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Neural Tube Defects in the Neonatal Period Workup

  • Author: Richard G Ellenbogen, MD; Chief Editor: Ted Rosenkrantz, MD  more...
Updated: Jan 02, 2015

Laboratory Studies

Presence of open neural tube defects (NTDs) can be detected with the measurement of AFP in the amniotic fluid or maternal bloodstream. AFP is the major serum protein in early embryonic life and is 90% of the total serum globulin in a fetus. It is believed to be involved in preventing fetal immune rejection and is first made in the yolk sac and then later in the GI system and liver of the fetus. It goes from the fetal blood stream to the fetal urinary tract, where it is excreted into the maternal amniotic fluid. The AFP can also leak into the amniotic fluid from open neural tube defects such as anencephaly and myelomeningocele, in which the fetal blood stream is in direct contact with the amniotic fluid.

The first step in prenatal screening is measuring the maternal serum AFP at 15-20 weeks' gestation. A patient-specific risk is then calculated based on gestational age and AFP level. For example, at 20 weeks' gestation, a maternal serum AFP concentration higher than 1,000 ng/mL would be indicative of an open neural tube defect. Normal AFP concentration in the maternal serum is usually lower than 500 ng/mL.

Determining precise gestational age is essential because fetal AFP levels are age specific and can peak in a normal fetus at 12-15 weeks' gestation. The measurement of maternal serum AFP levels is more than 75% accurate in detecting an open neural tube defect at more than 15 weeks' gestation. In patients in whom a question persists, amniotic AFP can be obtained. It is a significantly more accurate test, especially at 15-20 weeks' gestation, and detects approximately 98% of all open neural tube defects, although this method is not the preferred screening test. Amniotic fluid acetylcholinesterase levels add an increased degree of resolution.

A partial list of the fetal anomalies that are associated with elevated AFP levels is as follows:

  • Anencephaly
  • Spina bifida cystica
  • Encephalocele (leaking)
  • Gastroschisis
  • Exstrophy of the cloaca
  • Oligohydramnios
  • Sacrococcygeal teratoma
  • Polycystic kidneys
  • Fetal death
  • Urinary tract obstruction

Imaging Studies

Detection of a neural tube defect with fetal ultrasonography in the hands of a skilled ultrasonographer is usually 98% specific. False-positive findings can result from multiple pregnancies or inaccurate fetal dating. However, closed neural tube defects can sometimes remain undetected, especially in cases of skin-covered lipomyelomeningoceles and meningoceles, in which the AFP levels may also be normal. These closed neural tube defects comprise about 10% or more of total neural tube defects discovered. A skilled ultrasonographer can detect these lesions with almost 95% sensitivity.

Contributor Information and Disclosures

Richard G Ellenbogen, MD Professor and Chairman, Theodore S Roberts Endowed Chair in Pediatric Neurosurgery, Department of Neurological Surgery, University of Washington

Richard G Ellenbogen, MD is a member of the following medical societies: American College of Surgeons

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Brian S Carter, MD, FAAP Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Attending Physician, Division of Neonatology, Children's Mercy Hospital and Clinics; Faculty, Children's Mercy Bioethics Center

Brian S Carter, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Pediatric Society, American Society for Bioethics and Humanities, American Society of Law, Medicine & Ethics, Society for Pediatric Research, National Hospice and Palliative Care Organization

Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Eastern Society for Pediatric Research, American Medical Association, Connecticut State Medical Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Shelley C Springer, JD, MD, MSc, MBA, FAAP Professor, University of Medicine and Health Sciences, St Kitts, West Indies; Clinical Instructor, Department of Pediatrics, University of Vermont College of Medicine; Clinical Instructor, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health

Shelley C Springer, JD, MD, MSc, MBA, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

