Neural tube defects: Importance of Folic Acid and Vitamin B12 intake

Birth defects are a global problem, but their impact is particularly severe in middle and low income countries where more than 94 percent of the births with serious birth defects and 95 percent of the deaths of these children occur. Serious birth defect can be lethal. For those who survive, these disorders can cause lifelong mental, physical, auditory or visual disability. The report shows that at least 3.3 million children under five years of age die from birth defects each years. More than 70% of birth defects can be prevented. Educate the community about the birth defects and the opportunities for effective care and prevention.

1. Neural Tube Defects
Importance of Folic Acid
and Vitamin B12 Intake
during First Trimester
Vijaya Sawant
Director Oratechsolve Inc
www.oratechsolve.com

2. Birth Defects Statistics
•Every year, about 7.9 million infants (6% of worldwide births) are born
with serious birth defects.
•3.3 million children under five years of age die from birth defects each
year.
•Estimated 3.2 million of these children are disabled for life.
•Severe impact in middle and low income countries where more than 94
% of birth with serious birth defects and 95% of the deaths of these
children occur.
•Neural tube defects (323,904) constitute one of the common forms of
multifactorial congenital malformation with recorded birth prevalence as
high as 6 per 1,000 live births in China. In US, NTD is known to affect 1
out of 1000 live birth.
•70% of birth defects can be prevented or can be offered life saving care
or reduce the severity of disability

3. Pattern of Neural Tube Defects (NTD) in
Ethiopia
•TheoverallstatisticsonNTDinEthiopiaarenotavailableduetoscarcityof
informationandreportingsystem.Theburdenofdiseasesishighinlow
socioeconomiccountries.
•AsperPubMedarticle,studywasundertakeninJan2001toJun2005in
EthioSwedishChildren’sHospital,themostcommonNeuralTubeDefects
seenare:
64.4%Myelomeningocele
18.3%Meningovele
13%Encephalocele
28.7%Associatedanomalieslikeclubfootundescendedtestis,different
typesofhernias,hydroceles
http://www.ncbi.nlm.nih.gov/pubmed/19743784

4. Embryo Development
(Embryogenesis)
2 Week 4 Week
Implantation begins the first week and embryo continues to grow.
The embryo is about 1/100 of an inch long.
The embryo is about 1/6 inch long and has
developed a head and a trunk.

5. Neural Development
(neurogenesis)
Peak time of occurrence Developmental event
Primary neurulation (dorsal induction) 3-4 weeks antenatally
Primary neurulation (dorsal induction) 5-6 weeks antenatally
Neuronal proliferation
Cerebral 2-4 months antenatally
Cerebellar 2-10 months postnatally
Neuronal migration
Cerebral 3-5 months antenatally
Cerebellar 4-10 months antenatally
Neuronal differentiation
Axon outgrowth 3 months-birth
Dendritic growth and synapse formation 6 months-1 year postnatally
Synaptic rearrangement Birth-years postnatally
Myelination Birth-years postnatally
FUNCTIONAL TEST FOR FETAL BRAIN: THE ROLE OF KANET TEST 10.5005/JP -JOURNALS-10009-1309
The presentation focuses on what changes are happening in embryo during first 3-4 weeks after conception to
form Central Nervous System.

6. Neural Plate
TheNeuralplateisakey
developmentalstructurethatserves
asthebasisfornervoussystem.The
neuralplateappearsonthe17thday
afterconceptionasathickeningof
theembryonicectodermoverthe
notochord.Theformationoftheflat,
thickenedlayerofectodermalcells
knownastheneuralplate.This
neuroectodermgivesrisetothe
centralnervoussystem.

7. Primary Neurulation
Primaryneurulationbeginsafterthe
neuralplateforms.Onday18,the
edgesoftheneuralplatestartto
thickenandliftupward,formingthe
neuralfolds.Thecentreofthe
neuralplateremainsgrounded,
allowingaU-shapedneuralgroove
toform.Theneuralgroove
graduallydeepensastheneural
foldsbecome elevated,and
ultimatelythefoldsmeetand
coalesceinthemiddlelineand
convertthegroveintoaclosed
neuraltube.Thisneuralgroovesets
theboundarybetweentherightand
leftsidesoftheembryo.The
ectodermalwallformstherudiment
ofthenervoussystem.

