- What Is Spina Bifida (Meningomyelocele)?
Spina bifida is a congenital birth defect in which an area of the fetal spine doesn’t develop and close properly early in pregnancy, leaving a section of the spinal cord and spinal nerves exposed. Because of the opening in the spine, the nerves of the spinal cord may become damaged. A spinal cord that is damaged may not be able to send messages to and from the brain regarding body temperature, pain/touch sensations, bodily movements and other important functions.
Myelomeningocele is the most common and most serious form of spina bifida, in which part of the spinal cord and surrounding nerves push through the vertebrae in the spine and protrude from the fetus’ back. Usually, the exposed spinal cord and nerves are contained in a sac that is exposed to amniotic fluid in the womb. Continuous bathing of the fragile developing spinal cord in amniotic fluid can result in progressive neurologic injury.
A baby born with meningomyelocele may experience:
- Bladder and bowel problems (incontinence).
- Weakness, loss of sensation or paralysis below the defect.
- Chiari Malformation: A condition that affects how the back of the brain forms, leading to positioning near the upper spinal column. This lower-than-normal brain positioning obstructs the flow of fluid out of the brain, and may lead to hydrocephalus and cognitive impairments.
- Hydrocephalus (water in the brain): Occurs when there’s too much cerebrospinal fluid in the head.
- Abnormal development of the feet and legs, such as clubfoot.
- What Does Spina Bifida Repair Involve?
The decision to pursue prenatal or postnatal myelomeningocele spina bifida treatment is a very personal one that may be influenced by such factors a:
- Gestational age
- The extent of the myelomeningocele lesion on the spine
- Maternal health considerations
Because spinal cord damage is progressive during gestation, our maternal-fetal medicine experts may offer to treat your baby by performing a meningomyelocele repair in utero to help prevent further damage and give your baby improved quality of life.
When a fetus has meningomyelocele spina bifida, their nerves are exposed to elements that could cause further harm, like amniotic fluid, cerebrospinal fluid and direct trauma. Open fetal surgery may prevent other injuries or complications from developing during the remainder of the pregnancy. Our surgeons and available counselors will thoroughly explain the benefits and risks of spina bifida treatment so you can make the best treatment decision for your family.
Open Fetal Surgery for Spina Bifida Repair
During meningomyelocele fetal surgery, a surgeon will access the uterus and repair the defect in your baby’s spine using tiny instruments and image-guided technology. The opening will be closed with skin from your baby’s back to protect their developing spinal cord and nerves. This will all be done without interfering with your pregnancy. Once the procedure is finished, we leave the baby to keep growing and closely monitor you until delivery day.
Postnatal Spina Bifida Repair
If you and your fetal care team decide the best course of action is to repair your baby’s myelomeningocele after their birth, you will receive frequent ultrasounds to monitor the growth of your baby throughout the pregnancy. Surgical repair to close the spina bifida will likely take place within the first few days of your baby’s life.
Our care doesn’t stop there. We work with a multidisciplinary team of pediatric neurosurgery, urology, social work and other specialists as needed to provide support to help your baby thrive.
For Healthcare Providers
- Myelomeningocele: Introduction
Neural tube defects are the second most prevalent neonatal anomaly in the United States, ranking behind only cardiac malformations. Worldwide, 400,000 infants are born each year with a neural-tube defect (Rieder 1994). Myelomeningocele is an open spinal-cord defect that protrudes dorsally, is not covered by skin, and is usually associated with spinal-nerve paralysis. Technically, spina bifida refers to a cleft or opening in the vertebral body; this term is also used to collectively describe a group of disorders that involve the spinal cord. Lumbosacral lipomas are subcutaneous masses of fat in the lumbosacral region (Shurtleff and Lemire 1995). Myelomeningoceles are malformations that result from failure of the neural tube to fuse during early embryogenesis, at approximately 26 days post-ovulation, when the caudal neuropore is closing. Skin-covered defects, such as lipomyelomeningocele, result from abnormalities in secondary neurulation and retrogressive differentiation occurring between days 28 and 56 post-ovulation (Shurtleff and Lemire 1995).
The first medical report of a myelomeningocele was made by a Dutch physician, Nicholas Tulp, who practiced between 1593 and 1674. He described a series of six cases of patients with spina bifida (Tulp, 1716).
“Open” neural-tube defects (spina bifida aperta) are myelomeningoceles that are not covered by skin. Leakage of α-fetoprotein (AFP) from the cerebrospinal fluid (CSF) into the amniotic fluid results in an increased transport of AFP into the maternal circulation. Screening by maternal serum AFP analysis has resulted in an increased ability to detect these lesions prenatally.
Herniation of the spinal cord probably reduces intraspinal pressure. This allows the hindbrain to become downwardly displaced, resulting in the Chiari type II malformation, which is seen almost exclusively in patients affected with myelodysplasia. It is characterized by caudal movement of the cerebellar vermis, brain stem, and fourth ventricle. The Chiari type II malformation is responsible for many of the deaths during the first two years of life seen in patients affected with myelodysplasia. Chiari, a professor of pathology in Prague, wrote two papers in 1891 and 1896 that described four types of pathologic changes occurring in 40 affected patients (Rauzzino and Oakes, 1995). These changes concerned the abnormal position of the cerebellum in relation to the foramen magnum. Arnold, in contrast, published a single case report in 1894 that described a single patient with myelodysplasia and other congenital anomalies (Rauzzino and Oakes 1995).
Embryolgenesis and Pathogenesis of Myelomeningoceles
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 processes move 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).
Open neural tube defects
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, as well as 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, which 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).
Closed neural tube defects
Clinically, closed neural tube defects (spina bifida aperta) should be differentiated from open neural tube defects (spina bifida occulta) 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 contaning 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% of children affected by neural tube defects die (Moore et al., 1997); in the Netherlands, 35% (den Ouden et al., 1996); and in the United States, 10% (Shurtleff et al., 1994).
- Incidence of Myelomeningocele
The incidence and live-birth prevalence of myelo-meningocele are correlated strongly with ethnic and geographic factors. The highest frequencies of neural-tube defects are found in Great Britain, Ireland, Pakistan, Northern India, Egypt, and Arab countries. The lowest incidences are found in Finland, Japan, and Israel. Even in the United States, a geographic distribution of these defects occurs, with the frequency being the highest in the East and the South, and the lowest in the West (Harmon et al. 1995). There is an increased incidence of neural-tube defects in Hispanics, especially if the mother was born in Mexico (Shaw et al. 1994).
