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Around half of all mothers-to-be in Britain and the US are surprised to
learn they are pregnant. Usually they discover about two weeks after
conception by which time their developing embryo is about the size of a
full stop, and the neural structure that will eventually grow into the
baby’s brain and spinal cord has already formed. Disruptions of this process
result in the most common birth defects in the Western world – defects that
cause babies to be born with spina bifida or, worse still, without a brain.
Yet with a safe and cheap dietary supplement in the first weeks of
pregnancy, this is largely preventable. Unfortunately, by the time most
women discover they are pregnant, it is too late.

The effects of small doses of folic acid – a B group vitamin – have been
known for two years. Governments in both Britain and the US have accepted
reports published by their health departments which state that folic acid
can reduce these so-called neural tube defects by around 75 per cent. Both
reports recommended that staple foods like bread should be fortified with
folic acid so that all women of childbearing age get between 0.4 and 0.8
milligrams each day. But despite some vigorous campaigning by researchers,
the food industry has yet to act.

Judith Hall, a professor of paediatrics at the University of British
Columbia in Vancouver and a leading campaigner, has her suspicions about the
industry’s lack of urgency. ‘The whole area of congenital abnormality is
perceived as a women’s problem,’ she says.

Not just a women’s problem

Fortunately for those campaigning for fortification, new research is proving
him wrong. Not only does folic acid reduce the incidence of all forms of
congenital abnormality, but it may also guard against heart disease in
middle-aged men, according to recent findings in Ireland and the US.

Worldwide, as many as 400 000 babies are born with neural tube defects each
year. In Britain, 1 in 500 pregnancies is affected, although annually only
around 140 babies are born with neural tube defects because of screening and
termination. For women who have already had an affected pregnancy the risk
is up to 15 times greater, mostly, it is thought, because of a genetic
predisposition. Racial variations also point to a genetic component. For
example, conditions such as spina bifida are extremely rare in the US black
population but common among Canadian Sikhs.

All neural tube defects occur when a tiny disc of cells, known as the neural
plate, fails to curl up completely to form the brain and spinal cord. Most
commonly, this results in either spina bifida (incomplete closure of the
spine) or anencephaly (when the brain fails to develop). All infants with
anencephaly die shortly after birth, whereas the majority of babies born
with spina bifida grow to adulthood with, in severe cases, paralysis and
varying degrees of bowel and bladder incontinence.

What causes fetuses to develop such defects remains a mystery. But records
from the past 30 years show their prevalence to have varied considerably
over time and from place to place – as well as according to race and social
class. In Britain, neural tube defects are most common in Scotland, Ireland
and Wales, and in the US the incidence declines markedly from east to west.
A variety of environmental influences on embryonic development could
explain these trends, but diet was implicated early on as a key factor.

In the 1980s, the hunt for a dietary deficiency narrowed, and the
breakthrough came in the summer of 1991 with publication of results from a
Medical Research Council trial. Women who had previously had a pregnancy
affected by a neural tube defect were given 4 milligrams of folic acid
daily at least one month before conception and for the first three months of
pregnancy. The result was a 72 per cent reduction in risk compared with
those given a placebo.

Why folic acid should have such a dramatic effect remains unknown, although
knowledge of how it works under normal conditions is what prompted the MRC
investigation. In the human body it is converted to folate which helps
enzymes to catalyse the synthesis of DNA and RNA. Deficiency results in
slower cell division, most notable in rapidly dividing cells including red
blood cells, which is why deficiency results in anaemia. Folic acid also
seems to have a role in controlling the activities of genes. During normal
development, millions of genes must be turned on and off. And one way genes
can be deactivated is by DNA methylation, a biochemical process in which DNA
is temporarily decorated with methyl groups. Folate may be involved in
supplying such methyl groups.

Everyone agrees that unravelling the precise role of folic acid in embryo
development must await further research. Meanwhile, in the US, response to
the MRC finding was swift. In August 1991, the Centers for Disease Control
and Prevention at the Department of Health and Human Services issued an
interim recommendation: women who had a previous pregnancy affected by a
neural tube defect and wanted to conceive again should follow the regime
used in the MRC study, and take 4 milligrams of folic acid each day.

