Trends in Parasitology
Do disturbances within the folate pathway contribute to low birth weight in malaria?
Section snippets
Malaria as a cause of LBW and IUGR
The evidence implicating P. falciparum malaria as a cause of LBW is overwhelming, especially in primigravidae (women in their first pregnancy) 4, 5, 6. Odds ratios of up to 5.0 have been reported for excess LBW in primigravidae compared with multigravidae (women in subsequent pregnancies); the odds ratio is the ratio between the probability of getting disease if exposed and the probability of getting disease if not exposed. Population attributable risks of LBW owing to malaria of over 50% have
Folate–vitamin B12–methionine metabolic pathway
Folate is a vitamin that cannot be synthesized by humans. All mammalian cells require folate metabolism to recycle methionine and homocysteine, to convert deoxyuridylate to thymidylate in pyrimidine synthesis, and to form purines. In folate deficiency, dependent reactions slow down, and cell growth can be inhibited by an inadequate supply of required substrates or by the toxicity of accumulated intermediates. In mammalian cells, methionine synthesis from homocysteine requires folate as a methyl
Conclusions
In women with individual or combined deficiencies of folate and vitamins B6 and B12, folate restriction to the fetus caused by malaria could become acute and could occur at any stage in pregnancy. Higher fetal folate requirements late in pregnancy would predispose to maximal effects at this time. In addition to effects on fetal growth, this raises the possibility of poor folate and vitamin B12 status in newborn babies with LBW and IUGR. Effective antimalarial control throughout pregnancy is the
Acknowledgements
We thank I. Bates for her comments on our earlier draft of this article and L. Brabin for designing the figures. B.J. Brabin holds a joint appointment at the Department of Pediatrics, Emma Kinderziekenhuis, Academic Medical Center, University of Amsterdam, The Netherlands. This work was partly supported by a grant from the European Commission Research Directorates General, Fifth Framework (contract PREMA-EU-ICA4-CT-2001-10012).
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