Upper and Lower Neural Tube Defects- Review
1
2
3
Leelavathy N , Sayee Rajangam , Kulkarni RN ,
1
2
3
Department of Anatomy , Associate Professor , Professor , Professor & Head
1
2,3
Saptagiri Institute of Medical Science & Research Center , International Medical School, Bangalore
ABSTRACT
Normally neural tube closes around 18 to 28 days post
fertilization. Abnormal closure of the neural folds results in
neural tube defects. A defect occurring at the upper end of
neural tube results in upper neural tube defects;
exencephaly or anencephaly or encephalocele. A defect in
the lower end of neural tube leads to lower neural tube
defects; lumbosacral myelocele or meningomyelocele.
INTRODUCTION
Neural tube defects (NTDs) are mostly due to the failure of
closure of the neural tube in the anterior and posterior
neuropores resulting in the spinal cord or brain being 'open'
and its outer surface formed by the wall of the central canal
or ventricular system. A defect occurring at the upper end
results in upper NTDs (exencephaly, anencephaly,
encephalocele) and at the lower end in lower NTDs (spinal
lesions, lumbosacral myelocele, meningomyelocele.
Defects involving head and cervical and thoracic spines
lead to cranio-rachischisis, which are also included in
1
NTDs. Most NTDs have serious consequences .
The aim of the present study is to report the examples for
the upper and lower neural tube defects. It is also aimed to
review the incidence, formation, anomalies, etiology,
prenatal diagnosis, prevention and risk assessment of the
neural tube defects.
Department of Anatomy, International Medical School,
Bangalore, has 4 female specimens in the museum: 3 with
upper and one with lower neural tube defects: The upper
neural tube defects are 2 with anencephaly and
rachischisis and one with acrania and rachischisis and the
lower neural tube defect is meningomyelocele.
The aim of the article is to report the museum specimens
with anencephaly and rachischisis, acrania and
rachischisis and meningomyelocele, as the examples for
the upper and lower NTDs.
MATERIAL AND METHOD
Information is provided as a resource material for the
specimens with neural tube defects in the museum.
Department of Anatomy, International Medical School,
Bangalore, has 4 specimens in the museum: 2 with
anencephaly and rachischisis; one with acrania and
rachischisis; and one with meningomyelocele. They were
all female fetuses with age range from 4 months to full term.
They were considered for the museum as the teaching
specimens.
KEY WORDS neural tube defects, incidence, sex ratio,
types, management, etiology.
Figure 1. Dorsal view: Anencephaly, iniencephaly and rachischisis:
Note the partial absence of the brain; enlarged
foramen magnum and the clefts
in the vertebral column till midthoracic region.
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Upper and Lower Neural Tube Defects- Review
Figure 2. Dorsal view.
Acrania, iniencephaly & rachischisis, sacral dimple:
Note the absence of the cranium and a membrane like
covering; partial absence of the brain; enlarged foramen
magnum and clefts in vertebral arches of the vertebral
column till sacral region.
Figure 3: Dorsal view.
Meningomyelocele: Note the open spina bifida
cystica in thoraco-lumbar region with protrusion
of meninges and spinal cord through vertebral
defects and formation of sac filled with
cerebrospinal fluid and covered with a thin membrane.
A novel way of review has been attempted. From the text
books in Embryology and Human Genetics, the relevant
information pertaining to NTDs on the incidence, sex ratio,
formation, types of NTDs and associated anomalies,
etiology, management, prenatal diagnosis, prevention and
risk assessment are presented.
Incidence: (Table 1)
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Table 1: NTDs- Incidence
NTDs & types
Authors & Year
Moore and
3
Persaud 2008
Incidence
Spina bifida cystica
1/ 1000 births.
UK: South Wales: 4.2/ 1000 births
UK: Southeastern England: 1.5/
1000 births.
10% of normal people.
