دكتور نبيل نسبه تجمع البول في مثانه ابني من 12 الى 15 تقريبا عموما طبيب الأطفال الجراح فضل عمل تمرين عباره عن الضغط من أسفل السره نزولا وذلك لأفراغ ماتبقى من بول في المثانه وارجاء القسطره البوليه في الفتره الحاليه عمر ابني الآن سنتين ونصف سؤالي هل ستبقى المثانه عصبيه على طول وماهي الحلول المتبعه لأطفال spina bifda
بالنسبه للغتي الأنجليزيه جيدجدا والمامي بالمصطلحات الطبيه ممتاز لكن عليك مراجعه اداره المنتدى لأن النظام لايسمح الا بالعربي لكن اتمنى من الأداره الموافقه والمساعده لما هو أفضل للجميع.....

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د. نبيل

Myelomeningocele



Marvin A Fishman, MD
Grace B Villarreal, MD


UpToDate performs a continuous review of over 350 journals and other resources. Updates are added as important new information is published. The literature review for version 14.2 is current through April 2006; this topic was last changed on May 16, 2006. The next version of UpToDate (14.3) will be released in October 2006.

INTRODUCTION — Neural tube defects (NTDs) are the second only to cardiac malformations as the most prevalent congenital anomaly in the United States. Of these, myelomeningocele, anencephaly, and encephalocele are most common abnormalities. The clinical features, diagnosis, and management of myelomeningocele are reviewed here. Prenatal aspects and anencephaly and encephalocele and prevention of neural tube defects are discussed separately. (See "Prenatal screening and diagnosis of neural tube defects", see "Ultrasound diagnosis of neural tube defects" see "Anencephaly and encephalocele" and see "Prevention of neural tube defects").

EMBRYOLOGY OF NEURAL TUBE — The central nervous system (CNS) appears as a plate of thickened ectoderm called the neural plate at the beginning of the third week of embryonic life. The lateral ees of the neural plate become elevated to form the neural folds. These folds subsequently become further elevated, approach each other, and fuse to form the neural tube; the fusion begins in the cervical region and proceeds in both the cephalad and caudal directions. However, fusion is delayed at the cranial and caudal ends of the embryo so that the cranial and caudal neuropores form open communication between the lumen of the neural tube and the amniotic cavity. Closure of the cranial neuropore occurs on the 25th day after conception and closure of the caudal neuropore occurs approximately two days later [1]. Neural tube defects result from failure of the neural tube to close normally between 25 and 28 days after conception.

Myelomeningocele — Myelomeningocele (also known as myelocele and meningomyelocele), is due to failure of closure of the posterior neural tube. This leads to malformation of the vertebral column and spinal cord and other CNS anomalies. In severe forms, the neural plate appears as a raw, red, fleshy plaque through a defect in the vertebral column (known as spina bifida) and the integument. A protruding membranous sac containing meninges, CSF, nerve roots, and dysplastic spinal cord often protrudes through the defect. The majority of patients with myelomeningocele also have hydrocephalus and Chiari II malformations [2].

If disturbances occur during earlier stages of neural tube formation, canalization, and retrogressive differentiation, the resulting lesions are covered by skin. Approximately 10 percent of patients with spina bifida have a meningocele, in which only the meninges of the spinal cord herniate through the vertebral defect.

ETIOLOGY — The cause of NTDs is unknown. The majority are isolated malformations of multifactorial origin. NTDs also occur as part of syndromes, in association with chromosomal disorders, or as a result of an environmental exposure (show table 1) [3-9]. (See "Prenatal screening and diagnosis of neural tube defects").

Genetic factors — A genetic factor is suggested by the observations that NTDs have a high concordance rate in monozygotic twins, are more frequent among siblings, and are more common in females compared to males [10]. In addition, there is a high prevalence of karyotypic abnormalities among fetuses with NTDs, especially in the presence of other congenital anomalies. For example, a large study evaluating the frequency of aneuploidy in pregnancies with fetal NTDs found aneuploidy in 7 percent of affected cases [11]. The majority of the abnormal karyotypes were trisomies and most of the trisomic fetuses also had multiple congenital anomalies. A second series reported a similar rate (6.5 percent) of chromosomal abnormalities in fetuses with NTDs [12]. These data support the use of fetal karyotyping as an aid in diagnostic evaluation and recurrence risk counseling [11,12].

Folic acid deficiency — Adequate folate is critical for cell division due to its essential role in the synthesis of nucleic and certain amino acids. Folic acid deficiency has been implicated in the development of NTDs (folate sensitive NTDs) and folate supplementation has been shown to reduce the risk of NTDs. (See "Prevention of neural tube defects", section on Relationship between folate and NTDS).

Folic acid antagonists — Administration of folic acid antagonists (dihydrofolate reductase inhibitors and others) increases the risk of NTDs. In a large case-control study, the risk of NTDs (spina bifida, anencephaly, and encephalocele) was greater with than without exposure to folic acid antagonists (including carbamazepine, phenobarbital, phenytoin, primidone, sulfasalazine, triamterene, and trimethoprim) in the first or second month after the last menstrual period (adjusted odds ratio 2.8, 95% CI 1.7 to 4.6) [13]. The biologic mechanism for this association is largely unknown. (See "Risks associated with epilepsy and pregnancy" section on Antiepileptic drugs).

Metabolic disorders — Genetic abnormalities involving the metabolism of folate and homocysteine may account for some cases of NTDs [14]. These disorders may explain why supplementation with folic acid reduces but does not eliminate the risk of NTD. Genes affecting folate metabolism include those encoding methylene tetrahydrofolate reductase and methylene tetrahydrofolate dehydrogenase. Those affecting homocysteine metabolism include those encoding methionine synthase; its regulator, methionine synthase reductase; and cystathionine synthase.

Disruptive factors — Some cases of encephalocele may be due to disruptive factors. Encephalocele has been associated with amniotic bands, maternal hyperthermia between 20 and 28 days of gestation [15], and warfarin embryopathy [16].

INCIDENCE — The incidence of NTDs (of which myelomeningocele is the most common) is highly variable and depends upon ethnic and geographic factors. It usually ranges from one to five per 1000 live births. The highest rates are found in Ireland, Great Britain, Pakistan, India, and Egypt. Within the United States, rates are higher in the East and South compared to the West. In one series from Indiana, the overall incidence of isolated NTDs (excluding anencephaly) from 1988 to 1994 was one per 1000 births [17]. Girls are affected more often than boys.

INHERITANCE — The recurrence risk for any NTD was 1.5 to 3 percent in the United States when there was one affected sibling, based upon data from three large studies (show table 2) [18-20]. With two affected siblings, the risk was 5.7 percent in another United States study [21] and 12 percent in a British study [18].

