Pregnant women taking folic acid to protect their baby's development may be at greater risk of malaria as a result, Kenyan research suggests.
The supplement interacts with a common antimalarial drug, rendering it less effective, the work shows.
Expectant mums on high dose folic acid, as recommended in Kenya, were twice as likely as others to fail treatment with sulfacoxine-pyrimethamine (SP).
The study appears in Public Library of Science Clinical Trials.
The authors recommend pregnant women in malaria endemic areas, such as sub-Saharan Africa, be given lower doses of folic acid or folate to avoid this problem.
Health authorities recommend pregnant women take 0.4mg of folate per day to protect the developing embryo against spine and brain defects.
More studies looking at different doses may be needed
Professor Brian Greenwood from the London School of Hygiene and Tropical Medicine
But many African countries, including Kenya, use 5mg per day because this dose is more easily available there.
Some take it throughout pregnancy because it can also help to reduce the chance of anaemia in the mother.
Pregnant women are particularly vulnerable to malaria as pregnancy reduces their immunity, making them more susceptible to infection and increasing the risk of illness, severe anaemia and death.
For the unborn child, maternal malaria increases the risk of abortion, stillbirth, premature delivery and low birth weight - a leading cause of child mortality.
Up to 200,000 newborns die each year as a result of malaria in pregnancy.
For these reasons, the World Health Organization recommends malaria drugs to prevent and treat malaria in pregnant women.
In the study, after two weeks of treatment the malaria drug failed 27% of the women taking 5mg of folate daily - nearly double the 14% failure seen in those taking 0.4mg folate or placebo.
There was no difference in stillbirths, premature deliveries or neonatal deaths among the 488 pregnant women, however.
The study authors said: "Given the international recommendations, the relatively low prevalence of folate deficiency in pregnancy, and the compromised efficacy of SP for malaria treatment when folate 5mg is used, we believe it is reasonable to recommend folate 0.4mg daily for pregnant women in malarious areas in sub-Saharan Africa."
Professor Brian Greenwood from the London School of Hygiene and Tropical Medicine said: "This is an important result as folate is given frequently to pregnant women and it has not been clear before if this can interfere with SP when this is given at the same time.
"Theoretically, one would expect that this might be the case and there is evidence that giving folate with SP to children when they are treated for malaria does have an effect on the efficacy of the SP."
He said his own recent study in The Gambia did not find such an interaction between SP and folate.
But he said the difference might be related to the fact that the parasites in Kenya are more resistant to SP than those in The Gambia and that the doses of folate given may not have been the same. In The Gambia women received 0.5 - 1.5 mg of folic acid per day.
He cautioned: "The results from the Kenyan study may not be applicable everywhere and some more studies looking at different doses may be needed."