Global folate status in women of reproductive age: a systematic review with emphasis on methodological issues

Abstract

Inadequate folate status in women of reproductive age (WRA) can lead to adverse health consequences of public health significance, such as megaloblastic anemia (folate deficiency) and an increased risk of neural tube defect (NTD)-affected pregnancies (folate insufficiency). Our review aims to evaluate current data on folate status of WRA. We queried eight databases and the World Health Organization Micronutrients Database, identifying 45 relevant surveys conducted between 2000 and 2014 in 39 countries. Several types of folate assays were used in the analysis of blood folate, and many surveys used folate cutoffs not matched to the assay. To allow better comparisons across surveys, we attempted to account for these differences. The prevalence of folate deficiency was >20% in many countries with lower income economies but was typically <5% in countries with higher income economies. Only 11 surveys reported the prevalence of folate insufficiency, which was >40% in most countries. Overall, folate status data for WRA globally are limited and must be carefully interpreted due to methodological issues. Future surveys would benefit from using the microbiologic assay to assess folate status, along with assay-matched cutoffs to improve monitoring and evaluation of folic acid interventions, thus informing global efforts to prevent NTDs.

Keywords: folate; global; methodological issues; status; women.

Figure 1

Study flow diagram.

Figure 2

The reported prevalence of folate deficiency in women of reproductive age by the survey, indicating an interpretation of the prevalence estimate based on the assay and cutoff used in the survey. An assay factor, or the extent to which one assay measures higher or lower than another, was calculated as the ratio of the survey assay's results to the CDC MBA_C. Similarly, a cutoff factor was calculated as the ratio of the survey cutoff to the MBA_C cutoff. A prevalence factor (assay factor divided by cutoff factor) was calculated to estimate whether the reported prevalence estimates are likely correct (prevalence factor >0.85 and <1.15) or may represent an under‐ (prevalence factor ≥1.15) or overestimation (prevalence factor ≤0.85). Gray bars indicate serum/plasma folate and black bars indicate RBC folate. Prevalence estimates reported as <1% (or 0%) are shown as 1%. For two surveys (New Zealand 2008–200975 and the Philippines 200851), the interpretation of the reported prevalence was different for serum and RBC folate; thus, results by sample type are listed separately in the appropriate category. Surveys that did not report a prevalence for folate deficiency (n = 5) are not shown. CDC, the Centers for Disease Control and Prevention; MBA_C, contemporary microbiologic assay. The abbreviation after each survey indicates the economy: E1, low‐income; E2, lower‐middle‐income; E3, upper‐middle‐income; E4, high‐income.

Figure 3

The reported prevalence of folate insufficiency, based on red blood cell folate concentrations, in women of reproductive age by the survey, indicating an interpretation of the prevalence estimate based on the assay and cutoff used in the survey. An assay factor, or the extent to which one assay measures higher or lower than another, was calculated as the ratio of the survey assay's results to the CDC MBA_C. Similarly, a cutoff factor was calculated as the ratio of the survey cutoff to the MBA_C cutoff. A prevalence factor (assay factor divided by cutoff factor) was calculated to estimate whether the reported prevalence estimates are likely correct (prevalence factor >0.85 and <1.15) or may represent an under‐ (prevalence factor ≥1.15) or overestimation (prevalence factor ≤0.85). Prevalence estimates reported as <1% (or 0%) are shown as 1%. Surveys that did not report a prevalence of folate insufficiency (n = 34) are not shown. CDC, the Centers for Disease Control and Prevention; MBA_C, contemporary microbiologic assay. The abbreviation after each survey indicates the economy: E1, low‐income; E2, lower‐middle‐income; E3, upper‐middle‐income; E4, high‐income.