Spina bifida occulta in L5 or S1
vertebra
Acrania with anencephaly
Bradley –Smith
2
et al. 2010
4
Dudek 2010
Jorde et al. 2010
5
6
Sadler 2010
1/ 1000 births
NTDs
Northern Ireland: 1/ 300
USA: 1/ 1000
Types:
50%: spina bifida,
40%: anencephaly,
8.5%: encepahlocele 1.5%:
iniencepahly
NTDs
Ireland: 1/200 births
USA: 1/ 1000 births
NTDs
1- 3/ 1000 newborns
Northern China : 6/ 1000 births
Hungary: 1/ 300 births
NTDs
Overall in USA: 1/ 1000 births & in
North & South Carolina: 1/ 500
births.
Northern China: 1/ 100 births.
1/ 1000 births.
10% of normal people.
Spina bifida cystica
Spina bifida occulta
Sex ratio:
2
More females are known to be affected with NTDs;1M:1.3F. (Bradley-Smith et al 2010)
The gathered information from some of the text books in Embryology and Genetics is tabulated.
Table 2: Empiric Recurrence Risk for NTDs (Turnpenny and Ellard (2012)
Disorder
Incidence per
1000
Sex ratio Unaffected
Affected parents
parent having a having an
2nd affected child affected child
-
-
-
-
Anencephaly
1.5
1:2
4-5%
-
Spina bifida
2.5
2:3
4-5%
4%
NTDs
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In general, the recurrence risk for the NTDs may be 10%. Children born to diabetic mothers may have an increased
risk for the NTDs with a relative risk of 11.5%. In women with epilepsy, there exists the need for the review of the
2
treatment with the anticonvulsant. (Bradley-Smith et al. 2010)
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Table 3: Anencephaly and SB: Approximate recurrence risks without folate supplementation in
2
relation to the population incidence (Bradley-Smith et al. 2010)
Population incidence of
NTD- 0.005
%
0.002
%
0.001
%
One sibling
5
3
2
Two siblings
12
10
10
2
1
1
One 3 degree relative
1
0.75
0.5
One parent
4
4
4
Relationship of affected
individual to 'at risk'
pregnancy
nd
One 2 degree relative
rd
NTDs: Formation
Carlson (2004)1
The formation of the NT involves around 4 stages:
I transformation of the general embryonic ectoderm into the
neural plate;
ii) changes in the shape of the neural plate, which becomes
narrower and longer and also in the neuroepithelial cells as
well as the in the rearrangements between the cells;
iii) lateral folding of the neural plate resulting in neural
groove and neural folds;
iv) fusion of the neural folds resulting in the formation of NT.
Even though the closure of NT starts at 21 to 22 days old
embryo; two unclosed cephalic and caudal ends, the
th
anterior & posterior neuropores remain open and by 28
day the closure is completed. NTDs are mostly due to the
failure of closure of NT in the anterior and posterior
neuropores and also in other closure defects resulting in
the spinal cord or brain being 'open' and its outer surface
formed by the wall of the central canal or ventricular
system.
Turnpenny and Ellard (2012)
7
NTDs result from the defective closure of the developing
st
NT, during the 1 month of embryonic life. The different
types of NTDs relate to the different embryological closure
points of the NT.
Dudek and Fix (2008)
8
Anencephaly, an example for upper NTDs occurs because
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defect is the spina bifida (SB).
NTDs: Anomalies
1
Carlson (2004)
I & ii. Cranioschisis is the closure defect of the brain and
rachischisis is the closure defect of the spinal cord.
Cranioschisis results in death; on the other hand
rachischisis is associated with a wide variety of severe
problems, including chronic infection, motor and sensory
deficits and disturbances in the function of the bladder.
Usually both defects are accompanied with anencephaly, a
lethal defect wherein most of the brain failed to be formed.
iii. Meningomyelocele one of the examples for the other
closure defects is with bulging or entirely displaced spinal
cord into the protruding arachnoid space and associated
with displaced spinal roots and neurological problems.
Turnpenny and Ellard (2012)
7
I Defects at the upper end of the developing NT results in
exencephaly/ anencephaly or encephalocele;
ii) defects at the lower end of the NT leads to spinal lesions
such as a lumbosacral myelocele or meningomyelocele ;
iii) defects involving the head plus cervical and thoracic
spines lead to cranio-rachischisis.
