TY - JOUR
T1 - Folate and global health umbrella review series, part 1
T2 - methodological framework and syntheses on anaemia and neural tube defects
AU - Yoo, Samantha
AU - Montazeri, Azita
AU - Bennett, Derrick
AU - Bo, Yacong
AU - Chen, Peizhan
AU - Duthie, Susan
AU - Jensen, Natalie
AU - Kaminga, Atipatsa
AU - Lai, Jun-Shi
AU - Li, Xue
AU - MacFarlane, Amanda J
AU - Martinez, Homero
AU - McNulty, Helene
AU - Momoli, Franco
AU - Mossey, Peter
AU - Mullie, Patrick
AU - Munger, Ron
AU - Parajuli, Rajendra Prasad
AU - Kent, Monique Potvin
AU - Rubini, Michele
AU - Senekal, Marjanne
AU - Sikora, Lindsey
AU - Stintzi, Alain
AU - Theodoratou, Evropi
AU - Wang, Hui
AU - Yajnik, Chittaranjan
AU - Yaktine, Ann
AU - Little, Julian
N1 - © 2026 The Author(s)
PY - 2026/1/30
Y1 - 2026/1/30
N2 - BACKGROUND: Folate is essential for normal growth and in human health throughout the lifecycle. Clinical deficiency of folate impairs DNA synthesis and results in megaloblastic anaemia, while suboptimal folate status before and in early pregnancy results in an elevated risk of neural tube defects (NTD). The evidence on the association of folate status with other health outcomes is largely fragmented and understudied. We conducted a series of umbrella reviews examining the association between folate and multiple health outcomes in various populations and settings.METHODS: We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and DARE from inception to February 2024 for systematic reviews with or without meta-analyses examining an association between folate intake/status and any health outcome. We performed screening and data extraction in duplicate and assessed the risk of bias using the ROBIS tool. Evidence was then characterised into unique associations (unique exposure measure - unique outcome measure - unique setting). For each category of unique associations, we identified the evidence based on the statistical power, recency of publication and the potential risk of bias. All unique associations were evaluated for credibility using predefined criteria.RESULTS: We retrieved 3565 records and included 283 in the final synthesis. The evidence on anaemia consisted of four intervention trials demonstrating effectiveness of folic acid supplementation during pregnancy in reducing the risk of megaloblastic anaemia (relative risk (RR) = 0.21; 95% CI = 0.11, 0.38; I2 = 15%). Maternal folic acid use was also significantly inversely related to the prevention of NTD at birth (RR = 0.31; 95% CI = 0.16, 0.60; I2 = 0%) and NTD recurrence (RR = 0.30; 95% CI = 0.14, 0.65; I2 = 0%). This relationship was supported by the inverse association reported between low maternal blood folate concentrations and the increased risk of NTD. Further evidence showed that fortification of food with folic acid was associated with the lower prevalence of NTD on a population-level.CONCLUSION: In NTDs and anaemia, we identified strong evidence supporting the protective role of folate status based on intervention trials and observational studies. More recent reviews examining the role of folate in other less well understood health conditions will be presented in the subsequent reports.REGISTRATION: PROSPERO: CRD42021265041.
AB - BACKGROUND: Folate is essential for normal growth and in human health throughout the lifecycle. Clinical deficiency of folate impairs DNA synthesis and results in megaloblastic anaemia, while suboptimal folate status before and in early pregnancy results in an elevated risk of neural tube defects (NTD). The evidence on the association of folate status with other health outcomes is largely fragmented and understudied. We conducted a series of umbrella reviews examining the association between folate and multiple health outcomes in various populations and settings.METHODS: We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and DARE from inception to February 2024 for systematic reviews with or without meta-analyses examining an association between folate intake/status and any health outcome. We performed screening and data extraction in duplicate and assessed the risk of bias using the ROBIS tool. Evidence was then characterised into unique associations (unique exposure measure - unique outcome measure - unique setting). For each category of unique associations, we identified the evidence based on the statistical power, recency of publication and the potential risk of bias. All unique associations were evaluated for credibility using predefined criteria.RESULTS: We retrieved 3565 records and included 283 in the final synthesis. The evidence on anaemia consisted of four intervention trials demonstrating effectiveness of folic acid supplementation during pregnancy in reducing the risk of megaloblastic anaemia (relative risk (RR) = 0.21; 95% CI = 0.11, 0.38; I2 = 15%). Maternal folic acid use was also significantly inversely related to the prevention of NTD at birth (RR = 0.31; 95% CI = 0.16, 0.60; I2 = 0%) and NTD recurrence (RR = 0.30; 95% CI = 0.14, 0.65; I2 = 0%). This relationship was supported by the inverse association reported between low maternal blood folate concentrations and the increased risk of NTD. Further evidence showed that fortification of food with folic acid was associated with the lower prevalence of NTD on a population-level.CONCLUSION: In NTDs and anaemia, we identified strong evidence supporting the protective role of folate status based on intervention trials and observational studies. More recent reviews examining the role of folate in other less well understood health conditions will be presented in the subsequent reports.REGISTRATION: PROSPERO: CRD42021265041.
KW - Humans
KW - Neural Tube Defects/epidemiology
KW - Folic Acid/administration & dosage
KW - Global Health
KW - Female
KW - Pregnancy
KW - Anemia/epidemiology
KW - Systematic Reviews as Topic
KW - Folic Acid Deficiency
KW - Dietary Supplements
U2 - 10.7189/jogh.16.04014
DO - 10.7189/jogh.16.04014
M3 - Article
C2 - 41612855
SN - 2047-2978
VL - 16
JO - Journal of Global Health
JF - Journal of Global Health
M1 - 04014
ER -