8. Neural Tube
Neuraltubeistheembryo’sprecursortothe
centralnervoussystemwhichcomprisesthe
brainandspinalcord.
Differentportionsoftheneuraltubeformbytwo
differentprocesses:primaryneurulationand
secondaryneurulation
Inprimaryneurulation,theneuralplate
creasesinwarduntiltheedgescomein
contactandfuse.Itdividestheectoderm
intothreecelltypes:
•Internallylocatedneuraltube
•Externallylocatedepidermis
•Neuralcrestcells,whichdevelopintheregionbetweentheneuraltubeandepidermisbutthenmigratetonewlocation
Insecondaryneurulation,thecellsofthe
neuralplateformacord-likestructurethat
migratesinsidetheembryoandhollowsto
formthetube.
http://en.wikipedia.org/wiki/Neural_tube

9. Neural Tube Closure
Thesequenceofeventsbeginswithneuraltube
closure(closure1),whichisinitiatedatthe
hindbrain/cervical boundary (doubleasterisks).
Neuraltubeclosurespreadsrostrallyandcaudally
fromthissite.Aseconddenovoclosureevent
(closure2)occursattheforebrain/midbrain
boundary(singleasterisk),althoughmorerostral
andcaudallocationsofclosure2occurinsome
strains(dashedlinesandarrows).Closurealso
initiatesseparatelyattherostralextremityofthe
forebrain(closure3).Neurulation progresses
caudallyfromclosure3tomeettherostralspread
offusionfromclosure2,withcompletion of
closureattheanterior(orrostral)NEUROPORE .
Thespreadofclosurecaudallyfromclosure2
meetstherostrallydirectedclosurefromclosure1
tocompleteclosureatthehindbrainneuropore.
Thecaudalspreadoffusionfromclosure1
progressesalongthespinalregionovera36-hour
period,withfinalclosureattheposterior(or
caudal) neuropore.Secondary neurulation
proceedsfromtheleveloftheclosedposterior
neuropore,throughcanalizationinthetailbud
(shadedarea).Thecranialendoftheneuraltube
closesby24daysandthecaudalby25-26days.
Then,theneuraltubeiscovereddorsallyby
mesenchyme thatformsthevertebralarchesand
skull.Closureofthevertebralarchesiscompleted
at11weeksofgestation.
http://www.nature.com/nrg/journal/v4/n10/fig_tab/nrg1181_F1.html

10. Neural Tube Defect
Thecellsoftheneuralplatemakeupthefetus’
nervoussystem.Innormaldevelopment,theyfold
backontothemselvesinordertocreatewhatis
calledtheneuraltube,whichthenbecomesthe
backboneandthespinalcord.Afteranumberof
transformations,thesuperiorpoleeventually
becomesthebrain.
NeuralTubeDefect(NTD)isoneofthecommon
birthdefects.Duringthethirdweekof
development,specializedcellsonthedorsalside
offetusbegintofuseandformtheneuraltube.
Whentheneuraltubeunabletoclosecompletely
betweenthe20thand28thdayafterconception,
thecongenitalmalformationoccurs.Thegrowing
brainandspinalcordarethenexposeddepending
onthelocationoftheanomaly.
TherearetwotypesofNTDs-openandclosed.
OpenNTDoccurswhenthebrainandspinalcord
areexposedatbirththroughadefectintheskull
orspine.ClosedNTDhappenswhenthespinal
defectiscoveredbyskin.
http://neuropathology-web.org/chapter11/chapter11bNTD.html
http://www.futuremedicineonline.com/detail_news.php?id=278
Exencephaly
Anencephaly Anencephaly
MyelomeningoceleCraniorachischisis
Encephalocele
Occipital encephalocele
Dorsal meningomyelocele
Myelomeningocele
Anencephaly Spina bifida
Hydrocephalus