PRENATAL DIAGNOSIS — Prenatal diagnosis is accomplished by maternal screening of serum alpha fetoprotein (AFP) levels and/or ultrasonography. (See "Prenatal screening and diagnosis of neural tube defects" and see "Ultrasound diagnosis of neural tube defects").

Maternal AFP screening — Maternal serum alpha fetoprotein screening for NTDs is performed in the second trimester. AFP screening is primarily intended for the detection of open spina bifida and anencephaly, but can also uncover several nonneural fetal abnormalities (eg, ventral wall defects, tumors, dermatologic disorders, congenital nephrosis, aneuploidy). Screening can be performed between 15 to 20 weeks of gestation; however, optimal detection of NTDs is between 16 and 18 weeks. It does not detect closed spina bifida.

Ultrasound findings — Sonographic fetal markers pathognomonic for neural tube defects include the lemon sign, the banana sign, ventriculomegaly, microcephaly, and obliteration of the cisterna magnum. The lemon sign refers to a concave shape of the frontal calvarium and the banana sign describes the posterior convexity of the cerebellum in the presence of spina bifida. These changes result from the Chiari malformation (ie, herniation of the cerebellum and brainstem through the foramen magnum) which is present in 95 percent of cases of spina bifida.

The normal fetal spine has three ossification centers within the fetal vertebrae. The centers of the neural arches are parallel, with gradual widening toward the fetal head and tapering at the sacrum. Spina bifida appears as widening of the ossification centers in the coronal plane and as a divergence of the ossification centers in the transverse plane. In addition, a cystic sac may be visualized if the fetus has a myelomeningocele.

CLINICAL FEATURES — The diagnosis of myelomeningocele is usually obvious at birth because of the grossly visible lesion (show figure 1). The vertebral defect involves the lumbar (thoracolumbar, lumbar, lumbosacral) regions (the last portion of the neural tube to close) in approximately 80 percent of cases, although any segment may be involved [22]. Many segments can be affected, and the entire spine distal to the most proximal malformed vertebra is often involved.

Neurologic deficits — The specific neurologic deficits depend upon the level of the lesion. In most affected patients, the entire spinal cord distal to the site of the lesion is nonfunctional. Motor and sensory deficits in the trunk and legs correspond to the segments that normally would have been innervated. The deficits usually are severe, resulting in complete paralysis and absence of sensation. The bladder and bowel are affected in nearly all patients, resulting in urinary and fecal incontinence.

Occasionally, the distal cord may retain some function, but the afferent pathways to the brain are disrupted. In this case, tendon reflexes or withdrawal to pain may be preserved, although voluntary control of movement and appreciation of pain are absent. A partially functioning segment of the spinal cord sometimes retains some central connections, resulting in voluntary control of isolated movements or the appreciation of sensation in part of the involved limbs. Aberrant connections in the involved spinal cord may result in unusual findings such as contraction of the contralateral limb when tendon reflexes are elicited.

Hydrocephalus — The majority of patients with myelomeningocele have hydrocephalus. The etiology is obstruction of fourth ventricular outflow or flow of CSF through the posterior fossa due to Chiari malformation or an associated aqueductal stenosis [23]. In one series of 156 children with myelomeningocele, 80 percent developed this disorder [24]. Hydrocephalus was due to aqueductal stenosis in 73 percent. Signs of hydrocephalus were present at birth in 15 percent of cases.

The likelihood of hydrocephalus depends upon the site of the lesion. Hydrocephalus is associated with approximately 90 percent of thoracolumbar, lumbar, and lumbosacral lesions, and approximately 60 percent of occipital, cervical, thoracic, or sacral lesions [22].

Ventricular dilatation is common at birth, often without increased head circumference or signs of increased intracranial pressure [25]. Hydrocephalus typically develops in the neonatal period after surgical repair of the back lesion. This is due to accumulation of excess CSF that previously was decompressed into the large sac or through a leaking myelomeningocele. Shunting is required in most patients.

Chiari malformation — The Chiari malformation is an anomaly of the hindbrain present in nearly all patients with thoracolumbar, lumbar, and lumbosacral myelomeningocele. It is the primary cause of the associated hydrocephalus. The major features of the anomaly are [22]:

Inferior displacement of the medulla and fourth ventricle into the upper cervical canal
Elongation and thinning of the upper medulla and lower pons and persistence of the embryonic flexure of these structures
Inferior displacement of the lower cerebellum through the foramen magnum in the upper cervical region
Bony defects of the foramen magnum, occiput, and upper cervical vertebrae
The malformation is classified into three types, according to the degree of caudal displacement. Type II, in which the fourth ventricle and lower medulla are displaced below the level of the foramen magnum, is the form that is usually associated with myelomeningocele.

Brain stem dysfunction due to the Chiari malformation occurs in some patients with myelomeningocele. This results in problems such as swallowing difficulties, vocal cord paresis causing stridor, and apneic episodes, and is associated with a high mortality rate [22]. Strabismus and facial weakness can also occur.

Other CNS anomalies — Other CNS anomalies often accompany myelomeningocele. In one report, neuropathologic examination was performed on 25 children with myelomeningocele, Chiari malformation, and hydrocephalus [26]. Cerebral cortical dysplasia occurred in 92 percent. The majority had neuronal heterotopias or polymicrogyria. Other abnormalities noted included cerebellar dysplasia (72 percent), hypoplasia or aplasia of cranial nerve nuclei (20 percent), fusion of the thalami (16 percent), agenesis of the corpus callosum (12 percent), and complete or partial agenesis of the olfactory tract and bulb (8 percent).

Scoliosis — Scoliosis occurs in most children with meningomyelocele who have lesions above L2 [22]. This complication is unusual when the lesion is below S1.

MANAGEMENT — Management of children with spina bifida should involve a multidisciplinary team with expertise in developmental pediatrics, neurosurgery, orthopedics, neurology, urology, and physical medicine and rehabilitation. Physical and occupational therapists, nutritionists, social workers, wound specialists, and psychologists are also helpful. This team of specialists works together to coordinate care and evaluate the patient's progress.

Delivery — If a prenatal diagnosis of myelomeningocele has been made, delivery should occur at a hospital with personnel experienced in the neonatal management of these infants [27]. Delivery before term may be indicated if rapidly increasing ventriculomegaly is observed and fetal lung maturity has been documented, otherwise, term delivery is preferable [27]. Sterile nonlatex gloves should be used during delivery to minimize the risk of latex sensitization [28].

