Review of intervention products for use in the prevention and control of anemia.

Anemia remains a major public health problem, especially in low- and middle-income countries. The World Health Organization recommends several interventions to prevent and manage anemia in vulnerable population groups, including young children, menstruating adolescent girls and women, and pregnant and postpartum women. Daily iron supplementation reduces the risk of anemia in infants, children, and pregnant women, and intermittent iron supplementation reduces anemia risk in menstruating girls and women. Micronutrient powders reduce the risk of anemia in children. Fortifying wheat flour with iron reduces the risk of anemia in the overall population, whereas the effect of fortifying maize flour and rice is still uncertain. Regarding non-nutrition-related interventions, malaria treatment and deworming have been reported to decrease anemia prevalence. Promising interventions to prevent anemia include vitamin A supplementation, multiple micronutrient supplementation for pregnant women, small-quantity lipid-based supplements, and fortification of salt with iodine and iron. Future research could address the efficacy and safety of different iron supplementation formulations, identify the most bioavailable form of iron for fortification, examine adherence to supplementation regimens and fortification standards, and investigate the effectiveness of integrating micronutrient, helminth, and malaria control programs.

Critical assessment of the current indicator for antenatal iron-containing supplementation coverage: Insights from a mixed-methods study.

Daily consumption of iron-containing supplements is recommended for all pregnant women but there is no approved global standard indicator for assessing supplementation coverage. Furthermore, the validity of commonly used coverage indicators for iron-containing supplement consumption is questionable. The WHO-UNICEF Technical Expert Advisory Group on Nutrition Monitoring, and partners, have systematically worked to identify a feasible and valid indicator of iron-containing supplement coverage for reporting by countries. In 2019, we conducted key informant interviews with respondents in eight countries, fielded an online survey (in three languages using SurveyMonkey) to which 142 nutrition professionals from 52 countries responded, and used Demographic and Health Surveys (DHS) data from four countries to assess determinants of the quality of iron-containing supplement coverage data. Less than half (45%) of online survey respondents were satisfied with the current methods for collecting iron-containing supplement coverage data in their context. Recommended changes by study respondents include recall period <5 years, adding questions about counselling, including other beneficiary groups, and assessing supply chain functionality. The DHS analysis suggested an association between time since pregnancy and data quality. Data heaping on multiples of 30 was observed in 40%-75% of data. There is a clear demand for a revised indicator and measurement guidance for coverage of iron-containing supplementation during pregnancy. Future research should continue the development and validation of a global indicator, to more precisely validate the quality of recall data, including the distinction between distribution and consumption using various question formulations.

Self-management of iron and folic acid supplementation during pre-pregnancy, pregnancy and postnatal periods: a systematic review.

INTRODUCTION: While the use of folic acid pre-pregnancy and iron and folic acid (IFA) during pregnancy and postnatal have been demonstrated to be effective and are recommended interventions by WHO, ensuring individuals adhere to the supplementation regimen can be a challenge. Self-care interventions that support an individual's ability to promote their own health with or without the support of health workers could help promote the uptake and adherence to supplementation. This systematic review assessed the evidence around self-management of IFA or folic acid supplementation accessed over-the-counter during pre-pregnancy, pregnancy and postnatal periods. METHODS: Peer-reviewed studies were included if they compared self-management of IFA or folic acid supplementation with health worker-initiated supplement use on maternal and/or fetal and newborn health outcomes, end-users' or health workers' values and preferences, or cost and/or cost-effectiveness. We searched PubMed, CINAHL, LILACS and EMBASE for articles published through November 2020, hand-searched clinical trial registries, reviewed databases and contacted experts in the field. Abstract screening and full-text review were conducted independently by two reviewers. RESULTS: Overall, 2344 results were identified, and 28 studies were identified for full-text review. All studies were excluded, as they were not primary research, lacked the outcomes of interest, lacked specificity in supplement type, and/or lacked a comparison group. CONCLUSION: No evidence was identified that distinguishes self-management of folic acid supplements pre-pregnancy and of IFA supplements during pregnancy and postnatal, highlighting a gap in our current understanding of self-care related to dietary supplementation in pregnancy. The findings of this review identify an area for further research to support the current movement towards self-care interventions as an added choice to help individuals more fully attain their reproductive health and rights. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020205548.

Metabolism of Neonatal Vitamin A Supplementation: A Systematic Review.