Most of the NTDs have serious consequences;
anencephaly and cranio- rachichisis are not compatible
with survival for more than a few hours after birth and large
lumbosacral lesions usually cause partial or complete
paralysis of the lower limbs and also impaired bladder and
bowel continence.
Dudek and Fix (2008)
8
I Anencephaly: The resulting changes are the failure in the
development of the brain, formation of the lamina terminalis
and the bony cranial vault. It is incompatible with
extrauterine life; babies are still born or survive only a few
hours or weeks after birth and it is the most common
serious birth defect in stillborn fetuses.
ii. Rachischisis (cleft vertebral column) refers to the
vertebral abnormalities in a complex group of anomalies
(axial dysraphic disorders) affecting primarily the axial
structures.
iii. The most severe type of SB causes paralysis from the
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the sac which is filled with cerebrospinal fluid. It is a severe
type of SB cystica; the spinal cord and or nerve roots are
included in the sac; may be covered with skin or a thin
membrane and is associated with marked neurological
defects inferior to the level of the protruding sac. Nervous
tissue incorporated in the wall of the sac impairs the
development of the nerve fibers. Hence, SB with
meningomyelocele is a more common and a much more
severe anomaly than SB with meningocele.
level of the defect caudally and presents clinically as an
open NT that lies on the surface of the back. The neural and
vertebral defects may be extensive or restricted to a small
area.
Moore and Persaud (2008)
3
NTDs involve neural and non-neural structures, such as
meninges, vertebrae, muscles and skin.
I In acrania, the calvarium is absent; extensive defects of
the vertebral column are often present and are
incompatible with life.
Severe cases of SB with meningomyelocele involving
several vertebrae are often associated with partial absence
of the brain- merencephaly. Sphincter paralysis (bladder
and or anal sphincters) is common with lumbosacral
meningomyelocele. There is almost invariably a saddle
anesthesia when the sphincters are involved (loss of
sensation when the body region that would contact the
saddle during horseback riding).
ii. Anencephaly results from the failure of the cranial end of
th
the neural tube to close during the 4 week and then it
causes subsequent failure in the formation of the calvaria.
iii. Meroencephaly (partial absence of the brain) is the most
severe NTD as well as the common anomaly affecting
CNS. The term anencephaly is in use; but it is a misnomer
because a remnant of the brain tissue may be present.
iv.1.C. Some meningomyelocele associated with
craniolacunia (defective development of the calvaria) result
in the depressed non- ossified areas on the inner surfaces
of the flat bones of the calvaria.
iv. SB is the general term in use for the NTDs affecting the
spinal region. SB consists of the splitting of the vertebral
arches and may or may not include the nerve tissue; based
on which SB further classified as the SB cystica (iv.1) and
SB occulta (iv.2.)
iv.1.D. SB myeloschisis or rachischisis occurs occasionally;
because the neural folds did not elevate and remained as a
flat mass of neural tissue. SB with myeloschisis may result
from NTDs caused by a local overgrowth of the neural plate
resulting in the failure of the closure of the caudal
th
neuropore, at the end of 4 week. Myeloschisis the most
severe type of SB; the spinal cord in the affected area is
open because the neural folds failed to fuse; as a result the
spinal cord is represented by a flattened mass of nervous
tissue.
iv.1. SB cystica, severe types of SB, involving protrusion of
the spinal cord and or meninges through the defects in the
vertebral arches are referred collectively as SB cystica
because of the cyst like sac that is associated with these
anomalies. SB cystica shows varying degrees of
neurological deficits depending on the position and extent
of the lesion. There is usually a corresponding dermatome
loss of sensation along with complete or partial skeletal
muscle paralysis. The level of the lesion determines the
area of anesthesia and the muscles affected. SB cystica is
found to be common in the lumbosacral region & further
studied as the meningocele with only fluid- filled meninges
or meningomyelocele with neural tissue in the sac.
Bradley-Smith et al.(2010)
2
Included in the NTDs are the anencephaly, encephalocele,
m y e l o c e l e o r r a c h i s c h i s i s , i n i e n c e p h a l y,
meningomyelocele, spina bifida and spina bifida occulta.
