Comparison of Current World Health Organization Guidelines with Physiologically Based Serum Ferritin Thresholds for Iron Deficiency in Healthy Young Children and Nonpregnant Women Using Data from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Current WHO serum ferritin (SF) thresholds for iron deficiency (ID) in children (<12 µg/L) and women (<15 µg/L) are derived from expert opinion based on radiometric assays in use decades ago. Using a contemporary immunoturbidimetry assay, higher thresholds (children, <20 µg/L; women, <25 µg/L) were identified from physiologically based analyses. OBJECTIVE: We examined relationships of SF measured using an immunoradiometric assay from the era of expert opinion with 2 independently measured indicators of ID, hemoglobin (Hb) and erythrocyte zinc protoporphyrin (eZnPP), using data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). The SF at which circulating Hb begins to decrease and eZnPP begins to increase provides a physiological basis for identifying the onset of iron-deficient erythropoiesis. METHODS: We analyzed NHANES III cross-sectional data from 2616 apparently healthy children, aged 12-59 mo, and 4639 apparently healthy nonpregnant women, aged 15-49 y. We used restricted cubic spline regression models to determine SF thresholds for ID. RESULTS: SF thresholds identified by Hb and eZnPP did not differ significantly in children, 21.2 µg/L (95% confidence interval: 18.5, 26.5) and 18.7 µg/L (17.9, 19.7), and, in women, were similar although significantly different, 24.8 µg/L (23.4, 26.9) and 22.5 µg/L (21.7, 23.3). CONCLUSIONS: These NHANES results suggest that physiologically based SF thresholds are higher than the thresholds from expert opinion established during the same era. SF thresholds found using physiological indicators detect the onset of iron-deficient erythropoiesis, whereas the WHO thresholds identify a later, more severe stage of ID.

The VitMin Lab Sandwich-ELISA Assays for Iron and Inflammation Markers Compared Well with Clinical Analyzer Reference-Type Assays in Subsamples of the Nepal National Micronutrient Status Survey.

BACKGROUND: The low cost and small specimen volume of the VitMin Lab ELISA assays for serum ferritin (Fer), soluble transferrin receptor (sTfR), C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) have allowed their application to micronutrient surveys conducted in low-resource countries for ∼2 decades. OBJECTIVES: We conducted a comparison between the ELISA and reference-type assays used in the US NHANES. METHODS: Using the Roche clinical analyzer as a reference, we measured random subsets of the 2016 Nepal National Micronutrient Status Survey (200 serum samples from children aged 6-59 mo; 100 serum samples from nonpregnant women) for Fer, sTfR, CRP, and AGP. We compared the combined data sets with the ELISA survey results using descriptive analyses. RESULTS: The Lin's concordance coefficients between the 2 assays were ≥0.89 except for sTfR (Lin's ρ = 0.58). The median relative difference to the reference was as follows: Fer, -8.5%; sTfR, 71.2%; CRP, -19.5%; and AGP, -8.2%. The percentage of VitMin samples agreeing within ±30% of the reference was as follows: Fer, 88.5%; sTfR, 1.70%; CRP, 74.9%; and AGP, 92.9%. The prevalence of abnormal results was comparable between the 2 assays for Fer, CRP, and AGP, and for sTfR after adjusting to the Roche assay. Continued biannual performance (2007-2019) of the VitMin assays in CDC's external quality assessment program (6 samples/y) demonstrated generally acceptable performance. CONCLUSIONS: Using samples from the Nepal survey, the VitMin ELISA assays produced mostly comparable results to the Roche reference-type assays for Fer, CRP, and AGP. The lack of sTfR assay standardization to a common reference material explains the large systematic difference observed for sTfR, which could be corrected by an adjustment equation pending further validation. This snapshot comparison together with the long-term external quality assessment links the survey data generated by the VitMin Lab to the Roche assays used in NHANES.

Iron Deficiency in the United States: Limitations in Guidelines, Data, and Monitoring of Disparities.

