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Myelomeningocele, a common form of spina bifida, is a congenital birth defect in which a section of the neural tube that runs along the spine fails to close. This open neural tube defect results in babies born with abnormal spinal cord and spinal nerve function.
Complications are usually lifelong, involving bladder and bowel continence, hydrocephalus and inability to walk. Hydrocephalus – or excess water buildup in the brain – results in the need for a shunt from the brain to the abdomen (ventriculoperitoneal shunt or ventriculoperitoneal shunting) to remove this fluid. However, surgery for an unborn baby can improve outcomes.
Myelomeningocele is one of the most common types of neural tube defects, impacting between 1,500 and 2,000 of the more than 4 million babies born in the U.S. each year.
As a parent, learning your baby is facing a myelomeningocele diagnosis can be frightening. But the Colorado Fetal Care Center (CFCC) is at the forefront of treatment and care for this condition. Learn about the fetal care specialists at the CFCC who will help your family through this journey and onto a healthy delivery.
This congenital birth defect occurs when a section of the neural tube along the baby’s spine fails to close. As a result, babies with myelomeningocele can sometimes have a cyst of fluid extending from the back that contains a portion of the spinal cord, along with other nerves. Spina bifida symptoms vary depending on the severity of the defect but can result in babies born with abnormal spinal cord and spinal nerve function.
The good news is fetal surgery performed at the CFCC has shown to improve outcomes for our tiniest patients.
Children with this type of spina bifida can develop lifelong complications including bladder and bowel incontinence, as well as a difficulty or inability to walk. Often, they also develop hydrocephalus or an excess buildup of water in the brain. This may result in the need to place a shunt from the brain to the abdomen to relieve this collection of fluid.
While a myelomeningocele diagnosis for your baby feels life-changing, there are treatment options available that may help your child thrive, both during your pregnancy and after his or her birth.
The Colorado Fetal Care Center is one of the nation’s top care centers for babies with myelomeningocele over the last three years. We have successfully performed more than 50 surgeries on babies with an average age of delivery being 34 weeks.
There are some Myelomeningocele treatment options depending on the severity of the baby’s defect.
In severe cases, treatment of myelomeningocele in utero may improve outcomes. This is likely because open neural tube defects that have direct contact with amniotic often put the baby at risk for secondary injury, direct trauma or progressive hydrocephalus. Covering the defect in utero decreases the effects described here and decreases the need for a shunt in the first year of life.
The traditional prenatal care for fetuses diagnosed with myelomeningocele involves frequent ultrasounds to monitor fetal growth and cesarean section delivery at full term. A neurosurgeon will evaluate the baby after delivery and likely close the spina bifida within the first few days of life. The infant will be evaluated for signs of increased pressure in the brain and if present will likely receive a ventriculoperitoneal shunt which is a tube that assisted in draining spinal fluid from the infant’s brain that drains into the abdominal cavity. Further care would include follow-up in a clinic with multidisciplinary care incorporating specialists in Neurology, Neurosurgery, Orthopedics, Occupational Therapy, Pediatrics, Physical Therapy, Urology and others as needed.
Some patients may qualify for a prenatal closure of the spina bifida. The evaluation includes fetal ultrasound, MRI and echocardiography (heart ultrasound), and counseling with specialists. Prenatal repair is done by opening the pregnant uterus and exposing the spina bifida. The Neurosurgeon then closes the spina bifida similar to how it is done after birth. The uterus is then closed with the fetus in utero. Post-surgical care includes monitoring for early labor. The baby is delivered by cesarean section around 37 week’s gestation.
Incomplete closure and development of the fetal spine in very early pregnancy is the cause of Spina Bifida. The cause of this is not completely understood however various genetic and environmental factors are likely involved.
Spina Bifida is a lifelong disability. It is a complex condition involving the nervous, urinary, muscular and skeletal systems. The effects of spina bifida are different for every person.
Spina bifida occurs in the first 3-4 weeks of a woman’s pregnancy when the spinal cord is forming. The spinal canal remains open along several vertebrae in the back allowing the nerves and the membranes that cover the spinal cord to protrude out of the back.
Spina bifida can be closed or open. If the nerves are covered with skin, the defect is closed. If the nerves are not covered by anything, the defect is open. Open defects tend to be more severe because the nerves are damaged by amniotic fluid and contact with the uterine wall.
No, you cannot get spina bifida at any age. Spina bifida develops during the first 3-4 weeks of pregnancy. However, mild, closed spina bifida may not be diagnosed until the baby is born. Spina bifida occulta is often diagnosed much later, but is a normal variant that is often picked up on an x-ray of the back. This is not associated with back pain or a neurological disorder, and does not need to be followed or treated.
With any condition a loved one is going through, the most important thing you can do as a friend or family member is to offer support during this potentially trying period. Myelomeningocele (MMC) is a condition that can be difficult to understand for those without a medical background or direct explanation from a doctor. In order to help you understand what your loved one is going through, we have dedicated this page to providing information essential for you to know. Armed with this knowledge, we feel you as a family member or friend will be better able to lend support to those who need it.
This congenital disorder is a general term for conditions that are caused by an incomplete closing of the neural tube on an embryo. Like its name suggests, this condition affects the spine and leaves openings between vertebrae. It is one of the most common birth defects but its severity ranges in several categories. The milder category occurs when the vertebrae openings are too small for the spinal cord to protrude through. Individuals born with these mild forms are unlikely to suffer long term health problems and can lead normal lives. In the more severe category, a portion of the spinal cord protrudes through the vertebral opening and requires dedicated medical attention.
As mentioned above, spina bifida can occur in a severe form called myelomeningocele. Unlike the other categories this is an open neural tube defect which means the protrusion of the spinal cord is not covered by skin. This sac protrusion is covered by a membrane, and can contain both portions of the spinal cord as well as nerves. This malformation occurs early in gestation, between the first three to four weeks post ovulation. Prior to the mid 1980’s, diagnosis was only available through scanning of the fetal vertebrae. However in more recent years it has been recognized that testing the mother for increased alpha feto proteins (AFP) or for certain central nervous system abnormalities in the fetus can provide indicators for this condition. One such abnormality is the concavity of the cerebellar hemispheres, which are referred to as “fruit” findings. A positive ‘lemon’ or ‘banana’ sign does not necessarily mean a child has myelomeningocele, but is a good indicator it is possible.
