block II develop. of NS Flashcards
(187 cards)
1
Q
When does the NS start to develop?
A
The developing nervous system first appears during the 3rd week
2
Q
What gives rise to the NS?
A
The notochord and the paraxial mesenchyme of the intraembryonic mesoderm induce the overlying ectoderm to differentiate into the neural plate.
3
Q
What is neural induction?
A
The process of when the notochord and the intraembyonic mesodermn (paraxial messenchyme) induce the ectoderm to differentiate into the neural plate
4
Q
What helps the neural induction take place?
A
intercellular signaling molecules
5
Q
What develops into skin?
A
Ectoderm exposed to BMP 4 (bone morphogenic family of proteins) from
endoderm and mesoderm below develop into skin.
6
Q
What does the notochord secret for what type of formation?
A
BMP 4 antagonists , such as noggin, chordin, & follistatin, that allow a region of the ectoderm to develop into nerve tissue
7
Q
What makes the somites?
A
mesoderm adjacent to notochord
8
Q
What changes occur for the neural groove?
A
columnar cells change their morphology due to molecules secreted from notochord
9
Q
What influences changes in the neural plate?
A
secreted molecules by notochord and mesoderm (somite) will change the neural plate into a neural groove
10
Q
What is neurulation?
A
A neural plate and neural groove develop on the posterior aspect of the
trilaminar embryo, a process known as
11
Q
What si the neural plate?
A
a deeper neural groove by folding to form the neural tube
12
Q
What is the median hinge point?
A
forms as columnar cells adopt triangular morphology, through apical actin constriction (similar to closing a purse string), likely due to signaling from the notochord.
13
Q
What are the neural crests?
A
a forming from neuroectodermal cells in the edges of the neural groove, as the tube forms [days 22-23]
14
Q
by what does the change of neuroectodermal cells start?
A
4-6 somite start the morphologic changes
15
Q
what is the lateral hinge point?
A
forms by a similar mechanism as the median hinge point, likely due to signaling from nearby mesoderm
16
Q
What happens meanwhile the closure of the neural tube takes place?
A
Upon closure, the neural tube detaches from the surface ectoderm, with some
of the neuroectodermal cells of the neural crest remaining between the neural
tube and the surface ectoderm
17
Q
In what does the neural tube differentiate?
A
differentiates into the Central Nervous System (CNS)
18
Q
What gives rise to most of the PNS and ANS?
A
neural crest cells delaminate and migrate away to give rise to the cells of these systems
19
Q
What gives rise to the neural canal?
A
Fusion of the neural tube in cranial and caudal directions gives rise to a lumen (18-20 days)
20
Q
what does the neural canal communicate with?
A
communicates freely with the amniotic cavity
21
Q
Where does the fusion or closure of the neural tube start first?
A
cervical region
22
Q
Explain how the neural tube zips?
A
The neural tube then “zips” up towards the head and towards the rump, leaving
two openings: the rostral cranial, anterior) and caudal (posterior) neuropores
23
Q
what are the neuropores in contact with?
A
Amniotic cavity
24
Q
when does the cranial/rostral/anterior neuropore closes?
A
closes approximately on day 24 or 25 of
development
25
when does the caudal/posterior neuropore closes?
closes approximately 2 3 days later after cranial neuropore closes, around day 28. [cierre completo]
26
what forms the brain, brainstem and spinal cord?
the thickened walls of the neural tube
27
What structures are present in the closes area of the tube?
mesoderm structures (somites)
28
what do condensation of somites give rise to?
structures such as bones and muscles
29
What develops into the spinal cord?
neural tube caudal to the 4th pair of somites
30
what develops into the brain and brainstem?
neural tube cranial/rostral to the 4th somite
31
what structures does the somites give rise to?
Somites (blocks of paraxial mesoderm) give rise to the cells that form the
vertebrae and ribs, the dermis of the dorsal skin, the skeletal muscles of
the back, and the skeletal muscles of the body wall and limbs
32
what is the epithelium in the wall of the neural tube initially?
thick pseudostratified columnar neuroepithelium.
33
Where are the pseudostratified columnar neuroepithelium cells?
cells constitute the ventricular zone of the neural tube
34
what do the neuroepithelial cells give rise to?
will give rise to all neurons and macroglia (astrocytes and oligodendrocytes) of the CNS
35
marginal zone (outer parts of the neuroepithelial cells give rise to?
gives rise to the forming precursor of the white matter regions (axonal projections) of the spinal cord
36
what gives rise to the meningeal layers?