I Anencepahly, the lethal NTD is due to the failure of fusion
of the caudal folds of the NT from 18 to 28 days of
intrauterine life of the fetus with the result in the failure of the
development of the forebrain.
iv.1.A. SB cystica meningocele: The sac contains
meninges and CSF; the spinal cord and the spinal roots are
in their normal position; but there may be spinal cord
abnormalities.
ii. Chiari II malformation is the downward protrusion of the
medulla below the foramen magnum thereby it overlaps the
spinal cord and is seen in 70% of the cases with
meningomyelocele and the symptoms increase with age.
iv.1.B. SB cystica meningomyelocele occurs in the
thoracolumbar region with protrusion of meninges and
spinal cord through the vertebral defect and the formation of
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iii. Encepahlocele is the out-pouching of the brain mostly
through the occipital bony defect either in the apical part of
the occipital bone or through the posterior fontenelle.
diagnosed prenatally and the pregnancies terminated.
ii. Children with SB lose a degree of neurological function
based on the spinal cord level of the lesion and its severity.
Most defects of the spinal cord result from the abnormal
rd
th
closure of the neural folds in the 3 and 4 weeks of
development. The resulting NTDs may involve the
meninges, vertebrae, muscles and skin. SB is the general
term for NTDs affecting the spinal region. It consists of
splitting of the vertebral arches and may or may not involve
the underlying neural tissue.
iv and v. Iniencepahly/ cranioschisis are the development
abnormality of the skull and upper spines.
vi. SB cystica is the result of the failure of the fusion of the
rostral folds of the NT between the 18 to 28 days of
gestation. Lesions are common in the lumbosacral region.
vi.1. In SB meningomyelocele the spinal cord is also the
component of the cyst.
Two different types of spina bifida occur. One of the most
serious vertebral defects is the result of imperfect fusion or
non-union of the vertebral arches. Such an abnormality,
cleft vertebrae or spina bifida may involve only the bony
vertebral arches, leaving the spinal cord intact. The bony
defect is covered by skin and no neurological defects then it
is spina bifida occulta (ii.1). A more severe abnormality is
spina bifida cystica (ii.2.) in which NT fails to close,
vertebral arches fail to form, and neural tissue is exposed.
Any neurological defects depend on the level and extent of
the lesion.
vii. Isolated NTDs are usually associated with vertebral
anomalies and hydronephrosis.
Jorde et al. (2010)
5
NTDs, one of the most important groups of birth defects and
include anencephaly, spina bifida and encepahlocele.
I Anencephaly is characterized by the partial or complete
absence of the cranial vault and calvarium and also the
cerebral hemispheres. 75% of the anencephaly is still born
and the full term deliveries with anencephaly do not survive
more than few hours or days.
ii.1. SB occulta: A defect in the vertebral arches that is
covered by skin and usually does not involve underlying
neural tissue. It occurs in the lumbosacral region and
usually marked by a patch of hair overlying the affected
region. The defect is due to lack of fusion of the vertebral
arches.
ii. SB bifida is the most common type in NTDs with
protrusion of spinal tissue (meninges, spinal cord, nerve
roots) through the vertebral column. Nearly, 75% of the
patients affected with SB have secondary hydrocephalus,
which in turn gives rise to mental retardation. The other
observed anomalies are the paralysis or muscle weakness,
lack of sphincter control and club feet. The survival rates for
the SB patients have been studied in British Columbia and it
has showed a dramatic improvement over the past
decades: less than 30% of children born between 1952 and
1969 have survived to 10 years of age; whereas it is 65% for
the children born between 1970 and 1986.
ii.2. SB cystica is a severe NTD in which the neural tissue
and or the meninges protrude through the defect in the
vertebral arches and skin to form a cyst-like sac. Most lie in
the lumbosacral region and result in neurological deficits,
but are not associated with MR.
ii.2.A. SB with meningocele: In some cases with only fluid
filled meninges protrude through the defect.
iii. Encephalocele consists of the protrusion of the brain into
an enclosed sac and never compatible with survival.
ii.2.B. SB with meningomyelocele: In others with neural
tissue inclusion in the sac.
Vertebral anomalies and hydronephrosis are commonly
seen in isolated NTDs. Additional anomalies may be
present in 20% of the cases with NTDs; then the possibility
of the syndrome with single gene disorder or chromosomal
anomaly should be considered.