Since this is such a severe condition, fetal surgery is often necessary as a treatment. Myelomeningocele is a condition that requires the attention of many different specialists, and the understanding there are risks to both the mother and fetus. In prenatal surgery, the maternal risks involve obstetrical complications and can impact both the current pregnancy as well as future ones. There is some risk to the fetus during in utero surgery, but the benefits greatly outweigh the risks in waiting till after delivery. If left to wait, the fetus’s exposure to amniotic fluid will progressively damage their fetal neural tissue. Weighing the risks to both are essential, and surgery should be undertaken by a team with experience in open fetal surgery. Colorado Fetal Care Center has a dedicated team who have spent years researching and performing such surgeries. Dr. Timothy Crombleholme is the Director of The Colorado Fetal Care Center and was a co-investigator on the Management of Myelomeningocele (MOMS) study trial. His professional oversight has seen the creation of a Prenatal MMC Repair Oversight committee composed of doctors who specialize in MMC and are there to assist the mother and walk her through every option available. If you are interested in learning more about our fetal care specialists please contact the Colorado Fetal Care Center.
From an unexpected diagnosis of their unborn son to an amazing outcome, their little boy has made their family more “perfect”. Read this family’s journey and how the Colorado Fetal Care Center was there for them from diagnosis to treatment, giving them hope for their son JD.
Prior to the mid-1980s, sonographic diagnosis of myelomeningocele relied on the meticulous scanning of the fetal vertebrae for abnormalities. Using this method, neural tube defects were missed. More recently, the prenatal sonographic diagnosis of myelomeningocele has been enhanced by the recognition of specific brain abnormalities that generally precede detection of the spinal lesion (Blumenfeld et al., 1993) (Table 1).
The central nervous system (CNS) abnormalities described in neural tube defects include cerebral ventriculomegaly, microcephaly, abnormalities of the frontal bone, and obliteration of the cisterna magna with an apparently absent cerebellum or an abnormal concavity of the cerebellar hemispheres. These latter abnormalities have been referred to as the "fruit" findings, which include the lemon and the banana signs. The lemon sign describes a concave or flattened frontal contour of the fetal calvarium rather than a normal convex frontal contour. The banana sign describes the posterior convexity of the cerebellum within the posterior cranial fossa (Nicolaides et al., 1986). The lemon sign has been described in 1% of apparently normal fetuses, whereas the banana sign is not found in normal fetuses. The abnormal CNS sonographic findings are a consequence of the Arnold–Chiari malformation. In a prospective analysis, Campbell et al. (1987), who studied 436 fetuses at high risk for spina bifida, identified 26 fetuses with an open neural tube defect. Of the 26, 17 (62%) had a small biparietal diameter for gestational age, 9 (35%) had an abnormally small head circumference, and 100% had a positive lemon sign.
In addition, 25 of 26 fetuses (96%) had a cerebellar abnormality. Of these, nine had an absent cerebellum, and 16 had a positive banana sign. Only one fetus in the study with an open neural tube defect had a normal cerebellum. These findings were further defined by Van den Hof et al. (1990), who demonstrated that the CNS abnormalities seen in myelomeningocele evolve with gestation. These authors studied 130 fetuses with open spina bifida and demonstrated a relationship between gestational age and the presence of the lemon and banana signs. A lemon sign was present in 98% of fetuses with open spina bifida at <24 weeks of gestation, although this finding was seen in only 13% of fetuses at >24 weeks. Cerebellar abnormalities were seen in 95% of fetuses at any stage of gestation, although the banana sign was more typical at <24 weeks, and apparent cerebellar absence was typical of fetuses at >24 weeks. Because the lemon sign is due to decreased intracranial pressure because of caudal herniation of the hindbrain contents, lack of the lemon sign may be due to skull maturation. Alternatively, the cerebral ventriculomegaly that is very common in open spina bifida may compensate for the loss of the brain mass. This may displace the skull bones.
More recently, Ball et al. (1993) demonstrated that the lemon sign is not specific for myelomeningocele. In this report of 23 cases of a positive lemon sign, 12 were associated with an open spina bifida, and 6 were seen in cases of encephalocele. An additional 5 fetuses did not have a neural tube defect, although they had a variety of other abnormalities, including thanatophoric dysplasia, cystic hygroma, and agenesis of the corpus callosum. An additional CNS finding associated with myelomeningocele was effacement of the cisterna magna, which was seen in 19 of 20 fetuses studied with myelomeningocele (Goldstein et al., 1989). In a review of 234 fetuses with open spina bifida diagnosed at <24 weeks of gestation, Watson et al. (1991) demonstrated that all but two fetuses had at least one of the cranial abnormalities described for affected fetuses. They also questioned whether there was a higher positive predictive value for open spina bifida when more than one sign was observed antenatally. These authors also cautioned that evaluation of motor function in the fetus was not predictive of future neuromuscular status.
A common accompanying intracranial finding in myelomeningocele (MMC) is lateral ventriculomegaly, in which the atrial measurements of the posterior horns exceed 1 cm. In the second trimester, the biparietal diameter and head circumference may be below the 5% for gestational age (Shaer et al., 2007). When MMC is diagnosed between 16 and 24 weeks, microcephaly has been observed in up to 69% of fetuses (Campbell et al., 1987; Thiagarajah et al., 1990). As pregnancy progresses, both biparietal diameter and head circumference tend to normalize in late second trimester. Hydrocephalus, present in 75% of cases, tends to progress slowly during the third trimester (Shaer et al., 2007).