Iron deficiency and the more severe sequela, iron deficiency anemia, are public health problems associated with morbidity and mortality, particularly among pregnant women and younger children. The 1998 Centers for Disease Control and Prevention recommendations for prevention and control of iron deficiency in the United States is old and does not reflect recent evidence but is a foundational reference for many federal, clinical, and program guidelines. Surveillance data for iron deficiency are sparse at all levels, with critical gaps for pregnant women and younger children. Anemia, iron deficiency, and iron deficiency anemia are often conflated but should not be. Clinical guidelines for anemia, iron deficiency, and iron deficiency anemia give inconsistent recommendations, causing nonsystematic assessment of iron deficiency. Screening for iron deficiency typically relies on identifying anemia, despite anemia's low sensitivity for iron deficiency. In the National Health and Nutrition Examination Survey, more than 70% of iron deficiency is missed among pregnant women and children by relying on hemoglobin for iron deficiency screening. To improve assessment and diagnosis and strengthen surveillance, better and more complete data and updated foundational guidance on iron deficiency and anemia are needed that consider new evidence for measuring and interpreting laboratory results. (Am J Public Health. 2022;112(S8):S826-S835. https://doi.org/10.2105/AJPH.2022.306998).

Factors associated with anaemia in a nationally representative sample of nonpregnant women of reproductive age in Nepal.

We used cross-sectional data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anaemia among a nationally representative sample of nonpregnant women 15- 49 years (n = 1, 918). Haemoglobin, biomarkers of iron status and other micronutrients, infection, inflammation, and blood disorders were assessed from venous blood. Soil-transmitted helminth and Helicobacter pylori infections were assessed from stool. Sociodemographic, household, and health characteristics and diet were ascertained by interview. We conducted bivariate analyses between candidate predictors and anaemia (haemoglobin <12.0 g/ dL, altitude- and smoking-adjusted). Candidate predictors that were significant in bivariate models (P < 0.05) were included in the multivariable logistic regression model, accounting for complex sampling design. Anaemia prevalence was 20.2% (95% confidence interval [CI] [17.6, 22.8]). Associated with reduced anaemia odds were living in the Mountain and Hill ecological zones relative to the Terai (adjusted odds ratio [AOR] 0.35, 95% CI [0.21, 0.60] and AOR 0.41, 95% CI [0.29, 0.59], respectively), recent cough (AOR 0.56, 95% CI [0.38, 0.82]), hormonal contraceptive use (AOR 0.58; 95% CI [0.38, 0.88]), ln ferritin (micrograms per litre; AOR 0.43, 95% CI [0.35, 0.54]), and ln retinol binding protein (micrograms per litre; AOR 0.20, 95% CI [0.11, 0.37]). Residing in a house with an earth floor (AOR 1.74, 95% CI [1.18, 2.56]), glucose-6- phosphate dehydrogenase deficiency (AOR 2.44, 95% CI [1.66, 3.60]), and haemoglobinopathies (AOR 6.15, 95% CI [3.09, 12.26]) were associated with increased anaemia odds. Interventions that improve micronutrient status, ensure access to hormonal birth control, and replace dirt floors to reduce infection risk might help reduce anaemia in this population.

Factors associated with anaemia among adolescent boys and girls 10-19 years old in Nepal.

