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
Introduction Weekly 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 o...
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BMJ Publishing Group
2020-12-01
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| Series: | BMJ Global Health |
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| author | Lisa N Yelland Shalem Leemaqz Jennifer A Hutcheon Kaitlyn L I Samson Su Peng Loh Geok Lin Khor Maria Makrides Dian C Sulistyoningrum Marion L Roche Crystal D Karakochuk Siew Siew Lee Zalilah Binti Mohd Shariff Irmi Zarina Ismai Timothy J Green |
| author_facet | Lisa N Yelland Shalem Leemaqz Jennifer A Hutcheon Kaitlyn L I Samson Su Peng Loh Geok Lin Khor Maria Makrides Dian C Sulistyoningrum Marion L Roche Crystal D Karakochuk Siew Siew Lee Zalilah Binti Mohd Shariff Irmi Zarina Ismai Timothy J Green |
| author_sort | Lisa N Yelland |
| collection | DOAJ |
| description | Introduction Weekly 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.Methods We 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.Results At 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.Conclusion Weekly 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 number This trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12619000818134). |
| format | Article |
| id | doaj-art-9f1eae35ade44538b01bab973188487a |
| institution | OA Journals |
| issn | 2059-7908 |
| language | English |
| publishDate | 2020-12-01 |
| publisher | BMJ Publishing Group |
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| spelling | doaj-art-9f1eae35ade44538b01bab973188487a2025-08-20T02:21:04ZengBMJ Publishing GroupBMJ Global Health2059-79082020-12-0151210.1136/bmjgh-2020-003897Weekly 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 MalaysiaLisa N Yelland0Shalem Leemaqz1Jennifer A Hutcheon2Kaitlyn L I Samson3Su Peng Loh4Geok Lin Khor5Maria Makrides6Dian C Sulistyoningrum7Marion L Roche8Crystal D Karakochuk9Siew Siew Lee10Zalilah Binti Mohd Shariff11Irmi Zarina Ismai12Timothy J Green13School of Public Health, The University of Adelaide, Adelaide, South Australia, AustraliaSouth Australian Health & Medical Research Institute, Adelaide, AustraliaDepartment of Obstetrics and Gynaecology, University of British Columbia and the Children’s and Women’s Health Centre of British Columbia, Vancouver, BC, CanadaFood, Nutrition, and Health, The University of British Columbia, Vancouver, British Columbia, CanadaFaculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaFaculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaSAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, AustraliaSAHMRI Women and Kids, South Australia Health and Medical Research Institute, Adelaide, South Australia, AustraliaNutrition International, Ottawa, Ontario, CanadaDepartment of Food, Nutrition and Health, The University of British Columbia, Vancouver, British Columbia, CanadaFaculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaFaculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaFaculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaSAHMRI Women and Kids, South Australia Health and Medical Research Institute, Adelaide, South Australia, AustraliaIntroduction Weekly 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.Methods We 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.Results At 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.Conclusion Weekly 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 number This trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12619000818134).https://gh.bmj.com/content/5/12/e003897.full |
| spellingShingle | Lisa N Yelland Shalem Leemaqz Jennifer A Hutcheon Kaitlyn L I Samson Su Peng Loh Geok Lin Khor Maria Makrides Dian C Sulistyoningrum Marion L Roche Crystal D Karakochuk Siew Siew Lee Zalilah Binti Mohd Shariff Irmi Zarina Ismai Timothy J Green 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 BMJ Global Health |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://gh.bmj.com/content/5/12/e003897.full |
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