Folate fortification and supplementation—Are we there yet?
Introduction
Low folate levels and complication in pregnancy started to appear in literature in the 1960's [1], [2], [3], [4], [5], [6]. Maternal folate deficiency was linked with low birth weight, high incidence of abortion, abruptio placentae and fetal malformation [7]. The 1977 editorial in Lancet concluded that “If the association is confirmed, then the next step will be to judge its casualty directed directly, by preconception vitamin supplementation in mothers at high risk of neural tube defect” [8]. Folate is required during cell and tissue growth and deficiency in the early stages of pregnancy might reasonably be expected to cause defective nucleic-acid formation, impaired cell-growth and replication, damage to the fetus and placenta with defective implantation and organogenesis [9].
The role of folate in preventing neural tube defects (NTDs) was established by two randomized placebo control studies [10], [11]. Later, Daly et al. [12], in a case controlled study, characterized the dose response relationship between RBC folic acid levels and the incidence of NTD in Ireland. In this study they reviewed all women attending their first antenatal clinic in one of three hospitals in Dublin between March 1986 and March 1990 and collected 50,049 samples representing 70% of births at these hospitals and 25% of all Ireland. They documented graded risk reduction. NTD risk increases to more than three folds at levels below 700 nmol/L as compared with those above 900 nmol/L. At 900 nmol/L the odds ratio was 1.0 and this level has been accepted as the optimal folate concentration needed to minimize the incidence of NTD.
During pregnancy the folate requirement is increased by almost four folds. It is now well established that periconceptional supplementation with folic acid can reduce the risk of both the first occurrence as well as the recurrence of NTD [13], [14]. Folate fortification at 140 μg/100 g and 150 μg/100 g of flour respectively, became mandatory in 1998 in the USA and Canada [15], [16]. Since it is now almost ten years into folate fortification in North America, one would expect that population folate levels would have stabilized. The objective of the present study was to assess the percentage of women of reproductive age in Ontario who have protective levels of folate.
Section snippets
Method
We reviewed RBC folic acid test requests submitted to four general practice laboratories and two hospital laboratories in Ontario, Canada. All tests were requested by attending physicians as part of clinical care. Data were available for the following years: 1995 and 1997 (pre fortification), 1998 (start of fortification), and for most years from 2000 to 2006 (post fortification). All (six) laboratories were located in the Greater Toronto area. All samples were anonymous. Available data
Results
Although our total sample size was large, in many cases there was one or the other test result missing. Once we corrected for child-bearing age, hemoglobin and MCV, the final dataset for analysis was smaller. The data from 2002 and 2006 are from the same general practice laboratory and data from 2004 and 2005 are from the same primary care hospital laboratory. Both these laboratories used the same method (Beckman-Coulter, Instrument-DXI), for RBC folate analysis and therefore allowed us to
Discussion
Folic acid plays a major role as a coenzyme in one-carbon metabolism and is a key participant in the biosynthesis of DNA and RNA. The body's requirement for folate is thus related to the amount of cellular reproduction occurring at any particular time. Pregnancy imposes a unique requirement for additional folate due to pregnancy-associated increase in blood volume and active cell proliferation rates critical for fetoplacental growth and development. Although NTD is multifactorial, possibly due
Conflict of interest
None
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