We used data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anaemia (World Health Organization cut-points using altitude- and smoking-adjusted haemoglobin [Hb]) among nationally representative samples of adolescents 10-19 years. Hb, biomarkers of micronutrients, infection and inflammation were assessed from venous blood. Sociodemographic and household characteristics, dietary diversity, pica and recent morbidity were ascertained by interview. We explored bivariate relationships between candidate predictors and anaemia among boys (N = 967) and girls (N = 1,680). Candidate predictors with P < 0.05 in bivariate analyses were included in sex-specific multivariable logistic regression models. Anaemia prevalence was 20.6% (95% confidence interval [CI] [17.1, 24.1]) among girls and 10.9% (95% CI [8.2, 13.6]) among boys. Among girls, living in the Mountain and Hill ecological zones relative to the Terai (adjusted odds ratio [AOR] 0.28, 95% CI [0.15, 0.52] and AOR 0.42, 95% CI [0.25, 0.73], respectively), ln ferritin (µg/L) (AOR 0.53, 95% CI [0.42, 0.68]) and ln retinol binding protein (RBP) (µmol/L) (AOR 0.08, 95% CI [0.04, 0.16]) were associated with reduced anaemia odds. Older age (age in years AOR 1.19, 95% CI [1.12, 1.27]) and Janajati ethnicity relative to the Muslim ethnicity (AOR 3.04, 95% CI [1.10, 8.36]) were associated with higher anaemia odds. Among boys, ln RBP [µmol/L] (AOR 0.25, 95% CI [0.10, 0.65]) and having consumed flesh foods (AOR 0.57, 95% CI [0.33, 0.99]) were associated with lower anaemia odds. Open defecation (AOR 2.36, 95% CI [1.15, 4.84]) and ln transferrin receptor [mg/L] (AOR 3.21, 95% CI [1.25, 8.23]) were associated with increased anaemia odds. Anaemia among adolescents might be addressed through effective public health policy and programs targeting micronutrient status, diet and sanitation.

Effects of prenatal micronutrients supplementation timing on pregnancy-induced hypertension: Secondary analysis of a double-blind randomized controlled trial.

In this secondary analysis of data from a double-blind randomized controlled trial (clinicaltrials.gov identifier: NCT00133744) of micronutrient supplementation (multiple micronutrients [MMN], iron-folic acid [IFA] and folic acid [FA] alone), we examined the potential modifying effect of gestational age at enrolment on the association of antenatal supplementation and pregnancy-induced hypertension (PIH). We included 18,775 nulliparous pregnant women with mild or no anaemia who were enrolled at 20 weeks of gestation or earlier from five counties of northern China. Women were randomly assigned to receive daily FA, IFA or MMN from enrolment until delivery. We used logistic regression to evaluate the association between PIH and timing of micronutrient supplementation. The incidence of PIH was statistically significantly lower among women who began MMN supplementation before 12 gestational weeks compared with women who began MMN supplementation at 12 weeks or later (RR = 0.74, 95% CI: 0.60-0.91). A similar protective effect was observed for both early-onset (<28 weeks, RR 0.45, 0.21-0.96) and late-onset of PIH (≥28 weeks, RR 0.77, 0.63-0.96). No statistically significant association was observed between PIH occurrence and timing of supplementation for FA or IFA. Maternal MMN supplementation and antenatal enrolment during the first trimester of pregnancy appeared to be of importance in preventing both early- and late-onset of PIH.

Age, Ethnicity, Glucose-6-Phosphate Dehydrogenase Deficiency, Micronutrient Powder Intake, and Biomarkers of Micronutrient Status, Infection, and Inflammation Are Associated with Anemia Among Children 6-59 Months in Nepal.

BACKGROUND: Anemia is a major concern for children in Nepal; however, little is known about context-specific causes of anemia. OBJECTIVE: We used cross-sectional data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anemia in a nationally representative, population-based sample of children 6-59 mo (n = 1367). METHODS: Hemoglobin, biomarkers of iron status and other micronutrients, infection, inflammation, and blood disorders were assessed from venous blood samples. Soil-transmitted helminth (STH) and Helicobacter pylori infections were assessed from stool. Anthropometry was measured with standard procedures. Sociodemographic and household characteristics, diet, micronutrient powder (MNP) intake, pica, and morbidity recall were ascertained by caregiver interview. Multivariable logistic regression that accounted for complex sampling design, determined predictors of anemia (hemoglobin <11.0 g/dL, altitude adjusted); candidate predictors were variables with P < 0.05 in bivariate models. RESULTS: Anemia prevalence was 18.6% (95% CI: 15.8, 21.4). MNP intake [adjusted OR (AOR): 0.25, 95% CI: 0.07, 0.86], log (ln) ferritin (µg/L) (AOR: 0.49, 95% CI: 0.38, 0.64), and ln RBP (µmol/L) (AOR: 0.42, 95% CI: 0.18, 0.95) were associated with reduced odds of anemia. Younger age (6-23 mo compared with 24-59 mo; AOR: 2.29, 95% CI: 1.52, 3.46), other Terai ethnicities (AOR: 2.59, 95% CI: 1.25, 5.35) and Muslim ethnicities (AOR: 3.15, 95% CI: 1.30, 7.65) relative to Brahmin/Chhetri ethnicities, recent fever (AOR: 1.68, 95% CI: 1.08, 2.59), ln C-reactive protein (mg/L) (AOR: 1.23, 95% CI: 1.03, 1.45), and glucose-6-phosphate dehydrogenase deficiency (AOR: 2.84, 95% CI: 1.88, 4.30) were associated with increased odds of anemia. CONCLUSION: Both nonmodifiable and potentially modifiable factors were associated with anemia. Thus some but not all anemia might be addressed through effective public health policy, programs, and delivery of nutrition and infection prevention and control.

