - RCTØTTTS (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

Exclusion Criteria:• Fetal anomaly• Severe kyphosis• Risk of PTB• Placental abruption• BMI≥ 35kg/m2

• Contraindication to surgery (ie previous classical hysterotomy)

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

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 ResultsPrimary Outcome: Death or hydrocephalus at 12 months

68% 40%

98% 82%

Prenatal-Surgery Group

Postnatal-Surgery Group

Met criteria for primary outcome

Actually had a shunt placed

Decreased the risk of hydrocephalus by 30-50%

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

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Case Report Fetoscopic Repair of MeningomyeloceleMichael 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

Fetoscopic NTD Repair

Fetoscopic NTD Repair

ENDO

(N = 18 )

OPEN

(N = 31)p

Maternal age (years) 29 � 5 28 � 6 0.55

Race or ethnic groups, no.

(%)

White 9/18 (50) 23/31 (74) 0.16Black 1/18 (6) 3/31 (10) 0.61Hispanic 8/18 (44) 5/31 (16) 0.07Other 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

ENDO (N = 18)

OPEN(N = 31 )

p

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

No Difference in Preterm PROM

ENDO

(N = 18)

OPEN

(N = 31 )p

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

Higher Proportion of Vaginal Deliveries

ENDO(N = 18)

OPEN (N = 31 )

P value

Placental abruption (%) 1/18 (6) 1/29 (3) 0.73Membrane separation (%) 6/18 (33) 2/29 (7) 0.05

Oligohydramnios (%) 3/18 (19) 7/29 (25) 0.81Pulmonary edema (%) 2/18 (11) 1/29 (4) 0.67Chorioamnionitis (%) 0/18 (0) 2/29 (7) 0.69 Well healed scar (%) 10/ (100) 23/29 (79) 0.29Partial dehiscence (%) 0/10 (0) 5/29 (17) 0.39Any 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) 0.45Maternal LOS 5 [3-8] 6 [2-23] 0.81

No Differences in Obstetrical Complications

ENDO(N = 18 )

OPEN(N = 31 ) P value

Birth weight

Mean (g) 2444 � 694 2360 � 853 0.73

<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)* 0.60NICU ventilation (%) 1/17 (6) 4/29 (14)* 0.73Early 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) 0.43RDS (%) 2/17 (12) 9/29 (31) 0.26

Similar Perinatal Outcomes

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

Lancet 2013; 382: 1496–506

PLUTO trial

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