Women of childbearing age may present with a history of low socioeconomic status, lack of folic acid supplementation during pregnancy, family history, weakness, fatigue, dyspnea due to anemia, diabetes, and drug intake for epilepsy. Diagnosis is usually made both prenatal and postnatal. Prenatal diagnosis is made through ultrasound screening. Sometimes it may be discovered in older children or even adults.[15] Anencephaly is more lethal and so diagnosed easily antenatally. Urinary symptoms, neurological weakness, and cardiovascular complaints are often associated with NTDs.

Physical examination of NTDs varies according to the size and type of defects. Open NTDs are easily visible, whereas it may take through adults to detect closed types. The birth weight of the child may be low. About one-third of the cases are associated with other congenital anomalies present with cleft palate, undescended testis, omphalocele, talipes.[16] Increased circumference of the head complicated by hydrocephalus. Closed spinal defects are associated with lipomyelocele and lipomeningomyelocele. Dorsal enteric fistula, anal imperforation, cardiac and renal abnormalities in abnormal notochord formation, a tuft of hair, and scoliosis in case of diastematomyelia, polydactyly associated with encephalocele are the additional features may be present in rare conditions.[15] Myelomeningocele is often sac-like structure with CSF fluid leak. Late ambulation, cognitive impairment are present. The mother may be pale and anemic.

Ultrasound

It is the investigation of choice in prenatal screening. Ultrasound localizes the exact size and site of neural tube defects and vertebrae.[17]

Accurate diagnosis of anomalies with the help of ultrasound depends upon the gestational age of the fetus, careful evaluation of anomalies.

Serum Alpha-fetoprotein

Alpha-fetoprotein is a globulin protein formed by the fetal yolk sac, liver, and gastrointestinal tract. Initially, its concentration is greater in amniotic fluid and fetal plasma as compared to maternal serum. But as gestation advances, due to increased permeability of placenta, alfa-fetoprotein crosses the fetal-placental barrier so that maternal serum alfa-fetoprotein level rises and that of amniotic fluid and fetal plasma decreases. A high level of alfa-fetoprotein indicates neural tube defects. In addition, acetylcholinesterases level is estimated in the case of abnormally high levels of alpha-fetoprotein. Though serum alpha-protein level has an important role in the screening of neural tube defects, it is not a cost-effective approach.[18]

Magnetic Resonance Imaging (MRI)

MRI is performed in cases of uncertain ultrasound description to evaluate the anomalies more accurately. Although MRI has a diagnostic role in cases of neural tube defects, some studies in chick embryos showed that MRI exposure increases the incidence of neural tube disorders.[19]

Chromosomal Microarray

As it is clear that neural tube disorders have some contribution to genetic abnormalities, genetic testing estimates the association between genetic mutation and neural tube defects.[20]

Associated Anomalies

In many cases, neural tube defects are associated with other anomalies such as cardiovascular, cleft palate, urinary tract infections, coloboma, etc.

Maternal Serum Folic Acid Level

Maternal serum folic acid level before or during conception helps to rule out the causative factors of NTDs.[21]

Folic Acid Supplementation

Many studies suggested that periconceptional folic acid supplementation with the fortification of a diet rich in folic acid has significant results (50% to 70%) in preventing the neural tube disorders. The recommended dose of folic acid to all the women who are who want pregnancy is 0.4 to 0.8 mg per day.[22] But the women who already have had a child with NTD or positive family history should take 4 mg of folic acid daily one month prior to the conception through the first three months of pregnancy to prevent the recurrence. Some studies suggest that it takes around 20 weeks to achieve a normal red-blood-cell level of folic acid to prevent neural tube defects.[23] So women should receive folic acid 5 to 6 months prior to the conception.