Surrounding mesenchyme that condensates
37
What do some neuroepithelial cells in the ventricular zone differentiate into?
primordial neurons = neuroblasts
38
What do neuroblasts (primitive neurons) form?
form an intermediate zone (mantle layer) between the ventricular and marginal zones.
39
How do neuroblasts become neurons?
Neuroblasts become neurons as they develop cytoplasmic processes
40
identify
from left to right:
-condensation of messenchyme
-marginal layer
-intermediate zone (accumulation of celulas precursoras de celular gliales)
-ventricular zone
-neural canal
-
41
ventricular zone is composed of?
ependymal layer
42
intermediate zone is composed of?
neuroblasts - gray matter
43
marginal zone is composed of?
white matter
44
How do neuroblasts become neurons?
neurons as they develop cytoplasmic processes. They form the bulk of the
intermediate zone.
45
Explain differentiation process of neuroblasts
From neuroectoderm the first differentiation is apolar neuroblast, then it differentiates into bipolar neuroblast; later into unipolar neuroblast and lastly a neuron with its dendrites and axon. After this differentiation finishes, another one starts.
46
Explain astrocyte differentiation
From neuroectoderm, the glioblast [spongioblast] is located in the most external zone [marginal] of the neuroepithelium, these are precursors of glial cells. Then, they differentiate into astroblast or oligodendroblast. The last differentiation of astroblasts is into a protoplasmic or fibrous astrocye. The last differentiation of an oligodendroblast is into a an oligodendrocyte.
47
Explain the differentiation of mesenchymal cell
They originate from the exterior part of the neural tube and differentiate into a microglial cell
48
Explain the differentiation of ependyma?
These are located in the ventricular zone of the neural tube and give origin to the ventricular system [epithelium of choroid plexus]
49
how do glioblasts differentiate?
they differentiate from neuroepithelial cells when neuroblast formation has
ceased. As they form, they migrate into the intermediate and marginal zone.
50
Where do neurons migrate?
Neurons migrate along radial glia to establish layers within the CNS that are very important for its function.
51
what does disruption of neuron migration lead to?
may lead to malformations, missed or improper connections, and/or loss of
function in regions normally organized in layers, such as the cerebral and cerebellar
cortex.
52
What do radial glial cells do?
organize neurons along the thickness of the neural tube
53
what do glial cells and neurons in development establish?
layers such as cerebral cortex, cerebellum, spinal cord [gray matter, dorsal/ventral horns]
54
When do ependymal cells differentiate?
they differentiate from neuroepithelial cells when glioblast formation has ceased. They form the lining of the neural canal
(central canal of spinal cord, ventricles of brain).
55
Where are microglial cells derived from?
derived from mesenchymal cells, most
likely blood cells of the monocyte macrophage lineage.
56
What are the 4 plates of the neural tube?
1. roof plate
2. floor plate
3. alar plate
4. basal plate
57
What does the roof plate do?
Roof plate, a signaling center for BMPs and Wnts. for structures of dorsal aspect [sensory function] and ventral aspect [motor function]
58
What does the floor plate do?
Floor plate, a signaling center for Shh. for structures of dorsal aspect [sensory function] and ventral aspect [motor function]
59
What does the alar plate do?
Alar plate, precursor of sensory gray matter
60
What does the basal plate do?
Basal plate, precursor of motor gray matter
61
general functions of the 4 plates?
Help to guide the distribution of neurons or glial cells
62
What happens after the neural tube closure (regarding BMPs)
Neural tube separates from ectoderm later and BMPs from the skin (ectoderm) induce expression of BMPs in the roof plate which helps pattern the organization of the alar plate
63
What induces expression of Shh in the floor plate and what does it do?
Shh from notochord, helps pattern the organization of the basal plate
64
Which BMPs influence margins of the neural plate?
BMP-4,7.
65
Where do neural crests of the closing neural plate lie?
neural plate lie in an intermediate zone between Shh from the notochord and
BMPs from the overlying skin
66
how do cells differentiate into neural crest cells?
Under the influence of these factors and others from underlying mesoderm, they
separate from the neuroepithelium and
transform from epithelial cells into migratory mesenchymal cells , becoming neural crest cells
67
What do neural crest cells give rise to?
structures in PNS and other tissues
68
Where are sensory cells from PNS derived from?
