Myelomeningocele / Spina Bifida
Fetal Surgery for Spina Bifida / Myelomeningocele
Prenatal Diagnosis of Spina Bifida / Myelomeningocele | Prenatal Treatment for Spina Bifida / Myelomeningocele | References | Contact Us
Myelomeningocele / Spina Bifida is a protrusion of the meninges and spinal cord through a defect in the:
- Vertebral arches
- Muscle
- Skin
Myelomeningocele is associated with significant postnatal morbidity and lifelong disability and a small but significant mortality rate related to complications.
Myelomeningocele is a relatively common anomaly affecting 1 in 2000 live births. The disabilities associated with myelomeningocele include:
- Paraplegia
- Hydrocephalus
- Sexual dysfunction
- Skeletal deformities
- Bowel and bladder incontinence
- Cognitive impairment
Although most children with myelomeningocele have normal intelligence, 15% require some form of custodial care.
Dietary folate supplementation has been shown to prevent myelomeningocele in some cases.
To be effective folate must be supplemented soon after conception, but 50% of women of childbearing age do not take supplemental folate, and most pregnancies are unplanned.
In addition, it is estimated that 30% of neural tube defects are refractory to folate supplementation. For these reasons, despite folate supplementation, Myelomeningocele is an anomaly that likely will continue to affect children.
Traditionally, efforts to treat myelomeningocele have focused on postnatal surgical correction to prevent infection and to improve physical disabilities that cannot be corrected or reversed. The rationale for prenatal correction of myelomeningocele is to repair the defect before neurologic damage has occurred or when there is still potential for recovery.
The neurologic damage in myelomeningocele is hypothesized to result from the initial defective spinal cord development and the damage to the exposed spinal cord caused by failure of mesodermal migration. This has been referred to as the "two-hit hypothesis."
Examination of the spinal cords of midgestation fetuses with myelomeningocele shows near-normal cord development in most cases. In addition, leg movement in fetuses with myelomeningocele has been observed as early as 16 to 17 weeks of gestation.
In contrast, most myelomeningocele fetuses exhibit severe neurologic impairment of the lower extremities by the time of birth, suggesting that the neurologic injury may occur later in gestation. This injury may occur during labor or as a result of passage through the birth canal. The neurologic injury may also occur by direct abrasion of the exposed cord against the uterine wall during gestation.
An additional insult to the spinal cord may be a constituent of the amniotic fluid. However, amniotic fluid at 34 weeks of gestation was found to be more toxic to rat spinal cords in an in vitro organ culture model than was amniotic fluid from earlier in gestation.
Animal models that mimic human myelomeningocele have been developed in primates, rats, pigs and sheep. Perhaps the model that comes closest to simulating human Myelomeningocele is the ovine model. In this model, laminectomy is performed at 75 days of gestation and myelomeningocele repair is performed at 100 days of gestation.
At birth, lambs that do not undergo fetal repair have myelomeningocele-like lesions, flaccid paralysis, incontinence, and absent hind limb somatosensory-evoked potentials. In contrast, lambs that do undergo repair in utero are normal.
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Elevation of maternal serum a-fetoprotein concentrations obtained in the first trimester of pregnancy identified 75% to 80% of pregnancies with myelomeningocele before 16 weeks of gestation. Amniocentesis is performed in at-risk cases identified by maternal serum a-fetoprotein concentration screening and amniotic fluid.
a-Fetoprotein and acetylcholinesterase elevations suggest the presence of a neural tube defect. The structural defect can be readily identified by ultrasonography by 18 to 22 weeks' gestation.
The presence of an myelomeningocele may also be suggested by the presence of a "lemon" sign, which is a scalloping of the frontal bones. A full anatomic survey should be performed to detect associated anomalies such as:
- Ventriculomegaly
- Chiari malformation with hindbrain herniation
- Clubfoot
The presence or absence and quality of leg and foot movements should be assessed, but it may be difficult to distinguish spontaneous from reflex fetal movement. Ultrafast fetal magnetic resonance imaging (MRI) provides additional anatomic detail about the myelomeningocele and the brain.
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The first attempted repair in utero of a myelomeningocele was reported in a letter by Bruner and colleagues in 1987, using a fetoscopic technique to apply a skin graft in two fetuses.
A full report of this experience revealed that four fetuses were operated on between 22 and 24 weeks' gestation. There were two deaths: one from chorioamnionitis, requiring delivery 1 week postoperatively, and the second from placental abruption on the day of surgery.
The two other fetuses delivered at 28 and 35 weeks' gestation. Both fetuses required ventriculoperitoneal shunting postnatally and surgery to close the defect, and it is not clear that there was any neurologic benefit. This fetoscopic approach has since been abandoned.
The first evidence of improved neurologic function from repair of Myelomeningocele in utero was reported by Adzick and coworkers in 1998. Open fetal surgical repair of a large T11 to S1 myelomeningocele was performed at 23 weeks of gestation.