The live-birth prevalence of infants with myelomeningocele has changed dramatically since the advent of widespread maternal serum screening for AFP. Before 1980, the live-birth prevalence of infants with neural-tube defects was between 1.5 and 4.5 per 1000 live births. After 1980, this decreased to 0.74 to 2.5 per 1000 live births (Shurtleff and Lemire 1995). In the United States, the live-birth prevalence of infants with neural-tube defects is 0.41 to 1.43 per 1000. The lowest incidence of neural-tube defects is in African blacks, who have a live-birth prevalence of 1 per 10,000 (Shurtleff and Lemire 1995). Because the screening tests detect anencephaly as well as myelo-meningocele, and many parents decide to terminate pregnancies affected with the uniformly fatal anencephaly, the incidence of myelomeningocele has increased as a percentage of all cases of neural-tube defects (Rieder 1994).
In a review of factors associated with neural-tube defects in the NIH-sponsored Collaborative Perinatal Project that reviewed the pregnancies of 53,000 pregnant women, Myrianthopoulos and Melnick (1987) demonstrated that maternal diabetes mellitus, heart disease, lung disease, and use of diuretics, antihistamines, or sulfonamides were all associated with an increased risk of neural-tube defects. In addition, women who had a short interval between the end of the previous pregnancy and the current pregnancy had an increased incidence of neural-tube defects. Most of the cases reviewed in the Collaborative Perinatal Project demonstrated that the neural-tube defect was an isolated malformation. More recently, it has been shown that the use of the anticonvulsants valproic acid and carbamazepine are also associated with neural-tube defects. Similarly, maternal history of increased alcohol intake, nutritional deficiencies, and use of the folic acid inhibitor aminopterin are also associated with an increased incidence of neural-tube defects. Neural-tube defects are also associated with low socioeconomic status, a positive family history, and twinning. In general, females are affected more often than males (Källén et al. 1994).
- Sonographic Findings
Prior to the mid-1980s, sonographic diagnosis of myelomeningocele relied on the meticulous scanning of the vertebrae for abnormalities. Using this method, neural-tube defects were often missed. More recently, the prenatal sonographic diagnosis of myelomeningocele has been enhanced by 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 that have been 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 findings have been referred to as the “fruit” signs, which include the lemon sign and the banana sign. The lemon sign (Fig. 1) describes a concave or flattened frontal contour of the fetal calvarium rather than a normal convex frontal contour. The banana sign (Fig. 2) 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 has not been described 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 of gestation. Cerebellar abnormalities were seen in 95% of fetuses at any stage of gestation, although the banana sign was more typical at <24 weeks of gestation, and apparent cerebellar absence was typical of fetuses at >24 weeks of gestation. 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 cerebroventriculomegaly 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 meningomyelocele (Fig. 19-1B). 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 meningomyelocele 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 a 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.
Kollias et al. (1992) assessed the sonographic accuracy of the estimation of spinal level involved in the meningomyelocele. Of 28 cases studied, sonographic and pathologic levels were in agreement in 18 (64%) and within one spinal level in 22 (79%).
The 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 interrupt the normal parallel configuration of the vertebral arches (Fig.3). In the transverse plane, ossification centers in the neural arch either diverge or take on a U-shaped configuration (Fig.4). The presence of scoliosis or kyphosis is associated with neural-tube defects.
Other sonographic findings that may suggest a myelomeningocele include a cystic meningeal sac, which may have a shimmering effect with fetal motion (Fig.5) (Budorick et al. 1995). The sonographer should also examine the fetus’s lower extremities for the possibility of clubbed feet.
The incidence of associated anomalies in meningomyelocele is lower in reports derived from living children versus those in autopsy series. In one series of 181 patients with myelodysplasia, 5 had renal malformations and 3 had congenital heart disease (Kreder et al. 1992).
The adjunctive use of magnetic imaging (MRI) of the fetus has provided additional and complimentary information to ultrasound examination alone. The results of at least two studies suggest that fetal MRI 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). As a practical matter, we primarily rely on ultrasound to determine the spinal level of myelomeningocele. MRI 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.
Fetal MRI is also particularly useful in evaluating the posterior fossa in fetuses with myelomeningocele and determining the presence or absence of hindbrain herniation. Fetal MRI is also able to detect the presence of grey matter heterotopia which occurs in up to 20% of cases of myelomeningocele (based on autopsy studies). We consider fetal MRI an invaluable adjunct to ultrasound in the evaluation of the fetus with myelomeningocele. We also use post-operative fetal MRI to evaluate the response to prenatal myelomeningocele repair by rountinely obtaining a follow up MRI two weeks following the surgery to determine if there has been reversal of hindbrain herniation.
- Differential Diagnosis
The differential diagnosis for myelomeningocele includes isolated hemivertebrae. The lemon sign, as stated earlier, has also been seen in encephalocele, thanatophoric dysplasia, cystic hygroma, and craniosynostosis (Fig.1B). The demonstration of a mass near the fetal sacrum must also call to mind the possible diagnosis of sacrococcygeal teratoma. Sacrococcygeal teratomas are large cystic or solid masses arising from the coccyx. These masses may be associated with fetal hydrops or polyhydramnios. If the fetal sacral bones cannot be visualized, considerations in the differential diagnosis also include the caudal regression syndrome and sirenomelia.
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 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%), 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 compared outcomes with open fetal surgery performed at 18 to 25 6/7 weeks’ gestation with postnatal surgery.
Critical Assessment of the MOMS Trial
Summary of Results
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. (see Table 1) 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 (Adzick et al 2011). In the postnatal 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) (see Table 2 and Figure 1). 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.
