A paper to be published in the British Medical Journal this week suggests that there should be more research to determine if there is a long-term association between high doses of folate or folic acid in pregnancy and an increased risk of breast cancer in later life.

Researchers at the Universities of Bristol and Aberdeen followed up records on almost 3,000 women who had taken part in a trial of folate supplementation in Aberdeen during their pregnancies in the 1960s.

In the trial, some women were allocated to take a dummy or placebo tablet, some to take folic acid at 0.2mg per day and some to take folic acid at 5mg per day. The majority of the women started the supplements during the second trimester of pregnancy and continued until the end of pregnancy.

By the end of September 2002, 210 women had died: 134 in the placebo group (a mortality rate of 6.8 per cent) and 76 among those who had taken either dose of folic acid supplement (8.0 per cent).

When they analysed cause of death, researchers found a possible increase in risk of breast cancer among those taking the supplements. But because the number of cases is small, they say that the results should be treated with caution.

One of the report’s authors, Dr Andy Ness, from the University of Bristol, said:  “Our paper presents preliminary findings which are intended to point the way towards further research and it is published on that basis. It is entirely possible that this is a chance finding - so further scientific studies are required to examine the association, if there is one, before we reach any conclusions.”

It is known that folic acid supplements taken early in pregnancy reduce the risk of neural tube defects such as spina bifida in a developing baby.

The Department of Health advises prospective mothers to take supplements of 0.4mg per day of folic acid before conception, if possible, and continue until the 12th week of pregnancy.  The researchers emphasise that there is no reason to depart from that advice as the women in this study took folate throughout pregnancy, with most of them starting on the supplement after 12 weeks.

Dr Ness said: “It is important that we don’t confuse women about the need to take folic acid supplements early in pregnancy.              

“Women planning to become pregnant should take folic acid supplements as recommended as there is a considerable difference between the Aberdeen trial and the current guidelines to prospective mothers.  

“If confirmed, these findings have important implications for breast cancer research (namely that exposures in pregnancy may modify breast cancer risk). But as it stands the message to the public is carry on taking the supplements, particularly as dose and timing in the 1960s trials were different from the advice given now to prevent neural tube defects.”

Professor Marion Hall, Emeritus Professor at the University of Aberdeen, was involved in the original trial and the latest study. She added: “This was an unexpected but also a very preliminary finding and further research will be required to ascertain whether this is a “true” finding.

“No pregnant woman needs to change their current practice with folic acid but the study suggests that our findings should be taken into account when policies are being developed for advising pregnant women to take anything during pregnancy and at other times.”

Taking folate in pregnancy and risk of maternal breast cancer. Deborah Charles, Andy R Ness, Doris Campbell, George Davey Smith, Marion H Hall

The original study involved 2,928 women who attended the Aberdeen Maternity Hospital between June 1966 and June 1977.  The original study was to determine whether there was a connection between low folate levels and pregnancy complications including congenital malformation of the foetus, folic acid deficiency anaemia and placental obruption. 

Of the study group:

1977 were allocated to take a placebo
466 were allocated to take folic acid at 0.2mg per day
485 were allocated to take folic acid at 5mg per day

Folic acid deficiency and congenital malformation. Marion H Hall J Obstet Gynaecol Br Commonw 1972;79:159-61

Breakdown of mortality figures:

Total cancer deaths:

Women who took the placebo 69 (out of 1,977) (3.5%)
Women who took 0.2mg folate 19 (out of 466) (4.1%)
Women who took 5mg folate 24 (out of 485) (4.9%)

Breast cancer deaths:

Women who took the placebo  17  (0.9%)
Women who took 0.2mg folate  6  (1.3%)
Women who took 5mg folate  8  (1.6%)  

NHS direct advises:   “Folic Acid. Women attempting pregnancy or already pregnant should take 400 micrograms per day up to the twelfth week of pregnancy. This is over and above the 200 micrograms assumed to be obtained from their diet.