Evaluation of the fetal spine depends on the visualization of the three ossification centers within the fetal vertebra. The centers of the neural arches should be parallel or converging. In the longitudinal plane, the spine should appear like a "railroad track," with gradual widening toward the fetal head and tapering toward the sacrum. However, the distal part of the spine may not be ossified in healthy fetuses at <22 weeks of gestation (Budorick et al., 1995). Spina bifida can be demonstrated in both the coronal and transverse planes. In the coronal plane, widening of the ossification centers in the neural arch interrupts the normal parallel configuration of the vertebral arches. In the transverse plane, ossification centers in the neural arch either diverge or take on a U-shaped configuration. The presence of scoliosis or kyphosis is associated with neural tube defects.
Kollias et al. (1992) assessed the sonographic accuracy of the estimation of spinal level involved in the MMC. Of 28 cases studied, sonographic and pathologic levels were in agreement in 18 (64%) and within one spinal level in 22 (79%).
Other sonographic findings that may suggest a MMC include a cystic meningeal sac, which may have a shimmering effect with fetal motion (Budorick et aL, 1995). The sonographer should also examine the fetus's lower extremities for the possibility of clubfeet.
With the presence of skin covering the neural tube defect, the lesion is considered to be a closed neural tube defect, such as lipomyelomeningocele, which has a different etiology. Closed neural tube defects are not usually associated with Arnold—Chiari II malformations and they have a much more favorable prognosis (Tortori-Donati et al., 2000; Ramin et al., 2002).
The adjunctive use of magnetic resonance imaging (MRI) of the fetus has provided additional and complementary information to ultrasound examination alone. The results of at least two studies suggest that fetal MIZI is superior to ultrasound examination for prenatal diagnosis of the intracranial abnormalities associated with MMC (Dinh et al., 1990; Levine et al, 1999). In a comparison of sonography and MRI, both were equally accurate in assignment of MMC level (Aaronson et al., 2003). Mitl may be a particularly helpful adjunct to ultrasound examination when there is a large maternal body habitus, oligohydramnios, low position of fetal head, or posterior position of fetal spine present.
With the presence of an open neural tube defect there is increased in utero lethality. For example, at 8 weeks of gestation, one fourth of all conceptuses with neural tube defects will be liveborn, one-fourth will be stillborn, and one half will spontaneously abort (Main and Mennuti, 1986).
The formation of the neural tube begins at approximately day 19 with formation of the primitive streak. Epiblasts transform to ectoderm along the dorsal midline of the embryo. This gives rise to the neural plate, which then enfolds to form the neural groove. In the middle of the 4th week, neural folds on each side of the neural groove begin to fuse, thus forming the neural tube (Rieder, 1994). Current evidence suggests that there are two parallel processes that occur. At the level of the fifth somite, where the brain and spinal cord meet, the normal folds join in a zipper-like fashion that proceeds cranially and candally (Shaer et al., 2007). A second closure site appears in the forebrain; fusion also occurs at that site in two directions, and meets the zipper process proceeding from the hindbrain. In parallel, the zipper process moves to close the most rostral part of the forebrain. Lack of signaling between the neural tissue and overlying ectoderm and mesoderm may result in the bony defect that overlie the unfused sections of the neural tube (O'Rahilly and Muller, 2002).
More than 80% of children with a neural tube defect can be detected by maternal serum AFP screening before birth (Brock and Sutcliffe, 1972). Although the determination of amniotic fluid acetylcholinesterase can be helpful, ultrasound examination is the method of choice for the diagnosis of neural tube defects. Direct visualization of the fetal spine can usually be accomplished by 16 weeks' gestation. Since the 1980s, the sonographic diagnosis of MMC has been enhanced by the introduction of high-resolution imaging tools and by recognition of specific brain abnormalities (Blumenfeld et al., 1993). First described by Arnold and Chiari at the end of the 19th century (Arnold, 1894; Chiari, 1895), the Arnold- Chiari II malformation is defined as the maldevelopment of a small posterior fossa and the herniation of the cerebellar vermis and brainstem (including the fourth ventricle) through an enlarged foramen magnum. Additionally, agenesis of the corpus callosum, enlargement of the massa intermedia, cortical heterotopia, and polymicrogyria can be seen. The origin of the Arnold—Chiari II malformation remains in dispute. The predominant hypothesis maintains that an imbalance of hydrodynamic forces occurs secondary to loss of CSF from the lesion (Padget, 1968; McLone and Knepper, 1989; Paek et al., 2000; Bouchard et al., 2003). An alternative theory interprets the hindbrain herniation as the consequence of a traction injury caused by cranial growth imbalance (Penfield and Coburn, 1938; Lichtenstein, 1942; Hoffman et al., 1975; McLone and Knepper, 1989). Overgrowth of the cerebellum and brainstem, along with a posterior fossa that is smaller than normal, leads to downward dislodgment of these structures, resulting in Arnold—Chiari II malformation (Barry et al., 1957). Despite the controversies about the origin of MMC-associated hindbrain herniation, these lesions are identifiable in the embryo from as early as 8 weeks of gestation and are established in the fetus by the 12th week.
Pathologic studies of human embryos and fetuses with myelomeningocele (MMC) in earlier stages of gestation reveal an open neural tube but undamaged neural tissue with almost normal cytoarchitecture (Patten, 1953). This suggests that neural degeneration occurs at some point later in gestation (the "two-hit" hypothesis) (Ehlers et al., 1992; Hutchins et al., 1996). The first "hit" is the failure of neurulation early in gestation. The second "hit" is the spinal cord injury resulting from prolonged exposure of the neural tissue to the intrauterine environment. In theory, this secondary event can be prevented if an adequate prenatal covering of the exposed neural tube can be provided. To have the best outcome, this repair must be fashioned before the onset of irreversible neural damage. There are several observations in human embryos, fetuses, and infants to support this premise (Neumann et al., 1994; Meuli et al., 1997).
In a pathologic examination of spinal cords of stillborn human fetuses with MMC (19-25 weeks of gestation), varying degrees of neural tissue loss at the site of the lesion were observed, but the dorsal and ventral horns were normal proximal to the defect (Hutchins et al., 1996). This group was among the first to suggest the two-hit hypothesis because they attributed these alterations to injuries occurring subsequent to the failure of primary neural tube formation. A study of 10 additional fetuses had similar findings (Meuli et al., 1997). Additional support exists for the two-hit hypothesis from in vitro studies. Drewek et al. (1997) reported that damage to open neural tissue appears to be progressive and results from exposure to toxic substances in the amniotic fluid during the third trimester.
