Neural tube defects (NTDs) constitute one of the most common malformations of human
structure with a major public health burden (0.5-2/1000 pregnancies worldwide).1-3
They remain a preventable cause of still birth, neonatal and infant death, or significant
lifelong handicaps. The underlying pathology is the consequence of a defect in the
neurulation process very early in pregnancy, between 21 and 28 days after conception,
leading to failure of the neural folds to fuse in the midline and form the neural
tube.1 Secondary abnormal development of the mesoderm, responsible for forming the
skeletal and muscular structures that cover the underlying neural structures, follows
resulting in dysraphism, which indicates persistent continuity between the posterior
neural ectoderm and cutaneous ectoderm. Based on embryological considerations and
the presence or absence of exposed neural tissue, NTDs are classified as open or closed
types. Cranial dysraphism (failure of cranial neural tube closure) includes anencephaly
and encephaloceles, whereas spinal dysraphism (due to failure of caudal neuropore
closure) is divided into open spinal dysraphisms (myelomeningocele, myelocele, hemimyelocele,
and hemimyelomeningocele) and closed spinal dysraphisms. The latter can be associated
with subcutaneous mass and includes lipomas with dural defect and meningocele. Complex
dysraphic states are disorders characterized by aberrant formation or integration
of the notochord, which is the inductor of the neural ectoderm and constitutes the
foundation of the axial skeleton.1 These include caudal regression syndrome, which
ranges from agenesis of the coccyx to absence of the sacral, lumbar, and lower thoracic
vertebrae; to sirenomelia (or mermaid syndrome) characterized by fusion of the lower
limbs and other major organ malformations.4 Complex dysraphic states due to aberrant
integration of the notochord include split cord malformation (SCM) or diastematomyelia:
a congenital spinal anomaly in which there is longitudinal splitting of the spinal
cord.5,6
Causes of NTDs are multifactorial and defects in several different genes can underlie
the genetic basis of this disease.1 However, inheritance is commonly polygenic with
strong influencing environmental factors with strong implication of genes that regulate
folate one-carbon metabolism and planar cell polarity. In Saudi Arabia and several
other countries, consanguinity was suggested to contribute to the high incidence of
NTDs.7 A higher proportion (20%) of syndromic NTDs, often associated with chromosomal
anomalies, has also been documented compared with <10% elsewhere.7
The average incidence of NTDs is 1/1000 births, with a marked geographic variation
and declining incidence in developed countries over recent decades. However, it remains
high in the less-developed countries in Africa, Latin America, the Middle East, Asia,
and the Far East (>1 to 11/1000 births).2 Recognized risk factors associated with
NTDs include folate deficiency, maternal diabetes, obesity, maternal exposure to certain
teratogens such as valproic acid and carbamazepine taken by mothers who have epilepsy,
lead and tetrachloroethylene-contaminated drinking water, in utero exposure to arsenic,
pesticides, mycotoxins, and fungus contaminants of maize, heat exposure, influenza,
certain parental occupations, and low socioeconomic status.2
Most open NTDs are readily apparent at birth. Closed NTDs can present early with a
cutaneous marker such as a fluid-filled cystic mass, congenital dermal sinus, or hairy
patch (hypertrichosis).1 Later they may present with symptoms related to cord tethering
mainly neurological deterioration, urodynamic changes, or spine and feet deformity.1,5
Children with NTDs require comprehensive follow-up in a multidisciplinary setting
involving numerous specialties and subspecialties. These include neonatology, pediatric
neurology, neurosurgery, urology, pediatric orthopedics, and physical medicine.5,6,8,9
A model of this is depicted by the Spina Bifida Clinic (SBC) at King Khalid University
Hospital, College of Medicine, King Saud University, Riyadh, Saudi Arabia, which was
established in 1999.9 Through optimum urologic care, the SBC managed to maintain normal
renal function and normal social life for children with NTDs by maintaining their
urinary and stool continence.9 On the other hand, NTDs registries, similar to that
operating at King Faisal Specialist Hospital and Research Center, Riyadh,10 have met
their objectives by becoming a source of data that may significantly contribute to
the improvement of quality of care for NTDs patients through active publication of
registry findings and management approaches.
Screening for NTDs2 is based on biochemical testing of maternal blood for alpha-fetoprotein
and the use of ultrasonography, which is around 97% sensitive, and 100% specific in
diagnosing open NTDs. Further prenatal management requires parental decisions regarding
fetal karyotyping and whether to continue or terminate the pregnancy (with the local
ethical and legal backgrounds in perspective). Recently, endoscopic repair of myelomeningocele
by intrauterine approach resulted in significant improvement at 30 months in the composite
score for mental development and motor function of children with NTDs.2 Nevertheless,
periconceptional folic acid supplementation is the corner stone of prevention and
decreased the prevalence of NTDs by 50-70%. Since awareness of the benefits of folic
acid is still not optimum even in advanced industrialized countries, and to reach
women with unplanned pregnancies and those facing social deprivation, an obligatory
folic acid fortification of food was adopted in several countries including Saudi
Arabia.2 Prevention of NTDs can gain faster momentum if low income countries adopted
fortification of the staple food in their communities.
The idea of the current Supplement emerged following a pilot study on NTDs, which
was funded by Prince Salman Center for Disability Research (Project No. PSCDR/244/402).
The publication of the Supplement was gracefully sponsored by PSCDR to disseminate
important and intriguing information on NTDs. It is hoped that the present Supplement
will add to the commendable efforts and research activities of PSCDR11 with the goal
of optimum preventive and curative care pertaining to disability.