Folate Status in Women of Childbearing Age Residing in Southern California after Folic Acid Fortification

Periconceptional folic acid reduces neural tube defect (NTD) risk. Red blood cell folate concentration is inversely associated with NTD risk. In many countries there is a lack of information on NTD rates. Red cell folate status in women of childbearing age may be a surrogate for NTD rates and may be helpful in identifying countries or regions most likely to benefit from improved folate status. To predict NTD rates using red cell folate concentrations in women of childbearing age living in three Asian cities Design: Cross-sectional convenience samples of non-pregnant women living in Beijing (n=220), Kuala Lumpur (n=389), and Jakarta (n=129). Red cell folate concentrations were highest (p<0.001) in women from Jakarta at 872 nmol/L (95% CI; 833, 910) followed by Kuala Lumpur at 674 nmol/L (95% CI: 644, 704) and lowest in Beijing at 563 nmol/L (95% CI: 524, 601). Accordingly, predicted NTD rates were highest in Beijing at 30/10000 (95% CI: 27, 33), followed by Kuala Lumpur at 24/10000 (95% CI: 22, 25), and lowest in Jakarta at 15/10000 (95% CI: 14,15). Our red blood cell folate data suggests that of the three cities improving the folate status of women in Beijing would have the greatest impact on NTD rates.

Bringing clarity to the role of MTHFR variants in neural tube defect prevention

Background/Objectives: Gestational diabetes mellitus (GDM) prevalence in Australia has increased from 5.6% (2010) to 19.3% (2022), coinciding with the introduction of mandatory folic acid (FA) food fortification and increased supplementation. Animal studies show that high FA intake in pregnancy impairs maternal glucose regulation, but the underlying mechanisms are unknown. We investigated whether fortification has altered maternal folate status to increase GDM risk, and whether key hormones that regulate maternal glucose homeostasis are affected following FA fortification. Methods: Serum folate, red cell folate (RCF), prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early pregnancy samples from women enrolled in prospective cohorts: SCOPE (N = 1164; pre-fortification) and STOP (N = 1300; post-fortification). Associations with GDM were assessed. Results: Compared to pre-fortification, women post-fortification had a higher GDM incidence (5.0% vs. 15.2%), serum folate (↑ 18%), RCF (↑ 259%), hPL (↑ 29%), and GH2 (↑ 13%) concentrations. RCF concentrations above the clinical reference range were found in 57.6% of women post-fortification. Causal mediation analysis suggests that higher RCF contributed to increased GDM risk. Women with RCF excess had 48% more GDM cases, and higher PRL (↑ 24.2%) and hPL (↑ 12.7%) levels compared to those within the reference range. Conclusions: Maternal folate excess is likely contributing to the rising prevalence of GDM in Australia. These findings highlight the need to evaluate excess FA/folate safety in pregnancy, particularly in countries with mandatory fortification. Placental hormones may represent a mechanistic link between excess folate and GDM, warranting further investigation.

An Ontario-wide study of vitamin B12, serum folate, and red cell folate levels in relation to plasma homocysteine: is a preventable public health issue on the rise?

Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999–2000

Consumption of Folic Acid–Fortified Bread Improves Folate Status in Women of Reproductive Age in Chile

Three quarters of neural tube defects (NTD) can be prevented by sufficient dietary folate supplementation. Despite this knowledge, most women do not supplement their diet effectively. Red cell folate concentrations correlate with the risk of NTD, and levels of less than 900 nM are associated with an increased risk of these serious congenital anomalies. Laboratory tests to assess anemia include testing for folate. This study was conducted to estimate the potential benefits of informing women of reproductive age who are unaware of their low folate levels, uncovered in their anemia tests. The number of Ontario women of reproductive age who undergo folate tests and are at an increased risk of NTD was calculated. In addition, the authors calculated the number of NTD cases that could have been prevented if these women were informed of the possible consequences of their low folate levels should they become pregnant. In 1998, red cell folate concentrations were measured in 23,109 women of childbearing age (15-45 y). Approximately half of the women [n = 11,392 (49.3%)] had folate levels below 900 nM and thus were at an increased risk of giving birth to a child with NTD should they have become pregnant. Their overall mean relative risk (RR) of NTD was 1.95, or 1:512 births. If they would have been informed of this risk and subsequently increased their consumption of folate before becoming pregnant, 22.3 cases of NTD per year could have possibly been prevented at no extra cost, since the folic acid results were a part of investigational blood tests performed for another reason (anemia). Women of reproductive age who are being evaluated for the cause of anemia and have low red cell folate results constitute a high-risk group for NTD in their children. These women should be informed of the increased risk and of methods of dietary folate supplementation.