Korenromp et al. (1986) observed that fetuses with MMC exhibited leg movement at 16 to 17 weeks. These investigators suggested that the affected fetuses did have good function at that point in gestation. No follow-up could be reported in this series because pregnancies were interrupted. Furthermore, Sival et al. (1997) compared the leg movements of 13 fetuses with MMC prenatally and postnatally. Only one of the 13 had abnormal leg movements before birth, but 11 demonstrated abnormal leg movements postnatally. Two possible explanations for this phenomenon exist. The prenatal leg movements could be secondary to spinal cord reflex rather than of cerebral origin, thus permitting motion without electrical impulses conducted through the damaged spinal cord tissue. In addition, leg movements early in pregnancy could result from cerebral function conducted through an exposed spinal cord that is not yet damaged. However, even extremely experienced sonographers find it difficult to distinguish between spontaneous and reflex-based fetal leg movements (Filly, 1994).
Most newborns with MMC show severe neurologic impairment of the lower extremities at birth, a finding suggesting that the neurologic injury may occur later in gestation or even at the time of delivery. It is remarkable that patients with lipomeningomyelocele (in which the neural tissue is covered and protected by skin) often have almost normal lower leg function and continence, despite a neurulation abnormality that is nearly identical to that present in newborns with open neural tube defects. These studies support direct injury to the protruding spinal cord as the primary cause of damage and loss of function (Hutchins et al., 1996; Meuli et al., 1997). As the pregnancy progresses, the volume of the amniotic fluid decreases, and this may result in more frequent contact of the exposed neural tissue with the uterine wall. Chick models of oligohydramnios, in which pressure necrosis of prominent areas of the body developed, support this hypothesis (Thévenet and Sengel, 1986).
Clinically, closed neural tube defects should be differentiated from open neural tube defects because the embryogenesis appears to differ in most cases. In open defects, there is an essential failure during the primary neurulation, whereas closed neural tube defects appear to result from another form of disturbance during neural tube formation (McComb, 1996). With few exceptions, the structural malformations of closed neural tube defects are limited to the spinal cord and are not associated with the Arnold—Chiari II malformation or hydrocephalus. In contrast to open defects, newborns with a closed neural tube defect have no exposed neural tissue and do not leak CSF. Additionally, the prognosis of an infant affected by a closed defect is significantly better than one with an open neural tube defect. Generally, children born with closed defects have an intellectual function that is of the same distribution as the normal population, do not require CSF diverting shunts, and have considerably fewer problems with lower extremity sensorimotor function and with bladder and bowel function (McComb, 1997). Because the clinical manifestations of closed defects can be undetected for days or even years, the origin of this group of neural tube defects is unidentified; no link to genetic, environmental, or dietary factors have been found. The major forms of closed neural tube defect are briefly described in the sections below.
Meningoceles are commonly located in the lumbosacral region in the vertebral arches. These lesions are often covered with skin, and the bony abnormality rarely involves more than two to three vertebrae. The meningocele sac consists of both arachnoid and dural meninges with CSF. Most meningoceles also contain neural elements. Meningoceles are an infrequent and heterogeneous group of cystic lesions. The accurate prevalence of meningocele is subject to debate because meningoceles are often grouped with MMCs. Furthermore, their pathogenesis remains unknown. The neurologic outcome of affected newborns is normal, but surgical correction and resection of the herniated meninges are indicated (McComb and Chen, 1996).
Lipomatous malformations include all the closed neural tube defects with excessive lipomatous tissue present within or attached to the spinal cord or filum terminale. These lesions are called lipomyelomeningocele, lipomyelocele, leptomyelolipoma, lumbosacral lipoma, or lipoma of the filum terminale. The origin of lipomatous closed neural tube defects is controversial. Two different theories have been advanced: (1) lipomas arise from cells originating from the somatic mesoderm and (2) lipomatous closed neural tube defects are a true malformation resulting from defective neurulation (Catala, 1997). Most affected infants have a good prognosis with nearly normal leg and urologic function.
Anencephaly and MMC are important contributors to fetal and infant mortality. All newborns affected by anencephaly are stillborn or die shortly after birth, whereas children born with MMC usually survive. However, the risk of death with neural tube defects varies significantly worldwide, depending not only on the severity of the defect but also on such aspects as availability, use, and acceptance of medical and surgical intervention. For example, in some regions of northern China, nearly 100% (Moore et al., 1997); in the Netherlands, 35% (den Ouden et al., 1996); and in the United States, 10% (Shurtleff et al., 1994) of children affected by neural tube defects die.
Myelomeningocele (MMC) repair and treatment options are available. The severity of complications observed in children with MMC prompted interest in the potential of in utero myelomeningocele repair to prevent these complications. The rationale for repair in utero is that the open neural tube defect allows exposure of the spinal cord to secondary injury from exposure to amniotic fluid, direct trauma or hydrostatic pressure (Adzick and Walsh, 2003). This has been referred to as the "two-hit hypothesis" (Hutchins et al., 1996).
Meuli-Simmen et al. (1995) used the latissimus dorsi muscle flap for fetal myelomeningocele repair in seven sheep fetuses with an artificially created lumbar myelomeningocele. Three fetuses survived the pregnancy. At term, the sheep survivors had healed cutaneous wounds and normal hind-limb function. These authors concluded that the latissimus dorsi flap is suitable for fetal surgery and provides efficient coverage of the lesion.
As a result of experimental work in animals, it is known that the neurologic deficits associated with open spina bifida are due partly to chronic mechanical injury and chemical trauma induced by exposure to amniotic fluid. These exposures progressively damage the unprotected fetal neural tissue during gestation. In fetal sheep, in utero repair of neural tube defects restored neurologic function by the time of birth (Meuli et al., 1997).