11. Neural Tube Defects Symptoms
•Paralysis of the legs
•Partial or total lower
body weakness
•Learning disabilities
•Visual impairment
•Stunted growth
•Mental retardation
•Difficulty in movement
•Facial defects
•Increased muscle tone
•Respiratory issues
•Progressive enlargement
of the head
•Vomiting
•Nausea
•Coma
•Urinary and bowel
dysfunction
•Cardiac abnormalities

12. How to Detect
•Ultrasound examination : It is generally performed after 18 weeks of
pregnancy. Anencephaly could be detected earlier than 16 weeks.
•Maternal serum alpha-fetoprotein (MSAFP) test: Alpha-fetoprotein, a
plasma protein produced by fetus, may appear in the bloodstream of
a mother after crossing the placenta. High levels of AFP are
observed in case of open NTD.
•Amniotic fluid alfa-fetoprotein (AFAFP) test: Alpha-fetoprotein can
found in the amniotic fluid surrounding the fetus in the amniotic sac.
Elevated levels of the protein indicate malformation in the neural
tube.
•Amniotic fluid acetylcholinesterase (AFAChE) test:
Acetylcholinesterase (AChE) is an essential enzyme that maintains
proper transmission of impulses between nerve cells and muscles.
Prenatal diagnosis of NTD can be performed using amniocentesis or
amniotic fluid test. Low levels of AChE in the amniotic fluid may
indicate some form of fetal abnormality.

13. Treatment
•Around90%ofbabiesbornwithspinabifidawillalsodevelopHydrocephalus(fluidonthebrain)
meaningfurthermajorsurgery.Asurgeoncanimplantashunt-asmallhollowtubetodrainfluidto
relievepressureonthebrain.Treatinghydrocephaluscanpreventproblemssuchasblindness.
•Majorspinalsurgerytoclosethegapinthespineusuallytakesplacejust24hrsafterbirth.
•Aninfantwithmyelomeningocele,inwhichthespinalcordisexposed,canhavesurgerytoclosethe
holeinthebackbeforebirthorwithinthefirstfewdaysafterbirth.
•Encephalocelesaretreatedwithsurgery.Duringthesurgery,thebulgeoftissueisplacedbackinto
theskull.Surgeryalsomayhelptocorrectabnormalitiesintheskullandface.
•Tetheredspinalcord.Surgerycanseparatethespinalcordfromsurroundingtissue.
•Paralysisandlimitationinmobilityduetospinabifida.Useofbraces,crutches,walkersand
wheelchairs
•Myelomeningocelechildrenhavenervedamagethatpreventsthebladderfromcompletelyemptying,
aconditionthatcancauseurinarytractinfectionsandkidneydamage.Regularlyinsertacatheter
intothebladdercanhelpitemptyfully.Medications,injections,andsurgeryalsocanhelpcorrect
incontinenceandpreservekidneyandbladderfunctionforthelongtime.
•Notreatmentforanenceplalyoriniencephaly.Theseconditionsareusuallyfatalshortlyafterbirth.

14. Neural Tube Defects Causes
Healthexpertsarestillunawareoftheexactcausethatdisruptscompleteclosureoftheneuraltube,
resultinginseverephysicaldeformities.Itisoccasionallycausedbychromosomalabnormalities,single
genedefectsandteratogens.Someassumptionsaboutcertainmajorcontributoryfactorstothiscondition
havebeenmade.
•Low intake of folic acid such as prenatal vitamins
•Ingestion of folate antimelabolities, such as methtrexate which impair the function of folic acid
•Gestational diabetes in the third trimester of pregnancy
•Obesity during pregnancy
•Presence of Mycotoxins in a wide variety of crops
•Arsenic poisoning from contaminated water
•Elevated body temperature, due to failed thermoregulation
•Excessive exposure to radiation
•Cigarette smoking or exposure to secondhand smoke during maternity

