Research Title: Effectiveness of planned teaching program on prevention of

Neural tube defect in periconceptional period among mothers in selected Barangay

in Iligan.

REVIEW OF RELATED LITERATURE

Neural tube defects include defects of the spinal cord that occur as a result of failure
of neural tube closure in embryonic development. They may involve the entire length of the
neural tube or may be restricted to a small area. Defects involving failure of the osseous
(bony) spine to close are called spina bifida (SB); SB occulta occurs in lumbosacral area
(L5and S1), and there is no obvious external opening; SB cystica refers to a visible defect
withan external saclike protrusion. The two major forms of SB cystica are meningocele,
which encases meninges and spinal fluid but no neural elements and myelomeningocele
(ormeningomyelocele), which contains meninges, spinal fluid, and nerves. Meningocele is
notassociated with neurologic deficit, which occurs in varying degrees in
myelomeningocele.With myelomeningocele, the degree of neurologic dysfunction depends on where
the sacprotrudes through the vertebrae, the anatomic level of the defect, and the amount of
nervetissue involved. Most myelomeningoceles involve the lumbar or lumbosacral
area.Hydrocephalus is a frequently associated anomaly in 80% to 90% of children.1

There are several types of neural tube defects:

Spina Bifida

Spina bifida - is the most common type of neural tube defect. It occurs when the neural tube
does not close completely. An infant born with spina bifida usually has paralysis of the
nerves below the affected area of the spine, which can cause lifelong problems with walking
and other difficulties. Because bladder and bowel control are controlled by the lowest spinal
nerves, bowel and urinary dysfunction are common. Many infants who are born with spina
bifida will have normal intelligence, but some will have learning or intellectual disabilities.2

Several common types of spina bifida:

Spina bifida occulta- is the mildest form, and most experts do not consider it to be a true
neural tube defect. There is a small gap in the spine but no opening or sac on the back. The
nerves and spinal cord are not damaged, and the defect usually does not cause any
disability. Consequently, spina bifida occulta sometimes is called hidden spina bifida.3

Closed neural tube defect- is a malformation of the fat, bone, or membranes. In some
persons, it causes few or no symptoms, but other people might experience partial paralysis
or other symptoms. In some cases, the only outward sign might be a dimple or tuft of hair
on the spine.4

Meningocele - includes a sac of fluid that protrudes through an opening in the back, but the
spinal cord is not involved. Some people will have no symptoms, and some people will have
more severe problems.3
Myelomeningocele - is the most severe and also the most common form of spina bifida. In
this condition, the bones of the spinal column do not form completely, which causes some
of the spinal cord and tissues covering the spinal cord to bulge out of the opening. A person
with this condition usually has partial or complete paralysis in the parts of the body below
the spinal column abnormality. Bowel and urinary dysfunction are common. Children with
myelomeningocele may develop hydrocephalus (pronounced hahy-druh-SEF-uh-luhs)
(excess fluid on the brain). Hydrocephalus can lead to intellectual and learning disabilities.
Some infants born with myelomeningocele have severe intellectual disabilities.3

Anencephaly - is a more severe, but less common, type of neural tube defect. This
condition occurs when the neural tube fails to close at the top. The fetus has little or no
brain matter and also may be lacking part of its skull. Infants born with this condition are
usually unconscious as well as deaf and blind and unable to feel pain. They may have
reflex actions, such as breathing and responding to touch. All infants with anencephaly are
stillborn or die soon after birth.5,6

Encephalocele - Another rare type of neural tube defect, occurs when the tube fails to close
near the brain and there is an opening in the skull. The brain and membranes that cover it
can protrude through the skull, forming a sac-like bulge. In some cases, there is only a
small opening in the nasal or forehead area that is not noticeable. The infant may have
other problems as well, such as hydrocephalus, paralysis of the arms and legs,
developmental delays, intellectual disabilities, seizures, vision problems, a small head,
facial and skull abnormalities, and uncoordinated movements (ataxia). Despite the various
disabilities and developmental effects, some children with this condition have normal
intelligence.7

Iniencephaly - another rare but severe type of neural tube defect, is diagnosed when the
infants head is bent severely backward. The spine is exceptionally distorted. Often, the
infant lacks a neck, with the skin of the face connected to the chest and the scalp
connected to the back. Other abnormalities may exist as well, such as a cleft lip and palate,
cardiovascular irregularities, anencephaly, and malformed intestines. Infants born with this
condition usually do not live longer than a few hours. 6

Conditions associated with neural tube defects?