Breech presenting fetuses are typically delivered by cesarean section. (See "Delivery of the fetus in breech presentation"). The optimal route of delivery of the vertex fetus is controversial, and no prospective randomized trials have been performed.

One study compared the outcome of 47 infants with a prenatal diagnosis of isolated myelomeningocele without severe hydrocephalus delivered by cesarean section before labor to a historic cohort of 113 infants with myelomeningocele diagnosed after delivery (35 delivered by cesarean section after a period of labor and 78 delivered vaginally) [29]. The level of paralysis at two years of age was approximately two segments lower in the group delivered by elective cesarean section without labor. However, it is possible that advances in neonatal care and prenatal diagnosis led to interventions in the delivery room that resulted in a better outcome in the study group. Several other retrospective studies, but not all [30], have not found a benefit of cesarean delivery, with or without labor, compared to vaginal birth [31-36].

Most centers deliver these infants by cesarean birth. Since data are inadequate to make a general recommendation about the optimal route of delivery, this decision should be individualized [27]. Future trials should address the effects of both route of delivery and labor on neuromuscular function.

Neonatal assessment — Immediately after birth, the lesion should be briefly assessed to note its location, size, and whether it is leaking CSF. Sterile non-latex gloves should be used. The defect should be covered with a sterile saline-soaked dressing. Large defects should also be covered by plastic wrap to prevent heat loss. In most cases, only the neurosurgeon should remove the dressing. The infant should be placed in a prone or lateral position to avoid pressure on the lesion.

The newborn should be evaluated thoroughly to detect associated abnormalities in order to make appropriate decisions regarding treatment [37]. The parents should be counseled regarding the infant's prognosis and participate in decisions regarding management [38].

The presence of the following should be noted:

Signs of hydrocephalus
Clubfeet
Flexion or extension contractures of hips, knees, and ankles
Kyphosis
Other abnormalities such as congenital heart disease; structural defects of the airway, gastrointestinal tract, ribs; developmental dysplasia of the hip; or ultrasound evidence of renal malformations such as hydronephrosis
Early complications such as CNS infection
A thorough neurologic examination should be performed. (See "Neurologic examination in children"). This should include:

Observation of spontaneous activity
Extent of muscle weakness and paralysis
Response to sensation
Deep tendon reflexes
Anocutaneous reflex (anal wink)
Surgical closure — The back lesion should be surgically closed within the first 24 to 48 hours after birth. This decreases the risk of CNS infection. Prophylaxis with broad spectrum antibiotics until the back is closed also reduces the risk of CNS infection. In a retrospective study of infants with back closure performed after 48 hours of age, ventriculitis occurred less with than without antibiotic prophylaxis (1 versus 19 percent) [39].

Hydrocephalus — Ventricular size should be evaluated soon after birth by ultrasound, CT, or MRI. Serial neuroimaging should be performed to identify the development of hydrocephalus. Progressive hydrocephalus should be treated by insertion of a ventriculoperitoneal shunt.

In some infants, simultaneous meningomyelocele repair and shunt placement may be appropriate. In a retrospective review, the frequency of CSF infection, shunt malfunction, and symptomatic Chiari malformation was similar with simultaneous and sequential repair and shunting [40]. The rate of wound leak was lower and hospital length of stay was shorter in the simultaneous group.

Orthopedic problems — Orthopedic management should be directed at correcting deformities, maintaining posture, and promoting ambulation if possible, so that patients can function at their maximum capability. Factors that predict an increased likelihood of walking ability are motor level and sitting balance [41].

Orthopedic deformities result from congenital skeletal anomalies that often involve the feet, knees, hips, and spine; unbalanced muscle action around joints; and fractures, which often affect the legs of paraplegic patients. In a review from Spain of 393 infants with myelodysplasia, hip dislocation and feet deformities occurred in 24 and 50 percent, respectively [42]. Scoliosis also is common. Management techniques that often improve function include the use of casting and corrective appliances, surgical procedures on soft tissue and bone, and the use of orthoses.

Fractures — Fractures of the lower extremities occur in approximately 30 percent of patients with meningomyelocoele [43]. They may develop without known traumatic injury or may be related to vigorous physical therapy. Factors that increase the risk of fracture include the lack of protective sensation of the leg, osteopenia, nonambulation, foot arthrodesis (fusion of the joint), and higher level of paralysis [43,44].

A fracture should be strongly suspected when a patient with myelodysplasia presents with a red, warm, and swollen limb. These clinical signs are sometimes confused with cellulitis or osteomyelitis because some children with diaphyseal and metaphyseal fractures also have fever, elevated sedimentation rate, and leukocytosis [45], The diagnosis of fracture is confirmed with a radiograph of the limb.

Urinary tract complications — Nearly all patients with spina bifida have bladder dysfunction that can lead to deterioration of the upper urinary tract. The location of the spinal lesion or the neurologic examination do not predict the type of dysfunction. However, urinary continence with intermittent catheterization can be predicted by a positive anocutaneous reflex, which indicates a competent sphincter mechanism. In one report, continence was achieved in 26 of 29 patients (90 percent) with a positive reflex compared to 41 of 82 (50 percent) with a negative reflex [46]. Fewer patients with a positive reflex needed adjunctive surgery (7 versus 28 percent).

A baseline renal ultrasound and voiding cystourethrogram should be performed to identify patients at risk for upper tract deterioration. Function of the neurogenic bladder should be evaluated in affected newborns with a cystometrogram, which measures bladder capacity, compliance, voiding pressures, and the relationship between the detrusor and the urinary sphincter [47]. Vesicoureteral reflux may result from detrusor hyperreflexia or detrusor sphincter dyssynergy. In one report, urodynamic evaluation of 36 infants with myelodysplasia showed incoordination of the detrusor and external urethral sphincter, synergic activity of the sphincter, and no sphincter activity in 18, nine, and nine patients, respectively [48]. Infants with incoordination of the detrusor-external sphincter were at high risk for urinary tract deterioration. Of that group, 13 of 18 (72 percent) developed hydroureteronephrosis, compared to two of nine with synergy and one of nine with no sphincter activity.

Urologic function can deteriorate in affected children with normal urodynamic studies after surgical repair in the neonatal period [49]. Deterioration is due to spinal cord tethering, which is most likely to occur during the first six years of life. These children require close follow-up for the early detection and correction of tethered spinal cord (show figure 2).

Patients with vesicoureteral reflux should receive antibiotic prophylaxis, anticholinergic medication to lower detrusor filling and voiding pressures, and clean intermittent catheterization to prevent urinary tract deterioration [50,51]. The efficacy of this regimen was demonstrated in a sequential nonrandomized study that compared prophylactic (clean intermittent catheterization and oxybutynin) and expectant treatment in patients with these urodynamic findings [50]. During five years of follow-up, the upper urinary tract deteriorated less often in the treated group (8 versus 48 percent).

