Folate and vitamin B12 status and predicted neural tube defects risk among nonpregnant women of reproductive age from the Malawi National Micronutrient Survey, 2015-2016.

BACKGROUND: Maternal folate and vitamin B12 deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B12 status among women of reproductive age (WRA) in Malawi. OBJECTIVE: We assessed folate and vitamin B12 status among nonpregnant WRA in Malawi and predicted the risk of folate-sensitive neural tube defects (NTDs) were they to become pregnant. METHODS: Using data from the cross-sectional, nationally representative 2015-2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15-49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design. RESULTS: Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The proportion of vitamin B12 deficiency (<148 pmol/L) and insufficiency (≤221 pmol/L) was 11.8% (8.6, 16.0) and 40.6% (34.1, 47.4), respectively. RBC folate insufficiency (<748 nmol/L, defined as the concentration associated with the threshold for elevated NTD risk: >8 cases per 10,000 births) was widespread: 81.4% (75.0, 86.4). The predicted NTD risk nationally was 24.7 cases per 10,000 live births. RBC folate insufficiency and higher predicted NTD risk were more common among WRA living in urban areas or with higher education. CONCLUSIONS: These findings highlight the importance of nutritional and NTD surveillance in Malawi and the opportunity for improving folate and vitamin B12 nutrition among Malawian WRA.

Vitamin A biomarkers were associated with α(1)-acid glycoprotein and C-reactive protein over the course of a human norovirus challenge infection.

Retinol binding protein (RBP) is used as a proxy for retinol in population-based assessments of vitamin A deficiency (VAD) for cost-effectiveness and feasibility. When the cut-off of < 0·7 µmol/l for retinol is applied to RBP to define VAD, an equivalence of the two biomarkers is assumed. Evidence suggests that the relationship between retinol and RBP is not 1:1, particularly in populations with a high burden of infection or inflammation. The goal of this analysis was to longitudinally evaluate the retinol:RBP ratio over 1 month of follow-up among fifty-two individuals exposed to norovirus (n 26 infected, n 26 uninfected), test whether inflammation (measured as α-1-acid glycoprotein (AGP) and C-reactive protein (CRP)) affects retinol, RBP and the ratio between the two and assess whether adjusting vitamin A biomarkers for AGP or CRP improves the equivalence of retinol and RBP. We found that the median molar ratio between retinol and RBP was the same among infected (0·68) and uninfected (0·68) individuals. AGP was associated with the ratio and RBP individually, controlling for CRP, and CRP was associated with both retinol and RBP individually, controlling for AGP over 1 month of follow-up. Adjusting for inflammation led to a slight increase in the ratio among infected individuals (0·71) but remained significantly different from the expected value of one. These findings highlight the need for updated recommendations from the WHO on a cut-off value for RBP and an appropriate method for measuring and adjusting for inflammation when using RBP in population assessments of VAD.

Improving Anemia Assessment in Clinical and Public Health Settings.

We aim to provide a practical approach to assess anemia and its primary causes, both in clinical settings and in the context of public health programs. Anemia remains a global challenge; thus, to achieve goals for anemia reduction and assess progress, standardized approaches are required for the assessment of anemia and its causes. We first provide a brief review of how to assess anemia, based on hemoglobin concentrations and cutoffs that correspond to age, sex, and physiologic status. Next, we discuss how to assess the likely causes of anemia in different settings. The causes of anemia are classified as non-nutritional (for example, because of infection, inflammation, blood loss, or genetic disorders) or nutrition-specific (for example, because of deficiencies of iron, vitamin A, riboflavin, vitamin B12, or folate). There is an important overlap between these 2 categories, such as the increased likelihood of iron deficiency in the context of inflammation. Given the multifaceted nature of anemia etiology, we introduce a framework for anemia assessment based on the "ecology of anemia," which recognizes its many overlapping causes. This conceptual framework is meant to inform what data on anemia causes may need to be collected in population surveys. The framework has a supporting table with information on the diagnostic tests, biomarkers and proposed cutoffs, characteristics, and feasibility of collecting the myriad information that can help elucidate the anemia etiology. We also provide examples of how this framework can be applied to interpret the anemia risk factor data from population-based surveys that can inform decisions about context-specific interventions. Finally, we present research gaps and priorities related to anemia assessment.

Design, Methods, and Select Baseline Results from a School Nutrition Project for Adolescents in Bangladesh.