Infants born with neural tube defects that are not immediately fatal
may have other conditions that need treatment. Such conditions vary from one infant to
another, and some conditions develop or must be addressed over time or later in life. The
most severe issues tend to develop in those who have myelomeningocele, the most severe
form of spina bifida, in which the spinal cord is exposed.8

Hydrocephalus

Many infants born with spina bifida get extra fluid in and around the brain, a condition called
hydrocephalus, or water on the brain. The extra fluid can cause swelling of the head, which
may lead to brain injury.

Chiari II Malformation

The brains of most children with myelomeningocele are positioned abnormally. The lower
part of the brain rests farther down than normal, partially in the upper spinal canal. The
cerebrospinal fluid can get blocked and cause hydrocephalus. Although most affected
children have no other symptoms, a few may have upper-body weakness and trouble
breathing and swallowing.
Tethered Spinal Cord

Typically, the bottom of the spinal cord floats freely in the spinal canal, but for many people
with spina bifida, the spinal cord is actually attached to the spinal canal. Thus, in these
cases the spinal cord stretches as a person grows, and this stretching can cause spinal
nerve damage. The person might have back pain, scoliosis (crooked spine), weakness in
the legs and feet, bladder or bowel control problems, and other conditions.

Paralysis and Limitations in Mobility

People with spina bifida high on the back (near the head, for instance) might not be able to
move their legs, torso, or arms. People with spina bifida low on the back (near the hips, for
example) might have some leg mobility and be able to walk unassisted or with crutches,
braces, or walkers.

Lack of Bladder and Bowel Control

People with spina bifida often cannot control their bladder or their bowel movements. They
also can develop urinary tract infections.

Latex Allergy
Many people with spina bifidapossibly three-quarters of those with the conditionare
allergic to latex, or natural rubber. Although researchers still do not entirely understand why
this rate is so high, some experts believe such an allergy can be caused by frequent
exposure to latex, which is common for people with spina bifida who have shunts and have
had many surgeries.9
Learning Disabilities

Some studies have shown that up to 50% of children with myelomeningocele have a pattern
of characteristics and deficits consistent with nonverbal learning disabilities syndrome.10
This syndrome shares some of its characteristic features with Asperger syndrome.

Other Conditions

Some people with myelomeningocele have additional physical or psychological conditions,

including digestive, vision, sexual, social, and emotional problems; obesity; and depression.
CAUSES

The majority of NTDs are etiologically complex. Someone exposed to a large

amount of environmental risk may need to have only a relatively small genetic risk factor for
the condition to occur. Alternatively, someone with high genetic risk may only need to be
exposed to a small amount of environmental risk for the same result. Although research has
identified a number of factors that increase the risk for having a child with a NTD, the
interaction among these factors is not well understood, and there are likely more factors
that have yet to be identified.11
Well-established evidence shows that women who are obese, have poorly
controlled diabetes, or take certain antiseizure medications, such as phenytoin (Dilantin),
carbamazepine (Tegretol), and valproic acid (Depakote), or anti-folate (such as aminopterin)
are at greater risk than are other women of having an infant with spina bifida or
anencephaly12, 14. ome studies suggest that neural tube defects and miscarriage are more
common among fetuses of women who experience high temperatures (such as using a hot
tub or sauna or having a fever) during the first 4 to 6 weeks of pregnancy.12, 13,14 The impact
of folate deficiency on the risk of NTDs prompted the addition of folate to bread and many
other foods.
Having a family history of NTDs increases the risk of having a child with NTD. NTDs are
more common among individuals of Hispanic and Northern European descent. Changes in
genes involved in the folate metabolism pathway also increase risk.11