All sensory cells of the PNS, both somatic and visceral, are derived from neural crest cells. [Somas are organized in DRG of spinal nerves]
69
Into what do neural crest cells differentiate?
multipolar neurons of autonomic ganglia
70
into which multipolar neurons of autonomic ganglia do neural crest cells differentiate?
1. ganglia of the sympathetic trunks
that lie along the sides of the vertebral bodies
2. collateral, or prevertebral, ganglia in the plexuses of the thorax and abdomen (e.g., cardiac, celiac, and mesenteric plexuses)
3. parasympathetic, or terminal, ganglia in or near the viscera (e.g., submucosal, or Meissner, plexus)
71
what other cells do neural crest cells give origin to?
chromaffin cells, similar in many ways to the medullary cells of the suprarenal glands, are also derived [quimicos adrenergicos]
72
Explain the migration of sympathetic ganglion
loacted both sides of the vertebral bodies, they migrate and surround the aorta (abdominal cavity) and then they distribute like a web along the walls of the GI tract
73
The unipolar neurons in the spinal ganglia (dorsal root ganglia) are derived from
neural crest cells
74
What contains the sensory endings in somatic or visceral structures?
spinal ganglion cells
75
what constitutes the dorsal roots of spinal nerves?
central processes entering the spinal cord
76
When does myelination starts?
Myelination begins during the late fetal
period and continues during the first
postnatal year.
77
why is myelination important?
essential for allowing fast conduction of electrical impulses across the axons of a nerve.
78
myelininization in CNS?
oligodendrocytes
79
myelinization in PNS?
Schwann cells (neurolemmal)
80
When is myelinization complete?
around the same time the fibers become
functional.
81
Which fibers myelinate forst?
Motor fibers tend to be myelinated before sensory fibers.
82
How does the central canal of the spinal cord forms?
As neuroepithelial cells divide, differentiate, and migrate, the lateral walls of the neural tube become thicker and the size of the neural canal is gradually reduced, until it becomes the central canal of the spinal cord
83
What is the reason of different distribution and quantity of gray matter and white matter?
The extent of cell proliferation is not uniform along the circumference or the
length of the neural tube.
84
What does the cell proliferation produce in regards of the neural tube?
produces thick lateral walls and external dorsal/ventral thin roof plate/floor plate during the 6th week.
85
What does the thickening of lateral walls produce?
produces a shallow longitudinal
groove on each side of the neural (central) canal, the sulcus limitans
86
What is the sulcus limitans?
marks the limit between the dorsal and ventral parts of the developing spinal cord, known at this stage as the alar and basal plates, respectively.
87
why is the distinctions of the alar and basal plates important?
because they are associated with future afferent (sensory) and efferent (motor) functions of the spinal cord.
88
identify sulcus limitans
7
89
when does the spinal cord and vertebral column change its identical length?
Around the 3rd month of development.
90
How does the growth of vertebral column work?
As each vertebral body grows thicker, the overall length of the vertebral column
begins to exceed that of the spinal cord.
91
Why do nerve roots extend?
due to enlargement of column
92
What happens due to the vertebral column and dura mater growth is more rapidly than the spinal cord?
the direct relationship between the point of exit of the spinal nerves and the vertebral bodies does not persist for long (the embryonic spinal cord extends through the entire length of the vertebral canal)
93
Where does the spinal cord end in a newborn?
L3
94
Where does the spinal cord end in aa adult?
L1-L2
95
What appears as the tube closes and cell prolifereation takes place?
3 primary vesicles:
1.forebrain (prosencephalon)
2.midbrain (mesencephalon)
3. hindbrain (rhomboncephalon)
96
What happens to the primary vesicles at the 5th week?
the forebrain and hindbrain vesicles divide each in two, resulting in a total of five secondary brain vesicles
97
what are the secondary vesicles?
Forebrain divides into:
-telencephalon
-diencephalon
midbrain stays as mesencephalon
hindbrain divides into:
-metencephalon
-myelenchephalon
98
What walls & cavities do the telencephalon give rise to?
cerebral hemispheres / lateral ventricles
99
What walls & cavities do the diencephalon give rise to?