Sadler (2010)
iii. Occasionally the neural folds do not elevate but remain
as a flat mass of neural tissue SB with myloschisis or
rachischisis.
9
Dudek (2011)
6
NTDs, the congenital malformations of the nervous system
are further classified as per the sites and the contents of the
I Anencephaly is a lethal defect and most of these cases are
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defects.
I Cranium bifidum (CB) occurs because of the failure in the
formation of the bony skull, with defect in the skull, usually
in the occipital region.
i.1. CB with meningocele has the protruding meninges
through the defect in the skull and form the sac filled with
CSF.
i.2. CB with meningoencephalocele has the meninges and
the brain protruding through the skull defect and the form
the sac filled with CSF. The outcome of the defect is poor ;
the infants either die or have severe mental retardation.
i.3. CB with meningohydroencephalocele occurs when the
meninges, brain and portion of the ventricle protrude
through the defective skull.
ii. Anencephaly or meroanencephaly, the example for the
upper NTDs is due to the failure of the closure of the
th
anterior neuropore, during the 4 week of development. It
has failure of the development of the brain (? rudimentary
brain may be present), formation of the lamina terminalis
and the cranial vault. The condition is incompatible with
extrauterine life. Mostly the infants are stillborn or survive
from only a few hours to a few weeks.
iii. SB is formed because of the failure in the proper
formation of the bony vertebral arches, usually in the
lumbosacral region. SB includes SB with meningocele, SB
with meningomyelocele and SB with rachischisis.
iii.1. SB with meningocele: The meninges protruding
through the vertebral defect form a sac filled with CSF and
the spinal cord is normal in its position.
ii.2. SB with meningomyelocele: The meninges and the
spinal cord protrude through the defect in the vertebral
column and form a sac filled with CSF.
iii.3. SB with rachischisis: Due to the failure in the closure of
th
the posterior neuropore during the 4 week of
development. The most severe type of SB with paralysis
from the level of the defect caudally. The variation presents
clinically as the open NTDs on the surface of the back. The
condition is also under the classification of the lower NTDs.
iv. Arnold-Chiari malformation shows the herniated caudal
vermis and tonsils of the cerebellum and the medulla
oblongata through the foramen magnum. Clinical signs are
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possible adverse environmental factors.
risk for the NTDs with a relative risk of 11.5%.
Environmental factors involved in the etiology of NTDs
have been identified and include poor socio economic
status, multiparity and valproic acid embryopathy.
The increased risk is also proposed for the NTDs with prepregnancy obesity in women.
Dudek and Fix (2008)
Folic acid antagonist, valproate, the anti-convulsant is
st
considered to be teratogenic in the early 1 trimester of the
pregnancy.
9
The failure of fusion of NT is because of the faulty induction
by the underlying notochord or from the action of
teratogenic agents on the neuroepithelial cells in the neural
folds. NTDs with genetic etiology are part of the
chromosomal abnormality (Trisomy 13 or 18) or single
gene disorders (Meckel syndrome with autosomal
recessive mode of inheritance).
Moore and Persaud (2008)
Jorde et al. (2010)
The formations of the NTDs are because of the
combination of the genetic and or environmental factors.
Sadler (2010)
6
Environmental: Hyperthermia, valproic acid and
hypervitaminosis A produce NTDs as do a large number of
other teratogens. The origin of most NTDs is multifactorial
and the likelihood of having a child with such a defect
increases significantly once one affected offspring is born.
3
Mostly NTDs are isolated and then the etiology is genetic
and or environmental with multifactorial mode of
inheritance. For the genetic, it is considered to be the
additive effect of many genes and for the environmental, it
could be viral, occupational hazards, chemicals and drugs.
The considered teratogens may be the hyperthermia,
valproic acid and hypervitaminosis A. It is suggested that
the teratogen primarily disturbs the fate of the cells,
adhesion between the cells and the mechanisms behind
the closure of the NT. Valproic acid, an anticonvulsant drug
causes NTDs in 1 to 2% of pregnancies, if given in early
th
pregnancy i.e. 4 week of development and also at the time
when the neural folds are fusing and it is also associated to
the increase in the risk of meningomyelocele.