Postnatally, the infant had a right clubfoot with a neurologic L4 level and a left foot with an L5 level. Postnatal MRI demonstrated resolution of the hindbrain herniation, and there was no hydrocephalus. Almost all neonates with thoracolumbar Myelomeningocele are paraplegic and require ventriculoperitoneal shunting for hydrocephalus.
The outcome in this case suggested the potential neurologic benefit of in utero repair of myelomeningocele. Subsequent experience in 10 cases, between 22 and 25 weeks, by this same group demonstrated by pre- and postoperative fetal MRI that closure of the myelomeningocele in utero reverses the hindbrain herniation of the Chiari malformation.
In addition, only 1 of the 10 required ventriculoperitoneal shunting. Bruner and colleagues reported the Vanderbilt experience at the same time with 29 cases between 24 weeks and 30 weeks.
At birth there was evidence of hindbrain herniation in only 38% of these patients compared to 95% in a postnatal comparison group. In addition, 17 of the 29 (59%) required ventriculoperitoneal shunts which compared favorably with a postnatal comparison group in which it was required in 91%.
The Children's Hospital of Philadelphia (CHOP) group has reported experience with 50 cases in which fetal mmyelomeningocele repair resulted in resolution of hindbrain herniation in 100% of cases by 6 weeks postoperatively by fetal MRI 25.
In addition, the postnatal shunt rate in these patients was 43% which is lower than the predicted shunt rate of 84% based on 297 historical controls from the Children's Hospital of Philadelphia (CHOP) Spina Bifida clinic between 1993 and 2000.
It is important to note that there were 3 fetal deaths (6%) in this series. This is a substantial mortality considering myelomeningocele is not a lethal anomaly in utero. These deaths were due to:
- Fetal arrhythmia during the procedure caused by cord compression in 1
- Chorioamnionitis in 1
- Severe prematurity in the third
The preliminary results at 3 centers, CHOP, UCSF, and Vanderbilt, led to an National Institutes of Health-sponsored prospective randomized clinical trial of 200 patients comparing fetal surgery to postnatal treatment of myelomeningocele in the MOMS trial (Management of Myelomeningocele Study).
The selection criteria for the MOMS trial include:
- Myelomeningocele at T1 through S1 with hindbrain herniation, maternal age greater than or equal to 18 years
- Gestational age at randomization of 19 0/7 weeks to 25 6/7 weeks
- A normal karyotype
The exclusion criteria include:
- Non-US resident
- Multifetal pregnancy
- Insulin dependent pre-gestational diabetes
- Fetal anomaly unrelated to Myelomeningocele
- Fetal kyphosis of greater than 30 degrees
- History of incompetent cervix
- Placenta previa
- Other serious maternal medical condition
- Cervix less than 20 mm by ultrasound
- Obesity
- Previous spontaneous singleton delivery less than 37 weeks' gestation
- Maternal-fetal Rh isoimmunization
- Positive maternal human immunodeficiency virus or hepatitis B or C
- No support person to stay with the mother at the center
- Uterine anomaly
- Fails psychosocial evaluation
- Inability to comply with travel and follow up protocols
The primary outcome variable of the MOMS trial is whether or not fetal repair of Myelomeningocele at 19 to 25 weeks' gestation improves outcome measured by death or the need for ventriculoperitoneal shunting at 1 year of age.
Secondary outcomes include the effect on the Chiari II malformation by neuroimaging, neuromotor status at 12 and 30 months of age. Neonatal morbidity and need for postnatal surgical interventions will also be evaluated.
In addition, the long-term psychological and reproductive consequences in mothers who undergo intrauterine repair of myelomeningocele will be compared to those in the postnatal repair group.
This trial has been open and acquiring patients for 1 1/2 years. Although recruitment has been slower than anticipated, the trial has the advantage that there is no "back door." That is, there is no other center in the US offering this procedure while the trial is being conducted. It is hoped that the results of the MOMS trial will determine if fetal intervention can improve outcomes for children with spina bifida.
The results of fetal myelomeningocele repair are difficult to evaluate, especially given the limited duration of follow-up. Although hindbrain herniation definitely is reversed, ventriculoperitoneal shunting may still be needed.
With longer follow-up time, both the Philadelphia and Nashville groups have observed a progressive rise in the number of patients requiring ventriculoperitoneal shunting. Whereas some patients in the Philadelphia series appear to have significantly improved neurologic level of function, most have not, and none of the patients in the Nashville group have shown improved neurologic function.
These results will need to be evaluated in prospective trials with 4- to 5-year follow-up to determine if fetal myelomeningocele repair is truly beneficial. This is especially important, given the fetal deaths following fetal myelomeningocele repair for this nonlethal lesion.
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Adzick NS, Sutton LN, Crombleholme TM, et al: Successful fetal surgery for spina bifida. Lancet 352:1675, 1998.
Adzick NS, Walsh DS: Myelomeningocele: Prenatal diagnosis, pathophysiology, and management. Semin Pediatr Surg. 12: 168-174, 2003.
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Revised 3/05
