What’s on the Horizon for Fetal Surgery? Interventional Surgery...What’s on the Horizon for Fetal Surgery? Kenneth J. Moise, Jr., M.D. ... The spina bifida could not be associated
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What’s on the Horizon for Fetal Surgery? Kenneth J. Moise, Jr., M.D. Professor of OB-GYN Professor of Pediatric Surgery UT Health – University of Texas At Houston Texas Fetal Center Children’s Memorial Hermann Hospital
Professor of Pediatric Surgery UT Health – University of Texas At Houston
Texas Fetal Center Children’s Memorial Hermann Hospital
Definition of Maternal-Fetal
Surgery
• Operating on two patients simultaneously where both incur risks • Benefits to mother probably not medically definable • Opportunity to correct a surgically-treatable lesion or diminish its sequelae
Historical Perspectives • 1982: First open fetal surgery for obstructive uropathy
• 1981-1994: All surgeries performed for fetal defects considered lethal Diaphragmatic hernia Cystic adenomatoid malformation Bladder outlet obstruction Sacrococcygeal teratoma
• Overview • Myelomeningocoele • Twin-twin transfusion • Discordant anomalies • TRAP sequence • Diaphragmatic hernia • Where are we now? • Where are we going?
Myelomeingocoele
Hindbrain Herniation
Presenter
Presentation Notes
This is picture is taken by a special imaging equipment called magnetic resonance imaging or MRI. This is an image of a normal brain in a newborn infant. The red line indicates the top of the spinal canal. Note the there is no evidence of brain tissue located below this line. The red arrow is pointing to the ventricle of the brain that contains a normal amount of cerebrospinal fluid. Since there is no Chiari II malformation here, cerebrospinal fluid can flow freely down the spinal column. This MRI image is from a newborn with a Chiari II malformation. Note that some of the back of the brain protrudes downward below the red line. The red arrow marks the brainstem and the black arrow marks the cerebellum. The red star is located in the cerebral ventricle which is markedly dilated. This is called hydrocephalus. The Chiari II malformation shown here is associated with compression of certain parts of the brain that control swallowing and breathing. For this reason approximately, 10% of children with spina bifida and the Chiari II malformation may die at some time in their lives due to complications of aspiration or decreased breathing.
Mouse model
Stiefel et al. J Neurosurg 2007;106:213-21
Spina bifida Normal
Normal sheep spine
Spina bifida @ 75 days Followed by closure @
100 days Spina bifida @ 75
days w/o closure
Meuli et al. J Pediatr Surg 1996;31:397-402
Historical Perspectives
•1994: Bruner attempts laparoscopic repair of NTD (4 cases performed before stopping) •1998: Tulipan reports open repair at 28-30 weeks gestation in 4 fetuses
– All with absent hindbrain herniation at birth – 2 required ventricular shunts
•244 open cases to date (170 at VUMC, 52 at CHOP, 12 at UCSF, 10 at UNC)
Am J Obstet Gynecol 1997;176:256-7 Pediatr Neurosurg 1998;29:274-8
Feb 2003 – Dec 2010 $22.5 million
Presenter
Presentation Notes
In February of 2003, the National Institutes of Health began the Management of Myelomeningocele Study (also known as the MOMS trial). 200 patients were to be randomized – half to fetal repair and half to repair after birth. Three centers – Vanderbilt University in Nashville, Tennessee; Children’s Hospital of Philadelphia in Pennsylvania and the University of San Francisco in California provided the surgery for these patients. The trial took almost 8 years to complete and cost taxpayers over 20 million dollars.
• Singleton pregnancy
MOMS Inclusion Criteria (maternal)
• Gestational age at randomization of 190/7 to 256/7 weeks gestation
• Maternal age > 18 years
• No previous uterine incision in the active uterine segment
• No risk factors for preterm birth (short cervix, history of previous preterm delivery)
• Body mass index < 35
Presenter
Presentation Notes
For patients to be eligible for the MOMS trial, they had to meet certain maternal and fetal requirements. The pregnancy had to be associated with a single fetus between 19 and 25 completed weeks of gestation. Pregnancies with twins were excluded since the normal twin would be put at higher risk for premature delivery by the surgery. The gestational age limits were chosen based on the previous experience at the surgical centers from cases of fetal spina bifida repair performed prior to the MOMS trial. The mother had to be more than 18 years of age. Her body mass index (or BMI) had to be less than 35. This is a calculated number based on weight and height. A BMI > 35 is considered to indicate significant obesity and would make the fetal repair difficult and more risky to the mother. A history of a previous incision in the uterus such as a classical Csection was felt to be a contraindication to fetal repair since this history already puts the pregnant patient at risk for scar separation late in pregnancy. The investigators felt that making an second risky scar in the uterus for the fetal repair might place the pregnancy at a higher risk for loss. Finally, a short cervix measured with vaginal ultrasound in the current pregnancy or a history of premature delivery of a previous pregnancy were contraindications to enter the trial because patients undergoing fetal spina bifida repair are already at increased risk for premature delivery due to the uterine incision during the pregnancy.
