Overview of Folic Acid

What is Folic Acid?

Folic Acid, also known as a type of vitamin B9, is a vitamin known for keeping the blood healthy by building and maintaining adequate numbers and quality of red blood cells.¹ This vitamin also plays important roles as cells are created, undergo division, and multiply in number. While it is found naturally in various foods, especially fruits and vegetables, other types of foods can also have Folic Acid added. Some examples of the foods that are well-known to contain Folic Acid include:²

• Leafy, green vegetables
• Fruits
• Legumes, including beans, nuts, and peas
• Bread, cereal, pasta, and other similar grain products that have added Folic Acid

However, for some people and in certain situations, it is important to consider that the intake of Folic Acid through the food sources listed above alone may not be enough to achieve adequate nutrition. If this is the case for you, dietary supplements are also available either through prescriptions or over-the-counter to provide additional nutritional support.^1,2,3,4

Folic Acid should not be confused with Folate, which are commonly used interchangeably. The latter is the umbrella term not just for natural Folic Acid, but for all types of vitamin B9. The difference between the two is that Folate is a naturally occurring substance in the foods listed above. Meanwhile, Folic Acid, which does not occur naturally, is considered manmade.^3,4 Despite these differences, both natural and manmade forms of Folic Acid provide the body with the nutrients it requires to keep the body healthy and consistently growing.

Why is Folic Acid important?

Regardless of their age and ability to get pregnant, everyone must get enough Folic Acid through either or both of the methods discussed above. This vitamin helps keep the blood healthy and functioning at its highest level since its impact begins at the cellular level. Folic Acid plays important roles in creating cell DNA and RNA, and the performance of these different cell lifespan processes.³ Its roles at this critical level of human life make getting and maintaining adequate nutrition and strict adherence to medication and supplement schedules an absolute necessity. However, while rare due to the various methods of achieving normal Folic Acid levels through foods and supplements, people can still be deficient in this vitamin. Some of the factors that can put people at risk of developing Folic Acid deficiency include:³

• Poor diet
• Excessive alcohol consumption
• Malabsorptive disorders

Women who are pregnant or have the ability to become pregnant are one population group that must monitor their Folic Acid intake. It is one of the most important nutrients they must keep an eye on as they and their bodies prepare for and undergo pregnancy. Its roles involve helping babies grow and develop in the womb prior to their birth, assisting in brain and spinal cord development, and preventing Neural Tube Defects (NTDs).^1,2,3,4 Continue to the next sections to learn more about Folic Acid and its role in preventing NTDs, including one called Encephalocele.

Overview of Neural Tube Defects

What is the Neural Tube?

Pregnancy is a period in which the body of the person who is pregnant supports significant amounts of growth and development that happen in the womb as the baby develops. Throughout the entire span of the pregnancy, up until just before delivery, cells divide, multiply, and differentiate into various tissues that grow and develop further into the organs, bones, blood vessels, body parts, and body systems we recognize in ourselves and in other people, especially babies. The Neural Tube, which eventually develops into the brain and spinal cord of the baby, is one example of these premature tissues that play important roles in the normal development of a baby.³ The processes involved in the creation and closure of the neural tube occur during the first few weeks of pregnancy, specifically between the third and fourth weeks of gestation.^5,7

The creation and closing of the neural occurs in two ways. In the first one, called Primary Neurulation, the cells surrounding the neural plate oversee how the neural plate cells divide and multiply to shape, fold, elevate, combine, and close the neural plate, creating a hollow tube.⁵ In the process known as Secondary Neurulation, the neural tube is made through a cord of cells that enters the body of the developing embryo. The tube hollows out when the cells making up the inner part of it divide and multiply to change its current shape.⁶

The brain and spinal cord develop normally when their respective processes happen within the appropriate timeframe in pregnancy and are uninterrupted until they are completed. However, different personal, environmental, and genetic factors can disrupt the growth and development of the neural tube and cause it to not completely close. The development of the brain and spinal cord in babies during the remaining months of pregnancy can be compromised by this abnormality. Poor nutrition leading to insufficient Folic Acid levels is one example of how the neural tube does not completely develop.⁷ Without it, the neural tube cannot close normally and completely. This results in the abnormal development of the brain and spinal cord in babies and a variety of related disorders, such as Neural Tube Defects (NTDs).

What are Neural Tube Defects?

Neural Tube Defects (NTDs) are a group of disorders that result from the abnormal generation and closure of the neural tube during pregnancy. The brain and spinal cord, therefore, do not develop as they should since the neural tube does not close as it normally should.^7,8 Folic Acid insufficiency is one of the well-known causes of NTDs, as well as one of the most preventable.⁷ A pregnant woman requires significant amounts of various vitamins, minerals, and other nutrients that are essential in neural tube development and normal fetal development in general. Aside from Folic Acid, other nutrients that are critical in neural tube development include:⁷

• Inositol
• Zinc

NTDs are one of the most commonly reported groups of congenital disorders, with around 300,000 cases per year. Their prevalence is around 1 in every 1000 pregnancies worldwide, with reports of their appearances coming from both developed and underdeveloped countries.⁸ Due to the nature of these disorders, they are also one of the most common causes of life-threatening illnesses and death in infants. 