It has been shown that there may be evidence consistent
with a maternal effect, as well as a sex-influenced effect on
10
NTD (Kristen, 2008)
NTDs- Prenatal Diagnosis (PND):
PND procedures such as the elevated á-fetoprotein (AFP)
in the maternal serum or amniotic fluid and ultrasonography
detect the presence of the NTDs. The prenatal diagnosis is
considered to be the causes, in the decline in the incidence
of the open NTDs in live- and still- births and the other
factors are the general improvement in the diet and the
intake of the periconceptional folic acid. In England and
Wales, over the duration of 20 years, the combined
incidence of the anencephaly and the spina bifida in live
births and stillborn babies are declined from 1 in 250 in
7
1973 to 1 in 6250 in 1993. (Turnpenny and Ellard 2012)
Pregnant animals exposed to hyperthermia or high levels of
vitamin A are also associated to produce offsprings with
NTDs.
NTDs may also be secondary to or linked to lesions
affecting the degree of flexion imposed on the neural plate,
during the folding of the embryo.
- AFP: In 1972, it was recognized that many pregnancies in
which the baby had open type of NTDs, the NTDs could be
detected at 16 weeks gestation by the AFP assay in
maternal serum. AFP, the fetal equivalent of albumin is the
major protein in the fetal blood. In the fetus with open NTD,
the AFP level is increased in the amniotic fluid as well as in
the maternal serum as the result of the leakage from the
open NTD. Open NTDs are serious disorders; anencephaly
is fatal and between 80 and 90% of the babies who survive
with open lumbo-sacral lesions are severely handicapped.
Maternal serum AFP screening for the NTDs is 100%
neither sensitive nor specific. There exists the overlap, in
Nutritional and environmental factors undoubtedly play a
role in the formation of NTDs.
Bradley-Smith et al.(2010)
5
2
Isolated NTDs are categorized into the mutlfactorial mode
of inheritance with genetic and or environmental factors, as
the causes. Several genes are implicated in the process of
the elevation of the neural folds, which fuse to form the NT.
Children born to diabetic mothers may have an increased
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of folic acid is neither known nor suspected for the
proposed daily dose of folic acid and there are no
contraindications too. In spite of the high- dosage of folic
acid, the recurrence of NTD has occurred; then the
association of the NTD with any syndrome has to be
reconsidered. The recurrence risk may be 10% and
irrespective of the benefits, the high-dosage folate
supplementation should be continued for the next
pregnancy.
In women with epilepsy, there exists the need for the review
of the treatment with the anticonvulsant. In general,
because of the improved maternal nutrition, the birth
prevalence of the NTDs seemed to be declining. (Bradley2
Smith et al 2010)
Folic acid supplementation to mothers at the time of the
conception is a major epidemiological finding in the
prevention of NTD births. Several population studies have
confirmed the finding. 50 to 70% of NTDs are preventable
by dietary folic acid supplementation and folic acid
deficiency could account for part of the elevated sibling
recurrence risks for NTDs. However, there could be genetic
variation in the response to the folic acid and it may be the
reason that mothers with folic acid deficiency may not give
rise to births with NTDs and mothers with folic acid
supplementation may still give rise to births with NTDs.
Research is being carried out to test the associations
between NTDs and variants in several genes whose
products are involved in folic acid metabolism (MTHR5
methylene tetrahydrofolate reductase). (Jorde et al. 2010)
It is not clear whether the protective effect is due to the folic
acid or the combination of folic acid and other vitamins; but
studies have indicated that the periconceptional vitamin
supplementation is an effective prevention strategy. The
mechanism for the apparent effect is also not known.
Regarding the use of folate, two recommendations are put
forward: i) women who have had a child with NTD should
take 4 mg/day of folic acid in case of planning another
pregnancy ii) all women of reproductive age should take 0.4
mg/day of folic acid, the amount available in a typical
multivitamin tablet, throughout their reproductive years.
