 INTRODUCTION:

Pregnancy has always been an important time during any woman’s life, bringing a new life into the world
is a blessing. While on the other hand, complications during pregnancies are the last thing anyone wants to
hear or go through.
Brain is a relatively common site for malformations. The abnormalities in size, shape and symmetry of the
head and face often suggest underlying congenital malformations. The presence of any ectodermal
dysplasia and spinal deformities should alert to the possibility of associated abnormalities in the central
nervous system.
One major complication that can occur during pregnancy is known as a Neural Tube Defect. Neural tube
defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from early
in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal
side of the embryo begin to change shape and form the neural tube. When the neural tube does not close
completely, an NTD develops.
 NEURAL TUBE DEFECTS:
Neural Tube Defects are the congenital malformations of the CNS resulting from a defective closure of the
neural tube during early embryogenesis between 3rd & 4th week of intrauterine life.
 INCIDENCE:
NTDs are one of the most common birth defects, affecting over 300,000 births each year worldwide. In
India, the incidence of NTDs varies between 0.5 to 10 per 1000 live births in different regions of India.
Risk in second sibling is higher. The defect is obvious at birth. The severity of NTD varies from spina
bifida occulta to anencephaly.
 DEVELOPMENT OF NEURAL TUBE:
In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central
nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the
neural folds become elevated, and ultimately the folds meet and coalesce in the middle line and convert the
groove into the closed neural tube. The neural tube closure usually occurs by the fourth week of pregnancy
(the 28th day after conception). The ectodermal wall of the tube forms the rudiment of the nervous system.
The center of the tube is the neural canal.
 CEREBRO SPINAL FLUID : Cerebrospinal fluid (CSF) is a clear, colorless plasma-like fluid that
bathes the central nervous system (CNS). Cerebrospinal fluid circulates through a system of cavities
found within the brain and spinal cord; ventricles, subarachnoid space of the brain and spinal cord
and the central canal of the spinal cord.

- Most CSF is secreted by the specialized tissue called the choroid plexus, which is located within the
lateral, third and fourth ventricles. The secretion of CSF equals its removal, so there are around 150-
270 milliliters of cerebrospinal fluid within the CNS at all times.

- The main functions of CSF are to cushion the brain and spinal cord when they’re struck with
mechanical force, to provide basic immunological protection to the CNS, to remove metabolic
waste, as well as to transport neuromodulators and neurotransmitters.

- Secretion: Cerebrospinal fluid is produced by a specialized tissue called the choroid plexus.
Choroid plexuses are located in the walls of the lateral ventricles and in the roofs of the third and
fourth ventricles. A choroid plexus shows numerous villi, via which it secretes the cerebrospinal
fluid.

- Circulation: Cerebrospinal fluid is constantly produced at a secretion rate of 0.2-0.7 ml/min,

meaning that there is 600–700 ml of newly produced CSF per day. Since the total volume of CSF
averages around 150-270 mL, this means that the entire volume of CSF is replaced around 4 times
per day. The pathway of the cerebrospinal fluid is as follows:

i. The CSF passes from the lateral ventricles to the third ventricle through the interventricular
foramen (of Monroe).
ii. From the third ventricle, the CSF flows through the cerebral aqueduct (of Sylvius) to the
fourth ventricle.
iii. From the fourth ventricle, some CSF flows through a narrow passage called the obex and
enters the central canal of the spinal cord. However, the majority of CSF passes through the
apertures of the fourth ventricle; the median aperture (of Magendie) and two lateral
apertures (of Luschka). Via these openings, the CSF enters the cisterna magna and
cerebellopontine cisterns, respectively.
iv. From there, the CSF flows through the subarachnoid space of the brain and spinal cord.
v. It is finally reabsorbed into the Dural venous sinuses through arachnoid granulations.
 PATHOPHYSIOLOGY OF NEURAL TUBE DEFECT:
Pathophysiology of neural tube defect is multi factorial and multi staged. Etiological factors, which are
mostly classified under environmental causes and genetic causes cause faulty folate metabolism. Folate
has found to be essential for timely closure of neural tube during embryonic development. Decreased
folate metabolism bring negative effects on metabolism of proteins and lipids.
Proteins and lipids being the main constituent in genetical infrastructure, alteration in the metabolism of
lipids and proteins cause altered gene expression which ultimately lead to neural tube defects.