For an anticholinergic agent, oxybutynin syrup (Ditropan, 1 mg/mL) is used in a dose of 0.1 mg/kg PO three times a day for infants <12 months of age, and 1, 2, 3, or 4 mg/kg per dose three times a day for children one, two, or three years of age, respectively. For children 5 years old, we use oxybutynin tablets (Ditropan, 5 mg PO three times a day), or the extended release preparation (Ditropan XL, beginning with 5 mg PO daily and titrated to effect, with maximum dose 20 mg daily). An alternative drug is tolterodine (Detrol) in a dose of 1 to 2 mg PO twice a day or the long-acting preparation (Detrol LA), 2 to 4 mg PO daily.

Several surgical procedures are used to manage neurogenic bladder in patients with meningomyelocele. Ureteral reimplantation is sometimes performed in patients with persistent reflux and upper tract deterioration or with recurrent urinary tract infections in spite of clean intermittent catheterization and prophylactic antibiotics [52]. A vesicostomy is performed for bladder drainage in infants with high bladder pressure who continue to worsen while receiving clean intermittent catheterization and anticholinergic medication [53]. Vesicostomy is usually used for temporary diversion, but is a long-term option in patients unlikely to achieve continence [53,54].

The most common surgical approach is augmentation of the bladder [55]. In this procedure, a detubularized segment of intestine (ileum, colon, or stomach) is added to the bladder to increase capacity and lower pressure. The procedure usually results in the achievement of urinary continence. Linear growth and bone density are comparable in children with myelomeningocele with or without the procedure, although serum bicarbonate levels are lower and chloride levels are higher in those who have ileal, but not gastric augmentation [56]. Other complications include bladder calculi, bladder rupture, and excessive mucus in the urine that may lead to catheter obstruction [52].

Patients who are unable to catheterize their own urethra may benefit from a continent catheterizable channel (such as a Mitrofanoff or Monti ileovesicostomy). The new channel is constructed from appendix or bowel with a stoma placed at the level of the umbilicus or on the lower abdomen [57,58]. This more accessible location reduces the time required for clean intermittent catheterization, especially in females with lesions at the thoracic level. The most common complication is stenosis of the stoma at the level of the skin which may require dilation or surgical revision.

A surgical technique to bypass the neurologic defect through the microanastomosis of the fifth lumbar ventral root to the third sacral ventral root has been described [59]. Among 20 children with myelomeningocele who had this procedure, 17 achieved satisfactory bladder control and continence within 8 to 12 months after the procedure. These results await confirmation by other centers.

Neurogenic bowel — The innervation for internal and external sphincter control is at the level of S2 to S5. Thus, patients with meningomyelocoele may experience varying degrees of fecal incontinence. As children become preschool or school aged, fecal incontinence leads to embarrassment and social isolation and should be avoided.

The goal of a neurogenic bowel continence program is to achieve timed elimination of stool through the use of oral laxatives, suppositories, and enemas [60]. These methods are used singly or in combination. Accomplishment of continence requires patience and motivation on the part of the family, physician, and nurse educator. A second goal is to avoid fecal impaction and the related liquid encopresis that occurs and is often mistaken by families as an episode of diarrhea. (See "Definition; clinical manifestations; and evaluation of encopresis").

].At the initiation of a bowel management program, bowel clean-out may be necessary. If the history of the patient reveals that there are several days without a bowel movement, or there is palpable stool on abdominal exam or rectal exam, then bowel clean out with a Fleet's enema should be initiated. The Pediatric Fleet's enema, which contains approximately 60 mL of solution should be used for children between 2 and 10 years of age. An abdominal radiograph should be ordered if confirmation of stool quantity is needed (eg, in an overweight patient). The assistance of a gastroenterologist may be needed if routine enemas do not produce acceptable results.

Once the bowel clean out has been accomplished, the patient may be placed on a regular program of a daily oral agent. Alternative regimens include:

Senokot: 0.5 to 1 tsp (2.5 to 5 mL) PO at bedtime in children 2 to 6 years of age and 1 to 2 tsp (5 to 10 mL) at bedtime in older children
Perdiem (100 percent psyllium): 1 to 2 tsp (5 to 10 mL) PO each day with 8 ounces (240 mL) of fluid per dose)
Lactulose (10 g/15 mL): 0.5 to 1 tsp (2.5 to 5.0 mL) PO each day
In addition, to the oral agent, a glycerin or bisacodyl suppository (10 mg) should be administered once per day 15 to 20 minutes after a meal to take advantage of the gastrocolic reflex. This is followed by placing the young child on the toilet and making sure his or her feet are well supported.

Some patients require daily evacuation of stool with the use of the visi-flow enema, which requires 20cc/kg of saline. This enema system comes with a water regulator so that the parent or the patient can control the speed of the water (or turn it off altogether for a rest) if he or she experiences abdominal cramping. Completing the enema takes usually 20 to 30 minutes. School-aged patients appreciate having the opportunity to have a nightly enema and avoid school accidents the following day.

If conservative medical management fails, then a surgical option is the antegrade continence enema [61-65].In this procedure, the appendix and cecum (or ileum if the appendix is not available) are used to create a catheterizable stoma. The patient is able to clean out the colon from the proximal end of the large intestine while sitting on the toilet, reducing the risk of fecal soiling and constipation. Fecal continence is achieved with this technique in approximately 85 percent of patients with spina bifida [65].

Skin integrity — Disruption of skin integrity is an important cause of morbidity in children with myelomeningocoele and often leads to hospitalization [66,67]. Decubiti often develop on the sacrum, buttocks, back, and feet. Other lesions include burns, abrasions, and ammoniacal dermatitis. Affected children are especially susceptible to burns because their lower extremities lack sensation and may not detect an elevated temperature. They should not be placed under running water without supervision because they may not detect exposure to very hot water. Similarly, they should avoid leaving hot food on the lap for a prolonged period which may lead to burns of the anterior thighs.

Patients with high level lesions may develop pressure decubiti with subcutaneous tissue necrosis. Patients with defects at the thoracic level are at risk for skin breakdown over the perineum and gibbus (bony angulation of collapsed vertebrae). The skin breakdown over the perineum is due to asymmetrical weight bearing and fecal and urinary incontinence. A commonly affected area is the ischial tuberosities, which should be inspected closely.

