scholarly journals Effect of once weekly folic acid supplementation on erythrocyte folate concentrations in women to determine potential to prevent neural tube defects: a randomised controlled dose-finding trial in Malaysia

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e034598
Author(s):  
Kaitlyn L I Samson ◽  
Su Peng Loh ◽  
Geok Lin Khor ◽  
Zalilah Mohd Shariff ◽  
Lisa N Yelland ◽  
...  
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Controlled Trial ◽  
Folic Acid Supplementation ◽  
Dose Finding ◽  
Baseline Measure ◽  
Intention To Treat ◽  
Erythrocyte Folate ◽  
Randomised Controlled

IntroductionFolic acid (0.4 mg) taken prior to and during early pregnancy reduces the risk of neural tube defects (NTDs). Because these birth defects occur early in pregnancy, before women may know they are pregnant, many countries have mandated the addition of folic acid to food staples. In countries where fortification is not possible, and weekly iron folic acid programmes exist to reduce anaemia, the WHO recommends that 2.8 mg (7×0.4 mg) folic acid be given instead of the current weekly practice of 0.4 mg. Currently, there is a lack of evidence to support if the 2.8 mg folic acid per week dose is sufficient to raise erythrocyte folate concentrations to a level associated with a reduced risk of a NTD-affected pregnancy. We aim to conduct a three-arm randomised controlled trial to determine the effect of weekly folic acid with iron on erythrocyte folate, a biomarker of NTD risk.Methods and analysisWe will recruit non-pregnant women (n=300; 18–45 years) from Selangor, Malaysia. Women will be randomised to receive either 2.8, 0.4 or 0.0 (placebo) mg folic acid with 60 mg iron weekly for 16 weeks, followed by a 4-week washout period. The primary outcome will be erythrocyte folate concentration at 16 weeks and the mean concentration will be compared between randomised treatment groups (intention-to-treat) using a linear regression model adjusting for the baseline measure.Ethics and disseminationEthical approval was obtained from the University of British Columbia (H18-00768) and Universiti Putra Malaysia (JKEUPM-2018-255). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals.Trial registration numbersACTRN12619000818134 and NMRR-19-119-45736.

scholarly journals Study protocol for a randomised controlled trial evaluating the effect of folic acid supplementation beyond the first trimester on maternal plasma unmetabolised folic acid in late gestation

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040416
Author(s):  
Dian Sulistyoningrum ◽  
Tim Green ◽  
Debbie Palmer ◽  
Thomas Sullivan ◽  
Simon Wood ◽  
...  
Keyword(s):  
Folic Acid ◽  
Randomised Controlled Trial ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Controlled Trial ◽  
Folic Acid Supplementation ◽  
Autism Spectrum ◽  
Late Gestation ◽  
Acid Supplementation ◽  
Randomised Controlled

IntroductionTaking folic acid containing supplements prior to and during early pregnancy reduces the risk of neural tube defects. Neural tube defects occur prior to 28 days postconception, after which, there is no proven benefit of continuing to take folic acid. However, many women continue to take folic acid containing supplements throughout the pregnancy. At higher intakes, folic acid is not converted to its active form and accumulates in circulation as unmetabolised folic acid (UMFA). Recently, concerns have been raised about possible links between late gestation folic acid supplementation and childhood allergy, metabolic disease and autism spectrum disorders. We aim to determine if removing folic acid from prenatal micronutrient supplements after 12 weeks gestation reduces circulating levels of maternal UMFA at 36 weeks gestation.Methods and analysisThis is a parallel-design, double-blinded randomised controlled trial. Women ≥12 and <16 weeks’ gestation with a singleton pregnancy and able to give informed consent are eligible to participate. Women (n=100; 50 per group) will be randomised to receive either a micronutrient supplement containing 0.8 mg of folic acid or a micronutrient supplement without folic acid daily from enrolment until delivery. The primary outcome is plasma UMFA concentration at 36 weeks gestation. Secondary outcomes include red blood cell folate and total plasma folate concentration. We will assess whether there is a difference in mean UMFA levels at 36 weeks gestation between groups using linear regression with adjustment for baseline UMFA levels and gestational age at trial entry. The treatment effect will be described as a mean difference with 95% CI.Ethics and disseminationEthical approval has been granted from the Women’s and Children’s Health Network Research Ethics Committee (HREC/19/WCHN/018). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals.Trial registration numberACTRN12619001511123.

scholarly journals Weekly iron–folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia

2020 ◽  
Vol 5 (12) ◽  
pp. e003897
Author(s):  
Kaitlyn L I Samson ◽  
Su Peng Loh ◽  
Siew Siew Lee ◽  
Dian C Sulistyoningrum ◽  
Geok Lin Khor ◽  
...  
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Controlled Trial ◽  
Clinical Trial Registry ◽  
Double Blind ◽  
Folic Acid Supplements ◽  
Registration Number ◽  
Menstruating Women ◽  
Iron Folic Acid ◽  
Randomised Controlled

IntroductionWeekly iron–folic acid (IFA) supplements are recommended for all menstruating women in countries where anaemia prevalence is >20%. Anaemia caused by folate deficiency is low worldwide, and the need to include folic acid is in question. Including folic acid might reduce the risk of a neural tube defect (NTD) should a woman become pregnant. Most weekly supplements contain 0.4 mg folic acid; however, WHO recommends 2.8 mg because it is seven times the daily dose effective in reducing NTDs. There is a reluctance to switch to supplements containing 2.8 mg of folic acid because of a lack of evidence that this dose would prevent NTDs. Our aim was to investigate the effect of two doses of folic acid, compared with placebo, on red blood cell (RBC) folate, a biomarker of NTD risk.MethodsWe conducted a three-arm double-blind efficacy trial in Malaysia. Non-pregnant women (n=331) were randomised to receive 60 mg iron and either 0, 0.4, or 2.8 mg folic acid once weekly for 16 weeks.ResultsAt 16 weeks, women receiving 0.4 mg and 2.8 mg folic acid per week had a higher mean RBC folate than those receiving 0 mg (mean difference (95% CI) 84 (54 to 113) and 355 (316 to 394) nmol/L, respectively). Women receiving 2.8 mg folic acid had a 271 (234 to 309) nmol/L greater mean RBC folate than those receiving 0.4 mg. Moreover, women in the 2.8 mg group were seven times (RR 7.3, 95% CI 3.9 to 13.7; p<0.0001) more likely to achieve an RBC folate >748 nmol/L, a concentration associated with a low risk of NTD, compared with the 0.4 mg group.ConclusionWeekly IFA supplements containing 2.8 mg folic acid increases RBC folate more than those containing 0.4 mg. Increased availability and access to the 2.8 mg formulation is needed.Trail registration numberThis trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12619000818134).

Lower rates of neural tube defects in Israel following folic acid supplementation policy

2020 ◽  
Vol 139 ◽  
pp. 106064
Author(s):  
Annie Reiss ◽  
Matan J. Cohen ◽  
Ehud Kaliner ◽  
Efrat Gabai Kapara ◽  
Amihood Singer ◽  
...  
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Folic Acid Supplementation ◽  
Acid Supplementation
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