The results add to the well-established benefits of the vitamin that links folate deficiency in early pregnancy to increased risk of neural tube defects (NTD) - most commonly spina bifida and anencephaly - in infants.
This connection led to the 1998 introduction of public health measures in the US and Canada, where all grain products are fortified with folic acid - the synthetic, bioavailable form of folate.
While preliminary evidence indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence, parallel measures in European countries, including the UK and Ireland, are still on the table.
Women of childbearing age are currently recommended a daily dose of 400 micrograms starting before conception.
Moreover, in Norway where this new study was based, no folic acid fortification is in place and the country is said to have one of the highest rates of facial clefts in Europe.
"If folic acid is able to prevent a major birth defect in addition to neural tube defects, this benefit should be included among the risks and benefits of fortifying foods with folic acid, a matter of ongoing controversy in many countries," wrote lead author Allen Wilcox in the British Medical Journal.
The new study, by researchers from the US National Institutes of Health (NIH), and Norway's University of Bergen, University of Oslo, Oslo's Rikshospitalet, and Haukeland University Hospital, identified infants born between 1996 to 2000; 377 with cleft lip (with or without cleft palate), 196 with cleft palate only, and 763 healthy controls.
All mothers were surveyed using two questionnaires about their reproductive history, smoking, alcohol, drugs, and other exposures during early pregnancy. They were also asked to recall their diet during the first three months of pregnancy, whether they took folic acid supplements and, if so, when and how often they took them.
Women were asked similar questions about multivitamins, and the researchers then estimated each woman's total folic acid intake.
After adjusting for smoking and other confounding factors, the researcher report that folic acid supplementation of 400 micrograms or more a day reduced the risk of cleft lip with or without cleft palate by 40 per cent.
"No previous studies have collected information on daily folic acid intake less than 400 micrograms, and so we are unable to compare our findings of an apparent threshold effect with other studies," wrote Wilcox.
Independent of supplements, diets rich in fruits, vegetables, and other high folate containing foods reduced the risk by 25 per cent. The lowest risk of cleft lip was among women with folate rich diets who also took folic acid supplements and multivitamins, said the researchers.
However, the researchers stated that folic acid alone was not found to provide protection against cleft palate, leading them to acknowledge that their study alone cannot show that folic acid definitely prevents cleft lip. Combined with all the previous evidence, however, their work does suggest a real preventive effect.
"Given the current levels of folic acid supplementation in Norway, and the estimated reduction in risk with folic acid, we estimate that an additional 22 per cent of isolated cases of cleft lip with or without cleft palate could be averted if all pregnant women took greater than or equal to 400 micrograms of folic acid a day," they concluded.
Source: British Medical Journal Online First, ahead of print; doi: 10.1136/bmj.39079.618287.0B "Folic acid supplements and risk of facial clefts: national population based case-control study" Authors: A.J. Wilcox, R.T. Lie, K. Solvoll, J. Taylor, D.R. McConnaughey, F. Abyholm, H. Vindenes, S.E. Vollset, C.A. Drevon