Congenital malformations have been known and recognized for countries. It is an

estimating problem for research because of the high frequency of their occurrence and the
devastating effect they may have on the individual and his/her family. Central nervous
system anomalies are such anomalies which account for the higher mortality among the
newborn.15
There have been large variations in the incidence of central nervous system defects
in different parts of the World and at different periods. Neural tube defects are
malformations of the developing brain and spinal cord occurring during the third to fourth
week of gestation. 16
 World health organization (WHO) / United Nations Administrative Committee on
Nutrition stated that Iron and Folic acid deficiency affects more than 3.5 billion people in
developing world. In developed countries the prevalence are about 18 percentages in
pregnant women and 12 percentages in non-pregnant women. 17
World literature review on NTD in European countries revealed highest incidence
from Ireland and Wales (6.38-10.92/1000 births). Other parts of the World high prevalence
of NTDs are Northern India and Northern China.18
The incidence of NTDs in Sikhs living in British Columbia, Canada, was reported to
be 2.86/1000 while the overall rate was 1.86/1000 in that area. Michel, et al quoted a higher
incidence of NTDs in Indians living in the North Thames (West) region of UK. Prevalence of
NTD from different parts of India was reported to vary from 3.9 to 11/1000 births and more
so in the northern states (Punjab, Haryana, Delhi, Rajasthan, U.P, Bihar) (3.9-9.0 per /1000
births) compared to eastern, western (5.0/1000 and southern part (<5.0/1000) of India.
(2009). 19
The prevalence of NTDs among consanguineous and non consanguineous
marriage was 6.3-20.6/1000 and 5.9-8.4/1000 couple respectively. 20

In the United States, about 1,500 infants are born each year with spina bifida.The
other types of neural tube defects are less common. About 340 infants are born in the
United States each year with an encephalocele, and about 860 are born with anencephaly
21.
Iniencephaly is estimated to occur in 0.1 to 10 per 10,000 births.22 Anencephaly and
iniencephaly are more common in females. Many pregnancies that involve anencephaly
end in miscarriage.

In the Philippines, Congenital anomalies rank among the top 20 causes of death
across the life span and are the third leading cause of death in the infancy period. Despite
the magnitude of the problem, no formal systematic registration of birth defects was
practised in the Philippines until 1999. Various attempts to gather data were made by study
groups but there was no formal attempt to consolidate the information. However, hospitals
now use the WHO International Statistical Classification of Diseases (ICD) and the Related
Health Problems system, ICD-10 having been implemented in 1999.47

Dr. Marissa B. Lukban, head of Section of Pediatric Neurology, Departments of

Pediatrics and Neurosciences at the Philippine General Hospital (PGH), Manila, discussed
the burden of neural tube defects in the Philippines. According to the data she presented,
the occurrence of NTDs in the Philippines General Hospital is 23 per 10,000 live births;
there is no available national data. She also presented data from the 2008 National
Nutrition Survey of the Food and Nutrition Research Institute which suggests that 40-60% of
reproductive age women in the Philippines are folate deficient; a substantially larger
proportion are therefore folate insufficient and at risk of NTDs.48

The Centers for Disease Control and Prevention estimates that the birth rates in
2005 for 2 of the most common neural tube defects, Spina bifida and anencephaly, were
17.96 and 11.11 per 100 000 live births, respectively . 25

How many people are affected by or are at risk for neural tube defects?

Parents who have already had a child with spina bifida or another neural tube
defect have a 4% risk of having a second child with spina bifida. Parents who already have
two children with spina bifida have about a 10% chance of having another child with this
condition. When one parent has spina bifida, there is about a 4% chance that his or her
child also will have it.23. Women who have had one pregnancy with anencephaly have a 2%
to 3% risk of having a second neural tube defect in later pregnancies.24. To help prevent
recurrence, health care providers recommend that these women take 4 mg of folic acid
supplements a day starting 3 months before conception. This dosage is 10 times the 400
mcg normally recommended.

How do health care providers diagnose neural tube defects?

Neural tube defects are usually diagnosed before the infant is born, through
laboratory or imaging tests.

Prenatal laboratory tests include:

Triple screen blood test: One part of the triple screen blood test is a test for an elevated
level of alpha-fetoprotein (AFP), which is associated with a higher risk of neural tube
defects. The AFP test also can be done by itself. The two other parts of the triple screen
involve testing for human chorionic gonadotropin (hCG) and estriol. This test generally is
done during the second trimester.26
Amniotic fluid tests: Testing of amniotic fluid may also show a high level of AFP, as well as
high levels of acetylcholinesterase; health care providers might conduct this test to confirm
high levels of AFP seen in the triple screen blood test. The amniotic fluid also can be tested
27
for chromosomal abnormalities, which might be the cause of the abnormal AFP level.
Prenatal ultrasound imaging- usually detects almost all types of neural tube
defects.27When an infant with a diagnosed or suspected neural tube defect is born, the
health care provider will perform tests to assess its severity and complications. These tests
might include X-ray, magnetic resonance imaging, computed tomography scan to look for
spinal defects or excess fluid, and measuring the head circumference; assessing the
infants vigor, motor, and sensory functioning; and observing the infants urinary stream. In
some people who have milder spina bifida, the condition may not be diagnosed until later in
childhood or in adulthood.27

What is the best way to prevent neural tube defects?

