Old friends are the best friends

It occurred to us that we should talk about the good old medication that every woman has taken at least once in a lifetime. We will tell you about folic acid. We take it all right but which one? In what dose? For how long? And do we even need it? These are the questions we will try to answer.
What do we know?
About 4-5% of children around the world are born with serious congenital abnormalities. A little more than a half of these can be diagnosed during pregnancy by means of US or invasive diagnostic methods. Around 2% of disorders are diagnosed at birth or during the first year of life. It is known that folic acid administration BEFORE conception and at an early stage of pregnancy plays a tremendous role in preventing the development of neural tube defects as well as of other folate-sensitive congenital anomalies: anomalies of the cardiovascular and the urogenital systems, malformations of the facial region and of the extremities. By saying “BEFORE conception”, we literally mean “BEFORE the moment a woman learns about her pregnancy”. The neural tube develops until day 26-28 after conception corresponding to 3-4 weeks of pregnancy, i.e. when only very few of us can suspect the said pregnancy.
In the years 1991 and 1992, there were two large-scale studies that investigated the effect produced by folic acid in case of primary and secondary prophylaxis of neural tube defects.
The principal conclusions of these two studies consisted in the following: in case of primary prophylaxis of NTD, 0,8 mg of folic acid per day during the period of pregnancy planning and in the first 6 weeks of pregnancy nullifies the probability of the development of this abnormality altogether; and in case of secondary prophylaxis, the folate dose of 4 mg reduces the risk of NTD from 3.5% down to 1%.
What is so incredible about the effect of folic acid on our organism?
Without going into biochemical details, its journey through the human body can be described as follows. Upon reaching the gastrointestinal tract, folic acid turns into a tetrahydrofolate that is an active form of folic acid. It is tetrahydrofolates that participate in the synthesis of amino acids, epinephrines, DNA division and RNA synthesis as well as improve iron absorption. Tetrahydrofolates modify adrenalin and serotonin metabolism and hence, influence the neural system and the mood of a person.
However, it all starts not with pills, but with a specific diet helping to increase the level of folates in blood. The food containing a large amount of folic acid includes the following: broccoli, spinach, brussels sprout, peas, lentils, oranges, green peas, kidney beans, parsley, avocados, liver.
At the same time, one must bear in mind that thermal processing of food leads to the loss of almost 90 % of folic acid, whereas strong tea and certain drugs (oral contraception, Almagel, Phosphalugel) expedite folic acid excretion from the organism.
Folic acid is a water-soluble vitamin; hence, its long-term administration in the dose of 400 mcg-1 mg can neither create its depot nor induce an overdose. The long-term administration of folic acid in high doses (5 mg/day) did not lead to increased risks for a mother and a fetus either, but studies on this matter are still under way.
Folic acid neither protects from nor induces the risk of cancer of mammary glands, which is sometimes talked about in the forums. The protective role of folic acid as regards ovarian cancer has been identified but not proven.
The administration of folic acid decreases the risk of preeclampsia reliably but, unfortunately, does not affect the risk of preterm delivery, the delivery of children with low weight at birth or anemia in the third trimester.
It should be underlined that the repeated risk of NTD depends not only on a patient’s medical history but is also influenced by the medical history of a patient’s spouse. Consequently, if a patient’s husband has a familial medical history of NTD, the patient herself remains in the high-risk group.
The clinical features of folic acid status are very vague and non-specific, so if one wants to determine one’s folate status, it is easier to undergo a blood test.
The normal folic acid level in blood serum fluctuates between 3 and 25 ng/ml whereas the folic acid level in erythrocytes – between 100 and 425 ng/ml, according to the authors of this piece who utilize various investigation methods,
Some countries have a national programme for the enrichment of food with folic acid, but even in such a case it is not so easy to reach the required level of folic acid, hence:

Women on a folate-rich diet need to include medication containing folic acid into their daily ration;
All women of reproductive age that are planning a pregnancy either in fact or in theory must take multivitamins containing folic acid. Considering the large number of unplanned pregnancies, folic acid administration should be recommended by all doctors consulting patients at this age.

The confirmed risk factors for low folate levels in erythrocytes and for increased risk of NTD are the following:
Familial medical history

One or more of maternal or paternal side relatives had DNT, irrespective of how distant these relatives are;
MTHFR 677TT genotype – homozygous carriage;
677CST – heterozygous carriage.

Medical conditions

Malabsorption syndrome;
Crohn’s disease;
Celiac disease;
Type 1 or Type 2 diabetes mellitus;
Administration of metformin, combined oral contraception.

Female Factors

BMI higher than 30 kg/m2 or 80 kg of body weight;

Life style

Smoking;
Alcohol abuse;
Medication abuse;
Low socioeconomic status;
Low-calorie diets (below 1000 kcal/day)

The impact on the fetus
The intake of multivitamins containing folic acid is associated with a reduced risk of delivering children with the following diseases: neuroblastoma, leukemia, Wilms tumour, poorly-differentiated neuroectodermal tumours, ependymomas, autism.
The intake of folic acid may be associated with a high risk of giving birth to twins but at present, there is no definitive evidence that could confirm this assumption.
There are data in favor of the fact that a long-term administration of folic acid in the dose of 5 mg/day during pregnancy is associated with a slightly increased risk of rhonchi and respiratory infections in children. Other studies do not confirm the connection between the administration of folic acid and atopic conditions in children.

Practical recommendations:

In patients with BMI higher than 24 kg/m2 the connection between the intake of folic acid and the decreased risk of NTD is weaker than in patients with normal body weight;
It is recommended that patients of low-risk group (i.e. you did not find any factors in the table above that you could relate to) should go on a folate-rich diet and take folic acid in the dose of 0.,4 mcg/day over 2-—3 months prior to the planned pregnancy, during the whole period of pregnancy and during the post-delivery period or during the whole period of breast feeding;
Patients of increased-risk group (familial or personal medical history of folate-sensitive anomalies, familial history of NTD, Type 1 or Type 2 diabetes mellitus, the use of certain drugs, GIT diseases accompanied by malabsorption syndrome) should undergo the measurement of folic acid concentration in erythrocytes before medication containing folic acid is prescribed to them. In case the level of folic acid is lower than 906 ng/ml, folates are prescribed in the dose of 1 mg/day; if the value is higher, the dose should be 0.,4-—0,.6 mg/day. Patients are to start taking the drug 3 months prior to the conception and should go on until 12 weeks of pregnancy. In the 2nd and the 3rd trimester, after delivery and during the whole period of breast feeding, folic acid is taken in the dose of 0,.4— – 0.,6 mg/day;
4 mg of folic acid is prescribed to patients of high-risk group (personal medical history of NTD in a patient or in a spouse) 3 months prior to the planned pregnancy and during 12 weeks of pregnancy. Thereafter, a patient takes 0.,4-—1 mg of folic acid until she stops breast-feeding;
It is suggested that women who have been classified into a high-risk group should take one pill of multivitamins containing 400-—1000 mcg of folic acid as well as medication containing pure folic acid in order to reach the required dose (5 mg/day).

If a patient takes folic acid in the dose of more than 0.,6 mg/day over 6-—8 months and there are still no signs of pregnancy, the dose should be reduced down to the prophylactic 0,.4 mg/day.
If pregnancy does not occur in the next 6 months, you should visit a fertility specialist as well as measure your folate status.