Spina Bifida, Encephaloceles, and Anencephaly are the three most commonly reported and three most prevalent forms of NTDs.⁷ These three NTDs and many other NTDs can be divided into two groups, which are named Open NTDs and Closed NTDs. Open NTDs, such as Anencephaly, result in the out-of-body exposure of the neural tube and the surrounding tissue. In Spina Bifida and Encephaloceles, which are examples of Closed NTDs, the neural tube and the surrounding tissue are either partially or fully covered by the skin.⁹ Various multisystem physical and developmental manifestations can present in those with these disorders, since the nervous system runs through the entire body and all the other systems within it. However, depending on the specific NTD an infant has, each individual can have a different set of signs and symptoms. For example, some examples of the signs and symptoms that infants with Spina Bifida can present include:⁸

• Body paralysis
• Problems producing and expelling urine, feces, or both
• Hydrocephalus

Meanwhile, Encephaloceles have a set of signs and symptoms that differ from those of Spina Bifida. Despite it being an NTD, it has distinct processes of development and impacts on the human body that differ from other NTDs.

What is an Encephalocele?

Definition and How It Develops

An Encephalocele is a type of NTD, specifically an example of a closed NTD, characterized by the development of an abnormal lump within the tissues of the brain and spinal cord that grows through an opening in the skull. The growth contains either the brain, the meninges surrounding the brain, or a combination of both.⁹ Since these growths can appear at different locations on the head, their names and physical signs and symptoms change slightly depending on where these bulges appear. For example, the most common type of encephaloceles, which are called Occipital Encephaloceles, form at the back of the head.¹⁰ 

However, researchers and healthcare professionals have been puzzled by the development of this NTD. Similar to those of other NTDs, the specific mechanisms for its development are still relatively unknown beyond the genetic, nutritional, and environmental factors that have the potential to cause it. Still, others have pointed out that in normal fetal development, brain tissue and the tissue surrounding it develop after neural tube closure.¹¹ This puts into question how Encephalocele could develop in such circumstances. Because of this, theories have been proposed that Encephaloceles and the presence of the characteristic abnormal and nonfunctional brain tissue in the sac-like protrusion were caused by some other event in the pregnancy that happens following the creation and closure of the neural tube.¹¹ However, instead of the neural tube doing that, it remains open, allowing for the incomplete and abnormal development of the brain and spinal cord.

Signs and Symptoms on the Body

The physical bulging of the head detected in the baby found either before or after birth is one of the hallmark manifestations of this NTD. Much like the different subtypes of these herniations, other physical signs and symptoms that may present themselves in those with encephalocele depend on a number of factors. The location in which they are found, the brain and spinal cord tissue in the lump, and the presence of other tissues and structures contained within it are some factors that can influence what signs and symptoms those with this NTD present with.¹⁰ Some examples that have been reported include.^10,11

• Abnormal facial features, such as hypertelorism and proptosis
• Delays in growth and development
• Seizures
• Vision problems
• Ataxia
• Small head size
• Body paralysis
• Increases in intracranial pressure
• Intelligence and learning problems
• Hydrocephalus

Still, those with Encephalocele may also present no physical symptoms but still possess a variety of developmental manifestations like the ones listed above.

Diagnosis

A diagnosis of Encephalocele is made using the figures from various imaging technologies, such as Ultrasound and Magnetic Resonance Imaging (MRI).¹⁰ Ultrasound is used to make this diagnosis during pregnancy to determine the presence of the sac-like bulging characteristic of this NTD in the developing fetus. MRI has also been used to clearly visualize in detail the tissues surrounding the brain, the contents of the protrusion, and any possible signs of injury.¹² It is recommended that MRI be the preferred imaging test used for diagnosis since it provides more detail in the images it produces.

Treatment and Management

How people with Encephaloceles and their healthcare teams treat and manage Encephaloceles changes depending on the size of the growth. If the mass is small enough and if there are no other developmental abnormalities that may cause problems in the future, the post-birth surgical removal of the protrusion and reconstruction of the gap in the tissues and skull may be an option.^9,10,11,12 This procedure helps to prevent infections, avoid further damage to the affected tissues, and minimize the appearance of hydrocephalus and facial structure abnormalities. Should hydrocephalus still occur, however, it can be treated and managed by using a device called a shunt, which is placed to drain the fluid from the brain and move it elsewhere in the body.¹¹ However, if there are other developmental concerns or if the mass is too large or contains critical tissues, surgical removal may be too risky to perform.^10,12 It is important for you to thoroughly discuss the details of these procedures with your healthcare team to determine which ones would lead to the safe removal and management of the herniation without causing further problems and concerns.