A systematic review was conducted to summarize the absorption, transport, storage, and metabolism of oral neonatal vitamin A supplementation (NVAS). This review focused specifically on the neonatal period (first 28 d of life for humans) to inform guidance by WHO on recommendations related to NVAS. A systematic search of international and regional databases was conducted. Inclusion criteria were human or animal studies that gave oral vitamin A as a single or limited number of doses to apparently healthy neonates. Studies evaluating fortification or food-based approaches, dosing with retinoic acid, or studies of neonatal models of disease were excluded. The search retrieved 8847 unique records. After screening by title and abstract, 88 were screened using the full text, and 35 records met inclusion criteria: 13 human and 22 animal studies. Studies indicate that high-dose NVAS is absorbed well by neonates, typically mirroring fat absorption. Doses were primarily stored in the liver and transiently increased in the lung, kidney, spleen, adrenal glands, brain, skin, and adipose tissue, generally with a dose-response. Serum retinol and retinyl esters also transiently increased following NVAS. Although minimal acute adverse effects are noted, there is a lack of data supporting NVAS for improving organ maturation or sustained delivery to target organs. Research gaps include the physiological effects of the short-term increase of vitamin A concentrations in extrahepatic tissues, or whether there are unknown adverse effects over time.

Vitamin A Supplementation Programs and Country-Level Evidence of Vitamin A Deficiency.

Vitamin A supplementation (VAS) programs targeted at children aged 6-59 months are implemented in many countries. By improving immune function, vitamin A (VA) reduces mortality associated with measles, diarrhea, and other illnesses. There is currently a debate regarding the relevance of VAS, but amidst the debate, researchers acknowledge that the majority of nationally-representative data on VA status is outdated. To address this data gap and contribute to the debate, we examined data from 82 countries implementing VAS programs, identified other VA programs, and assessed the recentness of national VA deficiency (VAD) data. We found that two-thirds of the countries explored either have no VAD data or data that were >10 years old (i.e., measured before 2006), which included twenty countries with VAS coverage ≥70%. Fifty-one VAS programs were implemented in parallel with at least one other VA intervention, and of these, 27 countries either had no VAD data or data collected in 2005 or earlier. To fill these gaps in VAD data, countries implementing VAS and other VA interventions should measure VA status in children at least every 10 years. At the same time, the coverage of VA interventions can also be measured. We identified three countries that have scaled down VAS, but given the lack of VA deficiency data, this would be a premature undertaking in most countries without appropriate status assessment. While the global debate about VAS is important, more attention should be directed towards individual countries where programmatic decisions are made.

Applying inappropriate cutoffs leads to misinterpretation of folate status in the US population.

BACKGROUND: Folate cutoffs for risk of deficiency compared with possible deficiency were originally derived differently (experimental compared with epidemiologic data), and their interpretations are different. The matching of cutoffs derived from one assay with population-based data derived from another assay requires caution. OBJECTIVE: We assessed the extent of folate-status misinterpretation with the use of inappropriate cutoffs. DESIGN: In the cross-sectional NHANES, serum and red blood cell (RBC) folate were first measured with the use of a radioprotein-binding assay (RPBA) (1988-2006) and, afterwards, with the use of a microbiologic assay (2007-2010). We compared prevalence estimates for assay-matched cutoffs (e.g., with the use of an RPBA cutoff with RPBA data) and assay-mismatched cutoffs (e.g., with the use of microbiologic assay cutoff with RPBA data) for risk of deficiency on the basis of megaloblastic anemia as a hematologic indicator in persons ≥4 y of age (e.g., serum folate concentration <7 nmol/L and RBC folate concentration <305 nmol/L derived with the use of a microbiologic assay), possible deficiency on the basis of rising homocysteine as a metabolic indicator in persons ≥4 y of age (e.g., serum folate concentration <10 nmol/L and RBC folate concentration <340 nmol/L derived with the use of an RPBA), and insufficiency on the basis of elevated risk of neural tube defects in women 12-49 y old (e.g., RBC folate concentration <906 nmol/L derived with the use of a microbiologic assay). RESULTS: Pre-folic acid fortification (1988-1994), risks of deficiency for assay-matched compared with assay-mismatched cutoffs were 5.6% compared with 16% (serum folate), respectively, and 7.4% compared with 28% (RBC folate), respectively; risks declined postfortification (1999-2006) to <1% compared with <1% (serum folate), respectively, and to <1% compared with 2.5% (RBC folate), respectively. Prefortification (1988-1994), risks of possible deficiency for assay-matched compared with assay-mismatched cutoffs were 35% compared with 56% (serum folate), respectively, and 37% compared with 84% (RBC folate), respectively; risks declined postfortification (1999-2006) to 1.9% compared with 7.0% (serum folate), respectively, and to 4.8% compared with 53% (RBC folate), respectively. Postfortification (2007-2010), risks of insufficiency were 3% (assay matched) compared with 39% (assay mismatched), respectively. CONCLUSIONS: The application of assay-mismatched cutoffs leads to a misinterpretation of folate status. This confusion likely applies to clinical assays because no comparability data are available, to our knowledge.

Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines.