Thalami (nuclei/hypothalamus) / third ventricle
100
What walls & cavities do the mesencephalon give rise to?
midbrain / aqueduct
101
What walls & cavities do the metencephalon give rise to?
Pons, cerebellum / upper part of fourth ventricle
102
What walls & cavities do the myelencephalon give rise to?
Medulla / lower part of fourth ventricle
103
What does the ventral bending with head fold during the 4th week of brain development lead to?
produces the midbrain and cervical flexures
104
What happens after the midbrain and cervical flexures?
Later, unequal growth of the brain between these flexures produces the pontine flexure in the opposite direction, dividing the hindbrain into the metencephalon [pons] and myelencephalon (medulla) [1 week later]
105
What produces considerable variation in the manner in which the gray and white matter is distributed at different levels?
The brain flexures, compared with the uniform distribution found in the spinal cord
106
identify
midbrain and cervical flexures (mecencephalon)
107
identify
pontine flexure
108
identify
109
When does the sulcus limitans stops being seen?
Transition from midbrain to diencephalon
110
What is Pax-6 and what is it induced and repressed by?
Pax-6, a ventral marker, is induced by Shh in the floor plate and repressed by BMPs in the roof plate
111
What is Pax-7 and what is it induced and repressed by?
Pax-7, a dorsal marker, is repressed by Shh and induced by BMPs
112
What other markers aid in the development of anterior-posterior patterns?
FGF-8, En-1, and En-2
113
Identify
6 - telencephalo
5- diencephalo
4- mesencephalo
3- metencephalo
2- myelencephalo
1- spinal cord
114
identify
Myelencephalon, transition to spinal cord
115
identify
placas alares (sensorial) - azul claro
placas basales - azul oscuro
116
Explain the location of the roof plate and alar plates
The pontine flexure causes the lateral walls of the medulla to move laterally and the roof plate to become stretched and thinned. As the walls move laterally, the alar plates come to lie lateral to the basal plates
117
Where does sensorial function comes from in the medulla?
The neurons that arise from these plates will form nuclei that organize in columns on the basis of function (sensorial). The motor nuclei are found medial to the sensory ones
118
Explain the location of the nuclei regarding their function
These nuclei are organized on the basis of whether they serve a somatic or a visceral
function. The columns that are closer to the sulcus limitans are visceral and
those farthest from it are somatic in function.
119
identify
120
What is the tela choroidea?
Thin covering that results when the brain develops and each of the ventricles ends up with an area in which its roof or one
of its walls is very stretched and thinned,
composed only of the thin ependymal layer covered externally by the very vascular pia mater.
121
How does the choroid plexus forms?
Because of the active proliferation of the pia mater, the tela choroidea invaginates the ventricle, taking along with it its numerous blood vessels
122
Choroid plexus is an extension of?
pia, ependymal cells and vascularization. It forms inside the ventricles
123
Explain the relationship of CSF and choroid plexus
production of CSF and circulates in the ventricles, subarachnoid and plexus
124
Where is the pituitary gland located?
base of hypothalamus (diencephalon)
125
What is the hypophysial pouch of stomodeum?
upgrowth from roof of primitive mouth
126
What is the infundibulum of diencephalon?
Downgrowth from floor of forebrain
127
How does the pituitary start developing?
1. Between the 4th and 5th weeks of embryonic development, a diverticulum called the infundibulum develops in the floor of the third ventricle; it grows towards the stomodeum
2. Simultaneously, an ectodermal placode
appears in the roof of the stomodeum and
evaginates to form a diverticulum known as Rathke’s pouch . These two diverticuli grow towards each other
128
What happens after the Rathke's pouch loses connection with the stomodeum?
stomodeum and forms a discrete sac that is appressed to the cranial surface of the
infundibulum.
129
What does the sac formed by rathke's pouch differentiate into?
The sac differentiates to form the anterior lobe or adenohypophysis of the pituitary.
130
What does the infundibulum differentiate into?
The infundibulum differentiates to form the posterior lobe or neurohypophysis
131
When do cerebral hemispheres first appear?
The cerebral hemispheres first appear around the 5th week as a pair of bubble like outgrowths of the telencephalon. By 14 weeks, the rapidly growing hemispheres have expanded back to cover the diencephalon.
132
Explain the texture of the cerebral hemispheres and morphology
Initially the surface of the hemispheres is smooth. As growth proceeds, grooves (sulci) and convolutions (gyri) develop. The sulci and gyri permit a considerable increase in surface area without requiring an extensive increase in cranial size.
