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Providing perspectives on recent research into vitamins and nutritionals


Is Folate Supplementation in Late Pregnancy Also Worthwhile?

By Julia Bird

Increasing folate levels in women during the first trimester is associated with a reduced risk of birth defects. Although the precise mechanism of action is still being researched, folate deficiency affects DNA synthesis and methylation, which could lead to errors in cell growth. Adequate levels during the peri-conceptual period and first 8 weeks of pregnancy are desirable to ensure sufficient supply of folate to the embryo. There is little clinical evidence about whether folate can further influence pregnancy outcomes beyond the first trimester, despite considerable observational research that shows that signs of a functional folate deficiency are associated with risk of birth complications. In the American Journal of Clinical Nutrition, McNulty and colleagues report on a pilot randomized controlled trial in pregnant women that looked at the effects of folate supplementation on markers of deficiency.

Levels of three biomarkers can be used to assess folate status. Serum folate levels indicate recent intakes of folate, red blood cell folate concentrations provide a better estimate of functional sufficiency, and homocysteine levels are a non-specific indicator of the status of folate and other B-vitamins. In particular, elevated homocysteine levels occur during folate deficiency as folate is required to convert homocysteine to methionine. High homocysteine has unfortunately been associated with increased risk of birth complications, such as:

- Recurrent pregnancy loss, particularly in women with Polycystic Ovary Syndrome (see recent reports by Chakraborty and Kazerooni).

- Pre-eclampsia (research groups lead by FeiLaskowska, and Kim provide observational evidence)

- Preterm birth (Dhobale)

- Intrauterine growth retardation (Lindblad)

- Risk of small-for-gestational-age (HogeveenBergen)

These complications are related to the health of the placenta during pregnancy. High levels of homocysteine increase vascular complications, perhaps by interfering with the blood vessel dilator nitric oxide (Demir and co-workers), which could reduce blood supply to the fetus. Oxidative stress has also been implicated (Micle et al.).

In the current study, 60 women who had taken folate supplements in the first trimester were supplemented with 400 micrograms folate per day or placebo from the start of the second trimester. In non-supplemented pregnancies, homocysteine levels increase over the second and third trimesters, probably due to increased needs for folate, and circulating folate levels decline. This is what happened in the placebo group. The supplemented group maintained the same homocysteine levels, while circulating and red blood folate levels increased. This study did not contain enough participants to see effects on birth outcomes, although the folate status of the newborns was better in the offspring of supplemented mothers. Further research is needed to see whether these results translate to beneficial effects on pregnancy outcomes. -jb-

Main reference:

Breige McNulty, Helene McNulty, Barry Marshall, Mary Ward, Anne M Molloy, John M Scott, James Dornan, and Kristina Pentieva. Impact of continuing folic acid after the first trimester of pregnancy: findings of a randomized trial of Folic Acid Supplementation in the Second and Third Trimesters. Am J Clin Nutr 2013 ajcn.057489; First published online May 29, 2013. doi:10.3945/ajcn.112.057489