Fetal surgery to repair myelomeningocele is performed by maternal laparotomy and hysterotomy. The cystic membrane of the lesion is excised, the dura is closed over the placode and fascial layers are developed and closed over the defect. Lastly, skin flaps are developed laterally to complete closure of the defect (Adzick et al., 1998). Amniotic fluid is replaced with warmed lactated Ringer's solution. After repair, tocolysis was maintained with magnesium sulfate infusion, indomethacin rectal suppositories, and subcutaneous terbutaline.
The first attempt to repair by providing skin coverage for myelomeningocele was reported by Bruner et al. in 1997, using a maternal split thin skin graft endoscopically applied (Bruner et al., 1997). One patient died shortly after the surgery and the second patient showed no sign of improvement postnatally. Subsequently, the same group reported four patients who underwent open fetal surgical repair between 28 and 32 weeks' gestation with reversal of hindbrain herniation at birth (Tulipan and Bruner, 1998).
Similarly, the group at Children's Hospital of Philadelphia (CHOP) reported reversal of hindbrain herniation (Adzick et al., 1998). This was subsequently confirmed in a series of 10 patients undergoing MMC closure at 22 to 25 weeks' gestation (Sutton et al., 1999), in which 9 of 10 survived with reversal of hindbrain herniation. Four of the 9 later required ventriculoperitoneal shunting (Adzick and Walsh, 2003). Bruner et al. (1997) showed that 62% of 29 patients had a reversal of hindbrain herniation when operated on between 24 and 30 weeks' gestation. Ventriculoperitoneal shunting was required in 17 of 29 (59%) but still compared favorably with historical controls in which 90% required ventriculoperitoneal shunting (Rintoul et al., 2002).
Prior to the start of the Management of Meningomyelocele Study (MOMS) trial, experience with open fetal surgical repair had been performed at CHOP, Vanderbilt, University of North Carolina, and the University of California at San Francisco, with a combined experience of approximately 160 patients. Findings suggested improved outcomes compared to historical controls. Sutton et al. reported that hindbrain herniation was uniformly reversed in the CHOP experience and only 43% required ventriculoperitoneal compared to an 84% rate observed in 297 historical controls (Sutton et al., 1999; Rintoul et al., 2002). Of note in this series of 50 patients were 3 deaths from preterm delivery at 25 weeks. The average gestational age at delivery was 34 4/7 weeks (Rintoul et al., 2002). While this study suggested a reduced need for ventriculoperitoneal shunting, it should be pointed out that the controls were historical and neurosurgical indications for shunting had become more conservative during this period. In addition, some infants undergoing fetal surgery for myelomeningocele merely experienced delayed time for ventriculoperitoneal shunting.
Danzer et al. (2007) have reported that open fetal surgery for myelomeningocele alters the fetal head growth. Repaired myelomeningocele fetuses have disproportionately small head circumference measurements while the lateral ventricles progressively enlarge (Van den Hof et al., 1990; Babcock et al., 1994; Bannister et al., 1998). In a series of 50 fetuses undergoing open fetal surgery to repair myelomeningocele, Danzer et al. found a significant increase in the cortical index (head circumference/lateral ventricular diameter). Early neurodevelopmental evaluations at 2 years of age in the cohort of 51 myelomeningocele patients treated by open fetal surgery at CHOP reveal that 67% had cognitive language and personal-social skills in the normal range, 20% had mild delays, and 13% had significant delays (Johnson et al., 2006).
The lower extremity neuromotor evaluation following open fetal surgery for myelomeningocele suggests that 58% of patients had a better than predicted lower extremity function compared to infants with postnatally repaired myelomeningocele (Danzer et al., 2006; Carr, 2007). In this relatively early follow-up series (39 + 15 months) of open fetal surgically repaired MMC, 21 children (52.5%) walked independently, 8 (20%) walked with braces, 7 (15.5%) ambulated with a walker, and 4 (10%) used a wheelchair. This was in contrast to less favorable outcomes in postnatally repaired myelomeningocele in which only 1 child (6%) walked independently, 5 (29%) walked with braces, 10 (58.8%) ambulated with a walker, and 1 (6%) used a wheelchair (follow-up at 41.9 ± 16.6 months). This early assessment of lower extremity function may be misleading, as many children who had previously been able to ambulate with or without braces or walkers revert to a wheelchair at puberty due to increased weight and size that make ambulation very difficult.
Carr (2007) reported his experience with urodynamic evaluation of 22 patients who underwent fetal surgical repair of myelomeningocele at CHOP. In 13 of 22 patients, he evaluated voiding spontaneously with 3 of 22 (13.6%) achieving volitional voiding. This compares favorably with expected 2% to 3% volitional voiding in postnatal myelomeningocele repair (Carr, 2006). The remainder of the 22 patients had either vesicoureteral reflex (10%), urinary tract infections (33%), or required vesicostomy (5%), or clean intermittent catheterization.
In order to address many of the questions raised by early outcomes of open fetal surgery in myelomeningocele , the NIH funded the MOMS trial. This prospective randomized trial will compare outcomes with open fetal surgery performed at 18 to 25 6/7 weeks' gestation with postnatal surgery. As of 2008, the recruitment to the trial has been slow, with only one half of the anticipated 200 patients enrolled. The primary outcome variables for this trial are the need for a ventriculoperitoneal shunt at 1 year of age and fetal or infant mortality. Additional information regarding the MOMS trial can be obtained at the website www.spinabifidamoms.com.
Myelomeningocele (MMC) may be suspected either by abnormalities in maternal serum AFP screening or an abnormal sonographic examination. Once the MMC is suspected, the patient should be referred to a center capable of thorough anatomic diagnosis of the fetus. Confirmation of the MMC can be made by noting the presence of the cranial abnormalities discussed in the "Sonographic Findings" section. In addition, associated anomalies should be sought. Once the neural tube defect has been definitively identified, the parent should be offered the opportunity to obtain amniotic fluid for fetal karyotype analysis.