How Folic Acid Prevents Neural Tube Defects

A Summary of How Folic Acid Prevents Neural Tube Defects (NTDs)

NTDs can be prevented with proper nutrition, with a special focus on Folic Acid intake, if it begins as early as possible in the pregnancy.^7,8,9 A significant amount of growth and development occurs during pregnancy, and Folic Acid is one of the many nutrients that ensure its normal progression. One of the most critical roles of this form of vitamin B9 is that it helps create and close the neural tube, allowing it to eventually develop into the brain and spinal cord of the baby. This is because Folic Acid provides the pregnant woman with the nutrients needed for the level of cell growth, division, and multiplication that happens throughout pregnancy. Without adequate levels of this nutrient, the neural tube fails to close properly, leading to the brain, spinal cord, and other cells and tissues moving from their places into the surrounding tissues. This unusual movement of brain and spinal cord cells and tissues into other tissues is characteristic of NTDs.

The Importance of Timing

However, you may experience various challenges in getting the Folic Acid supplementation you need, regardless of whether you have been planning to get pregnant or not. Most people may be unaware of their pregnancy at the point when neural tube development and closure occur, which is around the first four weeks of pregnancy.^5,6,7,13 As a result, you may not be getting enough Folic Acid to facilitate that growth and development. Without the foundation that underlies many processes in pregnancy and fetal growth and development, it may lead to the appearance of signs and symptoms of abnormal pregnancy progression, such as the presentation of NTDs. Therefore, it is important for you and anyone who has the ability to get pregnant to get adequate intake, education, and assistance regarding Folic Acid prior to, during the early weeks of, and even after pregnancy.

Periodic monitoring of Folic Acid levels prior to and during pregnancy is required in order to determine whether consistent and adequate intake and absorption have been achieved. Doing so has proven successful in supporting the success of Folic Acid fortification projects in numerous countries around the world dedicated to using Folic Acid intake and supplementation to prevent the development of NTDs.⁸

Recommendations for Folic Acid Intake

For people who can get pregnant and those planning for pregnancy, the current recommended amount for adequate Folic Acid intake ranges anywhere between 400 to 800 micrograms (mcg) every day.^3,13 Depending on your specific needs and other contributing factors, these amounts can be adjusted, but first require in-depth discussions between you and your healthcare providers regarding what your recommended intake should be. Such discussions should also include plans on how to find reliable sources for the foods and dietary supplements you need. To reiterate, Folic Acid intake and supplementation must begin and be maintained as early as possible during the pregnancy, specifically before the first three to four weeks. If possible, it is recommended that such intake and supplementation begin at least one month prior to the pregnancy and should continue until the 12th week of pregnancy.^1,3,7

These and many other similar recommendations for adequate Folic Acid intake, supplementation, and level maintenance throughout the pregnancy help make sure that the baby undergoes the growth and development processes of a normal and healthy pregnancy. Alongside your healthcare team, you can help prevent NTDs and other similar preventable disorders from occurring and disrupting the growth and development involved in pregnancy. The World Health Organization (WHO), the NHS, the Centers for Disease Control and Prevention (CDC), and other organizations around the world regularly release data and information regarding NTDs and current efforts to prevent them through food and supplement fortification programs.^8,13 These efforts have come with a few challenges, such as the failure to initiate such programs in other countries and the inability to fully enact them in the countries where they were introduced to. Nonetheless, the intake of adequate Folic Acid, including periodic monitoring of Folic Acid levels, assistance in maintaining good nutrition, access to data and information on Folic Acid and how it prevents NTDs, and general health and wellness management throughout the pregnancy, is still regarded as the best plan for preventing NTDs

Summary

• Folic Acid, also known as vitamin B9, is a critical building block in cell generation, division, multiplication, and differentiation
• Folic Acid can be found naturally in various foods, as well as added to others to fortify their nutrient content
• Neutral Tube Defects (NTDs) develop during pregnancy when the neural tube, which develops into the brain and spinal cord, does not close properly and completely
• Encephaloceles are a type of NTD characterized by sac-like growths containing brain and spinal cord tissue that grow through any holes in the skull
• Folic Acid is one of the nutrients that help normally and completely close the neural tube, making adequate intake and supplementation important during the first three to four weeks of pregnancy
• A plan for adequate Folic Acid intake and supplementation must begin at least one month before getting pregnant and should continue up until the 12th week of pregnancy
• NTDs, especially Encephalocele, have been known to be successfully prevented with adequate Folic Acid intake and supplementation at key times before and during pregnancy