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.

Changes in growth, anaemia, and iron deficiency among children aged 6-23 months in two districts in Nepal that were part of the post-pilot scale-up of an integrated infant and young child feeding and micronutrient powder intervention.

There is limited research on integrated infant and young child feeding (IYCF) and micronutrient powders (MNPs) programmes operating at scale, despite widespread implementation. This study uses cross-sectional baseline (n = 2,542) and endline (n = 2,578) surveys representative of children 6-23 months in two districts in Nepal that were part of a post-pilot scale-up of a IYCF-MNP programme. Multivariable log-binomial regression models were used to estimate prevalence ratios (PRs) for stunting (length-for-age z-score <-2), wasting (weight-for-length z-score <-2), underweight (weight-for-age z-score <-2), anaemia (altitude-adjusted haemoglobin <110 µg/L), moderate or severe anaemia (altitude-adjusted haemoglobin <100 g/L), iron deficiency (inflammation-adjusted ferritin <12 µg/L), and iron deficiency anaemia (iron deficiency + anaemia [IDA]) at endline versus baseline and also to compare children in the endline survey based on frequency of mothers' interactions with female community health volunteers (FCHVs; >1× per month or monthly vs. <1× per month) and MNP coverage (1 or ≥2 distributions vs. none among children 12-23 months). Endline children were significantly less likely to be stunted than baseline children in both districts (multivariable-adjusted PR [95% CI]: 0.77 [0.69, 0.85], P < 0.001 and 0.82 [0.75, 0.91], P < 0.001 in Kapilvastu and Achham, respectively); however, only Achham had significantly lower prevalences of underweight, moderate/severe anaemia, iron deficiency, and IDA at endline. At endline, 53.5% and 71.4% of children had tried MNP in Kapilvastu and Achham districts, respectively, consuming an average of 24 sachets from the last distribution. Frequent maternal-FCHV interactions were associated with a reduced risk of stunting and underweight at endline, whereas repeat MNP coverage was associated with reduced risk of anaemia and IDA. Future research using experimental designs should verify the potential of integrated IYCF-MNP programmes to improve children's nutritional status.

Predictors of micronutrient powder (MNP) knowledge, coverage, and consumption during the scale-up of an integrated infant and young child feeding (IYCF-MNP) programme in Nepal.

Large-scale programmes using micronutrient powders (MNPs) may not achieve maximum impact due to limited/inappropriate MNP coverage, consumption, and use. We identify predictors of MNP coverage, maternal knowledge of appropriate use, and child MNP consumption in Nepal. A cross-sectional survey was conducted in 2,578 mother-child pairs representative of children 6-23 months in two districts that were part of the post-pilot, scale-up of an integrated infant and young child feeding-MNP (IYCF-MNP) programme. Children aged 6-23 months were expected to receive 60 MNP sachets every 6 months from a female community health volunteer (FCHV) or health centre. Outcomes of interest were MNP coverage (ever received), maternal knowledge of appropriate use (correct response to seven questions), repeat coverage (receipt ≥ twice; among children 12-23 months who had received MNP at least once, n = 1342), and high intake (child consumed ≥75% of last distribution, excluding those with recent receipt/insufficient time to use 75% at recommended one-sachet-per-day dose, n = 1422). Multivariable log-binomial regression models were used to identify predictors of the four outcomes. Coverage, knowledge of appropriate use, and repeat coverage were 61.3%, 33.5%, and 45.9%, respectively. Among MNP receivers, 97.9% consumed MNP at least once and 38.9% of eligible children consumed ≥75% of last distribution. FCHV IYCF-MNP counselling was positively associated with knowledge, coverage, repeat coverage, and high intake; health worker counselling with knowledge and coverage indicators; and radio messages with coverage indicators only. FCHV counselling had the strongest association with knowledge, coverage, and high intake. Community-based counselling may play a vital role in improving coverage and intake in MNP programmes.