Table 1.Baseline Characteristics of the Study Population.*
Fetal sex female – no (%) 35 (45) 51 (64) Gestational age at randomization – wk 23.6±1.4 23.9±1.3 Maternal age at screening – yr 29.3±5.3 28.8±4.9 Race or ethnic group – no. (%)† White 73 (94) 74 (92) Black 1 (1) 1 (1) Hispanic 2 (3) 4 (5) Other 2 (3) 1 (1) Married or living with partner – no. (%) 73 (94) 74 (92 Years of schooling – no. 14.8±1.7 15.0±1.6 Body-mass index at trial entry‡ 26.2±3.7 25.9±3.9 Current smoker – no. (%) 6 (8) 4 (5) Either parent with familial history of neural-tube defect – no. (%) 8 (10) 14 (18) Nullipara – no. (%) 33 (42) 36 (45) Previous uterine surgery – no. (%) 11 (14) 8 (10) Cervical length – mm 38.9±7.3 39.7±5.7 Anterior placenta – no. (%) 36 (46) 32 (40) Lesion level on ultrasonography – no. (%) Thoracic 4 (5) 3 (4) L1-L2 21 (27) 10 (12) L3-L4 30 (38) 45 (56) L5-S1 23 (29) 22 (28) Lesion level L3 or lower on ultrasonography – no. (%) 53 (68) 67 (84) Club foot on ultrasonography – no. (%) 20 (26) 15 (19)
*Plus-minus values are means ±SD. The only between-group comparisons that were significant were the female se of the fetus and a lesion level of L3 or lower on ultrasonography (P=0.02 for both comparisons). Percentages may not total 100 because of rounding. †Race or ethnic group was self-reported. ‡The body-mass index is weight in kilograms divided by the square in height in meters. Adapted from Adzick et al A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele. N Engl J Med. 2011 Feb 9. [Epub ahead of print]
From Adzick NS, Thom EA, Spong KY et al: A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 364: 993-1004, 2011
Table 2. Infant Outcomes at 12 Months.* Outcome Prenatal Surgery
P Value Primary Outcome-no. (%) 53 (68) 78 (98) 0.70 (0.58-0.84)† <0.001 Components of primary outcome – no. (%) <0.001 Death before placement of shunt 2 (3) 0 Shunt criteria met 51 (65) 74 (92) Shunt placed without meeting criteria 0 4 (5) Placement of shunt – no. (%) 31 (40) 66 (82) 0.48 (0.36-0.64) <0.001 Any hindbrain herniation – no./total no. (%) 45/70 (64) 66/69 (96) 0.67 (0.56-0.81) <0.001 Degree of hindbrain herniation – no./total no. (%) <0.001‡ None 25/70 (36) 3/69 (4) Mild 28/70 (40) 20/69 (29) Moderate 13/70 (19) 31/69 (45) Severe 4/70 (6) 15/69 (22) Any brainstem kinking – no./total no. (%) 14/70 (20 33/69 (48) 0.42 (0.25-0.71) <0.001 Degree of brainstem kinking – no./total no. (%) 0.001‡ None 56/70 (80) 36/69 (52) Mild 4/70 (6) 8/69 (12) Moderate 7/70 (10) 17/69 (25) Severe 3/70 (4) 8/69 (12) Abnormal location of fourth ventricle – no./total no. (%) 32/70 (46) 49/68 (72) 0.63 (0.47-0.85) 0.002 Location of fourth ventricle – no./total no. (%) <0.001‡
P Value Normal 38/70 (54) 19/68 (28) Low 28/70 (4) 29/68 (43) At foramen magnum 1/70 (1) 8/68 (12) Below foramen magnum 3/70 (4) 12/68 (18) Syringomyelia – no./total no. (%) 27/69 (39) 39/67 (58) 0.67 (0.47-0.96) 0.03 Epidermoid cyst – no./total no. (%) 2/67 (3) 1/66 (2) 1.97 (0.18-21.20) 1.00 Surgery for tethered cord – no./total no. (%) 6/77 (8) 1/80 (1) 6.15 (0.76-50.00) 0.06 Chiari decompression surgery – no./total no. (%) 1/77 (1) 4/80 (5) 0.26 (0.03-2.24) 0.37 Shunt infection – no./total no. (%) 5/77 (6) 7/80 (9) 0.73 (0.24-2.21) 0.58
*Percentages may not total 100 because of rounding.
†The relative risk for the composite primary outcome is reported with a 97.7% confidence interval.
‡The between-group comparison was performed with the use of the Cochran-Armitage test for trend. Adapted from Adzick et al A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele. N Engl J Med. 2011 Feb 9. [Epub ahead of print]
From Adzick NS, Thom EA, Spong KY et al: A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 364: 993-1004, 2011
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. (Table 3)
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 cautiously 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.
Maternal Risks and Complications
While the primary outcomes of the MOMS trial are encouraging, these results were achieved at significant maternal and fetal risk in the prenatal surgery group. (Table 4)
Table 3. Outcomes of Children at 30 months.* Outcome Prenatal Surgery
P Value Primary outcome score 148.6±57.5 122.6±57.2 0.007 Primary outcome components Bayley Mental Development Index† 89.7±14.0 87.3±8.4 0.53 Difference between motor function and anatomical levels‡ 0.58±1.94 -0.69±1.99 0.001 Bayley Mental Development Index – no./total no. (%)† ≥50 60/62 (97) 59.67 (88) 1.10 (1.00-1.21) 0.10 ≥85 46/62 (74) 45/67 (67) 1.10 (0.88-1.38) 0.38 Difference between motor function and anatomical levels 0.002§ -no./total no. (%)‡ ≥Two levels better 20/62 (32) 8/67 (12) One level better 7/62 (11) 6/67 (9) No difference 14/62 (23) 17/67 (25) One level worse 13/62 (21) 17/67 (25) ≥Two levels worse 8/62 (13) 19/67 (28) Bayley Psychomotor Development Index † Mean 64.0±17.4 58.3±14.8 0.03 ≥50 – no./total no. (%) 29/62 (47) 23/67 (34) 1.36 (0.89-2.08) 0.15 ≥85 – no./total no. (%) 10/62 (16) 4/67 (6) 2.70 (0.89-8.17) 0.06 Peabody Development Motor Scales ¶ Stationary score 7.4±1.1 7.0±1.2 0.03 Locomotion score 3.0±1.8 2.1±1.5 0.001 Object manipulation score 5.1±2.6 3.7±2.1 <0.001 Walking independently on examination – no./total no. (%) 26/62 (42) 14/67 (21) 2.01 (1.16-3.48) 0.01 Walking status – no./total no. (%) 0.03 None 18/62 (29) 29/67 (43) Walking with orthotics or devices 18/62 (29) 24/67 (36) Walking without orthotics 26/62 (42) 14/67 (21) WeeFIM score║ Self-care 20.5±4.2 19.0±4.2 0.02 Mobility 19.9±6.4 16.5±5.9 0.003 Cognitive 23.9±5.2 24.1±5.9 0.67
*Plus-minus values are means ±SD. Listed are data for 134 of 136 patients who underwent randomization before December 1, 2007; data for 2 patients were not available. Before 30 months, there were 5 deaths (2 in the prenatal-surgery group and 3 in the postnatal-surgery group), so data for those infants are not included in any category except the primary-outcome score. Percentages may not total 100 because of rounding.