In a study of 77 fetuses retrospectively identified with isolated neural tube defects (Harmon et al., 1995), karyotype information was available in 43. The risk for chromosomal abnormalities based on the maternal age of this population was 0.3%. In the study group, however, 7 chromosomal abnormalities were discovered, an incidence of 16.3%. The difference between the expected occurrence of chromosomal abnormalities based on maternal age and the observed incidence of chromosomal abnormalities was highly significant. In the study, two cases of trisomy 18, three cases of triploidy, one case of a balanced Robertsonian translocation, and one Xq inversion were demonstrated. Subsequent studies have confirmed that between 2% and 16% of isolated neural tube defects occur in association with a chromosome abnormality or single-gene defect (Shaer et al., 2007). The most commonly associated aneuploidy in MMC is trisomy 18. We recommend obtaining a fetal karyotype because knowledge of the fetal cytogenetic status affects prognosis, management of the pregnancy, intervention, as well as recurrence risks.
Once the diagnosis of neural tube defect is confirmed, the parents should be offered the opportunity to discuss the long-term prognosis for a child with MMC with pediatric subspecialists. This is best performed in the context of a multidisciplinary team. We recommend that parents meet with a neonatologist, geneticist, pediatric neurologist, pediatric neurosurgeon, pediatric urologist, pediatric orthopedic surgeon, and if available, the physician coordinating the MMC clinic.
Long-term prognosis is related to the location of the MMC. In general, the lower the defect is on the fetus, the better the prognosis. If the diagnosis is made at <24 weeks of gestation, the parents should be offered the opportunity to terminate the pregnancy. Data from the statewide California AFP Screening Program suggest that families will act on information regarding neural tube defects. At <24 weeks of gestation, 80% of pregnant women will terminate the pregnancy when the defect is nonfatal, and 93% will terminate the pregnancy when the defect is fatal, such as anencephaly (Budorick et al., 1995).
If the diagnosis is made at >24 weeks of gestation, or if the parents elect to continue the pregnancy, the risks and benefits of elective cesarean section delivery prior to labor should be discussed. In 1991, Luthy et al. (1991) described their results of performing elective cesarean section without labor on fetuses with neural tube defects. They documented a lower risk of severe paralysis and on average, a motor function that was 3.3 spinal segments better than that expected on the basis of the anatomic level of the lesion when the affected children were 2 years of age. These authors suggested that unsplinted neural tissue and its blood supply were potentially traumatized by intrauterine pressures generated during labor. The study was subsequently criticized because it was not randomized. With additional observations, the most recent recommendations for delivery are the following (Shurtleff and Lemire, 1995): elective cesarean section is indicated when the fetus demonstrates movement of the knees and ankles and an MMC sac is observed protruding dorsally beyond the plane of the infant's back; cesarean section is contraindicated for fetuses with a known chromosomal abnormality, other congenital anomalies that significantly interfere with survival, or the absence of fetal knee or ankle movement; cesarean section has not been shown to be beneficial in primiparous women with a fetus already engaged in the breech position, fetuses with gibbous deformities, and fetuses with hypoplastic spinal cords.
The newborn infant with myelomeningocele should be handled in as sterile a manner as possible. The spinal lesion should be immediately covered with a nonadherent dressing moistened with warm physiologic Ringer's lactate or normal saline. A firm, protective ring of sterile dressings should be placed around the sac, and the sac itself should be covered with a nonadhesive dressing (Hahn, 1995; Shurtleff and Lemire, 1995). If the infant needs to be intubated, this should be performed in the prone or in the lateral recumbent position if possible. At all times, normothermia must be maintained.
An initial physical examination should be performed by the neonatologist and the pediatric neurologist or neurosurgeon to assess the functional level and the extent of the neurologic deficit (Figure 8). The sensory level can be determined by stimulating dermatomes with pinpricks. The spinal column should be examined for evidence of early scoliosis or kyphosis. Consideration should be given to performing a cranial computed tomographic (CT) and/or MRI scan so that the neurosurgeon can plan the postnatal surgical approach. The parents should be informed that if hydrocephalus is not present antenatally, it may develop after repair of the neural tube defect. Generally, if a shunt is necessary, it is placed before subsequent urologic or orthopedic repair.
The Arnold–Chiari type II malformation is present in 95% of patients with MMC. In 6% of affected patients, central ventilatory dysfunction may be present, as demonstrated by central apnea, stridor, respiratory distress, or aspiration. Bulbar involvement may result in vocal cord paralysis or dysphagia. Unfortunately, approximately half of all newborns with MMC have pneumographic abnormalities or abnormal responses to increasing CO 2 content in inspired air (Petersen et al., 1995). Therefore, standard tests of respiratory function are not useful to predict which infants will become symptomatic because of an Arnold–Chiari malformation.
MOMS Plus: Surgeons at the Colorado Fetal Care Center (CFCC) have participated in the national MOMs Trial, which pointed to marked improvement for those having fetal intervention in the areas of hydrocephalus, with a dramatic reduction in the need for shunts and improved early mobility.
While the MOMs study excluded mothers from participating in the trial if their BMI (body mass index) was greater than 35%, the CFCC offers access to this procedure for patients with a BMI of up to 40% under an institutionally approved study. It is currently the only center in the nation to offer this procedure option.
3-D Printing to Improve Patient Outcomes: To better optimize surgical interventions for the treatment of myelomeningocele, the CFCC team is utilizing 3-D imaging and 3-D printing to create models for the purpose of aiding in patch design.
The availability of a patient-specific model prior to surgery allows for the most optimal operative planning. The result reduces operative times and works to increase outcome success.
The MOMS trial was stopped after recruitment of 185 of a planned 200 subjects when a significant difference was observed in the primary endpoint of the study was reached by 158 of the 185 subjects. Death or the need for a ventriculoperitoneal shunt by one year of age occurred in 98% of the postnatal surgery group but in only 68% of the prenatal surgery group. In the postnatal myelomeningocele (MMC) repair group 82% required a VP shunt placement while only 40% of the prenatal surgery group required a VP shunt. There was also significant improvement in the composite score for mental development and motor function at 30 months. There was also an improvement in hindbrain herniation at 12 months and percentage of patients who were ambulatory at 30 months of age.
