Friday, 29 April 2011

Why are women advised to take folate supplements before and during pregnancy?

Key points:

1. Your baby grows by the process of cell division and cells start dividing immediately after the sperm and egg meet (conception).

2. Neural tube defects result when the neural tube (the structure that will become your baby's brain and nerves) doesnt close properly, this event normally occurs by week 4 of pregnancy.

3. Folate plays an important role in the production and copying of DNA, which must occur every time a cell divides and is an important part of closing the neural tube.

4. It is important for women to ensure that their folate levels are sufficient before they fall pregnant, as well as during pregnancy, so that appropriate cell division occurs as soon as your baby starts developing.

5. The body absorbs more folic acid from supplements than folate found naturally in food, so it is important to take only the recommended daily intake of supplemental folic acid (400μg).

Folate is a B vitamin that is found in legumes, leafy green vegetables and some fruits (such as citrus fruits and juices). Folic acid is the man-made form of folate and the form often used in vitamin supplements and in fortified foods you may have seen in the supermarket. We are able to absorb about 70% more folic acid from supplements than we can from folate naturally contained in foods.

Folate plays a very important role in the normal functioning of all cells within our bodies, and it is particularly important when new cells are rapidly dividing, which is how your baby grows and develops during pregnancy. A baby forming from cells dividing is a hard thing to imagine, especially since its a process we dont actually see. But its very important to understand, so Ill try and break it down.

Your baby starts out as only 2 cells. To make more cells, these 2 cells rapidly divide (2 become 4, then these 4 become 8, 8 become 16 and so on) so that by the time you are only 5 days pregnant, your baby, (called a blastocyst at this stage) is made up of between 80-160 cells. Of these cells, one third will continue dividing to eventually become your baby and the remainder will become the placenta. By mid-pregnancy (20 weeks), the number of cells in your baby's brain alone is approximately 20 billion and when he/she is born, the total number of brain cells is about 40 billion. This process of cells dividing to form new cells is called mitosis and you can see a basic diagram of this in Figure 1.

When each cell divides, our DNA (the genetic code that make us who we are; our genes) is also copied so that there is an identical copy in each and every new cell that forms. Folate plays a key role in this process. If someone is folate deficient, or has low levels of folate in their blood, this has been shown to decrease the rate that DNA is produced and copied into each new cell. This basically means the cells dont divide and copy the genetic code as they should. This is how defects occur.

The most widely publicised role for taking folate/folic acid supplements during pregnancy is for the prevention of neural tube defects. This group of abnormalities affects development of the neural tube, the structure that eventually becomes your babies brain and nerves (see Figure 2). The neural tube should close by the time you are 4 weeks pregnant.

It is thought that a folate deficiency increases the risk of neural tube defects.

Specifically, instead of the genetic code telling the neural tube to close, it stays open. The two most common neural tube defects are anencephaly and spina bifida (see Figure 2). Anencephaly occurs when the skull part of the neural tube doesnt close properly, this is very serious and babies with anencephaly are usually stillborn (the baby is dead at the time of delivery), or die soon after birth. Spina bifida is when the spinal part of the neural tube doesnt close properly. This is also very serious, and if your baby survives, he/she will need extensive surgery and medical care. Babies with spina bifida who do survive usually suffer severe mental and physical disabilities. It is important to know that neural tube defects are usually not detected in pregnancy until the 18-20 week ultrasound.

But the news isnt all bad, scientific experiments and big clinical trials have shown that taking folic acid supplements before falling pregnant can significantly lower the risks of these neural tube defects.

The World Health Organisation (WHO) recommends that women have 400μg (micrograms) of folic acid each day in supplements, as well as eating foods that are folate rich. To ensure adequate folate levels for your babies' cells it is recommended that women start taking folic acid supplements 12 weeks before conception. Because we can absorb much more folic acid in supplements than folate contained in foods, it is important not to overdose on folic acid supplements, because this can mask some of the symptoms of vitamin B12 deficiency (which can cause other problems). It is recommended that the daily intake of supplemental folic acid is not more than 1,000μg per day. To work this out make sure you read the labels on supplements and fortified foods.

There maybe some circumstances in which your doctor may advise higher levels of folic acid supplements, such as if you have a past history of neural tube defects, are taking anti-epileptic drugs or if you have diabetes.

In summary, folate plays an important role in the division of new cells and it is important to understand that your babies growth and development occurs because cells are dividing. Folate levels should be adequate before conception and throughout pregnancy because cellular division is an essential part of your babies development from the very moment of conception.

Acknowledgments: Jake of Ranz for the figures and Dr. Leah-Anne Ruta for editing.

Disclaimer: All information contained within this blog represents my own interpretation of published scientific works. Before any supplement/dietary intervention is considered by a pregnant woman/woman planning on becoming pregnant, it should be discussed with your doctor.

The references I used during the preparation of this blog are listed below:

[1] Tucker M, Morphological scoring of human embryos and its relevance to blastocyst transfer.

[2] Samuelsen GB, et. al., The changing number of cells in the human fetal forebrain and its subdivisions: a stereological analysis. Cereb Cortex, 2003. 13(2): p. 115-22.

[3] Kamen B. Folate and antifolate pharmacology. Semin Oncol 1997;24:S18-30-S18-39.

[4] Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. New England Journal of Medicine 1992;327(26):1832-5.

[5] Anonymous. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet 1991;338(8760):131-7.

[6] De-Regil LM, et. al., Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database of Systematic Reviews 2010, Issue 10.

[7] McNulty H, Pentieva K. Folate bioavailability. Proceedings of the Nutrition Society 2004;63(4):529-36.