Ulceration over bony prominences and beneath orthotic devices can become very deep and involve muscle and/or bone. A chronic ulcer that does not improve with medical management should be evaluated for evidence of osteomyelitis. An abnormal radiograph or bone scan or an elevated sedimentation rate or C-reactive protein level may help distinguish an infected ulcer requiring long-term antibiotic therapy from a chronic ulcer that might benefit from consultation with a wound care specialist or plastic surgeon [68].

Neuropathic foot ulceration is common in patients who have low lumbar or sacral myelomeningocele. In one report, patients most likely to develop ulcers had foot rigidity, nonplantigrade position, and had undergone surgical arthrodesis [69

Factors contributing to skin breakdown include excessive pressure associated with limited mobility and overweight, infection, trauma, poor circulation, lack of sensation. and fecal and urinary incontinence. Prevention and management include [70,71]:

Careful inspection of the skin
Proper skin cleansing
Avoidance of occlusive clothing
Elimination of movements that cause friction
Proper fitting orthosis and wheelchairs
Symmetric weight bearing
Frequent weight shifts
Exposure of the affected skin to air
Prompt medical attention to an affected area
Protective skin lotions and ointments may reduce pain and erythema associated with perineal skin breakdown in incontinent patients. Although no studies are available in children, these preparations have been shown to be effective in incontinent elderly patients [72].

Latex allergy — Many children with myelomeningocele have allergic reactions to latex, ranging in severity from contact urticaria to anaphylactic shock [73]. In one review of 60 children with myelomeningocele, 48 percent were sensitized and 15 percent were allergic to latex [74]. In another review of 71 patients who were followed for 20 to 25 years, 33 percent were allergic to latex and 9 percent had experienced a life-threatening reaction [28]. The mechanism for development of allergy is thought to be repeated exposures to latex rubber during multiple surgical procedures, as well as daily bladder catheterization and bowel management, although there may be factors unique to the underlying condition [75]. Products containing latex should be avoided [76].

PROGNOSIS — The prognosis for patients with myelomeningocele depends upon decisions regarding their care, the level of the lesion, and the presence and severity of neurologic deficits, hydrocephalus, and other central nervous system anomalies, as illustrated below.

With aggressive treatment, the majority (approximately 85 percent) of patients survive the neonatal period [77,78]. In one review of 212 patients, 72 percent of survivors were ambulatory and 79 percent were considered to have normal cognitive development [77]. In another series of 200 patients, 74 percent were at least partially ambulatory and 87 percent had urinary continence [78]. There was a small, but statistically significant improvement in the first year survival rate of infants with spina bifida in the United States after the introduction of mandatory folic acid fortification of the grain supply (from 90.3 to 92.1 percent) [79]. (See "Prevention of neural tube defects", section on Relationship between folate and NTDS).

In children with myelomeningocele and hydrocephalus, high spinal cord lesions (T12 and above) are associated with more severe anomalous brain development. More severe anomalous brain development is associated with poor neurobehavioral outcomes on measures of intelligence, academic skills, and adaptive behavior [80].

The long-term outcome of myelomeningocele was outlined in a review of 118 children with myelomeningocele who were treated nonselectively [81]. Among the 71 patients who were available for follow-up at 20 to 25 years, the following findings were noted:

The overall mortality was 24 percent and continued to increase into young adulthood
86 percent of patients had undergone cerebrospinal fluid (CSF) diversion and 95 percent had undergone at least one shunt revision
32 percent had undergone release of tethered cord, after which 97 percent had improvement or stabilization in their preoperative symptoms
43 percent had undergone spinal fusion for scoliosis
23 percent had had at least one seizure
85 percent were attending or had graduated from high-school and/or college
Long-term survival may be related to the need for CSF diversion. In one review of 904 patients with myelomeningocele seen in a multidisciplinary clinic over 43 years, survival into adolescence was similar for patients with and without CSF diversion [28]. However, for patients alive at 16 years, survival after age 34 years was decreased for those with shunted hydrocephalus compared to those without a shunt.

FETAL SURGERY — In animals with a surgically created spinal defect, intrauterine closure of the exposed spinal cord tissue prevents secondary neurologic injury [82]. In one study in humans, intrauterine repair was performed at 24 to 30 weeks gestation in 29 patients with isolated fetal myelomeningocele [83]. The following results were reported:

Compared to matched controls, fewer infants in the treatment group required shunt placement for hydrocephalus at six months of age (59 versus 91 percent)
Compared to controls, the median age at shunt placement was later
(50 versus 5 days of age)

The incidence of hindbrain herniation was reduced (38 versus 95 percent).
The treatment group had a higher incidence of oligohydramnios (48 versus 4 percent) and preterm contractions (50 versus 9 percent) than the control group
The treatment group had lower mean gestational age (33.2 versus 37) and birth weight (2171 versus 3075 g) than the control group
In a subsequent report, the same group described 116 infants who had undergone intrauterine repair of spina bifida and had postnatal follow-up of at least 12 months [84]; 54 percent required the placement of a ventricluloperitoneal shunt by one year of age. Shunt placement was less likely to be necessary among fetuses who had a ventricular size of <14 mm at the time of surgery, who had surgery at 25 weeks gestation, and had defects located at or below L4 (all fetuses with defects at or above L1 required shunts).

In other reports, intrauterine repair did not improve lower extremity function [85] or affect the progression of ventriculomegaly [86]. This approach is not recommended until data on long-term follow-up and the results of an ongoing randomized trial are available [87].

PREVENTION — The prevention of neural tube defects is discussed separately. (See "Prevention of neural tube defects").

أشكرك على المعلومات القيمه لقد استفدت كثيرا وان شاء الله اناقش معك ماورد بهذه المذكره القيمه لقد توضحت لي الصوره تماما 100%...
لدي سؤال مااحتماليه تكرار الحاله في عائلتي أي هل هناك امل بأن يولد طفل اخر مصاب وماهي الأحتياطات الواجب فعلها كي نتجنب ذلك مره أخرى؟

اختي الكريمه
في هذا الموضوع تجدي كيفية اكتشافه و كيف نمنعة و يا ليت اطبائنا يقراون ليعرفوا ان الكثير من امراض الوراثة يمكن تفاديها . كما قلت لكي اقرائي جيدا و اي شيئ غير واضح انا موجود و اعذريني لعدم اتساع وقتي للترجمة فانا استعد لامتحان الدكتوارة في المانيا بعد 3 اسابيع . دعواتكم


Prenatal screening and diagnosis of neural tube defects

Lauri Hochberg, MD
Joanne Stone, MD


UpToDate performs a continuous review of over 350 journals and other resources. Updates are added as important new information is published. The literature review for version 14.2 is current through April 2006; this topic was last changed on April 28, 2006. The next version of UpToDate (14.3) will be released in October 2006.