15. Neural Tube Defect Prevention
Folicacid(VitaminB9)andcyanocobalamine(VitaminB12)play
animportantroleinneurogenesis.Folateisimportantfor
productionandmaintenanceofnewcells,forDNAsynthesis
andforRNAsynthesis.Italsoplaysanessentialroleinthe
nucleicacidsynthesisandmethylation.VitaminB12isvital
receptorinthefolicacidbiopathway.Theearlyhumanembryo
isvulnerabletofolatedeficiencyduetodifferencesofthe
functionalenzymes involvedinthispathwayduring
embryogenesis.Thestudieshaveshownthatdeficiencyof
vitaminB12contributestoNeuralTubeDefect.
ProperintakeoffolicacidandVitaminB12inthefirstfourweeks
ofpregnancy(firsttrimester)forneurulation,mayreducethe
occurrenceofNTD.Womenwhobecomepregnantareadvised
toeatfoodsfortifiedwithfolicacidandtakesupplementsin
addition.
Pregnantwomenareadvisedtoget400microgramsoffolic
aciddaily.

16. Foods Rich in Folic Acid
Folicacid,knownasfolateinitsnaturalform,isoneoftheB-groupvitamins.Ithasseveral
importantfunctions.Folicacidcannotbestoredinthebody,soyouneeditinyourdietevery
day.Mostpeopleshouldbeabletogettheamounttheyneedbyeatingavariedand
balanceddiet.ItworkswellwithvitaminB12toformhealthyredbloodcells.Ithelpsto
reducetheriskofcentralnervoussystemdefectssuchasspinabifidainunbornbabies.A
lackoffolicacidcouldleadtofolatedeficiencyanaemia.Adultsneed0.2mgoffolicacida
day.However,ifyouarepregnantorthinkingoftryingtohaveababy,takea0.4mg(400
microgram)offolicacidsupplementdailyfromthetimeyoustopusingcontraceptionuntil
the12thweekofpregnancy.Takingdosesoffolicacidhigherthan1mgcandisguisevitamin
B12deficiency.
Good sources of folic acid
•broccoli
•brussels sprouts
•liver
•spinach
•asparagus
•peas, beans and lentils
•chickpeas
•brown rice
•papaya
•avocado
•leafy green vegetables
•seeds and nuts
•fortified breakfast cereals

17. Foods Rich in B12
VitaminB12isanecessaryco-factorfortheproductionofDNA,thegeneticmaterialthatactsasthe
backboneofalllife.VitaminB12hasseveralimportantfunctionsandisinvolvedinmakingredblood
cellsandkeepingthenervoussystemhealthy,releasingenergyfromthefoodweeatandprocessing
folicacid.LowlevelsofvitaminB12canimpairproductionofserotonin,aneurotransmitterlinkedto
controlmood.Serotoninisthetargetformedicationsthattreatdepression.WhenlevelsofvitaminB12
getverylow,nervedamagecanhappen.Theinsulationsheathaboutnervefibresbeginstobreak
down,makingitharderforsignalstogettotheperiphery.AlackofvitaminB12couldleadtovitamin
B12deficiencyanaemia.Adultsneedapproximately0.0015mgadayofvitaminB12.Ifyoueatmeat,
fishordairyfoods,youshouldbeabletogetenoughvitaminB12fromyourdiet.However,because
vitaminB12isnotfoundinfoodssuchasfruit,vegetablesandgrains,vegansmaynotgetenoughof
thisvitamin.
Good sources of vitamin B12
•Sardines
•salmon
•tuna
•cod
•lamb
•scallops
•shrimp
•beef
•yogurt
•milk
•cheese
•eggs
•turkey
•chicken

18. Educate the community,
health professionals and workers, policy
makers, the media,
and other stakeholdres
about
the birth defects
and
the opportunities
for
effective care and prevention
Protect Mothers: Healthy Nation = Healthy Mothers + Healthy Children
Email: [email protected]