Abnormal folate one carbon metabolism (FOCM) causes NTDs. Folic acid (MTHFR) mediates
unidirectional transfer of methyl groups from folate cycle to methionine cycle. Thus, it represents a key
nexus in portioning one carbon units between FCOM functional outputs.
Methionine cycle inhibitors prevent neural tube closure. Similarly, inability to use glycine as one
carbon donor to the folate cycle causes NTDs.
 Overall, neural tube closure depends on activity of both the methionine and folate cycles, but transfer of
one carbon units between the cycles is not necessary.

 ETIOLOGY:

- NTDs are multifactorial, with contributions from both genetic and environmental factors. The
genetic basis is not yet well understood, but several nongenetic risk factors have been identified as
have possibilities for prevention by maternal folic acid supplementation.

- The incidence of NTD shows wide variations and is influenced by race, ethnicity, nutritional status,
geographical location and socio-economic status.

- Inadequate levels of folate (vitamin B9) and vitamin B12 during pregnancy have been found to lead
to increased risk of NTDs.

- Most frequently occurring factors are Maternal Folic Acid deficiency, prenatal exposure to
antiepileptic drugs (like Valproate, carbamazepine), Folic acid antagonists (Aminopterin), Maternal
Fever, Diabetes Mellitus and irradiation.

- It is also associated with Trisomy 13 & 18, Triploidy and Meckel syndrome.

- The risk of recurrence of NTD after one affected pregnancy is 2-10%.

- The association seen between reduced neural tube defects and folic acid supplementation is due to a
gene-environment interaction such as vulnerability caused by the C677T Methylenetetrahydrofolate
reductase (MTHFR) variant. Supplementing folic acid during pregnancy reduces the prevalence of
NTDs by not exposing this otherwise sub-clinical mutation to aggravating conditions.

 TYPES OF NTDs:

A. Primary Neural Tube Defect:

They happen due to primary failure of the neural tube or its disruption during 18-25 days. They account for
95% of NTDs. It is usually associated with malformations of pons & medulla, downwards displacement of
cerebellum, medulla and fourth ventricle into upper cervical cord. It includes;
- Myelomeningocele
- Encephalocele
- Anencephaly.

B. Secondary Neural Tube Defect:

It consists about 5% of NTDs. It is associated with abnormal development of lower sacral or coccygeal
segments during secondary neurulation. These lesions are covered with skin and are rarely associated with
hydrocephalus and neurological deficits. It includes:
- Meningocele
- Lipomeningocele
- Spina Bifida Occulta
- Diastematomyelia

 SPINA BIFIDA:
Spina Bifida is one of the commonest anomalies of neural tube development seen in infants. It is the
congenital defect of the spinal column due to failure of the fusion of vertebral arches with or without
protrusion of the meninges and dysplasia of the spinal cord. It is the malformation of the spine in which the
posterior portion of the lamina of the vertebrae fails to close. It can be only a small deformed lamina
separated by a midline gap or may be a complete absence of lamina.
Spina Bifida can be broadly divided into two groups;
a. Spina Bifida Occulta
b. Spina Bifida Cystica
i. Meningocele
ii. Meningomyelocele

 SPINA BIFIDA OCCULTA:

- It is most frequent and most benign NTD. There is defective closure of the posterior arch and
lamina of the vertebra, usually L5 & S1. There is no protrusion of the meninges. The dysplasia of
the spinal cord is a prominent feature. Most of the cases are asymptomatic.
- Some children are present with cutaneous lesions over the defect, as tuft of hairs, lipoma,
hemangioma, dermal sinus or as dimple in the skin. There may be intraspinal lesions like dermoid
cyst, intermedullary lipoma, etc. which produce neurological deficit. The symptomatic children are
usually found after 6-8 years of age with any of the followings,

a) Progressive deformity of the foot

b) Changes in micturition pattern
c) Alteration in the gait
d) Tropic ulcers on the toes and feet.
e) Other significant anomalies of the spinal cord may be found in association of the condition.
Progressive neurological deficits require surgical correction of the defect.

- Laminectomy is done and the intraspinal lesion is excised. Operation can be done even before
neurological deficit appears in selected cases.

- Myelo CT Scan & MRI help to confirm the diagnosis before OT.