Background: The School Nutrition for Adolescents Project (SNAP) provided weekly iron and folic acid (WIFA) supplementation and menstrual hygiene management (MHM) support for girls; actions to improve water, sanitation, and hygiene (WASH) practices; and behavior change interventions to adolescents aged 10-19 y in 65 intervention schools in 2 districts of Bangladesh. Objectives: We aimed to describe the project design and select baseline results of students and school project implementers. Methods: Girls (n = 2244) and boys (n = 773) in 74 schools (clusters) and project implementers [headteachers (n = 74), teachers (n = 96), and student leaders (n = 91)] participated in a survey assessing nutrition, MHM, and WASH knowledge and experience. Hemoglobin, inflammation-adjusted ferritin, retinol-binding protein, and serum and RBC folate (RBCF) levels in girls were measured. School WASH infrastructure was observed and drinking water was tested for E. coli. Results: IFA and deworming tablet intake in the last 1 and 6 mo were 4% and 81% for girls and 1% and 86%, respectively. Applying the Minimum Dietary Diversity for Women (MDD-W) tool, most (63%-68%) girls and boys achieved minimum dietary diversity. Fewer adolescents (14%-52%) had ever heard of anemia, IFA tablets, or worm infestation than project implementers (47%-100%). Girls (35%) missed school during menstruation; 39% reported of ever leaving school due to unexpected menstruation. The micronutrient status and deficiency severity varied: anemia (25%), RBCF insufficiency (76%), risk of serum folate deficiency (10%), deficiencies of iron (9%), and vitamin A (3%). WASH in school sustainable development goal (SDG) indicators achievement varied: basic drinking water service (70%), basic sanitation service (42%), and basic hygiene service (3%); 59% of sampled drinking water access points complied with WHO E. coli standards. Conclusions: There is room for improvement of nutrition and health awareness, practices, micronutrient status, SDG basic WASH in-school services, and E coli contamination in school drinking water.This trial was registered in clinicaltrials.gov as NCT05455073.

Association between Hemoglobin and Elevation among School-aged Children: A Verification of Proposed Adjustments.

BACKGROUND: Anemia is defined by a hemoglobin (Hb) concentration lower than normal based on cutoffs specific to age, sex, and pregnancy status. Hb increases with elevation as an adaptive response to lower blood oxygen saturation, thus, adjusting Hb concentrations for elevation is necessary before applying cutoffs. OBJECTIVES: Recent evidence among preschool-aged children (PSC) and nonpregnant reproductive-aged women (WRA) suggests that current World Health Organization (WHO)-recommended Hb adjustments for elevation need updating. To confirm these findings, we examined the cross-sectional association between Hb and elevation among school-aged children (SAC). METHODS: Using data from 9 population-based surveys, we examined 26,518 SAC aged 5-14 y (54.5% female) with data on Hb and elevation (-6 to 3834 m). We used generalized linear models to assess the association between Hb and elevation under varying conditions, including controlling for inflammation-corrected iron and vitamin A deficiency (VAD). Hb adjustments for each 500-m increase in elevation were estimated for SAC and compared with existing adjustments and those estimated for PSC and WRA. We evaluated the impact of these adjustments on anemia prevalence. RESULTS: Hb concentration (g/L) was positively associated with elevation (m). The SAC-elevation adjustments were consistent with those reported among PSC and WRA and suggest current recommendations may under-adjust Hb for those residing at lower elevations (<3000 m) and over-adjust Hb for those residing at higher elevations (>3000 m). Among the surveys included, the proposed elevation adjustments increased anemia prevalence among SAC by 0% (Ghana and United Kingdom) to 15% (Malawi) relative to current elevation adjustments. CONCLUSION: Results confirm that current recommended Hb adjustments for elevation may need updating, and anemia prevalence among SAC may be higher than currently estimated. Findings will inform the WHO's reexamination of global guidelines on the use of Hb adjustments for anemia assessment and may result in improved identification and treatment of anemia.

Interpreting alignment to the EAT-Lancet diet using dietary intakes of lactating mothers in rural Western Kenya.