The favorable initial results of the MOMS trial must be interpreted cautiously as the favorable outcomes may not prove to be durable and these results come at considerable maternal and fetal risk.
The primary outcome of the MOMS trial was the composite outcome of fetal or neonatal death or the need for a ventriculoperitoneal shunt at 12 months of age. This occurred in 68% of infants in the prenatal surgery group, but 98% of the postnatal surgery group (p<0.001). Consistent with this finding, the incidence of infants who had no evidence of hindbrain herniation in the prenatal setting was 36% versus only 4% in the postnatal surgery group. In addition, the prenatal surgery group had a lower rate of moderate or severe hindbrain herniation (25%) compared to the postnatal surgery group (67%). Although the rate of epidermical cysts was similar in both groups, the incidence of cord tethering requiring subsequent surgical release, was significantly higher in the prenatal surgery group (8% vs 1%). In contrast, the postnatal surgery group required more Chiari decompression surgery (4/80 5%) versus prenatal surgery group (1/77 1%) and had a higher incidence of brainstem kinking (moderate or severe 14% with prenatal surgery and 37% with postnatal surgery). The incidence of syringomyelia was 39% in the prenatal surgery and 58% in the postnatal surgery groups.
While most studies have only a single primary endpoint, the MOMS trial had a second primary endpoint, a score derived from a composite of the Bayley Mental Developmental Index and the difference between the functional level and the anatomical level at 30 months of age. This composite of the Bayley Mental Developmental Index and difference between the functional and anatomic level of the lesion was significantly better in the prenatal surgery group. However, when analyzed separately, there was no difference between the groups in the Bayley Mental Developmental Index. The prenatal surgery group did significantly better in the difference between motor function and anatomical level (p=0.001). This must be interpreted continuously as the differences between anatomic and functional levels have been reported previously in MMC.
Similarly, while there is a significantly higher incidence of children able to walk, with or without orthotics, in the prenatal surgery group, may not be a sustainable outcome. It is known that many more children will be ambulatory, with or without orthotics, as toddlers only to become wheelchair bound as teenagers as their body mass increases and the work of walking becomes excessive.
While the primary outcomes of the MOMS trial are encouraging, these results were achieved with significant maternal and fetal risk in the prenatal surgery group. It is important for any mother considering open fetal surgery to repair myelomeningocele that she understands the risks to her with the current pregnancy and all future pregnancies. Mothers in the MOMS trial who had prenatal surgery experienced significant greater rate of obstetrical complication than noted in the postnatal surgery group including chorioamniotic separation (26% vs 0%, p<0.001) pulmonary edema (6% vs 0%, p=0.03), oligohydramnios (21% vs 4% p=0.001), placental abruption (6% vs 0%, p=0.03), spontaneous rupture of membranes (46% vs 8%, p<0.001), spontaneous labor (38% vs 14%, p>0.001), required blood transfusion at delivery (9% vs 1%, p=0.03), and a hysterotomy scar that was very thin, partially dehisced or completely dehisced in 35% of prenatal surgery cases but was not observed in postnatal cases. The latter remains a potential problem for all future pregnancies as the weakened area in the uterus may rupture with labor and requires that all future pregnancies be delivered by cesarean section before the onset of labor.
The fetus with myelomeningocele undergoing fetal surgery to repair the MMC derives direct benefit from the procedure making the potential risks and complications acceptable to assume in the effort to benefit from the surgery. MMC is not ordinarily a lethal condition and would not be expected to result in intrauterine fetal demise or stillbirth. There are postnatal deaths associated with MMC which are most often due to cranial nerve dysfunction thought to be caused by hindbrain herniation resulting in apnea, swallowing difficulties and bradycardia. While decompression surgery may be beneficial it is not always the case and the two neonatal deaths in the postnatal surgery group of the MOMS trial were due to this complication. More often deaths associated with MMC relate to ventriculoperitoneal shunt infections or shunt malformation. In years past, renal failure and renal sepsis were common causes of morbidity and mortality in MMC but with a modern approach to MMC management, are now rarely observed.
There were two fetal deaths in the prenatal surgery group due to intrauterine fetal demise at 26 weeks and a neonatal death due to prematurity when the mother delivered at 23 weeks gestation.
Prematurity is an important complication, in all cases of open fetal surgery with the average gestation age at delivery in the prenatal surgery group being 34.1 weeks while the postnatal surgery group delivered on average at 37.5 weeks. But in the prenatal surgery group, 13% delivered prior to 30 weeks gestation versus 0% in the postnatal group and 46% delivered ≤ 34 weeks in the prenatal surgery group as compared to 5% in the postnatal surgery group. This much higher incidence of prematurity in the prenatal surgery group likely accounts for the smaller birth weight (2383 ± 688 versus 3039 ± 465 grams p<0.001), greater incidence of apnea (36% versus 22% p<0.06), and the greater incidence of respiratory distress syndrome (21% versus 6% p=0.008).
Every mother should have a full and complete understanding of all of the potential risks and complications that she would expose herself and her body to in order to have prenatal surgery to repair MMC. The mother derives no direct benefit from this surgery. The most analogous situation to prenatal surgery for MMC is a parent undergoing living related kidney donation for transplantation into their child. In the case of prenatal surgery for MMC, the observed risks are mostly obstetrical in nature. However, one must also consider the potential risks of general anesthesia, deep venous thrombosis, pulmonary embolism, amniotic fluid embolism, a massive hemorrhage from abruption requiring hysterotomy and death. None of these complications occurred in the MOMS trial but only 92 women were randomized to the prenatal surgery group. It is entirely possible that as more mothers undergo prenatal surgery, that these serious obstetrical complications may be observed more frequently. It is also possible that maternal complications may be seen more commonly as these procedures are undertaken by centers with limited experience with open fetal surgery. The results of the MOMS trial presents another management option for mothers to consider for their baby with MMC. It is by no means the only option nor necessarily the preferred option, but an option with considerable attendant risks for both the mother and her baby.