†On the Bayley Scales of Infant Development II, the Mental Development Index and the Psychomotor Development Index are both scaled to have a population mean (±SD) of 100±15, with a minimum score of 50 and a maximum score of 150. Higher scores indicate better performance.
‡For the difference between the motor-function level and the anatomical level, positive values indicate function that is better than expected on the basis of the anatomical level.
§The between-group comparison was performed with the use of Cochran-Armitage test for trend.
¶On the Peabody Developmental Motor Scales, the mean (±SD) score was 10±3, with a minimum score of 0 and a maximum score of 20.
Higher scores indicate better performance.
║On the WeeFIM evaluation, the score on the self-care measurement ranges from 8 to 56, and scores on the mobility and cognitive measurements range from 5 to 35, with higher scores indicating greater independence. Adapted from Adzick et al A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele. N Engl J Med. 2011 Feb 9. [Epub ahead of print]
From Adzick NS, Thom EA, Spong KY et al: A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 364: 993-1004, 201
Table 4. Maternal and Fetal or Neonatal Outcomes.* Outcome Prenatal Surgery
Postnatal Surgery (N=80) Relative Risk
P Value Maternal Outcome Chorioamniotic membrane separation – no. (%) 20 (26) 0 NA <0.001 Pulmonary edema – no. (%) 5 (6) 0 NA 0.03 Modified biophysical profile <8 – no. (%) † 13 (17) 6 (8) 2.22 (0.89-5.55) 0.08 Oligohydramnios – no. (%) 16 (21) 3 (4) 5.47 (1.66-18.04) 0.001 Placental abruption – no. (%) 5 (6) 0 NA 0.03 Gestational diabetes – no. (%) 4 (5) 5 (6) 0.82 (0.23-2.94) 1.00 Chorioamnionitis – no. (%) 2 (3) 0 NA 0.24 Preeclampsia or gestational hypertension – no. (%) 3 (4) 0 NA 0.12 Spontaneous membrane rupture – no. (%) 36 (46) 6 (8) 6.15 (2.75-13.78) <0.001 Spontaneous labor – no. (%) 30 (38) 11 (14) 2.80 (1.51-51.8) <0.001 Blood transfusion at delivery – no. (%) 7 (9) 1 (1) 7.18 (0.90-57.01) 0.03 Status of hysterotomy site at delivery-no./total no. (%) Intact, well-healed 49/76 (64) Very thin 19/76 (25) Area of dehiscence 7/76 (9) Complete dehiscence 1/76 (1) Fetal or neonatal outcome Bradycardia during fetal or neonatal repair – no. (%) 8 (10) 0 NA 0.003 Perinatal death – no. (%) 2 (3) 2 (2) 1.03 (0.14-7.10) 1.00 Gestational age at birth – wk 34.1±3.1 37.3±1.1 <0.001 Gestational age at birth – no. (%) <0.001‡ <30 wk 10 (13) 0 30-34 wk 26 (33) 4 (5) 35-36 wk 26 (33) 8 (10) ≥37 wk 16 (21) 68 (85) Outcome Birth Weight Mean – g 2383±688 3039±469 <0.001 Outcome Prenatal Surgery
Postnatal Surgery (N=80) Relative Risk
P Value Maternal Outcome 0 2 (2) NA 0.50 Less than 10th percentile – no. (%) 3 (4) 7 (9) 0.45 (0.12-1.66) 0.33 Dehiscence at repair site – no./total no. (%) 10/77 (13) 5/80 (6) 2.05 (0.73-5.73) 0.16 Apnea – no./total no. (%) 28/77 (36) 18/80 (22) 1.62 (0.98-2.67) 0.06 Pneumothorax – no.total no. (%) 1/77 (1) 1/80 (1) 1.05 (0.07-16.53) 1.00 Respiratory distress syndrome – no./total no. (%) § 16/77 (21) 5/80 (6) 3.32 (1.28-8.63) 0.008 Patent ductus arteriosus-no./total no.(%)¶ 3/77 (4) 0 NA 0.12 Sepsis-no./total no.(%) ║ 4/77 (5) 1/80 (1) 4.16 (0.48-36.36) 0.20 Necrotizing enterocolitis-no./total no.(%)** 1/77 (1) 0 NA 0.49 Periventricular leukomalacia-no./total no.(%) 4.77 (5) 2/80 (2) 2.08 (0.39-11.02) 0.44 Foot deformity-no./total no.(%) 39/78 (50) 36/80 (45) 1.11 (0.80-1.54) 0.53
* Plus-minus values are means ±SD. There were no instances of bronchopulmonary dysplasia, pulmonary interstitial emphysema, retinopathy of prematurity, pulmonary hypoplasia, grade 3 or 4 intraventricular hemorrhage, or confirmed seizures in either group. Data for neonatal outcomes are listed for 77 infants in the prenatal-surgery group, since 1 infant was stillborn. Additional rare adverse events are provided in Supplementary Appendix, along with the adverse events for 25 additional randomized patients and their offspring (median follow-up from randomization, 29.9 weeks) who underwent randomization on or after July 1, 2009. Percentages may not total 100 because of rounding. NA denotes not applicable.
† The modified biophysical profile is a test of fetal well-being that is calculated on the basis of results of ultrasonography evaluating presence of fetal breathing, movement, and tone, along with the amniotic fluid index. The highest possible score is 8.
‡ The between-group comparison was performed with the use of Cochran-Armitage test for trend.
§Respiratory distress syndrome was defined as a clinical diagnosis of the respiratory distress syndrome type 1 and the need for oxygen therapy (fraction of inspired oxygen, ≥0.40) at 24 hours of age or more.
¶ Patent ductus arteriosus was reported if the infant was treated with medications or surgery.
║Sepsis was defined as confirmation on blood culture, confirmed urinary tract infection, meningitis, or pneumonia.
