Prenatal Vitamins With Folate For Neural Tube Development

Pregnancy can often feel overwhelming and sometimes it can seem impossible to keep up with. This article provides simple and clear advice on the importance of folate during pregnancy. It is typically recommended to consume 0.4 milligrams of folic acid daily starting 1 month before pregnancy as well as during the first 3 months of pregnancy to avoid neural tube defects such as anencephaly and spina bifida which are caused when the neural tube does not close properly.^1,2

The neural tube is part of the embryo and is what eventually develops into the brain and spinal cord, therefore, developmental issues in this area can have severe consequences.³

Through this article, we will explore the development of the neural tube and what problems can occur, as well as what folate is and which kinds aid with normal neural tube development and finally what considerations should be made when taking folate/folic acid supplements.

Neural tube development

Initial steps

The neural tube begins to form during the third and fourth weeks of gestation. But before the tube can form, the embryo first develops into three unique layers.³ The ectoderm is one of these layers and it will form a neural plate, neural folds, and the neural groove.³

Sealing the tube

The neural folds will form a cylinder-like structure called the neural tube. These two flaps will fuse after meeting in the middle.³

Function of the neural tube

This neural tube is the primitive brain and spinal cord of the embryo. Later in development, the top end of the neural tube will develop into the brain while the bottom end will develop into the spinal cord.³

What can go wrong during neural tube development?

If the neural tube is not sealed properly a range of developmental defects can arise. The extent of unsealing and where the neural tube is unsealed will affect where the central nervous system (head and spine) is affected, and how severe this effect is.⁴

Anencephaly

The upper part of the neural tube develops into the brain, when the upper part of the neural tube fails to seal a baby can be born without parts of their brain and skull, this is a condition known as anencephaly. Unfortunately, this is incompatible with life and sadly babies often die shortly after being born with the condition.^2,5

The lower half of the neural tube develops into the spinal cord, when sealing is incomplete a condition called spina bifida can develop. Spina bifida refers to any amount of neural tube closure that is incomplete or affected by other neural tube defects.⁴

Spina bifida

The three most common kinds of spina bifida are:

• spina bifida occulta
• meningocele
• myelomeningocele⁶

Myelomeningocele is the most serious and most common type of spina bifida, accounting for 90% of cases.⁷

Myelomeningocele

Myelomeningocele is a type of spina bifida aperta.^8,9 This condition is caused due to a failure in neural tube closure during development.⁴ This leads to a fluid-filled sac bulging from the vertebral canal (also called other names such as the vertebral cavity and the spinal cavity.¹⁰

Within the sac there is cerebrospinal fluid, as well as some exposed neural tissue (including some of the spinal cord and some nerves).^6,8 The sac itself has the meninges (the layers of tissue that cover the spinal cord) of the spine as the outer layer with a break in the skin causing the meninges to protrude.^6,8,11

Myelomeningocele can cause multiple different conditions including issues with bladder function and sometimes bowel continence, with many children being unable to develop normal bladder control, there is also a risk of fluid build-up on the brain (hydrocephalus) which can cause the brain to experience increased pressure. 60% of children with myelomeningocele need an operation to place a shunt tube which will work to move excess fluid from the brain to the abdomen.

Additionally, mobility issues can appear, which differ between individuals, some children may require splints or walking aids. There is also a high risk of infection due to the lack of skin protecting the sac.¹²

Treatment for myelomeningocele is usually recommended prenatally, the surgery attempts to repair the lesion in the spine caused by the condition, this is done to try and prevent any further neurological damage or deficits.⁸

Meningocele

A more benign version of Spina bifida aperta is meningocele. The sac formed is similar to that in myelomeningocele in structure but usually has skin covering the sac (although the skin can be broken in some cases) and does not have any spinal cord and little to no nerves within the sac.^6,7There is no spinal cord in the sac in meningocele and as such nerve damage is minimal.⁶

Typically meningocele does not have any symptoms and is not associated with any acute conditions that affect the brain, however, its effect on the body and the severity can vary depending on the size and location of the bulge along the spinal cord. Symptoms can include but are not limited to

