Folate Receptor Antibodies and Preterm Birth: Folate Status is More Than Intake
Preterm birth is a significant contributor to global infant mortality and disability. Internationally, rates vary from 5% to 18% of all births (see WHO factsheet). Although preterm birth is defined as any birth before 37 weeks’ gestation, the earlier that babies are born, the greater the risk of complications. Causes of preterm birth are varied but resource-poor settings, lack of healthcare during pregnancy and poor access to reliable family planning are all factors.
Nutrition is known to play a role in preterm birth. Aside from poorer pregnancy outcomes in general in women who are malnourished or obese, folate as also been identified as important for pregnant women and their infants. Scholl and colleagues found that women with low folate intakes had a two-fold greater risk of preterm delivery and low infant birth weights when the authors controlled for various confounders. More recently, Chen and co-workers showed poorer folate status to be linked to preterm birth. However, regular readers of this blog will know that nutrient status is more than intake alone. The way that nutrients are absorbed, transported and used in the body are also important.
One of these important factors that can affect folate status is the presence of folate receptor antibodies. The folate receptor sits on the surface of cells and helps them to take up folate from the circulation (see Chen and associates). However, the body can also produce antibodies that prevent the folate receptors from taking up folate. This results in lower levels of folate in cells. The presence of folate receptor antibodies can mean that although intakes and absorption of folate are adequate, folate is not reaching the inside of cells where it is needed. Could the presence of folate receptor antibodies then cause ‘cellular’ deficiency and affect rates of conditions caused by a lack of folate?
This is the research question Vo et al. attempted to answer. They looked at the presence of folate receptor antibodies in 50 consecutive preterm and term pregnancies at the State University of New York Downstate Medical Center. They found that twice as many women with a preterm birth (65%) had folate receptor antibodies as women with a term birth (28%). When the authors adjusted for confounders, the presence of folate receptor antibodies increased the risk of term birth fivefold.
The authors suggest that the presence of folate receptor antibodies may cause fetal folate deficiency, which is a contributing factor to preterm birth. None of the women had signs of folate deficiency, however it is already known that blood levels of folate in pregnant women needed to prevent neural tube defects are considerably higher than levels needed to prevent folate deficiency in the general population. Testing for the presence of folate receptor antibodies and the administration of high doses of folate may be able to circumvent further deficiency in the fetus and perhaps reduce preterm birth rates. A clinical trial may help to answer this question definitively, and help us to understand better how folate is important for healthy pregnancies.
Vo HD, Sequeira JM, Quadros EV, Schwarz SM, Perenyi AR, The role of folate receptor autoantibodies in preterm birth, Nutrition (2015), doi: 10.1016/j.nut.2015.04.008. http://dx.doi.org/10.1016/j.nut.2015.04.008
Chen C, Ke J, Zhou XE, Yi W, Brunzelle JS, Li J, Yong E-L, Xu HE, Melcher K. Structural basis for molecular recognition of folic acid by folate receptors. Nature. 2013 08/22/print;500:486-9. http://www.nature.com/nature/journal/v500/n7463/full/nature12327.html
Ling-Wei Chen, Ai Lin Lim, Marjorelee Colega, Mya-Thway Tint, Izzuddin M Aris, Chuen Seng Tan, Yap-Seng Chong, Peter D Gluckman, Keith M Godfrey, Kenneth Kwek, Seang-Mei Saw, Fabian Yap, Yung Seng Lee, Mary Foong-Fong Chong, and Rob M van Dam. Maternal folate status, but not that of vitamins B-12 or B-6, is associated with gestational age and preterm birth risk in a multiethnic asian population. J. Nutr. 2015 145: 1 113-120; first published online November 12, 2014. doi:10.3945/jn.114.196352
Green R. Indicators for assessing folate and vitamin B-12 status and for monitoring the efficacy of intervention strategies. Am J Clin Nutr. 2011 Aug;94(2):666S-72S. doi: 10.3945/ajcn.110.009613. Epub 2011 Jul 6. http://www.ncbi.nlm.nih.gov/pubmed/21733877
Scholl TO, Hediger ML, Schall JI, Khoo CS, and Fischer RL. Dietary and serum folate: their influence on the outcome of pregnancy. Am J Clin Nutr April 1996 vol. 63 no. 4 520-525 http://ajcn.nutrition.org/content/63/4/520.abstract
World Health Organisation. Preterm Birth. Fact Sheet number 363. Updated November 2014. http://www.who.int/mediacentre/factsheets/fs363/en/