• Insulin-dependent diabetes
MOMS Exclusion Criteria (maternal)
• Infection with hepatitis B or C • HIV infection • Red cell/platelet alloimmunization • Unwillingness to accept blood transfusions
for religious or other reasons
Presenter
Presentation Notes
Additional risk factors that prevented a woman from being offered the intervention were insulin dependent diabetes, infection with hepatitis B or C, HIV infection, red cell alloimmunization and unwillingness to accept blood for religious reasons.
• Myelomeningocele defect between levels T1 to S1
MOMS Inclusion Criteria (fetal)
• No evidence of kyphosis (curved spine)
• No major fetal anomaly unrelated to the spina bifida
• Normal chromosomes by amniocentesis
Presenter
Presentation Notes
Fetal conditions that allowed a patient to enter the MOMS trial included the presence of a myelomeningocele located between the first thoracic vertebrae (T1) and the first sacral vertebrae (S1) levels. There could be no evidence of kyphosis (a curved spine). The spina bifida could not be associated with other fetal anomalies such as a heart defect. Finally, the fetus had to have normal chromosomes by amniocentesis.
MOMS Outcomes (Maternal) Outcome Fetal surgery Postnatal surgery
Membrane separation 26% 0% Rupture of membranes 46% 8% Pulmonary edema 6% 0% Abruption 6% 0% Infection 3% 0% Decreased amniotic fluid 21% 4% Status of uterine incision at delivery Very thin 25% Partial separation 10%
Presenter
Presentation Notes
The data from the MOMS trial indicates risks to the mother that are associated with in utero repair of spina bifida. Even though the fetal membranes are stapled to the wall of the womb when the incision is made, one in four patients were noted to have separation of the membranes from the wall after the surgery. This finding is a known risk factor for rupture of the membranes. This occurred in almost half of the patients after in utero repair and was six times more likely to occur than when the spina bifida repair was postponed until after the delivery of the baby. Both pulmonary edema (fluid on the mother’s lungs) and abruption (premature separation of the placenta often leading to early delivery) occurred more often in the fetal surgery group. Infection rates were comparable in the two groups. The risk for a decreased amount of amniotic fluid around the fetus (also known as oligohydramnios) was five times as likely to occur in the fetal surgery group probably as a result of leakage of fluid through the surgical incision. Most importantly, when the obstetricians looked at the time of Csection delivery at the uterine incision that had been used for the fetal spina bifida repair earlier in pregnancy, they found that the scar was very thin in 1 out of 4 cases and that there was evidence of scar separation in an additional 10% of cases.
MOMS Outcomes (Neonatal) Outcome Fetal surgery Postnatal surgery
Fetal repair of spina bifida was also associated with significantly increased risks for the newborn. The average gestational age at delivery was about 3 weeks earlier in the fetal surgery group – 34.1 weeks vs 37.3 weeks. 13% of babies were delivered before 30 weeks gestation, an additional one third were delivered between 30 and 34 weeks and another one third were delivered between 35 and 36 weeks. This means that only 1 in 5 babies were delivered at term after fetal surgery. Birthweight in the fetal surgery group was about 1.5 pounds less than the group that had post-delivery repair. Although there were no infant deaths in either group, the increased rate of prematurity in the fetal surgery group was also associated with a 21% incidence of respiratory distress syndrome requiring oxygen and ventilator support in the babies. This was three times higher than the postnatal repair group. Other complications in the nursery including necrotizing enterocolitis (an infection of the bowel), periventricular leukomalacia (abnormal brain finding associated with cerebral palsy) and overall sepsis (infection in the blood) were not increased in the fetal surgery group.