 MENINGOCELE:

- It is hernial protrusion of the meninges through a midline defect in the posterior vertebral arch. It
forms a fluctuating cystic swelling filled with CSF and covered by a thin transparent membrane or
with skin. It transilluminates easily. It is generally found in the lower back i.e., Lumbo-sacral
region. It may also be found in the Thoracic region and in the skull (Cranialmeningocle). The spinal
cord and nerve roots are usually normal. There is no dysplasia of the spinal cord and the child may
be found asymptomatic.

- It is relatively uncommon lesion, 4-5%. The symptomatic child may be present with weakness of
the leg or lack of sphincter control. Associated anomalies like hydrocephalus, Tethered cord may be
 present. As the skin or the membrane covering is thin, CSF leakage may be present with chances of
infection.

- Head circumference of the child should be measured daily and anterior fontanelle to be checked for
bulging or widening. These help to detect the development of hydrocephalus. The meningocele sack
should be protected from infection and injury. The infant should be positioned on the abdomen to
avoid pressure on the sack. If the sack is not covered with skin, it should be protected with sterile
moist dressing.

- X-ray spine and skull, CT Scan can be done to determine the defect and associated anomalies.

- Surgical closure of the sack should be done as early as possible to prevent infection. Prognosis is
generally good unless hydrocephalus and neurological deficits are developed.

 MENINGOMYLOCELE:

- It is a midline cystic sac of meninges with spinal tissue and CSF, which herniates through a defect
in the posterior vertebral arch. It is one of the commonest lesions (90-95%) and can be present
anywhere on the midline in the back. However, Lumbo-sacral area is the most common site. There
is dysplasia of the spinal cord and this is always accompanied by neurological deficit. This can be
found as 2 types:

a) Myelocele (open type)

b) Myelomeningocele (closed type)

- The commonest cystic lesion containing neural tissues which may be dysplastic spinal cord or nerve
fibers. Transillumination is not easy.

- The child with Myelomeningocele may be present with flaccid paralysis, absence of sensation and
drop reflex. Postural abnormalities like club foot, subluxation of hips may be present. Spasticity and
hyperactive reflexes may be present in thoracic or cervical myelomeningocele. Hydrocephalus is
usually associated with this anomaly. Musculoskeletal deformity and hydro syringomyelia may
occur in neonates. Later in older children, contractures of joints, scoliosis and kyphosis may
develop. There is risk of infection of CNS and rupture of sac.

- Primary diagnosis is done by clinical manifestations. Associated anomalies can be detected by

Xray, CT Scan, MRI and complete neurological assessment. Routine blood and urine examination
 are also necessary. Prenatal diagnosis can be done by Amniocentesis and estimation of Alpha feto-
protein.

- Management of the condition can be done by surgical correction of the defect and essential care of
the infant. Afterwards correction of musculoskeletal deformities and regulation of bladder and
bowel function should be performed. Additional support measures include prevention of injury and
infection of the sac by appropriate positioning with protective covering of sterile dressing.
Prevention of skin breakdown and monitoring of signs of hydrocephalus (Head circumference,
Fontanelle, Feeding behaviour).

- Other measures are provision of adequate nutrition, promotion of urinary elimination and bowel
regularity, prevention of leg/ hip deformities and other complications. Preoperative care, promotion
of growth and development, emotional and psychological support, health teaching regarding care of
the child are also important aspect of management.

 ANENCEPHALY:

- Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during
embryonic development. It is a cephalic disorder that results from a neural tube defect that occurs
when the rostral (head) end of the neural tube fails to close, usually between the 23rd and 26th day
following conception.
- Strictly speaking, the Greek term translates as "without a brain" (or totally lacking the inside part of
the head), but it is accepted that children born with this disorder usually only lack a telencephalon,
the largest part of the brain consisting mainly of the cerebral hemispheres, including the neocortex,
which is responsible for cognition. The remaining structure is usually covered only by a thin layer
of membrane—skin, bone, meninges, etc. are all lacking. With very few exceptions, infants with
this disorder do not survive longer than a few hours or possibly days after their birth.

- The child will be usually blind, deaf, unaware of its surroundings and unable to feel pain. Although
some individuals with anencephaly may be born with a main brain stem, the lack of a functioning
cerebrum permanently rules out the possibility of ever gaining awareness of their surroundings.
Reflex actions such as breathing and responses to sound or touch may occur.