INTRODUCTION — Neural tube defects (NTD) are the second most prevalent congenital anomaly in the United States, second only to cardiac malformations. Three factors have played a significant role in the assessment and prevention of this disorder in developed countries:

The widespread use of maternal screening programs to identify pregnancies at high risk [1]
Sonographic imaging combined with amniocentesis for diagnosis of affected fetuses [2,3]
Administration of folic acid supplements for prevention of the disorder [4,5].
Prenatal screening and diagnosis of NTDs will be reviewed here. Prevention of NTDs is discussed separately. (See "Prevention of neural tube defects").

INCIDENCE AND EPIDEMIOLOGY — The incidence of NTDs is highly variable and depends upon ethnic and geographic factors. Studies performed before the availability of prenatal screening and prophylactic vitamin supplementation reported the birth incidence of both spina bifida and anencephaly were higher in Caucasians than in blacks. In the United States, higher rates of NTDs were observed in the East and South than in the West [6].

Prenatal maternal serum screening programs for alpha fetoprotein (instituted in the 1970s and 1980s) combined with periconceptional folic acid supplementation and food fortification (instituted in the 1990s) have led to a decrease in the prevalence of NTDs where these interventions are practiced (see "Prevention of neural tube defects") [4,5,7-11]. As an example, the prevalence of NTDs in England and Wales declined by 96 percent between 1970 and 1997: from approximately 3.2 per 1000 births to 0.1 per 1000 births [7]. Forty percent of the decline was attributed to antenatal screening with termination of affected pregnancies and 56 percent was attributed to a decline in incidence, due at least in part to an increase in dietary folate.

EMBRYOLOGY — The central nervous system appears as a plate of thickened ectoderm called the neural plate at the beginning of the third week of embryonic life. The lateral ees of the neural plate become elevated to form the neural folds. These folds subsequently become further elevated, approach each other, and fuse to form the neural tube; the fusion begins in the cervical region and proceeds in both the cephalad and caudal directions. Since fusion is delayed at the cranial and caudal ends of the embryo, the cranial and caudal neuropores form temporary open communications between the lumen of the neural tube and the amniotic cavity until closure of the cranial neuropore on the 25th day after conception and closure of the caudal neuropore about two days later [12]. NTDs result from failure of the neural tube to close normally between the third and fourth weeks after conception (the fifth and sixth weeks of gestation).

TYPES OF NTDS — There are several anatomic types of NTDs, which affect either the spine or cranium. They can be classified as open (neural tissue exposed) or closed (neural tissue not exposed). Open NTDs often involve both the spine and cranium, while closed NTDs are usually localized and confined to the spine.

Spinal defects

Spina bifida — Spina bifida refers to a cleft in the spinal column. Spina bifida may be closed (the skin covering the defect is intact) or open (not covered by skin) (show ultrasound 1A-D).
Spina bifida occulta is the simplest form in which there is a failure of the dorsal portions of the vertebrae to fuse with one another. This abnormality, usually localized to the sacrolumbar region, is covered by skin and is not noticeable on the surface except for the presence of a small tuft of hair or other dermal lesion over the affected area. It is diagnosed, usually incidentally, by radiographs of the spinal vertebrae.

A meningocele develops if more than one or two vertebrae are involved in the defect and only the meninges of the spinal cord herniates through the opening. It is not associated with hydrocephalus or neurologic defects, but may be contiguous with a subcutaneous lipoma (ie, lipomeningocele).

A meningomyelocele or myelomeningocele occurs when both the meninges and the spinal cord herniate through the vertebral defect. It is often associated with hydrocephalus. (See "Myelomeningocele").

Cranial defects

Anencephaly — Anencephaly is the congenital absence of a major portion of the brain, skull, and scalp due to failure of the cephalic part of the neural tube to close. It is the most common NTD and is readily detected antenatally. (See "Anencephaly and encephalocele").
Exencephaly — In exencephaly the skull and scalp are absent, with exteriorization of the abnormally formed brain.
Encephalocele — Encephalocele refers to the herniation of cranial contents through a defect in the skull. (See "Anencephaly and encephalocele").
Iniencephaly — Iniencephaly is a rare malformation characterized by the triad of an occipital bone defect, cervical dysraphism (ie, defective fusion), and fixed retroflexion of the fetal head.

ETIOLOGY AND RISK FACTORS — The majority of NTDs are isolated malformations of multifactorial origin (ie, traits/conditions influenced by both environmental and genetic factors):

Folic acid deficiency — Adequate folate is critical for cell division due to its essential role in the synthesis of nucleic and certain amino acids. Folic acid deficiency has been implicated in the development of NTDs (folate sensitive NTDs) and folate supplementation has been shown to reduce the risk of NTDs. (See "Prevention of neural tube defects", section on Relationship between folate and NTDS).

Environmental factors — The frequency of NTDs is increased with exposure to certain environmental factors, such as drugs (valproic acid, carbamazepine, folic acid antagonists), hyperthermia, diabetes mellitus, obesity [13-17]. While some of the environmental associations are weak, or suffer from poor methodological studies, others (valproic acid) are quite strong. (See "Risks associated with epilepsy and pregnancy", section on Effect of antiepileptic drugs on the fetus).

Genetic factors — A genetic factor is suggested by the observations that NTDs have a high concordance rate in monozygotic twins, are more frequent among first degree relatives, and are more common in females than males [18]. NTDs also occur as part of several genetic syndromes (eg, Meckel-Gruber) and may be associated with the MTHFR variant (See "Prevention of neural tube defects", section on MTHFR variant and NTDS).

The risk of recurrence for NTDs is approximately 2 to 4 percent when there is one affected sibling [19-23]. With two affected siblings, the risk is approximately 10 percent [24]. The risk of NTD according to family history is illustrated in the table (show table 1). The risk of recurrence appears to be higher in countries such as Ireland where the prevalence if NTDs is high [25].

The recurrence risk for anencephaly is estimated at 2 to 5 percent [26]. Isolated encephaloceles have not been shown to be familial. However, encephaloceles may be part of specific genetic syndromes if there are associated anomalies; the inheritance pattern is autosomal recessive in these cases. As an example, the risk of recurrence for an encephalocele with Meckel Gruber syndrome (posterior encephalocoele, cleft palate, and polydactyly) is 25 percent.

