Using meta-research methods to examine the inclusion of women, pregnant women, and women-specific health outcomes in studies that contributed to the dietary reference intakes for one-carbon metabolism micronutrients

Purpose: Maternal micronutrient deficiencies occurring during periconceptional, pregnancy, and postpartum periods are a leading cause of adverse pregnancy outcomes globally. The Dietary Reference Intakes (DRIs) are a set of reference values used to assess and guide nutrient intakes of healthy individuals. However, the current DRIs for pregnancy and lactation may be limited in their methods and included populations. The present study analyzed the current DRIs for their inclusion of pregnant women and geographic representativeness. Methods: Meta-research methods were applied to the DRI report for vitamins B6, B12, folate, and choline in four steps: search, screening, full-text data extraction, and data analysis. For each target micronutrient, sections that contributed data to setting the average requirement were focused on, “Selection of Indicators for Estimating the Requirement,” “Findings by Life Stage and Gender Group,” and “Tolerable Upper Intake Limit” for adults, pregnancy, and lactation sub-sections. Screening involved reviewing the reference list to determine whether a reference directly contributed to setting the DRI. Full-text data extraction of primary data was conducted in areas of: 1) administrative information; 2) study methods; 3) human population characteristics; and 4) non-human subjects. Descriptive analyses were performed to describe the inclusion of women, pregnant women, geographic patterns, and demographic diversity. Results: For Vitamin B12, 100% of indicator studies and 71% of life stages studies included women, with a total of 3,246 women participants. However, none of the indicator studies and 15% of life stages studies included pregnant women, with a total of 556 pregnant women participants. None of the indicator studies and 8% of life stages studies reported health measurements specific to women, pregnancy, or lactation. Geographically, 54% of studies were conducted in the United States, and 18% took place in low-and middle-income countries. Data analysis is ongoing for the remaining micronutrients. Conclusions: Preliminary findings indicate that the body of evidence informing the current DRIs are limited in their inclusion of women and pregnant women. Numerous adverse pregnancy and birth outcomes are preventable through optimal maternal nutrition. Therefore, it is critical to ensure that the DRIs are suitable for their intended population. Despite their original intent for use in North America, the DRIs are widely adopted globally. Thus, geographic representation of the studies underlying the DRIs have implications for generalizability

Limited data exist to inform our basic understanding of micronutrient requirements in pregnancy.

Women and pregnant people have historically been underrepresented in research; this may extend to the basic research informing nutrient reference values, such as the United States’ and Canada’s Dietary Reference Intakes (DRIs). After screening the DRI reports for 23 micronutrients, we extracted metadata from 704 studies. Women were excluded in 23% of studies, and they accounted for a smaller proportion of the sample size (29%). Pregnant or lactating people were included in 17% of the studies. Studies that used rigorous design elements, such as controlled feeding and stable isotope studies, were the most likely to include men only. The majority of studies (>90%) did not report race and ethnicity. Although nutrient reference values are intended for use in the general population, we find that the basic science informing these values may not be generalizable. We call urgently upon funders and researchers to address fundamental gaps in knowledge with high-quality research