Neural Tube Defects

Importance of Folic Acid and Vitamin B12 Intake during First Trimester

Vijaya SawantDirector Oratechsolve Incwww.oratechsolve.com

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

Pattern of Neural Tube Defects (NTD) in Ethiopia

• The overall statistics on NTD in Ethiopia are not available due to scarcity of information and reporting system. The burden of diseases is high in low socioeconomic countries.

• As per PubMed article, study was undertaken in Jan 2001 to Jun 2005 in Ethio Swedish Children’s Hospital, the most common Neural Tube Defects seen are:

64.4 % Myelomeningocele

18.3 % Meningovele

13 % Encephalocele

28.7 % Associated anomalies like clubfoot undescended testis, different types of hernias, hydroceles

http://www.ncbi.nlm.nih.gov/pubmed/19743784

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.

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 antenatallyCerebellar 2-10 months postnatally

Neuronal migrationCerebral 3-5 months antenatally

Cerebellar 4-10 months antenatally Neuronal differentiation

Axon outgrowth 3 months-birthDendritic 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.

Neural PlateThe Neural plate is a key developmental structure that serves as the basis for nervous system. The neural plate appears on the 17th day after conception as a thickening of the embryonic ectoderm over the notochord. The formation of the flat, thickened layer of ectodermal cells known as the neural plate. This neuroectoderm gives rise to the central nervous system.

Primary NeurulationPrimary neurulation begins after the neural plate forms. On day 18, the edges of the neural plate start to thicken and lift upward, forming the neural folds. The centre of the neural plate remains grounded, allowing a U-shaped neural groove to form. The neural groove gradually deepens as the neural folds become elevated, and ultimately the folds meet and coalesce in the middle line and convert the grove into a closed neural tube. This neural groove sets the boundary between the right and left sides of the embryo. The ectodermal wall forms the rudiment of the nervous system.

Neural TubeNeural tube is the embryo’s precursor to the central nervous system which comprises the brain and spinal cord.Different portions of the neural tube form by two different processes: primary neurulation and secondary neurulation

In primary neurulation, the neural plate creases inward until the edges come in contact and fuse. It divides the ectoderm into three cell types:

• Internally located neural tube

• Externally located epidermis

• Neural crest cells, which develop in the region between the neural tube and epidermis but then migrate to new location

In secondary neurulation, the cells of the neural plate form a cord-like structure that migrates inside the embryo and hollows to form the tube.

http://en.wikipedia.org/wiki/Neural_tube

Neural Tube ClosureThe sequence of events begins with neural tube closure (closure 1), which is initiated at the hindbrain/cervical boundary (double asterisks). Neural tube closure spreads rostrally and caudally from this site. A second de novo closure event (closure 2) occurs at the forebrain/midbrain boundary (single asterisk), although more rostral and caudal locations of closure 2 occur in some strains (dashed lines and arrows). Closure also initiates separately at the rostral extremity of the forebrain (closure 3). Neurulation progresses caudally from closure 3 to meet the rostral spread of fusion from closure 2, with completion of closure at the anterior (or rostral) NEUROPORE. The spread of closure caudally from closure 2 meets the rostrally directed closure from closure 1 to complete closure at the hindbrain neuropore. The caudal spread of fusion from closure 1 progresses along the spinal region over a 36-hour period, with final closure at the posterior (or caudal) neuropore. Secondary neurulation proceeds from the level of the closed posterior neuropore, through canalization in the tail bud (shaded area). The cranial end of the neural tube closes by 24 days and the caudal by 25-26 days. Then, the neural tube is covered dorsally by mesenchyme that forms the vertebral arches and skull. Closure of the vertebral arches is completed at 11 weeks of gestation. http://www.nature.com/nrg/journal/v4/n10/fig_tab/nrg1181_F1.htm

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Neural Tube DefectThe cells of the neural plate make up the fetus’ nervous system. In normal development, they fold back onto themselves in order to create what is called the neural tube, which then becomes the back bone and the spinal cord. After a number of transformations, the superior pole eventually becomes the brain.

Neural Tube Defect (NTD) is one of the common birth defects. During the third week of development, specialized cells on the dorsal side of fetus begin to fuse and form the neural tube. When the neural tube unable to close completely between the 20th and 28th day after conception, the congenital malformation occurs. The growing brain and spinal cord are then exposed depending on the location of the anomaly.