There is a high prevalence of karyotypic abnormalities among fetuses with NTDs, especially in the presence of other congenital anomalies [27-30]. As an example, a series evaluating the frequency of chromosomal abnormalities in pregnancies with fetal NTDs found these abnormalities in 6.5 percent of affected cases (4/167 fetuses with an isolated NTD and 9/33 fetuses with a NTD and associated anomalies) [27]. Other series reported a similar (7 percent) or higher (13 percent) rate of chromosomal abnormalities in fetuses with NTDs, particularly when there were associated anomalies [28-30]. Trisomy 18 was the most common aneuploidy detected. These data support the use of fetal karyotyping as an aid in diagnostic evaluation and recurrence risk counseling.

Deformation — Some cases of encephalocele may be due to disruptive factors, such as amniotic bands.

Vitamin B12 deficiency — Serum vitamin B12 levels have also been noted to be lower in pregnancies complicated by NTDS [31-33]. A systematic review found serum vitamin B12 concentration was 38 ng/L lower in such pregnancies [31]. A relationship between vitamin B12 deficiency and NTDS may result from a vitamin B12 associated functional state of folate deficiency or hyperhomocysteinemia [33-35]. The relationship between maternal vitamin B12 status and NTDs needs further study before any clinical recommendations can be made.

SCREENING — We recommend offering screening for NTDs to all pregnant women. Early diagnosis of affected pregnancies allows couples the option of pregnancy termination or an opportunity to prepare for the birth of a child.

Alpha-fetoprotein — Alpha fetoprotein (AFP) is the maternal serum marker used in screening for NTDs. It is a fetal specific globulin, synthesized by the fetal yolk sac, gastrointestinal tract, and liver. The function of AFP is unknown, although data suggest that it may be involved in immunoregulation during pregnancy. Another function may be as an intravascular transport protein because of its similarity to albumin.

AFP can be measured in maternal serum, amniotic fluid, and fetal plasma. The maternal serum AFP (MSAFP) concentration is much lower than that in amniotic fluid or fetal plasma. It rises in early pregnancy, peaks between 28 and 32 weeks of gestation, and then falls (show figure 3). Increasing fetoplacental permeability and advancing gestation may explain the rise in MSAFP that occurs when amniotic fluid and fetal serum concentrations are declining.

AFP is secreted by the fetal kidney into the urine and then excreted into the amniotic fluid. The concentration of amniotic fluid AFP (AFAFP) is highest early in pregnancy, peaks between 12 and 14 weeks of gestation, then declines until it becomes undetectable at term (show figure 2). Amniotic fluid AFP levels are measured to aid in diagnosis of NTDs. (See "Prenatal diagnosis" below).

The concentration of fetal plasma AFP peaks between 10 and 13 weeks of gestation, then declines exponentially from 14 to 32 weeks, and falls even more dramatically near term (show figure 1) [36]. The fall in AFP can be explained by both decreased fetal synthesis and a dilution effect due to increasing fetal blood volume. There is no clinical role for measurement of AFP in fetal plasma.

Screening protocol — MSAFP screening at 15 to 20 weeks of gestation should be offered to all pregnant women as it is an effective method for detecting NTDs [15]. AFP screening is primarily intended for the detection of open spina bifida and anencephaly, but can also uncover several nonneural fetal abnormalities (eg, ventral wall defects, tumors, dermatologic disorders, congenital nephrosis, aneuploidy). It does not detect closed spina bifida. (See "Pregnancy complications predicted by second trimester maternal serum screening").

MSAFP results are expressed as multiples of the median (MoM) for each gestational week because these values are easy to derive, more stable, and allow for interlaboratory variation. The median value, rather than the mean, is used because it is not influenced by occasional outlying values. A value above 2.0 to 2.5 MoM is designated an abnormal result, depending upon the laboratory's preference for balancing the detection and false-positive rates in their population.

A first elevated test may be repeated because as many as 30 percent of moderately elevated MSAFP results will be below the threshold level upon repeating the test and such findings are not associated with an increased frequency of false-negative NTD diagnoses [37]. If the elevation persists, then the next step is to obtain a specialized ultrasound examination to further assess whether a NTD, or other anomaly, is present [15]. An advanced gestational age, patient anxiety, or a significantly elevated value may preclude repetition of the test, in which case sonography should be obtained expeditiously. (See "Ultrasound examination" below).

Sensitivity and specificity — Studies have consistently demonstrated the utility of MSAFP screening. Overall, the detection rate for open NTDs is 75 to 90 percent, with a greater than 95 percent detection rate for anencephaly. The risk of an affected fetus when the MSAFP is >2.5 MoMs is 4.5 percent [38]. The positive predictive value of an MSAFP level between 2.5 and 2.9 MoMs for NTDs is 1.45 percent; with an MSAFP level greater than 7 MoMs, the positive predictive value goes up to 13.5 percent.

Two representative examples are provided below:

A British collaborative study compared 18,684 singleton and 163 twin pregnancies without NTDs to 381 singleton pregnancies with fetal NTDs [37]. The authors established expectations for detection rates and defined 16 to 18 weeks of gestation as the most efficient time to screen. A MSAFP of greater than 2.5 MoMs at 16 weeks of gestation detected 82 percent of open spina bifida and 95 percent of anencephaly, with a false-positive rate of 2 to 5 percent.
An American series including 13,486 women with singleton pregnancies reported elevated MSAFP levels were 90.9 percent sensitive and 96 percent specific for spina bifida and 100 percent sensitive and 96 percent specific for anencephaly [39,40].
Factors affecting interpretation — Many factors influence the correct interpretation of MSAFP results. These include: gestational age, maternal weight, ethnicity, maternal diabetes mellitus, fetal viability, exclusion of other anomalies, and multiple pregnancy.
multiple gestation with a viable and a nonviable fetus. MSAFP results are not interpretable in this situation

Gestational age — Screening can be performed between 15 to 20 weeks of gestation; however, optimal detection of NTDs is between 16 and 18 weeks. Knowlee of gestational age is critical to interpretation of MSAFP (show figure 4). An incorrect gestational age will falsely raise or lower the reported MoM, which is based upon gestational age. (See "Ultrasound examination" below and see "Indications for diagnostic obstetrical ultrasound examination").
Maternal weight — Maternal weight affects MSAFP screening because of dilution of AFP in the larger blood volume of heavier women. Correction for maternal weight increases the detection rate for NTDs [41]. Maternal weight should be measured and reported to the MSAFP laboratory on the day of testing.
Diabetes mellitus — The prevalence of NTDs is higher in women with diabetes mellitus and their MSAFP level is 15 percent lower than in nondiabetics. For these reasons, there is a lower threshold MSAFP value (eg, approximately 1.5 MoM) to obtain the same sensitivity of detection of NTDS as in nondiabetic women. The presence of maternal diabetes should always be noted on the MSAFP laboratory requisition.
Fetal anomalies — NonNTD fetal defects can be associated with an elevated MSAFP. There is direct correlation between the degree of MSAFP elevation and the frequency of anomalies. In one study, the risk was 3 percent at a level of 2.5 MoMs and 40 percent at a level >7.0 MoMs [42].
Abdominal wall defects are commonly associated with elevated MSAFP levels. One representative series reported MSAFP was raised in 89 percent of fetuses with omphalocele and in 100 percent of fetuses with gastroschisis [43]. Fetal congenital nephrosis, teratomas, and benign obstructive uropathy can also be associated with elevated MSAFP levels.