MOMS Outcomes (12 months)
Outcome Fetal surgery Postnatal surgery Primary outcome 68% 98% Death 2 2
Shunt criteria met 65% 98%
Shunt placement 40% 82% Any hindbrain herniation 64% 96%
Presenter
Presentation Notes
The benefits of fetal repair of spina bifida appeared to be statistically superior to postnatal repair. The primary outcome of the study – death or need for a ventricular shunt in the first year of life was 30% less frequent in the fetal repair group. In the fetal repair group, one fetus died soon after in utero surgery and a second died in the nursery after a premature delivery at 23 weeks gestation . There were two deaths in the first year of life in the postnatal repair group due to complications of their spina bifida. The major differences in the two groups appeared to be related to the resolution of the Chiari II malformation and the resulting hydrocephalus in the fetal repair group. Babies that underwent fetal repair were half as likely to ever need a VP shunt (40% vs 82%). All fetuses that were entered into the study had evidence of hindbrain herniation on MRI during their mother’s pregnancy. The Chiari malformation was less common in the fetal repair group as compared to postnatal repair. Both herniation and kinking when present were of a milder degree in the fetal repair group.
Bayley scores (a standarized measurement of an infant’s performance) were similar for mental development in both groups. However Bayley scores for motor development were superior in the fetal surgery group. Motor function in the babies’ lower extremities was 2 levels higher than where the spina bifida was located in almost one third of the fetal surgery children. Twice as many children who underwent in utero repair were walking independently as compared to the postnatal group (42% vs 21%). Walking without braces was also twice as common in the fetal surgery children. The WeeFIM score is a measurement of the degree of disability in a child. Higher scores are associated with less disability. In the fetal surgery group, scores for self-care and mobility were higher than the postnatal surgery children; cognitive scores were similar.
Presenter
Presentation Notes
Once the abdomen is opened, ultrasound is used to locate the placenta inside of the womb. The placenta must be avoided so as to prevent bleeding complications since it provides both oxygen and nutrients to the fetus. If the placenta is on the front side of the uterus, the incision to gain access to the fetus may have to be made in an unusual location such as on the back side of the uterus.
Texas Fetal Center Experience Patient
No Age Gravidity GA @
Procedure Level of Lesion
GA @ Delivery
Outcome
1 39 G2P1 24 4/7 L1-L2 32 3/7 No shunt at one year
2 29 G2P0 25 L1-L2 25 4/7 No shunt at 10 mo of age
3 31 G4P3 22 4/7 L3 – S3 36 4/7 Revision of repair; shunt at 3 weeks of age
4 32 G7P2 24 L5-S1 30 0/7 No shunt at 38 days, baby doing well at home
5 37 G3P2 24 1/7 L2-S4 35 0/7 No shunt at 11 days, baby doing well at home
6 24 G1P0 25 4/7 L2-S3 30 Baby in NICU; shunt at 2 weeks of age
7 31 G1P0 23 5/7 T12-S5 32 1/7 Delivered on 12/8
8 26 G2P1 25 5/7 L4-S5 --- Ongoing
Twin – twin Transfusion Syndrome
DIAGNOSTIC CRITERIA • Like sex • Single placenta • Thin dividing membrane (monochorionic) • Massive hydramnios ( > 8 cm vertical pocket
/oligohydramnios (< 2 cm vertical pocket) • 10% of all monochorionic twins
Salomon et al. Am J Obstet Gynecol 2010;203:444.e1-7 Rossi et al. Obstet Gynecol 2011;118:1145-50
• No difference between donor and recipient
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Monochorionic Twins Learning Curve of Laser
Papanna et al. Am J Obstet Gynecol 2011;204:218 e1-4
Laser Programs