The EAT-Lancet reference diet intends to be good for planetary and human health. We compared single multiple pass method 24-h dietary intake of mothers (n = 242) from a cross-sectional study in Western Kenya to the recommended range of intake of 11 EAT-Lancet food groups (e.g., 0-100 g/day legumes; maximum score 11), defining alignment two ways: daily intake among food groups where a minimum intake of 0 g was either acceptable or unacceptable. Ordinal logistic regression models assessed associations between alignment and body mass index (BMI). Cost of mothers' diets and hypothetical diets within recommended ranges (lower bounds >0 g) were estimated using food price data from markets within the mothers' locality. Mean energy intake was 1827 (95% confidence interval [CI]: 1731-1924) kcal/day. Relative to the EAT-Lancet diet, mothers' diets were on average higher for grains; within recommendations for tubers, fish, beef and dairy; closer to lower bounds for chicken, eggs, legumes and nuts; and lower for fruits and vegetables. Mean (95% CI) alignment scores were 8.2 (8.0-8.3) when 0 g intakes were acceptable and 1.7 (1.6-1.9) otherwise. No significant associations were found between alignment and BMI. Mothers' diets and hypothetical diets within recommended ranges averaged 184.6 KES (1.6 USD) and 357.5 KES (3.0 USD)/person/day, respectively. Lactating mothers' diets were not diverse and diverged from the reference diet when an intake of 0 g was considered unacceptable. Lower bound intakes of 0 g for micronutrient-dense food groups are inappropriate in food-insecure populations. It would likely cost more than mothers currently spend to tailor their diets to the EAT-Lancet reference diet.

Using a cognitive framework with nurses to manage stress.

Nursing can be a stressful occupation with many nurses struggling to cope with stress on a day-to-day basis. Considerable evidence suggests that positive coping strategies can be an effective part of stress management education programs. This article describes the theoretical rationale for a cognitive framework for stress management that was developed as part of a well-being educational program for cancer nurses. This framework included an associated mnemonic (www.pst) to assist in the recall and utilization of positive coping strategies. The stress management framework was intended to increase nurses' perceptions of personal control which is central to stress management. The academic coping literature is complex, jargon laden and often conceptually abstract, and may not easily be understood by a nonacademic audience. The cognitive framework described here is an evidence-based, user-friendly tool that could be used and evaluated by counsellors, educators, and researchers in different settings.

Neurological patient and informal caregiver quality of life, and caregiver burden: A cross-sectional study of postdischarge community neurological nursing recipients.

Neurological conditions produce considerable disease burden.To describe quality of life in patients with neurological conditions and informal caregivers receiving postdischarge generic community neurological nursing services, and caregiver burden.A descriptive cross-sectional design was used with researchers administering the WHOQOL-BREF Australian Version questionnaire and Zarit Burden Interview.Most patients and caregivers rated quality of life as 'Good'. The patients' physical, psychological and environment domain scores, and caregivers' physical domain scores, were below norms. Half of the caregivers experienced burden and 42% had risk for depression.A heterogeneous group of patients with neurological conditions had considerable care and support needs for fundamental functioning postdischarge. Quality of life and caregiver burden measures highlight the impact of their circumstances on their health and wellbeing. Research is warranted to determine a comprehensive set of generic needs to guide integrated community nursing services for building patient and caregiver self-management capacity.

Isoniazid-associated pellagra during mass scale-up of tuberculosis preventive therapy: a case-control study.

BACKGROUND: Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population. METHODS: We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily. FINDINGS: Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement. INTERPRETATION: Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further. FUNDING: This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173.

Approaches to quantify the contribution of multiple anemia risk factors in children and women from cross-sectional national surveys.

BACKGROUND: Attributable fractions (AF) of anemia are often used to understand the multifactorial etiologies of anemia, despite challenges interpreting them in cross-sectional studies. We aimed to compare different statistical approaches for estimating AF for anemia due to inflammation, malaria, and micronutrient deficiencies including iron, vitamin A, vitamin B12, and folate. METHODS: AF were calculated using nationally representative survey data among preschool children (10 countries, total N = 7,973) and nonpregnant women of reproductive age (11 countries, total N = 15,141) from the Biomarkers Reflecting Inflammation and Nutrition Determinants of Anemia (BRINDA) project. We used the following strategies to calculate AF: 1) Levin's formula with prevalence ratio (PR) in place of relative risk (RR), 2) Levin's formula with odds ratio (OR) in place of RR, and 3) average (sequential) AF considering all possible removal sequences of risk factors. PR was obtained by 1) modified Poisson regression with robust variance estimation, 2) Kleinman-Norton's approach, and 3) estimation from OR using Zhang-Yu's approach. Survey weighted country-specific analysis was performed with and without adjustment for age, sex, socioeconomic status, and other risk factors. RESULTS: About 20-70% of children and 20-50% of women suffered from anemia, depending on the survey. Using OR yielded the highest and potentially biased AF, in some cases double those using PR. Adjusted AF using different PR estimations (Poisson regression, Kleinman-Norton, Zhang-Yu) were nearly identical. Average AF estimates were similar to those using Levin's formula with PR. Estimated anemia AF for children and women were 2-36% and 3-46% for iron deficiency, <24% and <12% for inflammation, and 2-36% and 1-16% for malaria. Unadjusted AF substantially differed from adjusted AF in most countries. CONCLUSION: AF of anemia can be estimated from survey data using Levin's formula or average AF. While different approaches exist to estimate adjusted PR, Poisson regression is likely the easiest to implement. AF are a useful metric to prioritize interventions to reduce anemia prevalence, and the similarity across methods provides researchers flexibility in selecting AF approaches.