133
When do most congenital anomalies of spinal cord happen?
result from defective closure of the neural tube during the 4th week of development.
134
What are NTD?
Neural Tube Defects (NTD’s) affect the
tissues overlying the future brain and
spinal cord, including meninges, cranium or vertebral arches, muscles and skin.
135
What are common teratogens that induce NTDs?
Hyperthermia valproic acid and hypervitaminosis A
136
Spina bifida meaning
Anomalies involving the vertebral
arches
137
Explain spina bifida occulta
-less severe
-L5 or S1
-usually requires no treatment
-Vertebral arch doesnt close
-missing spinous process
-appearance of hair
-meninges are present
138
identify
Spina bifida occulta
139
identify
Spina bifida occulta
140
identify
Spina bifida occulta
141
Explain spina bifida with meningocele
-menin (meninges) + gocele (herniation towards the exterior)
-Sac with meninges and CSF
-No spinous processes or lamina
-marginal sac (dura mater) herniates to the exterior
-Sac contains CSF
-Spinal cord is present
-Not as common
-Repaired with surgery and no paralysis involved
142
identify
Spina bifida with meningocele
143
Explain spina bifida with meningomyelocele
-Sac herniates with CSF + spinal cord section
-Affects motility
-No closure of ends
-arches of vertebrae affected
-Can happen in more than one level
-Occurs when the meninges and spinal cord protrude through a vertebral defect
and form a sac filled with CSF
-Postnatal surgery is performed to cover exposed spinal cord with skin.
-There is usually a need for a ventriculoperitoneal shunt for hydrocephalus during the first
year of life.
144
identify
spina bifida with meningocele
145
WHta are the consequences of meningomyocele?
Most children with meningomyelocele
survive, but they can present many forms
of disability, including paralysis, difficulty
with bowel and bladder control, a Chiari II
malformation, hydrocephalus (excessive
fluid in the brain), and developmental
delays. In general, the higher the spinal
opening occurs on the back, the greater the physical impairment.
Since some of these problems arise during
the second half of pregnancy, repairing the
closure defect at earlier stages may allow
some nerve function to be rescued or
restored, thus reversing further progression of the condition.
146
What is Chiari II malformation?
herniation of cerebellum toward spinal canal
147
Treatments for meningomyocele?
Fetal surgery is now a possible treatment option for some cases of meningomyelocele. Studies have shown that prenatal surgery significantly reduced the need to divert, or shunt, fluid away from the brain, improved mental development and motor function, and
increased the likelihood for the child to be able to walk unassisted.
148
What is spina bifida with myeloischisis?
-nervous tissue is completely exposed
-no vertebral arch
-neural tube did not close
-occurs when the posterior part of the neural tube (neuropore) completely fails to close at the 4 th week of development.
-most severe form of spina bifida
-causes paralysis caudally from the level of the defect.
149
identify
Spina bifida with meningomyocele
150
identify
Spina bifida with meningomyocele
151
identify
Spina bifida with meningomyocele
152
identify
Spina bifida with meningomyocele
153
identify
Spina bifida with myeloischisis
154
identify
Spina bifida with myeloischisis
155
identify
Spina bifida with myeloischisis
156
identify
Spina bifida with myeloischisis
157
What are congenital malformations of the brain?
Cranial Meningocele
Cranial Meningoencephalocele
Cranial Meningohydroencephalocele
158
identify
Cranial Meningocele [defect at posterior fontanelle of skull]
-no hay cierre del craneo, se hernian las meninges con CSF
159
identify
Cranial Meningoencephalocele [defect in skull at foramen magnum]
-tejido de cerebro en la herniacion
160
identify
Cranial Meningohydroencephalocele
-same as meningoencephalocele but includes a ventricle
-defect at posterior fontanelles of skull
161
What is anencephaly (meroanencephaly)?
Type of upper NTD that occurs when the
anterior part of the neural tube (anterior neuropore) fails to close at week 4 of development
162
Resumen anencephaly
1. Results in failure of the brain to develop and failure of the bony cranium to form.
2. Is incompatible with extrauterine life.
3. Is the most common serious birth defect seen in stillborn fetuses.
4. Is diagnosed by ultrasound, and a therapeutic abortion can usually be performed.
163
identify
Anencephaly (meroanencephaly)
164
What is microcephaly?