** Necrotizing enterocolitis was defined as a confirmed clinical diagnosis with any of the following findings observed on radiography, at the time of surgery, or at autopsy: unequivocal presence of intramural air, perforation, erythema and induration of the abdominal wall, intraabdominal abscess formation, or the formation of a stricture after an episode of suspected necrotizing enterocolitis. Adapted from Adzick et al A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele. N Engl J Med. 2011 Feb 9. [Epub ahead of print]
From Adzick NS, Thom EA, Spong KY et al: A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 364: 993-1004, 2011
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 significantly 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.
Fetal and Neonatal Complications
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 (Table 4).
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 modern approach to MMC management utilizing straight intermittent bladder catheterization, 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).
Weighing the Risks and Benefits of Prenatal Surgery for MMC
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, massive hemorrhage from abruption requiring hysterectomy and/or 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.
Prenatal MMC Surgery at the Fetal Care Center of Dallas
The Fetal Care Center of Dallas, which has one of the most experienced fetal surgeons in the world, is now offering prenatal surgery to repair MMC. The fetal surgery team includes experts with considerable experience with prenatal surgery for MMC. Timothy M. Crombleholme, MD, Director of the Fetal Care Center of Dallas performed 52 prenatal MMC repairs prior to the MOMS trial and co-authored the original reports in Lancet and JAMA demonstrating reversal of hindbrain herniation with prenatal MMC repair (Adzick et al 1998, Sutton et al 1999). He was a co-investigator on the MOMS Trial before moving from CHOP to Cincinnati to found The Fetal Care Center of Cincinnati in 2004. He participated in design and development of the MOMS Trial and in over 65 open fetal surgeries for repair of MMC since the MOMS trial closed.
Refined Criteria for Prenatal Repair of Myelomeningocele Ventriculomegaly
In the initial MOMS trial report results were published before all patients randomized could be fully assess for the primary endpoint (Adzick et al 2011). In a follow up report Tulipan et al, described the results for the entire cohort which included an analysis of factors which impacted the primary composite endpoint of death or need for ventriculoperitoneal shunting by one year of age. Logistic regression analysis adjusting for sex and lesion level revealed that ventricular size at screening and gestational age at randomization were associated with a differential effect of prenatal surgery on shunt placentment (Tulipan et al 2015). In the prenatal surgery group, 20% of those with ventricle size < 10 mm, 45.2% with ventricle size 10 to 15 mm and 79% with ventricle size >15 mm received a ventriculoperitoneal shunt. In contrast, the postnatal group 79.4%, 86%, and 87.5%, respectively, required a shunt (Tulipan et al 2015).
There has been the suggestion that even though a fetus with ventricles >15 mm will not have any reduction in the need for ventriculoperitoneal shunt there may be benefit to urologic function with reduced need for chronic intermittent bladder catheterization (Carr et al 2015).
At the Fetal Care Center of Dallas we consider lateral ventricles a the time of screening >15 mm as an exclusion criteria based on the MOMS trial report by Tulipan and our own outcomes. In a series of 65 patients, Dr Crombleholme found that fetus’s ventricles <10 mm at screening had only a 25% rate of ventriculoperitoneal shunt placement by one year of age, whereas those with ventricles >10 mm <15mm had a shunt rate of 37% and those with ventricles >15 mm had a 100% shunt rate. As a result we only offer prenatal myelomeningomyelocele repair to mothers who’s fetus has ventricles <15 mm at presentation.
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:
- Myelomeningocele at T1 through S1 with hindbrain herniation, level of MMC confirmed by ultrasound and hindbrain herniation confirmed by MRI.
- Lateral ventricles measure <15 mm
- Maternal age greater than or equal to 18 years.
- Gestational age 19 0/7 weeks to 26 0/7 at the time of prenatal surgery.
- Normal karyotype or FISH.
- Normal fetal echocardiogram.
- Singleton pregnancy.
- Willing to remain in greater Dallas area for at least 2 weeks after the surgery before being transferred back to the care of her referring Maternal Fetal Medicine Specialist
- Ventricles >15 mm
- Significant fetal anomaly not related to MMC.
- Kyphosis in fetus of greater than 30 degrees.
- History of incompetent cervix, cervix less than 20mm or presence of a cerclage.
- Morbid obesity as defined as a BMI of greater than 35.
- Maternal – fetal Rh isoimmunization, Kell sensitization or a history of neonatal alloimmune thrombocytopenia.
- Maternal HIV, Hepatitis B, Hepatitis C due to increased risk of transmission to the fetus during maternal – fetal surgery.
- Uterine anomaly such as large or multiple uterine fibroids or mullerian duct abnormality.
- Maternal medical condition which is a contraindication to abdominal surgery or general anesthesia.
- No support person to stay with mother at Ronald McDonald House.
- Patient does not meet psychosocial criteria as determined by the social worker evaluation.
- Previous hysterotomy in the active segment of the uterus either from previous classical cesarean section, uterine anomaly such as an arcuate or bicornuate uterus, major myomectomy resection or previous open fetal surgery.
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 insure: 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 representation of each respective discipline present to review these potential risks and complications.
Oversight of prenatal surgery for MMC at the Fetal Care Center of Dallas
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 Fetal Care Center of Dallas has a Prenatal MMC Repair Oversight Committee. 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.
Fetoscopic versus Open Fetal Surgery for Prenatal Myelomeningocele Repair
The results of the MOMS trial clearly showed that prenatal repair of myelomeningocele reversed or corrected hindbrain herniation and reduced the need for ventriculoperitoneal shunting by one of age (Adzick et al 2011). Prenatal repair reduced the need for ventriculoperitoneal shunting to 40% from 82% with postnatal repair. However, prenatal repair was associated with higher rates of obstetrical complications such as oligohydramnios, chorioamniotic membrane separation, placental abruption, premature rupture of membranes, preterm delivery, and uterine scar dehiscense compared to postnatal repair (Adzick et al 2011, Soni et al 2016).
Fetoscopic repair of myelomeningocele was proposed to reduce these complications. Initial results reported by groups in Germany and Brazil suggested reduced rates of obstetrical complications. However, these reports also had a high rate of membrane rupture, premature birth, and a an myelomeningocele closure technique that was unreliable with higher rates of CSF fluid leakage requiring postnatal revision of the myelomeningocele repair.