The second recommendation is in view of the fact that
nearly 50% of pregnancies in USA are unplanned. In USA
and other nations, folic acid is fortified to wheat and other
grain products and in the past decade, after the initiation of
the food fortification program, studies have demonstrated a
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effectiveness of surgery on NTDs. (Jorde et al. 2010)
5
A new treatment for the defect is to perform surgery in- utero
at approximately 28 weeks of gestation; the baby is
exposed by caesarian section, the defect repaired and the
infant is placed back in the uterus. Preliminary results
indicated that the approach reduced the incidence of
hydrocephalus, improved the bladder and bowel control
and increased motor development to the limbs. (Sadler.
6
2010)
NTDs: Risk Assessment:
Being multifactorial, the chances of having a child with NTD
increases significantly in the presence of an affected
offspring to the couple seeking genetic counseling and also
with positive family history. Appropriate measures could be
planned following genetic counseling under medical
guidance.
st
Empirical recurrence risk to the 1 degree relatives
(siblings and offsprings) vary according to the local
population incidence and are as high as 4 to 5% in areas
where NTDs are common. The incidence in the UK is
highest in the people of Celtic origin. Such individuals move
from their country of origin to another part of the world, the
incidence of NTDs in their offsprings declines, but remain
higher than amongst the indigenous population. These
observations have suggested that there is a relatively high
incidence of adverse susceptibility genes in the Celtic
7
population. (Turnpenny and Ellard 2012)
Careful evaluation of the pedigree is necessary to
determine the risk that applies to each pregnancy. Risks
can be determined based on empiric data. In high-risk
situations amniocentesis with assay of the chemical AFP
has been used for PND in the past. Scanning of the fetus in
conjunction with assay of maternal serum AFP has proved
equally if not more reliable. Even with the best possible
equipment and experienced sonographer, small closed
NTDs could still be missed. Fortunately, the latter types of
NTDs are not usually associated with the serious problems
seen with the large open NTDs. (Turnpenny and Ellard
7
2012)
Risk could be calculated for single gene disorders with the
help of basic mendelian genetics and the applied
probability theory. There are situations wherein, the
disorder does not manifest single gene inheritance or
13
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Review-Embryology
Upper and Lower Neural Tube Defects- Review
Pvt.Ltd; 2008
th
9.
Dudek RW. Embryology. 5 edition. Board Review
Series. New Delhi, India: Wolters- Kluwer (India) Pvt.Ltd;
2011
10.
Kristen L. Deak, Deborah G. Siegel, Timothy M.
George, Simon Gregory, Allison Ashley-Koch, Marcy C.
Speer. Further evidence for a maternal genetic effect and a
sex-influenced effect contributing to risk for human NTDs,
Birth defect research 2008; 82(10):662-669
11 .
M o n i k a J a q u i e r. w w w. a n e n c e p h a l i e info.org/e/prevention.php
12.
Pitkin RM. Folate and neural tube defects, Am J
Clin Nutr 2007; 85(1)2855-2885
13.
Hesekar HB, Mason JB, Selhub J, Rosenberg IH,
Jacques PF. Not all cases of NTD can be prevented by
increasing the intake of folic acid, Br J Nutr 2009;
102(2):173-180
14.
Heseker H. Folic acid and other potential measures
in the prevention of neural tube defects, Ann Nutr Metab
2011; 59(1):41-45
15.
Koumudi Godbole, Urmila Deshmukh, Chittaranjan
Yajnik. Nutri-genetic determinants of neural tube defects in
India, Indian Pediatrics 2009; 46:467-475
16.
Ashok Kumar. Neural tube defects: A neglected
problem, Indian Pediatrics 2009; 46:665-667
17.
Shubha Phadke, Meenal Agarwal. Neural tube
defects: A need for population based prevention program,
Indian J Hum Genet 2012; 18(2):145-147
CORRESPONDENCE ADDRESS
Dr. Leelavathy N
Associate Professor, Department of Anatomy
Saptagiri Institute of Medical Science
& Research Center, Chikkasandra,
Hesaragatta Main Road, Bangalore 560090
Mobile: 91 99010 24059,
<rrleela@rediffmail.com>, <rrleela@gmail.com>,
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Anatomica Karnataka, Vol-6, (3), Page 01-14 (2012)