Fetal and Postnatal Surgery for Myelomeningocele

Surgical repair of myelomeningocele in fetus seize leakage of spinal fluid and therefore arrest the herniation of cerebellum preventing the formation of hydrocephalus. Postnatal surgical closure of spina bifida should be done within 72 hours. Randomized control trials in the united states proposed that improved ambulation, cognitive behavior is more in prenatal as compared to postnatal surgery.[24] Recently published data indicate that prenatal repair may improve the bladder function and less trabeculation of the bladder as compared to conventional postnatal surgery. [25][26]

Ventriculoperitoneal Shunt

Hydrocephalus is treated by a ventriculoperitoneal shunt, which drains the  CSF from ventricles to the peritoneal cavity.

Antipyretics

The use of antipyretics in hyperthermia reduces the chances of NTDs.[27]

Prenatal counseling

Once the prenatal ultrasound and other investigations confirm the diagnosis of NTD, mother and family members should be counseled about the management, possible prognosis, complications, and referral to other specialties for a comprehensive approach of the disease.

Control of Gestational Diabetes

The pregnant mother with diabetes has chances of NTDs. So control of gestational diabetes helps to prevent and reduce the incidence of NTDs.

Postnatal Assessment and Management

In the absence of prenatal screening, NTDs child should be assessed immediately after birth about site of defects, size, leakage of cerebrospinal fluid, any infections and should be managed accordingly. Make sure of aseptic measures during the assessment. The use of non-latex gloves reduces the risk of latex sensitization. Broad antibiotics coverage to prevent infections, sterile and saline-soaked dressing, the neurological assessment helps in a wide range to facilitate postnatal life. The surgical management of closed neural tube defects is challenging and complex. Practitioners must be familiar not only with the underlying embryology associated with the specific defect but also the contemporary surgical management to reduce the risk of CSF fistula formation or neurologic compromise, which leads to high morbidity.

Neural tube disorders are classified on the basis of site and covering and its contents. So they have to be differentiated from each other at first for proper approach and interventions. They may be open or closed, spinal cord originated, or brain originated. Open spinal dysraphisms are myelomeningocele, hemimyelocele and lipomyelomeningocele, meningocele, lipomyelocele are the few closed types. Anencephaly is seen.[15] Few other differentials are briefed as follows:

Iniencephaly

It is the rare and lethal spondylocostal dysplasia associated with spina bifida, heart defects, cleft palate, and renal abnormalities.[28] The involvement of thoracic vertebra and the absence of ribs along with the presence of kyphosis helps to differentiate this disease from neural tube defects through such clinical presentation that may be minimally present or absent, making it difficult for diagnosis.

Meckel-Gruber Syndrome

Meckel-Gruber syndrome is an autosomal recessive disease comprising of a group of disorders involving the malfunction of cilia. Neural tube defects, mostly occipital encephalocele, are part of this syndrome. Besides encephalocele, this syndrome consists of involvement of other systems which has cilia as main functioning role such as respiratory tract, oviduct or efferent ducts, renal tubules, brain ventricles, etc. Presence of respiratory disease, infertility, polycystic kidney disease hydrocephalus is important to rule out isolated neural tube disorders from Meckel-Gruber syndrome.[29]

Tethered Cord Syndrome

Adhesions cause an abnormal stretching of spinal cords, mostly due to lipoma, dermoid cysts, rumors, etc.

Viral and Neonatal Meningitis

The primary causative organisms of neonatal meningitis are group B streptococcus and enterovirus for viral meningitis. Meningitis cause premature births along with signs and symptoms such as neck rigidity, fever that confuses with meningitis in patients with neural tube defects.

Lipomyelomeningocele

It is an intradural lipoma attached to surrounding soft tissue leading to the tethered spinal cord deteriorating the neurological functions.[30] The formation of hump mainly in the cervicothoracic region confuses neural tube defects.