The CFCC, one of the most experienced fetal surgery centers in the world, offers prenatal surgery to repair MMC. The fetal surgery team includes experts with considerable experience with prenatal surgery for myelomeningocele. Leading the surgical team is Dr. Timothy M. Crombleholme, director of the CFCC. Dr. Crombleholme was a co-investigator on the MOMS Trial before moving from The Children's Hospital of Philadelphia to the Fetal Care Center of Cincinnati in 2004 and then to the Colorado Fetal Care Center in 2011. He participated in design and development of the MOMS Trial and in over 50 open fetal surgeries for repair of MMC. Team members include noted pediatric neurosurgeon Dr. Michael Handler, and fetal surgeons Dr. Ken Liechty and Dr. Rony Marwan.
The criteria used to qualify patients for this treatment option are based on our previous experience with open fetal surgery for MMC and the results of the MOMS trial. In order to be considered for prenatal MMC repair the following criteria must be met:
If a mother meets all of the qualifying criteria and wishes to proceed with prenatal surgery, she will undergo counseling by a Maternal Fetal Medicine Specialist not part of the operative team to ensure: 1.) she has been appropriately counseled about the potential obstetric, maternal and fetal risks and complications and; 2.) she has an accurate appreciation of the implications of these risks and complications prior to being consented for the surgery. A separate consent team meeting is held to review the potential anesthetic, obstetrical, neurosurgical and fetal surgical and neonatal risks of the procedure with the representation of each respective discipline present to review these potential risks and complications.
Prenatal repair of MMC is a new treatment option that has only recently become available with reporting of the MOMS Trial results. In order to independently assess each case offered prenatal MMC repair, the Colorado Fetal Care Center has a Prenatal MMC Repair Oversight Committee. The committee is composed of a senior Pediatric Neurosurgeon, Maternal–Fetal Medicine Specialist, Neonatologist, Pediatric Surgeon and Developmental Pediatrician who specializes in MMC. The members of the committee will review the case of every mother offered prenatal MMC repair to be certain that a.) all criteria are met, b.) she was appropriately counseled about the potential risks and complications and c.) review each adverse event or complication, d.) review maternal and fetal outcomes of the surgery. This committee will be empowered to stop prenatal MMC repair surgery being offered in the event of a maternal or fetal complication until a more thorough investigation can be completed. This committee will decide the number of cases necessary to discontinue oversight as indicated when results comparable or superior to the MOMS trial are achieved.
1. At least two of the following:
2. The presence of marked syringomyelia (syrinx with the expansion of spinal cord) with ventriculomegaly (undefined).
3. Ventriculomegaly (undefined) and symptoms of Chiari malformation (stridor, swallowing difficulties, apnea, bradycardia)
4. Persistent cerebrospinal fluid leakage from the myelomeningocele wound or building at the repair site.
As compared with postnatal surgery, prenatal surgery for myelomeningocele that was performed before 26 weeks of gestation decreased the risk of death or need for shunting by the age of 12 months and also improved scores on a composite measure of mental and motor function, with adjustment for lesion level, at 30 months of age. Prenatal surgery also improved several secondary outcomes, including the degree of hindbrain herniation associated with the Chiari II malformation, motor function (as measured by the difference between the neuromotor function level and anatomical lesion level), and the likelihood of being able to walk independently, as compared with postnatal surgery.
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. The improvements were probably associated with the timing of the repair, which may have permitted more normal nervous-system development prenatally. Reductions in rates of shunt placement (or need for shunting) in the prenatal-surgery group were probably due to the reduction in rates of hindbrain herniation and improved flow of cerebrospinal fluid. In the case of infants with low lumbar and sacral lesions, in whom less impairment in lower-limb function may be predicted, the normalization of hindbrain position and the minimization of the need for postnatal placement of a cerebrospinal fluid shunt may be the primary indication for surgery.
Potential benefits of prenatal surgery must be balanced against the risks of prematurity and maternal morbidity. Prenatal surgery was associated with higher rates of preterm birth, intraoperative complications, and uterine-scar defects apparent at delivery, along with a higher rate of maternal transfusion at delivery. Chorioamniotic separation, which increases the risk of premature membrane rupture, 2° was observed on ultrasonography in one fourth of women after prenatal surgery. Preterm labor leading to early delivery, placental abruption, and pulmonary edema associated with tocolytic therapy are well-known complications of prenatal surgery. The assessment of the hysterotomy site at the time of delivery revealed thinning or an area of dehiscence in more than one-third of the women. Since uterine dehiscence and rupture in a subsequent pregnancy are recognized risks of prenatal surgery, 22 mothers who undergo prenatal surgery must understand that all subsequent pregnancies should be delivered by cesarean before the onset of labor.
Several aspects of the prenatal-surgery technique that was used in this trial warrant comment. All surgeons used a stapling device with absorbable staples for uterine entry. This approach minimizes blood loss and, in contrast with the use of metal staples, does not impair subsequent fertility. 21-23 In all cases, a multidisciplinary team of experts followed a standard protocol to perform fetal surgery. The results of this trial should not be generalized to patients who undergo procedures at less experienced centers or who do not meet the eligibility criteria. For example, a body-mass index of 35 or more was an exclusion criterion for safety reasons, even though obesity is common among women carrying a fetus with myelomeningocele. Although the prenatal-surgery group had better outcomes than the postnatal surgery group, not all infants benefited from the early intervention, and some had a poor neuromotor outcome. Finally, for the children in this study, continued follow-up is needed to assess whether the early benefits are durable and to evaluate the effect of the prenatal intervention on bowel and bladder continence, sexual function, and mental capacity.
Previous cohort studies have suggested improved outcomes with prenatal surgery for myelomeningocele. 24-28 However, since comparisons between infants who were treated in utero and historical controls are subject to substantial bias, results from a randomized trial were needed to confirm benefits and inform risks. In our study, prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months, but the early intervention was associated with both maternal and fetal morbidity (Adzick et al., 2011)
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Cardiology - Pediatric, Pediatrics
Surgery - Pediatric, Surgery
Ob/Gyn Obstetrics & Gynecology
Ob/Gyn Obstetrics & Gynecology, Maternal-Fetal Medicine