Folate fortification and supplementation—Are we there yet?

Abstract

Background

Folic acid fortification of flour has significantly decreased the incidence of neural tube defects (NTDs). We aimed at examining whether Ontario women of child-bearing age exhibit protective levels of RBC folate.

Methods

We reviewed laboratory databases on RBC folic acid from pre and post fortification years. The data included age, gender, RBC folate, hemoglobin, mean cell volume and pregnancy test. We examined a sub-set of females at ages 14–45 years who were non-anemic and normocytic. Complete protection against NTD was defined as RBC folate concentration above 900 nmol/L.

Results

In 2006, 40% of the women of child-bearing age and 36% of pregnant women, exhibited RBC folate levels below 900 nmol/L, rendering them sub-optimally protected against NTD.

Conclusion

A considerable proportion of pregnant women is still at risk of having a baby with NTD. This should be remedied by increasing the mandatory concentrations of folic acid required in flour, complemented by public education and increasing the folic acid in prenatal supplements.

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.