Patient experience surveys for children's community health services: A scoping review.

Patient experience surveys have a user focus and measure the quality of person-centered health care for hospital inpatients and consumers of community health services, providing a governance process to evaluate the quality of care and to action improvement. Experience of care has been described as effective communication, respect and dignity, and emotional support. Measurement criteria for these domains are not standardized, leading to inconsistent reporting of patient experience. The objective of this scoping review was to synthesize evidence for measuring experience of care in children's community health services using the Joanna Briggs Institute framework for scoping review method. Three parent-reported surveys met the inclusion criteria, and 50 survey items were assessed by expert reviewers for fit to domains of healthcare experience. Conceptual domains of parent experience in children's community health services included respect and dignity, effective communication, and emotional support. A gap was identified, in that few items in identified surveys measured emotional support. This contribution will promote consistent reporting of healthcare experience, informing policy and practice for person-centered health care.

Evaluation of Hemoglobin Cutoff Levels to Define Anemia Among Healthy Individuals.

Importance: Anemia, defined as low hemoglobin (Hb) concentration insufficient to meet an individual's physiological needs, is the most common blood condition worldwide. Objective: To evaluate the current World Health Organization (WHO) Hb cutoffs for defining anemia among persons who are apparently healthy and to assess threshold validity with a biomarker of tissue iron deficiency and physiological indicator of erythropoiesis (soluble transferrin receptor [sTfR]) using multinational data. Design, Setting, and Participants: In this cross-sectional study, data were collected and evaluated from 30 household, population-based nutrition surveys of preschool children aged 6 to 59 months and nonpregnant women aged 15 to 49 years during 2005 to 2016 across 25 countries. Data analysis was performed from March 2020 to April 2021. Exposure: Anemia defined according to WHO Hb cutoffs. Main Outcomes and Measures: To define the healthy population, persons with iron deficiency (ferritin <12 ng/mL for children or <15 ng/mL for women), vitamin A deficiency (retinol-binding protein or retinol <20.1 µg/dL), inflammation (C-reactive protein >0.5 mg/dL or α-1-acid glycoprotein >1 g/L), or known malaria were excluded. Survey-specific, pooled Hb fifth percentile cutoffs were estimated. Among individuals with Hb and sTfR data, Hb-for-sTfR curve analysis was conducted to identify Hb inflection points that reflect tissue iron deficiency and increased erythropoiesis induced by anemia. Results: A total of 79 950 individuals were included in the original surveys. The final healthy sample was 13 445 children (39.9% of the original sample of 33 699 children; 6750 boys [50.2%]; mean [SD] age 32.9 [16.0] months) and 25 880 women (56.0% of the original sample of 46 251 women; mean [SD] age, 31.0 [9.5] years). Survey-specific Hb fifth percentile among children ranged from 7.90 g/dL (95% CI, 7.54-8.26 g/dL in Pakistan) to 11.23 g/dL (95% CI, 11.14-11.33 g/dL in the US), and among women from 8.83 g/dL (95% CI, 7.77-9.88 g/dL in Gujarat, India) to 12.09 g/dL (95% CI, 12.00-12.17 g/dL in the US). Intersurvey variance around the Hb fifth percentile was low (3.5% for women and 3.6% for children). Pooled fifth percentile estimates were 9.65 g/dL (95% CI, 9.26-10.04 g/dL) for children and 10.81 g/dL (95% CI, 10.35-11.27 g/dL) for women. The Hb-for-sTfR curve demonstrated curvilinear associations with sTfR inflection points occurring at Hb of 9.61 g/dL (95% CI, 9.55-9.67 g/dL) among children and 11.01 g/dL (95% CI, 10.95-11.09 g/dL) among women. Conclusions and Relevance: Current WHO cutoffs to define anemia are higher than the pooled fifth percentile of Hb among persons who are outwardly healthy and from nearly all survey-specific estimates. The lower proposed Hb cutoffs are statistically significant but also reflect compensatory increased erythropoiesis. More studies based on clinical outcomes could further confirm the validity of these Hb cutoffs for anemia.