- Meroanencephaly is a rare form of anencephaly characterized by malformed cranial bones, a

median cranial defect, and a cranial protrusion called area cerebrovasculosa. The most common type
of anencephaly, where the brain has entirely failed to form, except for the brain stem. Infants rarely
survive more than one day after birth with Holoanencephaly.
- Due to the presence of the brainstem, children with anencephaly have almost all the primitive
reflexes of a newborn, responding to auditory, vestibular and painful stimuli. This means that the
child can move, smile, suckle and breathe without the aid of devices.

- Anencephaly can often be diagnosed before birth through an ultrasound examination. The maternal
serum alpha-fetoprotein (AFP screening) and detailed fetal ultrasound can be useful for screening
for neural tube defects such as spina bifida or anencephaly.

- There is no cure or standard treatment for anencephaly. Prognosis is extremely poor, as many
anencephalic fetuses do not survive birth and infants that are not stillborn will usually die within a
few hours or days after birth from cardiorespiratory arrest.

 ENCEPHALOCELE:

- Encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the
membranes that cover it through openings in the skull. These defects are caused by failure of the
neural tube to close completely during fetal development. Encephaloceles cause a groove down the
middle of the skull, or between the forehead and nose, or on the back side of the skull. The severity
of encephalocele varies, depending on its location.

- Encephaloceles are often accompanied by craniofacial abnormalities or other brain malformations.

Symptoms may include neurologic problems, hydrocephalus (cerebrospinal fluid accumulated in the
brain), spastic quadriplegia (paralysis of the limbs), microcephaly (an abnormally small head),
ataxia (uncoordinated muscle movement), developmental delay, vision problems, mental and
growth retardation, and seizures.

- Although the exact cause is unknown, encephaloceles are caused by failure of the neural tube to
close completely during fetal development. Both environmental and genetic factors have been seen
to contribute to the cause of encephaloceles. Some studies have revealed a higher occurrence in
female embryos, suggesting a genetic cause. Research has indicated that teratogens (substances
known to cause birth defects), trypan blue (a stain used to color dead tissues or cells blue), and
arsenic may damage the developing fetus and cause encephaloceles.

- Proper levels of folic acid have been shown to help prevent such defects when taken before
pregnancy, and early in pregnancy.

- Usually, encephaloceles are noticeable deformities and are diagnosed immediately after birth, but a
small encephalocele in the nasal or forehead region can go undetected. Various physical and mental
developmental delays can indicate the presence of encephaloceles.
- Encephaloceles of the face are generally classified as nasofrontal, naso-ethmoidal, or naso-orbital,
however, there can be some overlap in the type of encephalocele. They can also appear along any
part of the cranial vault, as they result from abnormal closure of cranial bones; the most common
location for encephaloceles is the occipital region.

- Currently, the only effective treatment for encephaloceles is reparative surgery, generally performed
during infancy. The extent to which it can be corrected depends on the location and size of the
encephaloceles; however, large protrusions can be removed without causing major disability.
Surgery repositions the bulging area back into the skull, removes the protrusions, and corrects the
deformities, typically relieving pressure that can delay normal brain development. Occasionally,
shunts are placed to drain excess cerebrospinal fluid from the brain.

- Recovery is difficult to predict prior to surgery, and depends on the type of brain tissue involved
and location of the encephaloceles. If surgery is successful, and developmental delays have not
occurred, a patient can develop normally. Where neurologic and developmental damage has
occurred, the specialists will focus on minimizing both mental and physical disabilities.

- In general, when the bulging material consists of primarily cerebrospinal fluid, a complete recovery
can occur. When a large amount of brain tissue is present in the encephaloceles, there is a higher
chance of perioperative complication.

 HYDRANENCEPHALY:

- Hydranencephaly is a condition in which the cerebral hemispheres are missing and instead filled
with sacs of cerebrospinal fluid. People are born with hydranencephaly, but most of the time, the
symptoms appear in a later stage.

- Newborns with hydrancephaly can swallow, cry, sleep and their head are in proportion to their
body. However, after a few weeks, the infants develop increased muscle tone and irritability. After a
few months, the brain starts to fill with cerebrospinal fluid (hydrocephalus). This has several
consequences. Infants start to develop problems with seeing, hearing, growing, and learning.