Folic acid (also known as folate or vitamin B9) has been shown to reduce the risk
that a fetus will develop a neural tube defect.28 About 50% to 70% of all neural tube defects
can be prevented by taking 400 mcg of folic acid daily both before and during pregnancy.29

Since 1992, all women of childbearing age have been advised to consume 400 mcg
of folic acid daily to reduce the risk of a pregnancy affected by a neural tube defect. The
best way for women to get enough folic acid is through vitamin supplements and also by
eating foods to which folic acid has been added (most cereals, breads, pasta, and other
grain-based foods). Although a related form of the supplement (called folate) is present in
orange juice and leafy, green vegetables (such as kale and spinach), folate is not absorbed
as well as folic acid.30

The advisory about folic acid includes all womennot just those who are now
pregnantbecause neural tube defects occur so early during the pregnancy, often before a
woman even knows she is pregnant. The advisory also includes women who are not even
planning on pregnancy, because half of all pregnancies are not planned. All pregnant
women and women who may become pregnant should take 400 mcg of folic acid daily,
preferably in the form of a supplement.

In 1996, the U.S. Food and Drug Administration mandated that folic acid be added to
breads, cereals, and other grain products.28. Since that mandate was issued, the number of
infants born with spina bifida has dropped by 31%,31

and the number of infants born with anencephaly has dropped by about 16%.28. One study
showed that each year, about 1,000 fewer infants are born with a neural tube defect as a
result of enriching foods with folic acid in the United States.30

Women who have already had a pregnancy affected by a neural tube defect or who have
spina bifida themselves should take 4 mg (10 times the 400 mcg usually recommended) of
folic acid daily at least 3 months prior to becoming pregnant and during pregnancy.29

CURE

There is no cure for neural tube defects, and any nerve damage or loss of function
present at birth is usually permanent. However, a variety of treatments can sometimes
prevent further damage and help with related conditions.

Infants born with anencephaly or iniencephaly are usually stillborn or die soon after birth.

TREATMENT

Preventing neural tube defects is the best cure.32

Encephaloceles are sometimes treated with surgery. During the surgery, the bulge of
tissue is placed back into the skull. Surgery also may help to correct abnormalities in the
skull and face.
Treatment for spina bifida depends on the severity of the condition and the presence of
complications. For some people, treatment needs may change over time depending on the
severity or complications.33

Open spina bifida. An infant with myelomeningocele, in which the spinal cord is exposed,
can have surgery to close the hole in the back before birth or within the first few days after
birth.35
Hydrocephalus. If an infant with spina bifida has hydrocephalus (water on the brain), a
surgeon can implant a shunta small hollow tube to drain fluidto relieve pressure on the
brain. Treating hydrocephalus can prevent problems such as blindness.35
Tethered spinal cord. Surgery can separate the spinal cord from surrounding tissue.33
Paralysis and limitations in mobility.People with spina bifida use different means to get
around, including braces, crutches, walkers, and wheelchairs.35
Urinary tract infections; lack of bladder and bowel control.People with
myelomeningocele often have nerve damage that prevents the bladder from completely
emptying, a condition that can cause urinary tract infections and kidney damage. Health
care providers may address this problem by regularly inserting a catheter into the bladder to
allow it to empty fully. Medications, injections, and surgery also can help correct
incontinence and preserve kidney and bladder function for the long term.35

There is no treatment for anencephaly or iniencephaly.34 These conditions are usually fatal
shortly after birth.