Folate levels in pregnant women who smoke: An important gene/environment interaction

Folate Status of Young Canadian Women after Folic Acid Fortification of Grain Products

Influencia de factores bioquímicos y genéticos en las concentraciones de homocisteína

Plasma and red blood cell folate concentrations (L. casei-activity) have been studied at term in 166 infants born after normal pregnancies, and in 139 of their mothers. Iron (but not folic acid) supplementation was given during pregnancy. The mothers did not develop folate deficiency during pregnancy as judged from their plasma and red blood cell folate concentrations and peripheral red blood cell pictures. A positive correlation was observed between the red cell folate concentrations in the mothers and the birth weights of the infants (r = 0.18, n = 136, p less than 0.05). A positive correlation was also observed between the red cell folate concentrations of the infants and the birth weights and lengths (r = 0.16, n = 147, p less than 0.05 and r = 0.22, n = 147, p less than 0.01, respectively). The present evidence is insufficient to settle whether these correlations are causal. Hematological parameters in the mothers were correlated to those of the infants. The results suggest a relationship between the maternal and infant erythropoiesis.

Plasma and red cell folate values in newborn infants and their mothers in relation to gestational age

Folic acid fortification has been introduced in several countries to reduce the incidence of neural tube defects. However, it could mask the hematologic signs of vitamin B12 deficiency. L‐5‐methyltetrahydrofolic acid (MTHF), which is unlikely to mask vitamin B12 deficiency, may be a safer fortificant, but is not stable in most food matrices. Microencapsulation of MTHF with antioxidant sodium ascorbate is an effective means of preventing loss during baking and storage. The aim of the study was to investigate the bioavailability of microencapsulated MTHF in bread in a 16‐wk, double‐blind, randomized placebo trial. Healthy volunteers 18–45 y (n=45) were randomly assigned to bread containing MTHF (452 μg), folic acid (400 μg) or placebo. Fasting blood was analyzed for red cell and plasma folate concentrations at baseline, 8, and 16 wks. At 16 wk, after adjustment for baseline concentrations, mean (95% CI) red cell folate was 572 (341, 804) and 428 (200, 656) nmol/L higher in the MTHF (P&lt;0.001) and folic acid (P=0.002) groups, respectively, than in the placebo group. Mean plasma folate was 28 (15, 41) and 26 (13, 39) nmol/L higher in the MTHF (P&lt;0.001) and folic acid (P=0.01) groups, respectively, than in the placebo group. In conclusion, bread fortified with MTHF was at least as effective as folic acid in raising red cell and plasma folate concentrations in this population. (Supported by the Advanced Food Materials Network)

The recent advent of fortifying grain products with folic acid is expected to provide an average added daily intake of 100 μg. The present study attempted to estimate the efficacy of this measure by removing a similar amount from the diet of young women choosing to eat folate-fortified food on a regular basis. Twenty-one women who claimed to take fortified foods at least once a week ("consumers") were compared with 30 others ("nonconsumers"). None of the women were pregnant or planning a pregnancy. The participants were instructed to replace fortified foods with equivalent amounts of isoenergetic, unfortified foods for 12 weeks. Consumers had significantly higher total folate intakes than nonconsumers (265 vs. 197 μg/d) and higher red blood cell folate concentrations (403 vs. 342 μg/liter). Excluding folate-fortified foods led to significant reductions in average total folate intake and red cell folate levels in consumers but not in nonconsumers. Serum folate levels did not differ significantly in the two groups. These findings seem to indicate that providing an extra 100 μg of folate per day will significantly improve red cell folate status in women and that fortified foods are an effective way of doing this. Hopefully, a substantial reduction in neural tube defects will result. Am J Clin Nutr 1999;70:234–239

Neural tube defects and folic acid in Japan: Prologue introduction ‐ Understanding of the current status of Japan and the proposal from Japanese Teratology Society