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
Lisa N Yelland,
Shalem Leemaqz,
Jennifer A Hutcheon,
Kaitlyn L I Samson,
Su Peng Loh,
Geok Lin Khor,
Zalilah Mohd Shariff,
Maria Makrides,
Dian C Sulistyoningrum,
Jessica J Yu,
Marion L Roche,
Luz Maria De-Regil,
Tim J Green,
Crystal D Karakochuk
Affiliations
Lisa N Yelland
SAHMRI Women and Kids, South Australia Health and Medical Research Institute, Adelaide, South Australia, Australia
Shalem Leemaqz
SAHMRI Women and Kids, South Australia Health and Medical Research Institute, Adelaide, South Australia, Australia
Jennifer A Hutcheon
Healthy Starts, British Columbia Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
Kaitlyn L I Samson
Food, Nutrition, and Health, The University of British Columbia, Vancouver, British Columbia, Canada
Su Peng Loh
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
Geok Lin Khor
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
Zalilah Mohd Shariff
3 Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
Maria Makrides
SAHMRI Women and Kids, South Australia Health and Medical Research Institute, Adelaide, South Australia, Australia
Dian C Sulistyoningrum
SAHMRI Women and Kids, South Australia Health and Medical Research Institute, Adelaide, South Australia, Australia
Jessica J Yu
1 Food, Nutrition, and Health, University of British Columbia, Vancouver, British Columbia, Canada
Marion L Roche
Nutrition International, Ottawa, Ontario, Canada
Luz Maria De-Regil
8 Global Technical Services, Nutrition International, Ottawa, Ontario, Canada
Tim J Green
5 SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
Crystal D Karakochuk
Food, Nutrition, and Health, The University of British Columbia, Vancouver, British Columbia, Canada
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.