• Back pain¹³
• Incontinence¹³
• Paresthesias (a burning or prickling feeling)¹³
• Paraparesis (a weakness affecting the legs which can be incurable)^13,14
• Decreased muscle tone¹⁵
• Hypermobility (sometimes called hyperextensibility which can have many side effects such as increased risk of dislocating joints, and muscle or joint pain^15,16 

Surgery is typically enough to treat meningocele effectively and is recommended as soon as is practical. The prognosis (prediction of the course of the disease) after treatment is seen as “excellent”.⁷

Spina bifida occulta

Spina bifida occulta (also known as hidden spina bifida is the mildest type of neural tube defect and is the counterpart to the previously mentioned spina bifida aperta.⁶ Spina bifida occulta does not usually cause any kind of disability or any issue at all and many times isn’t found out until late childhood or adulthood.^4,6,17

Those with spina bifida occulta typically lack any obvious differences from those without the condition. There are sometimes hairy patches of skin or dimples present near the affected area.⁴

Spina bifida occulta like spina bifida aperta, is caused by an issue in neural tube closure during development.^4,18 Spina bifida occulta is a small gap in the spine.⁶

Most individuals with spina bifida occulta will not need surgery, and there is evidence to suggest that in some cases with the continued closure and fusion of backbones that occurs naturally during growth, spina bifida occulta may be less prevalent as age increases.

Folate and folic acid: what are they, how are they different, what do they do?

Definition and types of folate

Folate is a water-soluble vitamin sometimes called folacin ora vitamin B9.¹⁹ Folic acid is a type offolate, with the term folate being used to refer to anything that is a form of vitamin B9 Despite this the terms are often used interchangeably.^19,20

Only Folic acid helps prevent neural tube defects

The only form of folate proven to help with preventing neural tube defects is folic acid, so it is important if taking supplements that contain folate to check how much of the folate content is actually folic acid.²⁰

How is folic acid helpful to pregnant women and those who may become pregnant

The American Centre for Disease Control and Prevention recommends pregnant women consume 400 micrograms (also written as mcg or μg) of folic acid a day, 1 month before pregnancy and for the first 3 months of pregnancy. It is recommended that all women who are of a reproductive age should have 400 micrograms of folic acid a day as a precautionary measure to help prevent neural tube defects in any pregnancy that may occur.

Women who have previously had a pregnancy affected by neural tube defects are recommended to have an increased intake of folic acid, instead consuming 4,000 micrograms of folic acid a day 1 month before pregnancy and for the first 3 months of pregnancy. The recommended dosage can change based on the government body providing advice, with the NHS in the UK recommending a dosage of 5,000 micrograms of folic acid instead.²¹ It is as important to consult your clinician if you have had a pregnancy affected by neural tube defects in the past.²²

The reason the American Centre for Disease Control and Prevention recommend that all women “of reproductive age” take 400 micrograms (or 4,000 micrograms) of folic acid 1 month before pregnancy is due to neural tube defects occurring 3-4 weeks after conception which is before most women realise they are pregnant.²² To put it into perspective the United Nations estimates that almost half of all pregnancies world-wide are unintended, with 121 million unintended pregnancies each year.²³

How to get folic acid and folate in your diet

Before taking any supplements it is very important that you consult your clinician, they may even be able to assist you with which supplements you can take. One good reason for this is supplements can interact with other medications you may be on. Also ensure that you keep a complete record of which supplements you take, this can then be shared with your clinicians to discuss the best actions for your overall health.²⁴

Here is a link to a useful template by the US National Institute of Health and the US Office of Dietary Supplements to help with keeping track of dietary supplements:

What is folic acid?

Folic acid is a synthetic molecule that is not often found in nature.²²

Where to find folic acid and which foods contain folic acid

Folic acid is found mainly in fortified foods (sometimes called enriched foods) which are foods that have had vitamins and minerals added in, and can often include folic acid.^25,26 Folic acid can also be found in dietary supplements.¹⁹ The degree to which foods are fortified with folic acid and which foods are fortified varies depending on the country.

