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Prevention of anencephaly


by Monika Jaquier


If all women of child-bearing age took 0.4mg of Folic Acid every day before and at least until the end of the first term of their pregnancy, between 50 and 70 % of potential cases of anencephaly and spina bifida could be prevented.


- What is a neural tube defect?
- What is anencephaly?
- What is spina bifida?
- Why do NTDs occur?
- What is Folic Acid?
- What role does Folic Acid play in NTD prevention?
- At what point and for how long should one take Folic Acid?
- How much Folic Acid should one take?
- Does a balanced diet provide enough Folic Acid?
- What food has a high Folic Acid content?
- Folic Acid side effects
- What more should one know about Folic Acid?
- References



What is an neural tube defect?

A neural tube defect (NTD) is a congenital malformation which occurs between the 20th and 28th day after conception. The 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. One can liken this process to a coin whose edges merge at its center. In the case of an NTD, the neural tube is unable to close completely. The growing brain and spinal cord are then exposed (depending on the location of the anomaly). The most common forms of NTD are anencephaly and spina bifida.


What is anencephaly?

Anencephaly occurs when the head end of the neural tube fails to close. Infants with this disorder are born without a scalp or cerebellum. Their meninx, both hemispheres of the brain and the vault of the cranium/skull are also missing, though they usually do have part of the brain stem. The remaining brain tissue is protected only by a thin membrane. The infant can be blind and has no, or very few, reflexes. 25% of anencephalic children who live to the end of the pregnancy die during delivery; 50% have a life expectancy of between a few minutes and 1 day, 25% live up to 10 days (Jaquier 2006).


What is Spina Bifida?

If the neural tube remains open at the caudal extremity, it is a case of Spina Bifida. The spinal cord and the back bone are not able to develop completely and infants have an opening in their back from which a sac full of liquid containing part of the spinal cord may emerge. The extent of the permanent disability depends of the location of the defect on the back bone. The higher the lesions, the greater the risk of lower-member paralysis. When the lesions are lower, the risk is smaller and the most frequent consequences are lack of bladder and intestine control. Spina bifida can be compounded by a hydrocephalus. Infants with Spina Bifida are operated on at birth in order to prevent further damage to the nervous system.


Why do NTDs occur ?

It is not known what causes NTDs. They are probably triggered by a combination of environmental and genetic factors (Sadler 2005). Any woman of child-bearing age can potentially give birth to a child suffering from an NTD. In our region (Switzerland), one child in 1000 is afflicted by an NTD. It is not possible to predict which women will have an NTD pregnancy. 95% of NTDs affect women who do not have an NTD history in their families.


What is Folic Acid?

Folic Acid is a vitamin (a substance which is essential to the body and which is provided in small quantities by the food we eat). It belongs to the B complex group. It plays an essential role in cellular division. It is also called folate or folacin. It is soluble in water and is destroyed by heat.


What role does Folic Acid play in NTD prevention?

Folic Acid is a coenzyme. It plays an important role in many metabolisms. The developing unborn child needs it to grow cells, tissue and organs. During that phase, the folic acid requirements are higher than usual. As far back as 1976, scientists noticed that women who gave birth to NTD babies had low serum rates for folates and low vitamin levels in their red cells. In 1980, Professor Smithhells from Leeds (UK) was able to show that an additional intake of 0.4 mgs of Folic Acid before and at the start of a pregnancy significantly reduced NTD rates. This finding was confirmed by many other serious clinical studies using large numbers of women (over 250 000). The conclusive proof of the preventive effect of Folic Acid, even for women with no NTD history, came when a Hungarian study showed that, of the 2014 women who had taken additional Folic Acid, none developed an NTD, whereas, of the 2052 who had not, 6 cases were detected (Czeizel and Dudas, 1992). Recent research on NTD pathogenesis suggests that disorders linked to methioninesynthase activity could be one of the factors involved. This enzyme transforms homocysteine into methionine. To do so, it needs a methyle group which is provided by Folic Acid intake. If this transformation fails to take place, be it because of an enzyme anomaly or lack of Folic Acid, homocysteine levels increase. This would appear to prevent the closure of the Neural Tube. An additional intake of Folic Acid, coupled with an intake of vitamin B12 can rectify this anomaly which is in part connected with enzymes. Other studies have also shown that further anomalies such as heart malformations, lift and palate clefts and urethra malformations can be prevented by an additional intake of Folic Acid (Czeizel 1993, Antony 2000).


At what point and for how long should one take Folic Acid?

Folic Acid should be taken at least 4 weeks before a planned pregnancy.