There are two types of NTDs- open and closed. Open NTD occurs when the brain and spinal cord are exposed at birth through a defect in the skull or spine. Closed NTD happens when the spinal defect is covered by skin.

http://neuropathology-web.org/chapter11/chapter11bNTD.htmlhttp://www.futuremedicineonline.com/detail_news.php?

id=278

Exencephaly

Anencephaly Anencephaly

MyelomeningoceleCraniorachischisis

Encephalocele

Occipital encephaloceleDorsal meningomyelocele

Myelomeningocele

Anencephaly Spina bifida Hydrocephalus

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

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.

Treatment• Around 90 % of babies born with spina bifida will also develop Hydrocephalus (fluid on the brain) meaning further major surgery. A surgeon can implant a shunt - a small hollow tube to drain fluid to relieve pressure on the brain. Treating hydrocephalus can prevent problems such as blindness.

• Major spinal surgery to close the gap in the spine usually takes place just 24hrs after birth.

• 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.

• Encephaloceles are 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.

• Tethered spinal cord. Surgery can separate the spinal cord from surrounding tissue.

• Paralysis and limitation in mobility due to spina bifida. Use of braces, crutches, walkers and wheelchairs

• Myelomeningocele children have nerve damage that prevents the bladder from completely emptying, a condition that can cause urinary tract infections and kidney damage. Regularly insert a catheter into the bladder can help it empty fully. Medications, injections, and surgery also can help correct incontinence and preserve kidney and bladder function for the long time.

• No treatment for anenceplaly or iniencephaly. These conditions are usually fatal shortly after birth.

Neural Tube Defects CausesHealth experts are still unaware of the exact cause that disrupts complete closure of the neural tube, resulting in severe physical deformities. It is occasionally caused by chromosomal abnormalities, single gene defects and teratogens. Some assumptions about certain major contributory factors to this condition have been made.

• 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

Neural Tube Defect PreventionFolic acid (Vitamin B9) and cyanocobalamine (Vitamin B12) play an important role in neurogenesis. Folate is important for production and maintenance of new cells, for DNA synthesis and for RNA synthesis. It also plays an essential role in the nucleic acid synthesis and methylation. Vitamin B12 is vital receptor in the folic acid biopathway. The early human embryo is vulnerable to folate deficiency due to differences of the functional enzymes involved in this pathway during embryogenesis. The studies have shown that deficiency of vitamin B12 contributes to Neural Tube Defect.

Proper intake of folic acid and Vitamin B12 in the first four weeks of pregnancy (first trimester) for neurulation, may reduce the occurrence of NTD. Women who become pregnant are advised to eat foods fortified with folic acid and take supplements in addition.

Pregnant women are advised to get 400 micrograms of folic acid daily.

Foods Rich in Folic Acid Folic acid, known as folate in its natural form, is one of the B-group vitamins. It has several important functions. Folic acid cannot be stored in the body, so you need it in your diet every day. Most people should be able to get the amount they need by eating a varied and balanced diet. It works well with vitamin B12 to form healthy red blood cells. It helps to reduce the risk of central nervous system defects such as spina bifida in unborn babies. A lack of folic acid could lead to folate deficiency anaemia. Adults need 0.2mg of folic acid a day. However, if you are pregnant or thinking of trying to have a baby, take a 0.4mg (400 microgram) of folic acid supplement daily from the time you stop using contraception until the 12th week of pregnancy. Taking doses of folic acid higher than 1mg can disguise vitamin B12 deficiency.

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

Foods Rich in B12Vitamin B12 is a necessary co-factor for the production of DNA, the genetic material that acts as the backbone of all life. Vitamin B12 has several important functions and is involved in making red blood cells and keeping the nervous system healthy, releasing energy from the food we eat and processing folic acid. Low levels of vitamin B12 can impair production of serotonin, a neurotransmitter linked to control mood. Serotonin is the target for medications that treat depression. When levels of vitamin B12 get very low, nerve damage can happen. The insulation sheath about nerve fibres begins to break down, making it harder for signals to get to the periphery. A lack of vitamin B12 could lead to vitamin B12 deficiency anaemia. Adults need approximately 0.0015mg a day of vitamin B12. If you eat meat, fish or dairy foods, you should be able to get enough vitamin B12 from your diet. However, because vitamin B12 is not found in foods such as fruit, vegetables and grains, vegans may not get enough of this vitamin. Good sources of vitamin B12• Sardines• salmon• tuna• cod• lamb• scallops• shrimp• beef• yogurt• milk• cheese• eggs• turkey• chicken

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

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