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Neonate with a lumbar myelomeningocele with an L5 neurologic level. Note the diaphanous sac filled with cerebrospinal fluid and containing fragile vessels in its membrane. Also, note the neural placode plastered to the dorsal surface of the sac. This patient underwent closure of his back and an untethering of his neural placode. The neural placode was circumnavigated and placed in the neural canal. A dural sleeve was fashioned in such a way to reconstruct the neural tube geometry.
This anteroposterior skull radiograph demonstrates the craniolacunia or Luckenschadel seen in patients with myelomeningocele and hydrocephalus. Mesodermal dysplastic changes cause defects in the bone. The thin ovoid areas of calvaria are often surrounded by dense bone deposits. They are most likely the result of defective membranous bone formation typical of neural tube defects and not increased intracranial pressure as once thought. These characteristic honeycomb changes are seen in about 80% of the skulls in children with myelomeningocele and hydrocephalus.
Sagittal T1-weighted MRI image of a child after closure of his myelomeningocele. Child is aged 7 years. Note the spinal cord ends in the sacral region far below the normal level of T12-L1. It is tethered at the point in which the neural placode was attached to the skin defect during gestation. The MRI showed dorsal tethering, and the child complained of back pain and had a new foot deformity on examination. By definition, all children with a myelomeningocele have a tethered cord on MRI, but only about 20% of children require an operation to untether the spinal cord during their first decade of life, during their rapid growth spurts. Thus, the MRI must be placed in context of a history and examination consistent with mechanical tethering and a resultant neurologic deterioration.
Sagittal T1 MRI image of a child with a myelomeningocele and associated Chiari II malformation. Note the cerebellar vermis and part of the brainstem has herniated below the foramen magnum and into the cervical canal (arrow). This patient had multiple brainstem symptoms and findings to include stridor and cranial nerve paresis (cranial nerves III, VI, IX, X) despite having a well-functioning ventricular-peritoneal shunt. He required a posterior fossa decompression of his hindbrain in order to relieve the symptoms of hindbrain herniation and brainstem compression. A minority of myelomeningocele patients require a Chiari II decompression. Those that do usually present in their first year of life with similar symptoms, stridor and cranial nerve paresis. A functioning shunt is imperative prior to exploring the posterior fossa in these children. Often times, especially in older children, a shunt revision may alleviate some of the symptoms of hindbrain compression.
Neonate with a large occipital encephalocele lying in the prone position prior to surgical intervention. Note the large skin-covered sac that represents a closed neural tube defect. Often called cranium bifidum, it is a more serious condition that represents a failure of the anterior neuropore to close. In this patient, a defect in the skull base (basicranium) was associated with this large sac filled with cerebrospinal fluid and a small, disorganized remnant of brain. The patient fared satisfactorily after the surgery in which the encephalocele was excised. However, the patient needed placement of a ventricular-peritoneal shunt to treat the resultant hydrocephalus, which is not uncommon. At age 5 years, the child was doing well and had only moderate developmental delay.
Autopsy specimen on a child with anencephaly. This is one of the most common CNS malformations in the West. The neonate, like almost all with such a severe forms of neural tube defects, did not survive more than a few hours or days. This malformation represents a failure of the anterior neuropore to close. This photograph also reveals an absence of the calvaria and posterior bone elements of the cervical canal, as well as the deficiency in the prosencephalon. Photo courtesy of Professor Ron Lemire.
Ventral view of a child with anencephaly that, like the previous picture, shows the loss of cranium and enclosed nervous tissue. In addition to the primary defect in development, a secondary destruction of nervous tissue occurs. Direct exposure to the caustic amniotic fluid causes progressive destruction of the remaining neural structures and secondary proliferation of a thin covering of vascular and glial tissue. Photo courtesy of Professor Ron Lemire.
These 2 photographs depict the lumbar regions on 2 different children with closed neural tube defects. Both children have lipomyelomeningocele. The child in the left has a dorsal lipoma that is pedunculated. The child on the right has a more common-appearing lipomatous mass that is heaped up beneath the skin. Both lipomas lead from the subcutaneous tissue, through the dura and into the intradural space, where they are attached to the spinal cord. Photos courtesy of Professor J.D. Loeser.
Photograph of a child undergoing a neurosurgical procedure in which the spinal cord is being detached (untethered) from the intradural and extradural lipomatous mass that fixes it to the subcutaneous tissue. The white arrow shows the laser char on the lipoma that has been shaved off the spinal cord and was connected to the extradural mass. The black arrow shows the extradural lipoma, which crept through the dura and attached to the spinal cord, thereby firmly fixing the spinal cord at too low and too dorsal a location in the sagittal plane.
Table 1. Human CNS Malformations
Days of Gestation Event Resultant Malformation
0-18 Formation of 3 germ layer and neural plate Death or unclear effect
18 Formation of neural plate and groove form Anterior midline defects
22-23 Appearance of optic vessels Hydrocephalus (18-60 d)
24-26 Close anterior neuropore Anencephaly
26-28 Close posterior neuropore Cranium bifidum, spina bifida cystica, spina bifida occulta
32 Vascular circulation Microcephaly (30-130 d), migration anomalies
33-35 Splitting of prosencephalon to make paired telencephalon Holoprosencephaly
70-100 Formation of corpus callosum Agenesis of the corpus callosum
Table 2. Anomalies of the CNS Associated with Myelomeningocele
Anomalies Associated with Myelomeningocele Approximate Percent of Patients
Chiari II malformation >90%
Hydrocephalus >90%
Syringomyelia 88%
Brainstem malformations (cranial nerve) 75%
Cerebral ventricle abnormalities >90%
Cerebellar heterotopias 40%
Cerebral heterotopias 40%
Agenesis of the corpus callosum 12%
Polymicrogyria 15-30%
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