Use of the Electronic Health Record to Assess Prevalence of Anemia and Iron Deficiency in Pregnancy.

BACKGROUND: In the United States, the prevalence of anemia, iron deficiency (ID), and iron-deficiency anemia (IDA) during pregnancy remains largely unknown as data at the national or state level are limited or nonexistent, respectively. OBJECTIVES: In an effort to identify opportunities to improve maternal health surveillance, we assessed the feasibility of anemia, ID, and IDA surveillance among first-trimester pregnancies using electronic health records (EHRs). METHODS: We identified pregnancies among Kaiser Permanente Northwest members aged ≥18 y during 2005-2016 with first-trimester prenatal care (n = 41,991). Earliest laboratory test results for hemoglobin or hematocrit and ferritin were selected. We describe the proportion of pregnancies screened for and the prevalence of anemia, ID, and IDA; the concordance of anemia status by hemoglobin compared with hematocrit; and the proportion of pregnancies with laboratory-confirmed anemia that also had an International Classification of Diseases diagnostic code related to anemia. RESULTS: Identified pregnancies included women who were 73.1% non-Hispanic (NH) white, 11.5% Hispanic, 8.5% NH Asian/Pacific Islander, and 2.9% NH black. Hemoglobin and hematocrit results were available for 92.7% (n = 38,923) pregnancies. Anemia prevalence was 2.7% (n = 1045) based on hemoglobin <11.0 g/dL or hematocrit <33%;  45.2% of anemia cases had both low hemoglobin and low hematocrit. Among pregnancies with anemia, 18.9% (n = 197) had a ferritin result; of those, 48.2% had ID (ferritin <15 µg/L). In pregnancies without anemia, 3.4% (n = 1275) had a ferritin result; of those, 23.5% had ID. Based on 1472 pregnancies with both anemia and ID assessed, prevalence of ID and IDA was 26.8% and 6.5%, respectively; estimates likely represent selective screening. CONCLUSIONS: EHR data have potential to monitor anemia prevalence and trends in health systems where prenatal anemia screening is nearly universal. However, if iron assessment is not routine, then representative estimates of ID or IDA are unattainable.

Vitamin A deficiency has declined in Malawi, but with evidence of elevated vitamin A in children.

BACKGROUND: Reduction of vitamin A deficiency (VAD) in Malawi coincided with introduction of vitamin A-fortified staple foods, alongside continued biannual high-dose vitamin A supplementation (VAS). OBJECTIVE: We describe coverage of vitamin A interventions and vitamin A status in the 2015-2016 Malawi Micronutrient Survey. METHODS: Food samples and biospecimens were collected within a representative household survey across 105 clusters. Retinol was measured using ultraviolet excitation fluorescence (sugar) and photometric determination (oil). Preschool children (PSC, aged 6-59 mo, n = 1102), school-age children (SAC, aged 5-14 y, n = 758), nonpregnant women (n = 752), and men (n = 219) were initially assessed for vitamin A status using retinol binding protein (RBP) and modified relative dose response (MRDR). Randomly selected fasted MRDR participants (n = 247) and nonfasted women and children (n = 293) were later assessed for serum retinol, retinyl esters, and carotenoids. Analyses accounted for complex survey design. RESULTS: We tested sugar and oil samples from 71.8% and 70.5% of the households (n = 2,112), respectively. All of the oil samples and all but one of the sugar samples had detectable vitamin A. National mean retinol sugar and oil contents were 6.1 ± 0.7 mg/kg and 6.6 ± 1.4 mg/kg, respectively. Receipt of VAS in the previous 6 mo was reported by 68.0% of PSC. VAD prevalence (RBP equivalent to <0.7µmol retinol/L) was 3.6% in PSC, and <1% in other groups. One woman and no children had MRDR ≥0.060 indicating VAD. Among fasted PSC and SAC, 18.0% (95% CI: 6.4, 29.6) and 18.8% (7.2, 30.5) had >5% of total serum vitamin A as retinyl esters, and 1.7% (0.0, 4.1) and 4.9% (0.0, 10.2) had >10% of total serum vitamin A as retinyl esters. Serum carotenoids indicated recent intake of vitamin A-rich fruits and vegetables. CONCLUSIONS: Near elimination of VAD in Malawi is a public health success story, but elevated levels of vitamin A among children suggests that vitamin A interventions may need modification.