Some countries require by law that certain foods are fortified with folic acid, such as; New Zealand, Australia, Canada, the USA , and Liberia along with many other nations (30) with the UK soon to follow.^19,27,32

It is important to note that if you live in the UK, there are still breakfast cereals which are fortified with folic acid, despite this the UK National Health Service still recommends that pregnant women take 400 microgram folic acid supplements daily.²¹
The most common foods fortified are wheat and flour with some countries also fortifying rice and maize.³⁰

Folic acid supplements, tablets, and liquids

As mentioned before folic acid can also be taken as a dietary supplement there are also tablets and liquids which can be taken.^24,33

Supplements can come in many forms including but not limited to

• capsules
• gummies
• tablets²⁴

Even in the US where a lot of food is fortified with folic acid the American college of Obstetricians and Gynaecologists still recommends that most women who are pregnant take prenatal vitamin supplements to make sure they are taking in enough folic acid (among other nutrients).¹⁹

Folic acid Tablets can be taken with water, with or without food.³³ The liquid can be taken with a plastic syringe or spoon which can help with measuring the dose and can be taken with or without food.³³

Why Folate intake is important in pregnancy and general health

Folate is still important for many functions within the body such as producing nucleic acids such as DNA and RNA which are important for making proteins in the body.^19,34 This role is why the need for folate increases in pregnant women. To address the need for more folate the American Food and Nutrition Board recommend that pregnant mothers increase their daily folate intake from the pre-pregnancy recommendation of 400mcg to 600 mcg a day.¹⁹

Insufficient levels of folate have been associated with an increased risk of low infant birth weight, preterm delivery, and foetal growth retardation.¹⁹ It is recommended that folate is taken regularly as humans are unable to make it themselves so need to consume folate from other sources.³⁵

Where to find folate

To consume more folate in your diet you can eat foods rich in natural folate such as; beans, citrus, fruits, and leafy green vegetables.²⁰ Here is a link to a page by the American National Institute of Health explaining folate in more detail, importantly it contains a table with common foods and their folate content: Folate - Health Professional Fact Sheet (nih.gov)

Folate supplements

It may be difficult for women to take in the recommended daily amount of folate from their diet alone.¹⁹ If you are struggling with getting enough folate in your diet it may be worth considering folate supplements.

Risks and considerations

Medications and folate (including folic acid)

Many different medications are affected by folate supplements (including folic acid supplements) conversely folate levels are also affected by many different medications. These include but are not limited to

• Methotrexate (anti-cancer and anti-autoimmune disease medication) which interferes with anti-cancer effects
• Antiepileptic medications and medication used for psychiatric conditions.These drugs can reduce the levels of folate in serum and Folate can reduce the levels of these medications in serum
• Sulfasalazine (used to treat ulcerative colitis)can cause folate deficiency by stopping the intestine from absorbing folate¹⁹

Here is a link to a list of drug interactions with folic acid by the UK National Institute for Health and Care Excellence: Folic acid | Interactions | BNF | NICE

Too much folate (including too much folic acid)

Taking more than 1mg of folic acid a day (1,000 micrograms) can hide symptoms of vitamin B12 deficiency, which can lead to vitamin B12 deficiency anaemia.²¹ Vitamin B12 deficiency anaemia is when a lack of vitamin B12 causes the body to produce abnormally large red blood cells that are unable to function properly and if left untreated can eventually cause damage to the nervous system.^21,36

There have not been any definite evidence to suggest that exceeding the recommended 400 micrograms of folic acid a dayhas lead to cancer, diabetes, thyroid related disorders, or hypersensitivity outcomes. However, there are reports that in rare cases people may experience gastrointestinal upsets due to taking more than the recommended 400 micrograms of folic acid. These findings are not certain however and more investigations are needed in this area.³⁵

Summary

This article stresses the importance of folate, especially folic acid, in preventing neural tube defects during pregnancy. It recommends daily intake of 0.4 milligrams of folic acid starting before conception and during early pregnancy. The piece advises consulting healthcare providers for proper supplementation due to medication interactions and the risk of excessive folate intake. It also mentions dietary sources rich in folate and its significance for overall health and fetal development.