Myelocystocele

Myelocystocele is a closed neural tube defect that resembles myelomeningocele, especially when complicated by hydrocele.[31]

Neurenteric Cyst

It is formed due to an abnormal connection between ectoderm and endoderm. They are common in neural crest cells though found in the brain and spinal cord in rare cases mimicking neural tube defects.[32]

Persistence of Terminal Ventricle

It is a rare case present as a cavity in conus medullaris can be visualized in radiological investigations.[32]

Prenatal screening advancement has brought sound improvement in the management of neural tube defects.[33] Earlier diagnosis and intervention has significantly reduced the postnatal complications of NTDs prolonging life. The most important prognostic factor is the level of disorder and extent of the segmental span. Higher-level lesion and larger segment lesion have poorer prognosis with non-ambulation, dysphasia, more time wheelchair use, etc. Prenatal surgical repair has better outcomes in terms of ambulation, cognition, and other neurological functions than postnatal repair.[24] The presence of other congenital anomalies with NTDs increases the mortality and morbidity of patients.[34]

Stillbirths and Abortion

Stillbirths and preterm labor leading to abortion is the serious complication NTDs.[6]

Polyhydramnios

It is typically associated with anencephaly because there is no mechanism for swallowing reflex so that amniotic fluid remains accumulated in the amniotic sac. This is obvious, patients with neural tube disorders have a learning disability as the development of neural tissue has been arrested. According to the conducted study, it is estimated that around 27% of pregnancies with anencephaly developed polyhydramnios few requiring amniodrainage in the third trimester[35] Polyhydramnios usually develops in second and third trimesters in about 50% of patients.

Arnold-Chiari Malformation

It is defined as the downward displacement (herniation) of part of the cerebellum into the foramen magnum because of the tethering of the spinal cord in the vertebral column due to its abnormal development (spina bifida).[36]

Hydrocephalus

Brain malformation has a direct impact on the development of hydrocephalus. Encephalocele is associated with the communicating type of hydrocephalus.

Meningitis

Continuous leakage of cerebrospinal fluid paves the easy access to meninges for normal naso-oropharynx such as streptococci, enterococci. The children with NTDs are susceptible to meningitis.[37] 

Cognitive disability:  Normal CSF pressure, osmolarity, and constituents of CSF are required for the proper development of the brain, mainly the cerebral cortex. Patients with NTDs have less cortical development even with the normal head size due to the free flow of CSF down through spina bifida. Neural cell proliferation and migration are deranged by abnormal CSF physiology.[38]

Spinal fistula: Spinal fistula formation and a continuous discharge of CSF is common in some cases.

Complications due to fetal surgery: Preterm delivery, obstetric complications, pulmonary edema percutaneous fetoscopic vs. open repair: preterm birth and placental rupture are more common in percutaneous fetoscopic surgery whereas the rate of uterine dehiscence is more in open surgery.[39]

NTDs are preventable in most cases. Negligence of community participation in comprehensive health care awareness about dietary management, prenatal screening, and sanitation hits back with neural tube disorders and other congenital anomalies. Proper folic acid supplementation reduces the chances of NTDs in folate preventable cases, and methionine and inositol reduce the NTDs in non-folate preventable cases.[1] Women who are taking antiseizure drugs should be minimized optimally as much as possible, and these patients need a higher dose of folic acid to overcome the antagonism of antiepileptic drugs. A blood test, usually around the fourth month of pregnancy, should be encouraged. Ultrasound screening has been an essential part of every pregnant woman with suspicion, family history, and in the areas of high prevalence rate. Prenatal surgical repair has good outcomes. Genetic counseling of the family should be part of a national campaign. Patients and families have the right to know about the information on the disease process, complications, treatment methods, and outcomes of management. Keeping in view of family counseling, long term follow up is required regardless of initial treatment.[40]

Nutritionists for folic acid supplementation plays a central role in preventing the disease in coordination with lab technicians and radiologists for prenatal screening and diagnosis. The approach of neurosurgery to reduce future complications and restore neurological development should go side by side. Fetal surgery has complications in both mother and child, so gynecologist and obstetrician consultation is a must. Genetic analysts are essential in genetic cases. In the modern era, researches have a huge impact on the evaluation of causes, risk factors, and modulation of treatment methods. Associated syndromes like Meckel-Gruber syndrome, VACTERL syndrome necessitates the call for multiple specialties like cardiologists, nephrologists, neurologists, rheumatologists, etc.