Adjusting plasma or serum zinc concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

BACKGROUND: The accurate estimation of zinc deficiency at the population level is important, as it guides the design, targeting, and evaluation of nutrition interventions. Plasma or serum zinc concentration (PZC) is recommended to estimate zinc nutritional status; however, concentrations may decrease in the presence of inflammation. OBJECTIVES: We aimed to assess the relation between PZC and inflammation in preschool children (PSC; 6-59 mo) and nonpregnant women of reproductive age (WRA; 15-49 y), and to compare different inflammation adjustment approaches, if adjustment is warranted. METHODS: Cross-sectional data from 13 nationally representative surveys (18,859 PSC, 22,695 WRA) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed. Correlation and decile analyses were conducted, and the following 3 adjustment methods were compared if a consistent negative association between PZC and C-reactive protein (CRP) or α-1-acid glycoprotein (AGP) was observed: 1) exclude individuals with CRP > 5 mg/L or AGP > 1 g/L; 2) apply arithmetic correction factors; and 3) use the BRINDA regression correction (RC) approach. RESULTS: In 6 of 12 PSC surveys, the estimated prevalence of zinc deficiency increased with increasing CRP deciles, and to a lesser extent, with increasing AGP deciles. In WRA, the association of PZC with CRP and AGP was weak and inconsistent. In the 6 PSC surveys in which adjustment methods were compared, application of RC reduced the estimated prevalence of zinc deficiency by a median of 11 (range: 4-18) percentage points, compared with the unadjusted prevalence. CONCLUSIONS: Relations between PZC and inflammatory markers were inconsistent, suggesting that correlation and decile analyses should be conducted before applying any inflammation adjustments. In populations of PSC that exhibit a significant negative association between PZC and CRP or AGP, application of the RC approach is supported. At this time, there is insufficient evidence to warrant inflammation adjustment in WRA.

Comparing hemoglobin distributions between population-based surveys matched by country and time.

BACKGROUND: Valid measurement of hemoglobin is important for tracking and targeting interventions. This study compares hemoglobin distributions between surveys matched by country and time from The Demographic and Health Survey (DHS) Program and the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. METHODS: Four pairs of nationally representative surveys measuring hemoglobin using HemoCue® with capillary (DHS) or venous (BRINDA) blood were matched by country and time. Data included 17,719 children (6-59 months) and 21,594 non-pregnant women (15-49 y). Across paired surveys, we compared distributional statistics and anemia prevalence. RESULTS: Surveys from three of the four countries showed substantial differences in anemia estimates (9 to 31 percentage point differences) which were consistently lower in BRINDA compared to DHS (2 to 31 points for children, 1 to 16 points for women). CONCLUSION: We identify substantial differences in anemia estimates from surveys of similar populations. Further work is needed to identify the cause of these differences to improve the robustness of anemia estimates for comparing populations and tracking improvements over time.

The Co-Occurrence of Overweight and Micronutrient Deficiencies or Anemia among Women of Reproductive Age in Malawi.