Neural tube defects (NTDs) such as spina bifida, anencephaly, and encephalocele are serious birth defects of the brain and spine that occur during the first month of pregnancy when the neural tube fails to close completely. Randomized controlled trials and observational studies have shown that adequate daily consumption of folic acid before and during early pregnancy considerably reduces the risk for NTDs. The U.S. Public Health Service recommends that women capable of becoming pregnant consume 400 µg of folic acid daily for NTD prevention. Furthermore, fortification of staple foods (e.g., wheat flour) with folic acid has decreased folate-sensitive NTD prevalence in multiple settings and is a highly cost-effective intervention.

Five National Cancer Institute-designated cancer centers' data collection on racial/ethnic minority participation in therapeutic trials: a current view and opportunities for improvement.

BACKGROUND: To ensure that National Institutes of Health-funded research is relevant to the population's needs, specific emphasis on proportional representation of minority/sex groups into National Cancer Institute (NCI) cancer centers' clinical research programs is reported to the NCI. METHODS: EMPaCT investigators at 5 regionally diverse comprehensive cancer centers compared data reported to the NCI for their most recent Cancer Center Support Grant competitive renewal to assess and compare the centers' catchment area designations, data definitions, data elements, collection processes, reporting, and performance regarding proportional representation of race/ethnicity and sex subsets. RESULTS: Cancer centers' catchment area definitions differed widely in terms of their cancer patient versus general population specificity, levels of specificity, and geographic coverage. Racial/ethnic categories were similar, yet were defined differently, across institutions. Patients' socioeconomic status and insurance status were inconsistently captured across the 5 centers. CONCLUSIONS: Catchment area definitions and the collection of patient-level demographic factors varied widely across the 5 comprehensive cancer centers. This challenged the assessment of success by cancer centers in accruing representative populations into the cancer research enterprise. Accrual of minorities was less than desired for at least 1 racial/ethnic subcategory at 4 of the 5 centers. Institutions should clearly and consistently declare their primary catchment area and the rationale and should report how race/ethnicity and sex are defined, determined, collected, and reported. More standardized, frequent, consistent collection, reporting, and review of these data are recommended, as is a commitment to collecting socioeconomic data, given that socioeconomic status is a primary driver of cancer disparities in the United States.

Translating research into action: WHO evidence-informed guidelines for safe and effective micronutrient interventions.

In 2009 WHO adopted a new process by which recommendations for safe and effective micronutrient interventions are developed, ensuring the use of best practices and available evidence. This process includes nine steps ranging from establishing steering and guideline groups and prioritizing needs to planning the implementation and updating the guidelines. Systematic reviews of evidence are used to address critical outcomes for decision making, considering the balance among risks and benefits, values, preferences, and costs. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology is used to assess the overall evidence quality and establish the strength of the recommendations. Guideline development is underway for interventions covering iron and vitamin A supplementation, home fortification with multiple micronutrient powders, and fortification of staple foods. Global guidelines are disseminated through the WHO electronic Library of Evidence for Nutrition Actions, a resource of the evidence and tools for scaling-up micronutrient interventions. The WHO Department of Nutrition for Health and Development and the Evidence-Informed Policy Network will support countries to scale-up the delivery of micronutrient interventions by adapting these evidence-informed guidelines and policies to make them context specific. This will be accomplished by providing summaries of the best available evidence on micronutrient interventions, evidence on health systems, and effective delivery systems along with capturing the tacit knowledge of the countries' realities. With a systematic approach that uses the WHO strategy on research for health as the connecting thread, the challenges to successfully implement safe and effective micronutrient programs can be addressed.

Vitamin A deficiency in a newborn resulting from maternal hypovitaminosis A after biliopancreatic diversion for the treatment of morbid obesity.

BACKGROUND: Biliopancreatic diversion (BPD) has been advocated for the treatment of morbid obesity. This procedure has the theoretical advantage that patients retain normal eating capacity and lose weight irrespective of their eating habits. However, vitamin deficiencies may develop because BPD causes malabsorption. OBJECTIVE: This report describes a 40-y-old mother and her newborn infant, who developed vitamin A deficiency as a result of iatrogenic maternal malabsorption after BPD. Our primary objective is to show that BPD patients need close follow-up and lifelong micronutrient supplementation to prevent nutrient deficiencies in themselves and their offspring. DESIGN: The medical records of the mother and infant were reviewed, and their clinical course was followed until 10 mo postpartum. The mother was also interviewed on several occasions about her medical care, follow-up, and supplemental vitamin use. RESULTS: The mother developed night blindness with undetectable serum vitamin A concentrations in the third trimester of her pregnancy. Her vitamin A deficiency was untreated until she delivered her infant. At delivery, the infant also had vitamin A deficiency. He may have permanent retinal damage, but this is still unclear because the ophthalmologic examination performed at 2 mo of age was inconclusive. CONCLUSIONS: Complications of BPD may take many years to develop, and the signs and symptoms may be subtle. Because of the malabsorption that results from BPD, patients need lifelong follow-up and appropriate vitamin supplementation to prevent deficiencies. These nutrient deficiencies can also affect the offspring of female BPD patients.