1. Studies related to meaning of neural tube defect:

NTDs are serious birth defects of the brain and spine. There are two common
forms of NTDs, anencephaly and spinal bifida, which account for 90 percentage of all cases
(Centers for Disease Control 2000), NTDs occur very early in pregnancy, between 18 and
28 days post ovulation, often before a women knows that she is pregnant.36
The defect occurs when the Neural tube, which later becomes the brain and
spine, does not form or close completely. Anencephaly the condition that results when the
upper end of the Neural tube does not close completely and the brain and the skull are
missing or under developed is a fatal birth defect. (Seilet 2006) .The Spina bifida
Association of America estimates that there are 70,000 people currently living with Spina
bifida is the United State .36
2. Studies related to types of neural tube defect
There are two types of NTDs. The most common are called open type NTDs,
Open NTDs are occur when the brain and / or Spinal cord are exposed at birth through a
defect in the skull or vertebrae (back bone). E.g. of the open NTDs are Spina bifida
(myelomeningocele), Anencephaly and Enencephalocele.37
Rare type of NTDs is called closed NTDs. Closed NTDs occur when the Spinal
bifida is covered by skin. Common examples of closed NTDs are Lipomyelo-meningocele
and lipomeningocele. Spina bifida occulta (SBO) in potentially another from of a NTDs in
which there is a typically benign (non-symptom causing) bony change in one or more
Vertebrae, but not involving the nervous within the Spinal column. About 80% of those
affected will have normal intelligence, according to the Spina Bifida Association, but some
will have learning disabilities.37
3. Studies related to etiology of neural tube defect:
The studies show etiology as multifactorial / polygenic trait.Where NTDs could be
caused by one or more genes interacting with environmental factors , which include
multiparty , chemicals and drugs materials illness (Diabetes mellitus) , temperature, obesity
, leads to drinking water ,occupational hazard, poor nutrient content diet etc. .among the
environmental factors , folic acid deficiency has proved.38
A prospective study was conducted over a period of one year in the city of Al
Madinah in Saudi Arabia detected 18 cases of Spina Bifida. The incidence was 1.09 per
1000 live births, the male to female ratio 2:1 and the increase in the incidence is attributed
to cansanguinity which was found to be in 89% of the Spina Bifida parents as compared
with the 67% of the control.39
A study reported 25% of the 64 mother were on folate supplementing during
affected pregnancy, to prove that the NTD is closely related to folic acid defiency. Double
blind randomized trial of Medical Research Council, Great Britain shows that
supplementation of 5mg per day for at least one month prior to conception to 3 months post
conception reduce the risk of reoccurrence of NTD by 70%.40
4. Studies related to prevention of neural tube defect in periconceptional period.
 A case control study on neural tube defect of neonate and folic acid awareness
.and conducted in teaching hospital in Sri Lanka, during the study period 14,580 live births
took place at GH Kandy and twenty of them had NTDs. The number of babies with NTDs
transferred from other hospitals was 39. The control group comprised 150 mothers with
normal babies. Fourteen (28%) of the affected group were able to idenyify folic acid tablet
as a vitamin taken during pregnancy, in comparison to 87 (58%) of the control group. One
(2%) from the affected group and 70 (46%) from the control group knew about the value of
preconceptional FA .None of the affected mothers had used FA pre-conceptionaly whereas
54 (26%) of the control group mother believed that folic acid helped in preventing birth
defects.40
A prospective study, conducted at M G H Medical College and My Hospital, Indore M
P between October 2008- 2009. Total 52 cases of Spina bifida admitted in the hospital were
evaluated about maternal antenatal history, folic acid intake, birth order, family history &
socio-economic status. Out of the total 52 cases, 20 belong to 2nd birth order, 16 belong to
1st birth order, 10 belong to 3rd birth order, 5 belong to 4th birth order & 1 belong to 5th birth
order. Maternal folic acid intake was not found in all cases during preconception & 1st
month of gestation. Two mothers gave history of viral fever during 2nd month of gestation.
Family history was not found in any case. All except 2 cases belong to low socio economic
status.41
A retrospective study, suggest that the association of folic acid supplementation with
twinning is the result of confounding by infertility treatment and by differential reporting of
folic acid use. This study examined the association between risk for twinning in 176 042
women and exposure to a multivitamin or folic acid supplementation before or during
pregnancy. After adjustment for age and parity, the authors reported an OR of 1.59 for twin
delivery after periconceptional folic acid supplementation. After accounting for the under