In a recent systematic review and meta-analysis Kababgambe et al found that comparing fetoscopic to open fetal surgery to repair myelomeningocele had no differences in ventriculoperitoneal shunt or ventriculostomy rates at 12 months (42% for fetoscopic; 40% for open). There were no differences between fetoscopic and open techniques in reversal of hindbrain herniation, motor response relative to anatomic level, birth <30 weeks’ gestation, chorioamniotic membrane separation, and placental abruption.
Fetoscopic myelomeningocele repair was associated with higher rates of wound closure dehiscense and/or CSF leakage requiring postnatal myelomeningocele repair site revision (30% for fetoscopic; 7% for open, p<0.01), and preterm premature rupture of membranes (79% for fetoscopic: 36% for open, p=0.04). In contrast, the rate of partial or complete uterine wound dehiscense was higher in open repair (11%) compared to fetoscopic rapair (0%, p<0.01).
There are futher differences in the fetoscopic techniques employed which affect the rate of complications. The German group use an entirely percutaneous technique which does not close the trocar hysterotomy sites. In contrast, Belford et al, externalize the uterus for placement of two 4 mm trocars after securing the membranes to the uterine wall for the procedure and these trocar sites are closed at the conclusion of the procedure. This group reported that these trocar sites are well healed at the time of cesarean section delivery (Belford et al 2015).
The duration of the operative procedure is another factor for which fetoscopic surgery is significantly longer with range of 98 to 480 minutes when performed percutaneously and 145 to 480 minutes when performed with uterine exteriorization. This is in contrast to the 34 to 130 minutes for open fetal surgical myelomeningocele repair. This has been postulated to be a contributing factor in the development of preterm premature rupture of membranes. But perhaps an even more important factor is the CO2 insufflation used during fetoscopic myelomeningocele repair due to the lack of carbonic anhydrase in the fetus which metabolizes CO2. This can result in profound fetal academia during the 21/2 to 8 hours duration of the fetoscopic procedure. Although fetal stability, as assessed by intraoperative ultrasound and Doppler velocimetry during these cases, there has not been any direct measurement of fefal pH during any of these cases. In studies n sheep, the use of CO2 amniotic insufflation has resulted in fetal pH of 6.9 with one hour of CO2 insufflation. It is unknown what effect this inability to metabolize CO2 will have on feal development and neonatal outcomes and requires further study.
Advances in treatment for myelomeningocele
Dr Crombleholme of the Fetal Care Center of Dallas has 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 Fetal Care Center Dallas offers access to this procedure for patients with a BMI of up to 40% under an institutionally approved study. Dr Crombleholme was the first to recognize that it is unethical to exclude mothers with a BMI of >35 from this treatment option for their baby and the first in the nation to offer this procedure option for mothers with BMI >35.
Changes in Hysterotomy Closure Technique
One of the most striking findings of the MOMS trial was the high rate of obstetric complications related to the hysterotomy closure (Adzick et al 2011). In the MOMS trial 35% of mothers having prenatal repair had either thinning of the hysterotomy scar (24%), partial (10%) or complete dehicense (1%). Crombleholme developed a modification of the hystertomy closure technique which has largely eliminated this complication (Zaretsky et al 2017). This modified hystertomy closure embricates the last layer of the closure obtaining serosa to serosa apposition in a 3rd layer of U shaped stitches (figure). A total of 49 pateints underwent prenatal myelomeningocele repair using this technique for hysterotomy closure. 95.4% of patients has completely intact hysterotomy closure with only 1 patient having partial dehiscense and 1 patient having thinning of the scar (Zaretsky et al 2017)
Changes in Anesthetic Management
One of the most important aspects of performing open fetal surgery is the ability to perserce uteroplacental gas exchange during the hysterotomy and the fetus surgical procedure. This is possible due to the properties of maternal inhalational anesthesia which has potent relaxing effects on the uterus. The standard anesthetic management has used high does of either desflurane or ceveoflurane for the entire procedure. While this is highly effective in achieving uterine relaxation, it does so at the cost of depressing cardiac function in the fetus. We have found that we can achieve the same degree of uterine relaxation by using supplemental intravenous anesthesia (SIVA, Boat et al) . SIVA uses intravenous fentanuyl and propofol to have the mother go off to sleep and the inhalational agent is only used once the uterus has been exposed and needs to be relaxed. Using this approach, we have been able to perform open fetal surgery with half the dose of inhalational agents for half the time markedly reducing the cardiac dysfunction in the fetus during the operation. In a report of their experience with 100 cases at CHOP following the closure of the MOMS trial Rychik et al reported a 7% incidence of acute cardiac events during open fetal surgery requiring CPR, or aborting the case. In contrast using SIVA in a series of 65 cases, we had no acute cardiac events during the procedure (Wood et al 2018)
Management of Pregnancy
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 and 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.
Management of the Newborn
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.
As compared with postnatal surgery, prenatal surgery for myelomeningocele performed before 23 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, 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. 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 if the early benefits are durable and to evaluate the effect of the prenatal intervention on bowel and bladder continence, sexual function and mental capacity.
- Surgical Treatment
The earliest recorded surgical treatment of a child with spina bifida was performed in 1910 (Hahn 1995). With the development of antibiotics, there was increased interest in treating this condition. It is currently recommended that surgical closure should occur within the first 24 to 48 hours of life to decrease morbidity and mortality.
Exposure of neural tissue to trauma during birth potentially causes a shock-like state to the neural placode. The goals of operative repair include preserving all viable neural tissue, reconstituting a normal anatomic environment, and minimizing the chance of infection or preventing ascending infection of the neural axis (Hahn 1995). During repair, the neurosurgeon must:
- Identify the neural placode, intermediate epi-thelial layer, and the pia, arachnoid, and dura.
- Preserve neural tissues.
- Reconstitute a normal neural environment with reconstitution of the pia—arachnoidal, dural, fascial, and skin layers.
- Complete skin closure.
- Prevent leakage of cerebrospinal fluid (Pang 1995).
The operative mortality for myelomeningocele repair is near 0%.
Currently there is expected to be a 95% or higher survival rate for the first 2 years of life (Hahn 1995).
Hydrocephalus develops in 80% of cases of myelo-meningocele. This is often not apparent until the neural-tube defect is repaired. It is not uncommon to require a shunt placement within a few days after neural-tube defect repair.
There have been significant changes in the indication for ventriculoperitoneal shunt placement over the last decade and the MOMS trial developed criteria to standardize the indications for shunt placement. These criteria were used for the MOMS trial and have been widely adapted for use in newborn nurseries to assess the need for ventriculoperitoneal shunging for myelomeningocele.