The brain fails to grow sufficiently,
resulting in a smaller than normal
brain
-In most cases children are mentally retarded
-2-12 cases per 10,000 live births in the US
165
Why is microcephaly caused?
It is most often caused by genetic abnormalities such as Down’s syndrome, chromosomal syndromes, and neurometabolic syndromes or by exposure to teratogens during pregnancy, such
as alcohol , cytomegalovirus , rubella german measles), varicella (chicken pox) virus, or possibly Zika virus
166
What is holoprosencephaly (HPE)?
Spectrum of defects in which the forebrain fails to develop into two hemispheres, with a resulting loss of midline structures that lead to malformations of the brain and face.
167
WHat happens in severe cases of HPE?
In severe cases, the lateral ventricles merge into a single telencephalic vesicle , the eyes are fused, and there is a single nasal chamber along with other midline facial defects.
168
How recurrent is HPE?
HPE occurs in 1/15,000 live births but is present in 1/250 pregnancies that end in early miscarriage.
169
What are the causes of HPE?
Mutations in Shh result in some forms of
holoprosencephaly.
Other causes include defective cholesterol
biosynthesis and alcohol abuse
170
IDENTIFY
Holoprosencephaly
171
What is hydrocephalus?
Defects related to an accumulation
of cerebrospinal fluid (CSF)
172
What is obstructive or non-communicating hydrocephalus?
Obstructive or non communicating is due to a blockade of one or more of the foramina connecting the ventricles to one another. The site where blockage most commonly occurs is in the cerebral aqueduct of Sylvius in the mesencephalon
173
What is non-obstructuve or communicating hydrocephalus?
Non obstructive or communicating
is due to a blockade of the uptake of CSF at the subarachnoid space. Results in the enlargement of all the ventricular cavities as well as the subarachnoid space
174
by what is CSF absorbed?
By granulations in the venus sinuses of the brain
175
identify
hydrocephalus
176
What is Arnold-Chiari malformation?
Caudal displacement and herniation of cerebellar structures through the
foramen magnum [invades through the spinal canal]
177
Explain Arnold chiari
1. Most common congenital anomaly involving the cerebellum (1:1000 births) and frequently associated with spina bifida with meningomyelocele, spina bifida with myeloschisis and hydrocephalus
2. Syrinx is a fluid filled cavity due to factors such as craniocervical abnormalities, trauma or tumor
178
identify
Arnold Chiari in a 23 week fetus
179
identify
Arnold Chiari in a 23 week fetus
180
What is dandy-walker syndrome?
a congenital brain malformation involving the cerebellum and the fluid filled
spaces around it
181
What does dandy walker syndrome involve?
1. This syndrome involves an enlarged fourth ventricle, a partial or complete absence of the cerebellar vermis [central lobe] (the area between the two cerebellar hemispheres), and cyst formation near the internal base of the skull.
2. There can also be an increase in the fluid space sizes surrounding the brain, resulting in hydrocephalus.
182
identify
Dandy Walker Syndrome
183
What are the incidences of NTDs?
Varies among different countries In the U S it is about 1 per 1,000 live births. But the incidence varies among different
populations and may be as high as 1/100 births in some areas, such as northern China.
-high in hispanic populations
184
What is the etiology of NTDs?
It is known that environmental and nutritional factors play a role in
producing this type of birth defect If a couple has already had a child with a NTD, the chances of the defect occurring in a
second child increases by about 2%. If one of the parents has a NTD, the chances of having a child with the defect increase by
about 3-5%
185
Detection of NTD’s before birth
NTD’s can be diagnosed prenatally by ultrasound and by an elevated level of alpha fetoprotein ( in the mother’s
blood serum and amniotic fluid. The vertebra can be visualized by 12 weeks of gestation, and defects in closure of the vertebral arches can be detected. A new treatment for the defect is to perform surgery in utero at aprox 22-28
weeks of gestation (cesarean exposure, defect is repaired, and infant is placed back in the uterus)
186
Prevention of NTD’s:
There is evidence that folic acid (folate reduces the incidence of NTDs by as much as 70% if 400 mg is taken daily beginning 3 months prior to conception and continuing throughout gestation. Since approx
50% of all pregnancies are unplanned, it is
recommended that all women of child bearing age take a multivitamin containing 400 mg of folic acid daily
187
