Throughout the world, folic acid has now become the sacred cow of preconceptual health advice because of its apparent ability to reduce the rate of neural tube defects. But is this faith justified?
In one sense, yes, as it does appear to help prevent neural tube defects.
When the Medical Research Council conducted a trial on vitamin supplementation in the prepregnancy period for those women who had already had
a child with NTD, they concluded that supplementation with vitamins and 4 mg of folate daily could reduce the incidence of a subsequent affected baby by 72 per cent (Lancet, 1991; 338: 131-7).
A year later came a Hungarian study of 7500 women who had no previous affected babies; they took either 0.8 mg daily of folic acid plus other vitamins, or a 'placebo like' mineral supplement. None of the 2000 mothers who had the folic acid/vitamin supplement produced a baby with NTD, but six of the control mothers did. Folic acid supplementation also lowered the risk of other malformations, such as limb and urinary tract abnormalities (N Engl J Med, 1992; 327: 1832-5).
The authors of the MRC trial went as far as to recommend that we should consider fortifying foodstuffs such as flour with folate to make sure that women get what they need. Such was the enthusiasm for this idea that one group of American researchers pleaded, "We must not let our ignorance about the biochemical mechanism of how folic acid prevents NTDs stand in the way of public and private efforts to increase folic acid consumption now" (JAMA, 1996; 275: 1636).
Such a measure, however, seems to bypass the important questions: Why are some women low in folic acid? And what are the known causes of NTDs?
Diet alone is probably not the answer. When a women is put on the Pill, for instance the other sacred cow of reproductive health she is rarely told that this will lower her folic acid levels and that it may take up to four months after stopping the pill for tissue levels to return to normal.
On the other hand, does folic acid deficiency alone explain why NTDs are more common in some countries than in others? (The rate of NTDs is on average 2.8 per 1000 in the US and 4.5 per 1000 in the UK).
NTDs are known to be multifactorial in origin, and it is highly unlikely that all women who have a baby with an NTD are lacking in folate. For instance, those women who do have affected babies, but seem to have adequate levels of folate, may have a problem with absorbing and utilising the nutrient.
Low levels of zinc have also been cited as a potential risk for NTDs and other congenital abnormalities, as have high levels of heavy metals in water and a polluted environment. Studies show, for instance, that mothers who smoke are more likely to have babies with all kinds of congenital abnormalities. There is evidence that, if the father is a heavy smoker, the rate of malformations doubles. The influence of food additives and agrochemicals has not been fully addressed. It's unlikely that taking folic acid or any other single magic bullet can make up for any of these risk factors.
Unlike the MRC (who failed to produce follow up information), the Hungarians did follow the babies for the first year of life. There was little difference between the two groups except that the babies who had folic acid/vitamins in the womb had more asthma, bronchitis and allergic skin problems (Arch Dis Child, 1994; 70: 229-33).
Whether the folic acid contributed to this is a question which should be asked and followed up with more studies.
In the Hungarian data, other differences emerged between the supplemented and non supplemented groups. The supplemented mothers appeared to conceive more quickly (Br J Obstet Gynaecol, 1996; 103: 569-73). They also had more multiple births, particularly identical twins (N Engl J Med, 1994; 330: 1687-8). Twins, of course, are more likely to be premature or handicapped or to die at birth.
More recently, the Hungarian researchers have raised another concern, this time over the possible mechanism by which folic acid works. Further analysis of their data has shown that the folic acid group had a 16 per cent higher miscarriage rate than the placebo group (Lancet, 1997; 350: 513-5). Among the 27,000 supplemented women, there were 27 fewer malformations, but 51 more spontaneous abortions almost twice as many as the number of defects avoided. (It is interesting to note that the rate of increased abortion in the MRC trial was 15 per cent, though this figure was dismissed at the time as insignificant). If folic acid is a weak abortifaceant, it is unlikely to be selective. Healthy babies as well as those with malformations may be rejected.
If this is true (and it has been hotly disputed), then women, particularly those prone to miscarriage, are left with a terrible dilemma. A woman who habitually miscarries may be told, often without any substantiating proof, that she is producing a baby that is in some way damaged. She may be vigorously encouraged to take folic acid to help her conceive a healthy baby. However, if she takes the folic acid and still miscarries, does the problem lie with her or the supplement?
The Hungarian research does not turn everything that we know about folic acid on its head. But it does raise some very uncomfortable questions. We are a long way from fully understanding why abnormalities occur. Folic acid works, but we are also in the dark about how it works or whether it works properly only in tandem with a full diet and supplement programme. Without good data on its mechanism and potential risks women cannot make informed rational decisions about choosing or refusing to supplement, based on their own individual risks.