NTDs are birth defects that occur between the 20th and the 28th day after conception, before most women know that they are pregnant. Because about half of all pregnancies are unplanned, it is important to include at least 0,4 milligrams of folic acid in every childbearing age woman's diet. However, for those women fortunate enough to confirm pregnancy very early on (i.e. 14 days post ovulation), and who have not been taking Folic Acid supplements prior to conception, you should begin immediately as there still may be some time for the supplement to benefit the developing embryo. Given that many pregnancies are not planned, the best way to prevent these birth defects is for all women of child-bearing age to ensure that they are taking enough Folic Acid everyday.

Women also need more Folic Acid during pregnancy and breast-feeding. Hence it is wise to continue to take pills after the critical moment when the Neural tube closes.


How much Folic Acid should one take?

0.4 mgs per day, in addition to the folates present in food. Multivitamin supplements containing less than 0.4 mgs of Folic Acid should not be taken in higher dosage in order to increase Folic Acid content. Too high an intake of other vitamins is harmful.
Czeizel presented a study in 2004 which showed that multivitamins containing 0,4 - 0,8mg of folic acid were more effective for the reduction of NTDs and other congenital abnormalities than high dose of folic acid, while Wald found in 2001 and 2022 that the higher dose (4 - 5mg/day) has been shown to be more effective.


Does a balanced diet provide enough Folic Acid?

Unfortunately, it does not. It is almost impossible to draw enough Folic Acid from one's own diet, even if it has a high Folic Acid content. One must therefore take 0.4 mgs of Folic Acid in pill form, and combine this with a high Folic Acid content diet, and even an enhanced diet. In several countries, the Government systematically enriches basic food such as flour and bread with Folic Acid.


What food has a high Folic Acid content?

Vegetables: beetroot, asparagus, Brussels sprouts, spinach, avocados, kidney beans, lentils, lettuces

Fruit: melons, strawberries, kiwis


Folic Acid side effects

If the intake is below 10 mgs per day (25 times the normal daily amount!), there are no side effects. In some rare cases, however, there can be an allergic reaction (skin rash, bronchospasms), even when the intake is low. The intake of 15mgs of Folic Acid can cause insomnia, agitation, hyperactivity, nausea and flatulence. It can affect the sense of taste and can result in allergic reactions such as rashes, pruritus and nettle rashes. The intake of over 1 mg of Folic Acid per day can obscure a pernicious anaemia (an illness which occurs usually only from between the ages of 40 and 50).


What more should one know about Folic Acid?

Folic Acid might weaken the effects of certain medicines prescribed against epilepsy.

Some medicines cause the level of Folic Acid to fall, hence increasing the risk to the unborn child.

Here are a few examples:

Hormonal contraception (the pill)
Some antiepileptics (valproic acid, carbamazepine)
Some antibiotics (trimethroprim=bactrim, pyrimethamine)
Some antimetabolics (methotrexate, aminopterine)
Alcoholic beverages



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Botto, L.D. et al, 1999. Neural-Tube Defects. N England J Med 341:1509-1519

Czeizel AE, 1993. Prevention of congenital abnormalities by periconceptional multivitamin supplementation. BMJ 1993;306:1645-1648

Czeizel AE, Dudás I. 1992. Prevention of the first occurrence of neural tube defects by periconceptional vitamin supplementation. N Engl J Med 327:1832-1835.

Czeizel AE. The primary prevention of birth defects: Multivitamins or folic acid? Int J Med Sci. 2004;1(1):50-61. doi: 10.7150/ijms.1.50. Epub 2004 Mar 20. PMID: 15912190; PMCID: PMC1074510.

Jaquier M, Klein A, Boltshauser E., 2006. Spontaneous pregnancy outcome after prenatal diagnosis of anencephaly, BJOG 2006; 113:951-953

Milunsky A, et al. 1989, Multivitamin / Folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects. JAMA; 262:2847-2852

MRC Vitamin Study Research Group: Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. Lancet 1991; 338:131-137

Sadler, T.W., 2005. Embryology of Neural Tube Development. American Journal of Medical Genetics Part C 135C:2-8

Smithells RW, Sheppard S, Schorah CJ. 1976. Vitamin deficiencies and neural tube defects. Arch Dis Child 1976;51:944-950

Smithells RW, Nevin NC, Seller MJ, et al 1983. Further experience of vitamin supplementation for prevention of neural tube defects recurrences. Lancet 1983;1:1027-1031

Wald NJ, Law MR, Morris JK, et al. Quantifying the effect of folic acid. Lancet 2001; 358: 2069–2073.

Wald NJ. Folic acid and neural tube defects: Discovery, debate and the need for policy change. J Med Screen. 2022 Jun 23:9691413221102321. doi: 10.1177/09691413221102321



Last updated July 19, 2022