Postnatal Indications for Ventriculoperitoneal Shunting
- At least two of the following:
- An increase in the greatest occipital-frontal circumference adjusted for gestational age defined as crossing percentiles. Patients who cross centiles and subsequently plateau do not meet this criteria
- A bulging fontanelle (defined as above the bone assessed when the baby is in an upright position and not crying) or split sutures or sunsetting sing (eyes appear to look downward with the sclera prominent over the iris)
- Increasing hydrocephalus on consecutive imaging studies determined by increase in ratio of biventricular diameter to biparietal diameter according to the method of O’Hayon et al. (O’Hayon BB, Drake JM, Ossip MG, et al. Frontal and occipital horn ratio: a linear estimate of ventricular size for multiple imaging modalities in pediatric hydrocephalus. Pediatr Neurosurg. 1998; 29:245-9).
- Head circumference >95th percentile for gestational age
- Presence of marked syringomyelia (syrinx with expansion of spinal cord) with ventriculomegaly (undefined).
- Ventriculomegaly (undefined) and symptoms of Chiari malformation (stridor, swallowing difficulties, apnea, bradycardia)
Persistent cerebrospinal fluid leakage from the myelomeningocele wound or building at the repair site.
- Long-Term Outcome
The long-term considerations for the infant and child with myelomeningocele include neuromuscular and urologic function, as well prevention of orthopedic abnormalities. To stand erect, motor function is needed to at least the third lumbar level. To walk, the child must exhibit motor function from the fourth to the fifth lumbar level. To function sexually as an adult, the individual must have motor function to at least the second to fourth sacral level.
The degree of handicap and survival rate depends on the level of spinal segments, the severity of the lesion, the treatment program, and the associated anomalies (Budorick et al. 1995). The lower the spinal level, the better the prognosis. Prediction of long-term IQ is impossible. Approximately one-fourth of patients have an IQ below 50, one-fourth of patients have an IQ above 100, and 50% of patients have a learning disability (Budorick et al. 1995).
The Arnold–Chiari malformation is the most common cause of death. Hindbrain dysfunction causes death within the first year of life in 10 to 15% of patients (Rauzzino and Oakes 1995). Symptomatic patients present with apnea, aspiration, swallowing difficulties, and opisthotonos. Considerations for surgical decompression of the hindbrain include:
- Inspiratory stridor at rest.
- Aspiration pneumonia due to palatal dysfunction or gastroesophageal reflux.
- The presence of central apnea with or without cyanosis, especially during sleep.
- Functionally significant or progressive spasticity of the upper extremities or truncal or appendicular ataxia (Rauzzino and Oakes 1995).
In recent years, there has been an increased appreciation of the long-term consequences of renal failure in adulthood (Zawin and Lebowitz 1992). Therefore, urologic management is more aggressive and directed toward maintaining normal renal function (Stone 1995). After the neural-tube defect has been closed and a shunt has been placed, urodynamic studies are recommended. If the patient has high pressures due to bladder–sphincter dyssynergia, a voiding cystourethrogram (VCUG) can be performed to rule out vesicoureteric reflux. For many cases, anticholinergics or smooth muscle relaxants are recommended to alter the overreactivity of the abnormal detrusor. This treatment is meant to increase the capacity of the bladder. Prophylactic antibiotics are used to prevent urinary tract infection. Children are taught how to perform clean, intermittent bladder catheterization. This technique safely and effectively empties the bladder, preventing both upper-tract deterioration and overflow incontinence (Zawin and Lebowitz 1992). If frequent urinary tract infection is a problem, a vesicostomy can be performed, creating a fistula between the bladder and the abdominal wall. Eighty percent of children with neural-tube defects achieve continence by intermittent catheterization and the use of anticholinergic medications.
Surgical treatment is complicated by a widespread latex allergy seen in affected children.
The presence of myelodysplasia can lead to musculoskeletal deformities. The goals of the orthopedic surgeon are to maintain mobile and pain-free joints, as well as to prevent decubitus ulcers in insensate limbs (Karol 1995). The spine is at risk for the subsequent development of kyphosis and scoliosis. Significant spine deformities that require surgery develop in 10% of children with lesions at the thoracic level. Scoliosis is the most commonly encountered spinal deformity, which is treated by spinal fusion. Although patients with myelomeningocele can dislocate their hips, they are rarely surgically reduced. Contractures at the hip are surgically released to allow children to fit orthoses. External tibia rotation is commonly seen at the ankles. Sixty percent of children with myelomeningocele have club feet (see Chapter 104). This is treated differently for the child with myelomeningocele as compared with otherwise normal children. Neurologic club feet are more rigid than idiopathic club feet. The application of skin casts with stretching—the usual treatment for idiopathic club foot—can lead to skin breakdown for the child with myelomeningocele. Surgical treatment is generally recommended, but this should be delayed until the child is developmentally ready to stand.
Hunt (1990) and Hunt and Poulton (1995) have described the long-term follow-up of 117 babies (50 boys, 67 girls) born between 1963 and 1971. All of these infants had surgical repair within the first 48 hours after birth. Of this cohort, 25 infants died within the first year of life, 15 died between ages 1 and 5 years, 8 died between ages 5 and 16 years, and 8 died between 16 and 25 years (Fig. 19-8). The reports cover 69 survivors in 1990 and 61 survivors in 1995. Remarkably, 16 of the 56 deaths were from renal failure. In general, survival was lowest and disability greatest when the sensory level affected was above T11 (Fig. 19-9). The survival was highest and disability the lowest when the sensory level was below L3 (Fig. 19-10). Most severely affected cases had a poor renal prognosis due to neuropathic obstruction of bladder outflow. Of the survivors in 1990, 50% could walk for 50 yards or more and 50% were wheelchair-bound. Forty-seven of the 69 survivors had an IQ of >80, 12 had an IQ of between 60 and 79, and 10 had an IQ of <60. Approximately half of the young adults remained continent or managed their own incontinence. The other half needed help from other adults, and 43% of survivors used some sort of adult diaper or padding.
With regard to disability, 12% of patients walked normally and had a normal IQ. Fifty percent of patients could walk 50 yards and had normal intelligence. Twenty-five percent of patients were severely disabled and could not walk or stand and were mentally retarded. Twelve percent of patients were very severely disabled and were blind, mentally retarded, and needed help with transfers, dressing, and incontinence.