reporting of folic acid use and in vitro fertilization, the or for twin delivery after
preconceptional supplementation decreased to 1.02 and was no longer statistically
significantly greater than the risk for women who did not take folic acid.42
A cohort study shows that women who were considering pregnancy and gave them
multivitamins containing 0.8 mg (800 g) of folic acid 1 month before planned conception.
The authors reported a protective effect of folic acid against neural tube defects: 1 neural
tube defect occurred in 3056 women who took folic acid supplements and 9 occurred in
3056 women who did not. The difference between the supplemented and unsupplemented
groups was statistically significant after adjustment for birth order, chronic maternal
disorders, and history of fetal death or congenital abnormality.42
The U.S. Public Health Service recommeed the daily consumption of 0.4 mg (400
g) of folic acid in women of childbearing age (15 to 44 years). In 1996, the USPSTF made
a similar recommendation on the basis of several studies, including large randomized,
controlled trial (RCT) that demonstrated a statistically significant reduction in incidence of
neural tube defects in women who took a multivitamin with 0.8 mg (800 g) of folic acid in
the periconceptional period. The USPSTF recommended that all women planning
pregnancy take a daily multivitamin containing folic acid at a dose of 0.4 to 0.8 mg
beginning at least 1 month before conception and continuing through the first trimester, to
reduce the risk for neural tube defect.43
5. Studies related to the awareness among mothers regarding prevention of neural
tube defect in periconceptional period.
A questionnaire-based study conducted a study on the level of awareness among
female college students on the importance of preconception folic acid supplementation in
preventing neural tube defects (NTDs). Five hundred questionnaires were distributed to the
female students of the 3 colleges, namely, Humanities, Sciences, and Health in Jeddah,
Kingdom of Saudi Arabia in April 2008. Two hundred and seventeen questionnaires were
filled, and returned (43.4%). Mean age +/- SD was 20.96 +/- 2.25 years. Almost 88% were
not aware of the importance of folic acid in preventing NTDs. After listening to the lecture,
82.9% thought that they will surely use folic acid preconception, and 98.6% will relay the
important message about the importance of folic acid to others. Similar educating
programme are required, in order to decrease the high rate.44
A study was conducted to assess the knowledge of neural tube defect (NTD)
prevention by folic acid and periconceptional practices in young women. Young minority
women were enrolled in a folic acid program at 3 urban Houston, Texas, reproductive health
clinics and assessed for NTD knowledge and preventive practices. A 3-month supply of
multivitamins was also dispensed at enrollment. A 3-month program follow-up survey of a
randomly selected sample at 2 sites was conducted. Of 387 women (mean age: 18 1.9
years), 72% were black and 28% were Hispanic. At enrollment, clinics were a major source
of information of NTD prevention (44%); 52% had heard of folic acid, 45% had heard of
NTDs, and 50% had heard of birth defects prevention by multivitamins. Significantly more
Hispanic than black young women had heard of NTDs (59% vs. 39%). Pregnancy history,
regular birth control use, and education level for age were independently associated with
knowledge. In young women with low education level for age, regular birth control use was
significantly associated with knowledge. At enrollment, daily multivitamin intake was very
low (9%) and folate-rich foods were consumed in inadequate amounts. Adequate folate diet
was not associated with knowledge. The program follow-up survey indicated that 88% to
92% had knowledge of NTDs and folic acid, and 67% reported taking a daily multivitamin.
Preliminary evidence suggests that a promotion program improves knowledge, and
dispensing of multivitamins increases multivitamin use.45
A study was conducted to ascertain knowledge of periconceptional folate for
prevention of neural tube defect (NTD) and to estimate folate intake in young women. Three
hundred young women were questioned about their knowledge of folate for prevention of
NTD. Their folate intake was assessed by food frequency questionnaire. Fourteen per cent
of 1619 year olds and 41% of undergraduates were aware of the need to increase folate
intake before conception. Median folate intake was estimated to be 235 g/day in 1619
year olds and 248.5 g/day in undergraduates. More than a quarter of women in both
groups had folate intakes less than the reference nutrient intake (RNI) (200 g/d) below
which prevalence of NTD rises dramatically and these women would therefore be at
increased risk of having a child with NTD should they have an unplanned pregnancy.
Strategies are required to increase folate intake among young women and inform them of
the benefit of periconceptional folate supplementation.46