- The missing parts of the brain and the amount of cerebrospinal fluid can also lead to seizures,
spasm, problems with regulating their body temperature, and breathing and digestion problems.
Besides problems in the brain, hydranencephaly can also be seen on the outside of the body.
Hydrocephalus leads to more cerebrospinal fluid in the brain, which can result in an enlarged head.
- The cause of hydranencephaly is not clear. Hydranencephaly is a result of an injury of the nervous
system or an abnormal development of the nervous system. The neural tube closes in the 6th week
of the pregnancy, so hydranencephaly develops during these weeks of the pregnancy. The cause of
these injuries/development is not clear.

- Theories regarding the causes of hydrancephaly include:

i. Blockage in the carotid artery: some researchers think that a blockage of the carotid artery
leads to the under-/no development of the brain. The carotid artery is the most important
blood supplier of the brain. With a blockage, the brain barely receives blood. Blood is
necessary for development and keeping intact of the brain.

ii. Inherited condition.

iii. Infections: during the pregnancy, a woman can develop an infection in the uterus what can
lead to problems with the neural tube.

iv. Environmental toxins: during the pregnancy, a woman can be exposed to environmental
toxins what can have effect on the health of the infant.

 INIENCEPHALY:

- Iniencephaly is a rare neural tube defect that results in extreme bending of the head to the spine. The
diagnosis can usually be made on antenatal ultrasound scanning, but if not will undoubtedly be
made immediately after birth because the head is bent backwards and the face looks upwards.
Usually, the neck is absent. The skin of the face connects directly to the chest and the scalp
connects to the upper back. Individuals with iniencephaly generally die within a few hours after
birth.

 PREVENTIONS:

- There are prevalent regulations requiring the addition of folic acid to enriched breads, cereals, flour
and other grain products. It is important to note that during the first four weeks of pregnancy (when
most women do not even realize that they are pregnant), adequate folate intake is essential for
 proper operation of the neurulation process. Therefore, women who could become pregnant are
advised to eat foods fortified with folic acid or take supplements in addition to eating folate-rich
foods to reduce the risks of serious birth defects.

- Women who may become pregnant are advised to get 400 micrograms of folic acid daily. Women
who have previously given birth to a child with a neural tube defect may benefit from a supplement
containing 4.0 mg/5.0 mg daily.

 SUMMERIZATION:
Neural Tube Defects are the congenital malformations of the CNS resulting from a defective closure of the
neural tube during early embryogenesis between 3rd & 4th week of intrauterine life. In India, the incidence
of NTDs varies between 0.5 to 10 per 1000 live births in different regions of India. NTDs are
multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet
well understood, but several nongenetic risk factors have been identified as have possibilities for prevention
by maternal folic acid supplementation. It is classified into primary and secondary neural tube defects.
Spina Bifida is one of the commonest anomalies of neural tube development seen in infants. Spina Bifida
can be broadly divided into two groups; Spina Bifida Occulta and Spina Bifida Cystica (Meningocele and
Meningomyelocele). Other types of NTDs are anencephaly, hydranencephaly, etc.

 CONCLUSION:

Human birth defects, today, continues to be a highly investigated research. There remain many convoluted
combinations of genetic and environmental factors that can cause birth defects. While some conditions are
easily repaired through surgery, neural tube defects (NTDs) present problems even after surgery. Many
steps can be taken for the pregnant mother to prevent any chances of birth defects.

 BIBLIOGRAPHY:

1. Dutta Parul, ‘Pediatric Nursing’, Published by Jaypee Brothers Medical Publishers; 4th Edition
2018, page no: 104-108.

2. Singh Meharban, ‘Care of the Newborn’, Published by CBS Publishers & distributors, 8th
Edition, 2017, page no:301-313.

3. Marlow Dorothy R, ‘Textbook of Pediatric Nursing’, Published by Elsevier, South Asian

Edition 2013, page no: 323-334.

4. Paul VK, Bagga A, ‘Ghai Essential Pediatrics’, Published by CBS Publishers & Distributors
Pvt Ltd, 9th Edition, 2013, page no: 125 – 136.

5. [Link]

6. [Link]