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Discordant Anomalies in
Monochorionic Gestations
Monochorionic Twins Risk of Single Demise
– Old theory of “bad humors” crossing to the live twin discounted – Acute hemodynamic changes the more likely etiology – No benefit from acute delivery
– 15% of cases associated with IUFD of co-twin • ↑ 5X over dichorionic twins
– 26% of survivors with neurologic sequelae • ↑ 5X over dichorionic twins
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Risk of in-utero death of affected twin
Fusi et al. Obstet Gynecol 1991;78:517-20 Hillman et al. Obstet Gynecol 2011;118:928-40
39
40
↓ BP ↓ BP
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42
Bipolar Umbilical Cord Occlusion
44
2 cm
Starburst™ SDE RFA Needle
12 cm
17 g
45
RFA (N = 17) Bipolar (N = 34) p value
Operative time 31.8 + 22 29.8 + 22 0.78
Type of anesthesia IV sedation
Spinal General with ETT
17 0 0
23 4 7
0.03
PPROM 1 (6%) 8 (24%) 0.24
Weeks gained 13.8 + 6.8 13.0 + 5.6 0.71
GA @ delivery 34.4 + 5 33.9 + 5 0.78
Survival (O/E) 17/19 (90%) 31/36 (86%) 1.0
RFA vs. Bipolar
Roman et al. Ultrasound Obstet Gynecol 2010;36:37-41
Twin Reversed Arterial Perfusion Syndrome
(TRAP)
Acardius anceps
83% Survival
Lee et al. Am J Obstet Gynecol 2008;199:S4
Diaphragmatic Hernia
R
L
Lung
R
L
X X
Diaphragmatic Hernia (LHR Ratio)
LHR = AP X TRANS of contralateral lung Head circumference (mm)
Diaphragmatic Hernia (LHR Ratio) LHR Liver N Survival > 1.4 NA 10 80%
Deprest et al. Semin Perinatol 2005;29:94-103
Diaphragmatic Hernia (LHR Ratio) LHR Liver N Survival > 1.4 NA 10 80%
1.0 – 1.4 ↓ 7 71%
Deprest et al. Semin Perinatol 2005;29:94-103
Diaphragmatic Hernia (LHR Ratio) LHR Liver N Survival > 1.4 NA 10 80%
1.0 – 1.4 ↓ 7 71%
↑ 7 57%
Deprest et al. Semin Perinatol 2005;29:94-103
Diaphragmatic Hernia (LHR Ratio) LHR Liver N Survival
> 1.4 NA 10 80%
1.0 – 1.4 ↓ 7 71%
↑ 7 57%
< 1.0 ↓ 12 42%
Deprest et al. Semin Perinatol 2005;29:94-103
Diaphragmatic Hernia (LHR Ratio) LHR Liver N Survival
> 1.4 NA 10 80%
1.0 – 1.4 ↓ 7 71%
↑ 7 57%
< 1.0 ↓ 12 42%
↑ 17 6% Deprest et al. Semin Perinatol 2005;29:94-103
Treatment • 1986: First attempt at open fetal surgery • 1986 – 1993: “Liver up” not amenable to
open repair due to kinking of umbilical vein w/repair
• 1993 – 1996: NIH sponsored trial for open repair
Diaphragmatic Hernia
Fetoscopic treatment of diaphragmatic hernia
• 26 – 28 weeks’ gestation • General maternal anesthesia • IM fetal pancuronium, atropine,
fentanyl • 1.2 mm scope; 0.8 ml balloon • Remove at 34 weeks
Diaphragmatic Hernia
Deprest et al. Semin Perinatol 2005;29:94-103
• 210 cases • 47% PPROM
– median: 30 days post-procedure – within 3 wks of procedure: 17% – Gest age at delivery: 35.3wks (30% @ < 34 wks)
• 10 neonatal deaths related to balloon removal • Overall survival
– L sided: 24% → 49% – R sided: 0% → 35%
Diaphragmatic Hernia
Jani et al. Ultrasound Obstet Gynecol 2009;34:304-10
Diaphragmatic Hernia
Ruano et al. Ultrasound Obstet Gynecol 2012;39:20-7
Parameter FETO Controls P or RR No of patients 20 21 ----- GA @ delivery (wks) 35.6 + 2.4 37.4 + 1.9 < 0.01 Survival to 6 mo 50% 4.8% 10.5 (1.5 – 74.7) Survival to 6 mo (received treatment)
52.9% 5.3% 10.0 (1.4 – 70.6)
Selection of Patients 100 antenatal
diagnoses
13 Right sided 87 Left sided
30 with LHR < 1.0
20 with liver up
Current Therapy Offered • EXIT procedure • Open fetal surgery for certain lessions (NTD,
rarely CCAM & sacrococcygeal teratoma) • Laser for TTTS • Selective reduction for discordant fetal
anomalies in MC twins • Shunt placement (thoracic/urinary) • Intrauterine transfusions
Future Therapy Offered
• Trachael balloon for diaphragmatic hernia
• Invasive fetal cardiac therapy • Fetal stem cell transplant • Robotic surgery for NTD or