Multiple gestation — The concentration of MSAFP is proportional to the number of fetuses, thus the upper limit for a twin pregnancy is twice (eg, 4 to 5 MoMs) that of a singleton gestation.
Race — The MSAFP level is 10 percent higher in black women. Thus, an adjustment based upon race should be made by the laboratory when calculating MSAFP results.
Fetal viability — Fetal death raises the MSAFP value. This is not of diagnostic concern except in cases of multiple gestation with a viable and a nonviable fetus. MSAFP results are not interpretable in this situation.
PRENATAL DIAGNOSIS — Pregnancies that screen positive (a value above 2.0 to 2.5 MoM) require further evaluation to determine whether a NTD, or other abnormality, is present. All such pregnancies should undergo ultrasound examination to confirm gestational age, fetal viability, number of fetuses (see "Factors affecting interpretation" above) and to perform a detailed fetal anatomic survey.

Ultrasound examination — Ultrasound is an effective technique for detecting NTDs, and can potentially detect more NTDs than MSAFP [44]. The diagnosis of anencephaly is based upon the absence of brain and calvarium superior to the orbits on coronal views of the fetal head. The sonographic diagnosis of this condition is highly accurate and should not be missed on any routine second or third trimester ultrasound examination. The sensitivity of sonographic diagnosis of other NTDS is high, but depends in part upon the size and location of the defect, the position of the fetus, the volume of amniotic fluid, maternal habitus, and the skill and equipment of the sonographer. (See "Ultrasound diagnosis of neural tube defects").

Amniocentesis — As discussed above, ultrasound examination may be diagnostic of a NTD. However, ultrasound findings may be uncertain or show an apparently normal fetus. In these cases, further evaluation is usually indicated. Amniotic fluid AFP (AFAFP) and amniotic fluid acetylcholinesterase (AChE) are the primary biochemical tests performed on amniotic fluid for detection of open neural tube defects. AChE is an enzyme contained in blood cells, muscle, and nerve tissue. An elevation of both AFP and AChE values suggests an open fetal NTD with 96 percent accuracy and a false positive rate of 0.14 percent [3]. Blood contamination of the amniotic fluid sample is responsible for one-half of false-positive AChE results. (See "Amniocentesis: Technique and complications")

Sonographic versus amniotic fluid diagnosis — Some authors have suggested that the rate of detection of NTDs by ultrasound examination alone may preclude the need for amniocentesis [45-48]. These findings are illustrated by the following examples.

In one study of over 2000 women with an elevated MSAFP, sonography alone was 97 percent (66 of 68 cases) sensitive and 100 percent (2189 cases) specific in diagnosing an open NTD [46]. Suspicious findings on sonography led to an amniocentesis for confirmation of NTD in the two cases of NTD not specifically diagnosed on ultrasound examination.
A second series of 905 pregnancies found that 49 neural tube defects were correctly diagnosed by ultrasound alone; one was not [47]. The sensitivity, specificity, and positive and negative predictive values of ultrasound evaluation for the detection of NTDs were 98, 100, 100, and 99.9 percent, respectively. Forty-three other abnormal fetuses were also detected in patients with an elevated MSAFP, including 19 with abdominal wall defects, seven with findings suggestive of chromosomal abnormalities, five with urinary tract abnormalities, one with a cardiac abnormality, and 11 others; two fetuses with chromosomal abnormalities were not detected. The authors felt that ultrasound could be used reliably to detect NTDs, thereby avoiding the risks of amniocentesis.
A review of the ultrasound findings in 51 consecutive fetuses with pathologically confirmed spina bifida, encephalocele, gastroschisis, or omphalocele calculated the sensitivity of ultrasonography for these diagnoses and the probability of an affected fetus in women with a given level of MSAFP and a normal second trimester sonogram at their facility [45]. These four types of anomalies were correctly identified in all 51 cases, yielding a sensitivity of 100 percent. The probability of an affected fetus ranged from 0.01 to 0.15 percent for MSAFP levels ranging from 2.0 to 3.5 MoMs, respectively. The authors concluded that this level of risk was less than the reported risk of a procedure related spontaneous abortion after amniocentesis (0.3 to 0.5 percent) and, therefore may lead some women with an elevated MSAFP to decide not to proceed with amniocentesis.
Cost-benefit analyses have revealed savings of approximately $36 to $49 million dollars in annual savings if ultrasound examination replaced amniocentesis for the diagnosis of NTD [49].
In contrast, a series of 161 cases of open spina bifida identified by the California Maternal Serum Alpha-Fetoprotein Screening Program reported 8 percent of NTDs were not diagnosed by the initial ultrasonographic evaluation and three defects were not recognized until birth [50]. The authors concluded that ultrasonography was not sufficiently sensitive to forego amniocentesis. Small encephaloceles and spina bifida may be missed with ultrasonography and factors cited above, such as large maternal body habitus, fetal position, and lack of experience of the sonographer contribute to the difficulty of sonographic diagnosis [50,51].

Summary — Based upon review of existing data, the most sensitive approach to the prenatal diagnosis of NTDs is MSAFP screening followed (if the MSAFP is elevated) by a combination of ultrasound examination and amniocentesis [15]. Detection rates for NTDs are greater than 95 percent with rare false positives with both of these modalities. If one is certain of the diagnosis based upon the elevated MSAFP level and the ultrasound findings, an amniocentesis for confirmation may not be necessary. However, if there is any uncertainty about the diagnosis, or if the patient wishes to find out the karyotype (given the association with chromosomal abnormalities) an amniocentesis is warranted. The information may be particularly useful for diagnosis and estimating recurrence risk if there are associated anomalies.

We, and others, feel that a fetal karyotype should be obtained at the time of amniocentesis since this test adds no additional risk to the procedure, there is an elevated risk of chromosomal abnormalities with NTDs, and this information assists in accurate diagnosis of the current pregnancy and may be important for counseling regarding recurrence risks [30,52]. However, other authors have not recommended chromosome analysis in women under 35 years of age in the presence of a normal sonogram because of the cost and low risk of abnormality (0.3 to 0.6 percent) [53,54].