Since 1991, other studies, notably one in Hungary funded by the WHO, have
extended the MRC’s findings by showing that all women can benefit from a low
dose of folic acid. The Hungarians, using a daily dose of 0.8 milligrams and
other groups using 0.4 milligrams – both rather arbitrary measures, but the
most common doses found in multivitamin pills – have consistently found
abnormalities reduced by around three-quarters.

Now the US Centers for Disease Control and Prevention recommends that ‘all
women of childbearing age in the US who are capable of becoming pregnant
should consume 0.4 mg of folic acid per day’. The higher dose for women who
have already had an affected pregnancy still stands. In Britain, the
Department of Health made similar recommendations in its report, published
last December. It also advises women intending to become pregnant to take a
supplement and continue until three months into the pregnancy. All women
are urged to eat plenty of foods rich in folic acid, such as green leafy
vegetables, whole grains, wheat germ, salmon and root vegetables. These
natural sources at present account for between 0.1 and 0.2 milligrams of the
nutrient in the average diet.

Experts agree, however, that diet alone is unlikely to provide enough folic
acid. So what steps can be taken to ensure that all women get at least 0.4
milligrams each day? Multivitamins are not necessarily the answer. As the US
recommendations point out: ‘Caution should also be taken to prevent
excessive use of multivitamin supplements . . . containing vitamin A, since
excess vitamin A may cause birth defects.’ Even if folic acid capsules are
made freely available – at present they are most likely to be available from
small, independent health food stores – an education programme would be
required. Many scientists researching neural tube defects believe that
fortification of staple foods with folic acid is the only effective way to
reach those most at risk women from deprived backgrounds, with poor diets
and a high incidence of unplanned pregnancies.

No sense of urgency

Progress is slow. The US Food and Drug Administration is still considering
recommendations made last November to develop regulations allowing
appropriate staple foods to be fortified. Foods on sale in the US labelled
‘enriched’ must contain specified amounts of various supplements, and one
suggestion is that folic acid be included among these. But even if this is
agreed, the question still remains, how much folic acid to add.

In Britain, most cereals contain enough folic acid to give about a quarter
of the daily dose now recommended. But there is only one branded bread,
Mighty White, which has added folic acid. The government has urged the
Federation of British Bakers, whose members make about three-quarters of
British bread, to inform its members about the recommendation to fortify
bread. All members were sent a copy of the report early this year, though
Tony Casdagli, director of the Federation describes the idea as ‘a slightly
strange request’. ‘Usually,’ he says, ‘the pressure comes the opposite way,
wanting us to take things out rather than put things in.’ Casdagli remains
pessimistic about the scale of the bakers’ likely response. ‘They are
disinclined to add folic acid other than in breads they are promoting as
particularly healthy,’ he says.

Nicholas Wald, professor of environmental and preventive medicine at St
Bartholomew’s Hospital in London and a member of the Department of Health’s
expert committee on folic acid, says: ‘The government has a responsibility
that goes beyond just informing manufacturers about the options.’ Wald
accepts that legislation would not be in keeping with government policy and,
instead, suggests that an advertising campaign be launched along the lines
of the cot death initiative. ‘If the government said ‘make sure the bread
you buy is fortified with folic acid’ then manufacturers would feel left
behind if they didn’t offer such a product.’

But even if manufacturers can be persuaded, the introduction of artificially
high levels of folic acid to the food chain is bound to have its critics.
There remains some uncertainty about the optimal dose, so the aim is for a
supplemented diet to contain at least 0.4 milligrams, but not more than 1
milligram. Above this level folic acid may mask pernicious anaemia – a
disease resulting from vitamin B12 deficiency. Normally this is identified
early and then easily cured with a supplement of the deficient vitamin. In
anticipation of such problems, Hall and other scientists working on neural
tube defects have called for the establishment of a new agency. This would
monitor the way in which folic acid is added to food as well as
investigating doses and safety.

With improved nutritional standards and prenatal diagnostics, the number of
babies born with spina bifida and anencephaly is already on the decline. As
Tony Britain from the Association of Spina Bifida and Hydrocephalus points
out: ‘The general public needs to be made aware that very simple steps could
stop this tragedy occurring.’