With regard to general health, one-third of patients had precocious puberty, one-third were overweight, and visual defects were common among these patients, including blindness in two of them. The presence of a history of ventriculitis, septicemia, or intracranial hemorrhage was associated with mental retardation, epilepsy, and blindness.
Sixteen of the 69 adult survivors were employed. Their occupations included light assembly work, clerical jobs, garage mechanic, gardener, and hairdresser. These authors concluded that most of the surviving young adults were badly handicapped. Thirty percent were mentally retarded, as defined by an IQ of <80.
These authors stated that the sensory level to pinprick at birth was especially useful in the determination of long-term disability. When the sensory level was above T11, there was 50% survival to adult life. If the patient survived, there was a 50% chance of a normal IQ. Most of these patients were severely disabled, with no prospect of walking or continence and only a 10% chance of being able to live independently. When the sensory level was between T11 and L3, there was a 55% chance of survival to adulthood. If the patient survived, there was a 70% chance of a normal IQ. Of this group of patients, 40% could walk, 15% were continent, and 45% were able to live independently. For the patients with a sensory level below L3, there was a 70% chance of survival to adulthood, and for the survivors there was an 80% chance of a normal IQ. Of these patients, 90% could walk and 45% were continent. Eighty-five percent of this group were able to live independently (Hunt 1990; Hunt and Poulton 1995). It should be noted that much as changed in the care and management of childrens with myelomeningocele in the last 20 years and it is likely that these numbers do not reflect current outcomes.
- Genetics and Recurrence Risk
The vast majority of neural-tube defects are isolated and multifactorial in origin (Main and Mennuti 1986). In a landmark study, Holmes et al. (1976) classified 106 stillborn and liveborn infants with neural-tube defects. They identified six different causes for the anomalies. This study consisted of a retrospective analysis of 79 autopsy cases and a prospective analysis of 27 live-born infants. Of the 27 liveborn infants, 23 had an isolated neural-tube defect, and of these 15 had anencephaly. Of the 79 retrospective cases, 67 were consistent with multifactorial inheritance. Five of the cases were consistent with a single-gene disorder, and all were thought to be due to Meckel–Gruber syndrome, an autosomal recessive condition. One case was clinically diagnosed as trisomy 13, although the definitive chromosome analysis was unavailable. One of the 79 was an infant of a diabetic mother. Three cases were due to amniotic bands, and 2 cases were due to cloacal exstrophy. These authors suggested that the cause of neural-tube defects was highly variable and that genetic counseling could not support a uniform 5% recurrence risk for all patients.
More recently, authors have suggested a recurrence risk of 1.5 to 3%, although with two affected siblings the recurrence risk increases to 5.7% in the United States and 12% in the United Kingdom (Main and Mennuti 1986). For sisters of the mother who gives birth to an affected child with a neural-tube defect, there is an increased risk. The presence of spina bifida occulta of a single vertebra in a parent does not seem to increase the risk for a neural-tube defect in the offspring. The recurrence risks and associated anomalies vary between closure sites, so it is hoped that in the future, more accurate genetic counseling will be given based on the location of the neural-tube defect in the proband (Van Allen et al. 1993).
Women who have already given birth to an affected infant with a neural-tube defect should be given 4 mg of folic acid preconceptually prior to the next pregnancy (Wald et al. 1991). Several studies to date have demonstrated the preventive effect of folic acid supplementation prior to conception. These studies have been summarized by Rieder (1994). In one study, 11 cases of neural-tube defects were observed in 1188 pregnancies supplemented with folic acid, or a prevalence of 0.9 per 100 live births. The patients not taking supplements had 54 cases of neural-tube defects in 1286 live births, for a prevalence of 4 cases per 100. The mechanism by which folic acid mediates neural-tube closure is unknown, although the preventive effect has been shown even in low-risk women (Milunsky et al. 1996). It is currently recommended that all women of childbearing age take at least 0.4 mg of folic acid every day (Baty et al. 1996; Wald et al. 1991).
Prenatal diagnosis of neural-tube defects in a subsequent pregnancy can be performed by maternal serum AFP screening, amniotic fluid AFP screening, and prenatal sonographic examination.
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Figure 1. (A) Transverse view of a fetal head demonstrating the “lemon sign” in a fetus with meningomyelocele. (B) Similar sonographic presentation of an apparent lemon sign. This fetus, however, has craniosynostosis.
Figure 2. Suboccipital bregmatic view of a fetal head demonstrating the “banana sign,” which derives from anterior curving of the cerebellar hemispheres with simultaneous obliteration of the cisterna magna.
Figure 3. Sonographic view of fetal spine demonstrating widening of vertebral arches in a case of meningomyelocele. (Photograph courtesy of Dr. Michael Paidas.)
Figure 4. Transverse view of ossification centers in the neural arch with a U-shaped configuration.
Figure 5. Sagittal view of lower fetal spine demonstrating the presence of a large sac. (Photograph courtesy of Dr. Marjorie Treadwell.)
Figure 6. Fetal MRI in sagittal section of a fetus at 23 weeks of gestation demonstrating a very large meningomyelocele with a large intact sac extending from T10 to L5.
Figure 7. Intraoperative view of fetal surgical procedure to repair the meningomyelocele seen on the MRI in Figure 19-6. The cyst has been excised and skin flaps have been mobilized and a valved shunt is being inserted just prior to completing the skin closure.
Figure 8. Overall survival for a cohort of 117 babies born with myelomeningocele between 1963 and 1971. (Reprinted, with permission, from Hunt GM, Poulton A. Open spina bifida: a complete cohort reviewed 25 years after closure. Dev Med Child Neurol 1995;37:19–29.)
Figure 9. Illustration of sensory areas affected by the different anatomic locations of the neural-tube defect. The hatch marks and coloration used in this figure relate to the data in Figure 19-8. (Reprinted, with permission, from Hunt GM, Poulton A. Open spina bifida: a complete cohort reviewed 25 years after closure. Dev Med Child Neurol 1995;37:19–29.)
Figure 10. (A) Long-term survival as a function of age, sensory level, and gender. (B) Long-term disability as a function of age, sensory level, and gender. (Reprinted, with permission, from Hunt GM, Poulton A. Open spina bifida: a complete cohort reviewed 25 years after closure. Dev Med Child Neurol 1995;37:19–29.)