BACKGROUND: In low-resource settings, urbanization may contribute to the individual-level double burden of malnutrition (DBM), whereby under- and overnutrition co-occur within the same individuals. OBJECTIVE: We described DBM prevalence among Malawian women by urban-rural residence, examined whether urban residence was associated with DBM, and assessed whether DBM prevalence was greater than the prevalence expected by chance given population levels of under- and overnutrition, which would suggest DBM is a distinct phenomenon associated with specific factors. METHODS: We analyzed nationally representative data of 723 nonpregnant women aged 15-49 y from the 2015-2016 Malawi Micronutrient Survey. DBM was defined as co-occurring overweight or obesity (OWOB) and ≥1 micronutrient deficiency or anemia. We used Poisson regression models to examine the association between urban residence and DBM and its components. The Rao-Scott modified chi-square test compared the observed and expected DBM prevalence. RESULTS: Nationally, 10.8% (95% CI: 7.0, 14.5) of women had co-occurring OWOB and any micronutrient deficiency and 3.4% (95% CI: 1.3, 5.5) had co-occurring OWOB and anemia. The prevalence of co-occurring OWOB and any micronutrient deficiency was 2 times higher among urban women than rural women [urban 32.6 (24.1, 41.2) compared with rural 8.6 (5.2, 11.9), adjusted prevalence ratio: 2.0 (1.1, 3.5)]. Co-occurring OWOB and anemia prevalence did not significantly differ by residence [urban 6.9 (0.6, 13.2) compared with rural 3.0 (0.8, 5.3)]. There were no statistically significant differences in observed and expected prevalence estimates of DBM. CONCLUSIONS: This analysis shows that co-occurring OWOB and any micronutrient deficiency was higher among women in urban Malawi compared with rural areas. However, our finding that co-occurring OWOB and any micronutrient deficiency or anemia may be due to chance suggests that there may not be common causes driving DBM in Malawian women. Thus, there may not be a need to design and target interventions specifically for women with DBM.

Changes in micronutrient and inflammation serum biomarker concentrations after a norovirus human challenge.

BACKGROUND: To accurately assess micronutrient status, it is necessary to characterize the effects of inflammation and the acute-phase response on nutrient biomarkers. OBJECTIVE: Within a norovirus human challenge study, we aimed to model the inflammatory response of C-reactive protein (CRP) and α-1-acid glycoprotein (AGP) by infection status, model kinetics of micronutrient biomarkers by inflammation status, and evaluate associations between inflammation and micronutrient biomarkers from 0 to 35 d post-norovirus exposure. METHODS: Fifty-two healthy adults were enrolled into challenge studies in a hospital setting and followed longitudinally; all were exposed to norovirus, half were infected. Post hoc analysis of inflammatory and nutritional biomarkers was performed. Subjects were stratified by inflammation resulting from norovirus exposure. Smoothed regression models analyzed the kinetics of CRP and AGP by infection status, and nutritional biomarkers by inflammation. Linear mixed-effects models were used to analyze the independent relations between CRP, AGP, and biomarkers for iron, vitamin A, vitamin D, vitamin B-12, and folate from 0 to 35 d post-norovirus exposure. RESULTS: Norovirus-infected subjects had median (IQR) peak concentrations for CRP [16.0 (7.9-29.5) mg/L] and AGP [0.9 (0.8-1.2) g/L] on day 3 and day 4 postexposure, respectively. Nutritional biomarkers that differed (P < 0.05) from baseline within the inflamed group were ferritin (elevated day 3), hepcidin (elevated days 2, 3), serum iron (depressed days 2-4), transferrin saturation (depressed days 2-4), and retinol (depressed days 3, 4, and 7). Nutritional biomarker concentrations did not differ over time within the uninflamed group. In mixed models, CRP was associated with ferritin (positive) and serum iron and retinol (negative, P < 0.05). CONCLUSION: Using an experimental infectious challenge model in healthy adults, norovirus infection elicited a time-limited inflammatory response associated with altered serum concentrations of certain iron and vitamin A biomarkers, confirming the need to consider adjustments of these biomarkers to account for inflammation when assessing nutritional status. These trials were registered at clinicaltrials.gov as NCT00313404 and NCT00674336.

Data needed to respond appropriately to anemia when it is a public health problem.

Although the proportion of anemia amenable to change varies by population, the World Health Organization (WHO) criteria used to describe the public health severity of anemia are based on population prevalences. We describe the importance of measuring iron and other etiologic indicators to better understand what proportion of anemia could be responsive to interventions. We discuss the necessity of measuring inflammation to interpret iron biomarkers and documenting anemia of inflammation. Finally, we suggest assessing nonmodifiable genetic blood disorders associated with anemia. Using aggregated results from the Global Burden of Disease 2016, we compare population prevalence of anemia with years lived with disability (YLD) estimates, and the relative contributions of mild, moderate, and severe anemia to YLD. Anemia prevalences correlated with YLD and the relative proportion of moderate or severe anemia increased with anemia prevalence. However, individual-level survey data revealed irregular patterns between anemia prevalence, the prevalence of moderate or severe anemia, and the prevalence of iron deficiency anemia (IDA). We conclude that although the WHO population prevalence criteria used to describe the public health severity of anemia are important for policymaking, etiologic-specific metrics that take into account IDA and other causes will be necessary for effective anemia control policies.