Monitoring and surveillance for multiple micronutrient supplements in pregnancy.

The World Health Organization (WHO) recommends iron-folic acid (IFA) supplementation during pregnancy to improve maternal and infant health outcomes. Multiple micronutrient (MMN) supplementation in pregnancy has been implemented in select countries and emerging evidence suggests that MMN supplementation in pregnancy may provide additional benefits compared to IFA alone. In 2015, WHO, the United Nations Children's Fund (UNICEF), and the Micronutrient Initiative held a "Technical Consultation on MMN supplements in pregnancy: implementation considerations for successful incorporation into existing programmemes," which included a call for indicators needed for monitoring, evaluation, and surveillance of MMN supplementation programmes. Currently, global surveillance and monitoring data show that overall IFA supplementation programmes suffer from low coverage and intake adherence, despite inclusion in national policies. Common barriers that limit the effectiveness of IFA-which also apply to MMN programmes-include weak supply chains, low access to antenatal care services, low-quality behaviour change interventions to support and motivate women, and weak or non-existent monitoring systems used for programme improvement. The causes of these barriers in a given country need careful review to resolve them. As countries heighten their focus on supplementation during pregnancy, or if they decide to initiate or transition into MMN supplementation, a priority is to identify key monitoring indicators to address these issues and support effective programmes. National and global monitoring and surveillance data on IFA supplementation during pregnancy are primarily derived from cross-sectional surveys and, on a more routine basis, through health and logistics management information systems. Indicators for IFA supplementation exist; however, the new indicators for MMN supplementation need to be incorporated. We reviewed practice-based evidence, guided by the WHO/Centers for Disease Control and Prevention logic model for vitamin and mineral interventions in public health programmes, and used existing manuals, published literature, country reports, and the opinion of experts, to identify monitoring, evaluation, and surveillance indicators for MMN supplementation programmes. We also considered cross-cutting indicators that could be used across programme settings, as well as those specific to common delivery models, such as antenatal care services. We then described mechanisms for collecting these data, including integration within existing government monitoring systems, as well as other existing or proposed systems. Monitoring data needs at all stages of the programme lifecycle were considered, as well as the feasibility and cost of data collection. We also propose revisions to global-, national-, and subnational-surveillance indicators based on these reviews.

Effects of Prenatal Micronutrient Supplementation on Spontaneous Preterm Birth: A Double-Blind Randomized Controlled Trial in China.

In this secondary analysis of data from a double-blind randomized controlled trial carried out in northern China, we aimed to assess the effect of prenatal supplementation with multiple micronutrients (MMN) or iron + folic acid (IFA), versus folic acid (FA) alone, on risk of spontaneous preterm birth (SPB) and the impact of supplementation timing on SPB. A total of 18,775 nulliparous pregnant women enrolled between 2006 and 2009 were randomly assigned to receive daily FA, IFA, or MMN from the period before 20 weeks' gestation to delivery. The incidences of SPB for women consuming FA, IFA, and MMN were 5.7%, 5.6% and 5.1%, respectively. Compared with women given FA, the relative risks of SPB for those using MMN and IFA were 0.99 (95% confidence interval: 0.85, 1.16) and 0.89 (95% confidence interval: 0.79, 1.05), respectively. SPB incidence in women who started consuming FA, IFA, and MMN before the 12th week of gestation (4.6%, 4.2%, and 3.9%, respectively) was significantly reduced compared with starting supplement use on or after the 12th gestational week (6.9%, 7.2%, and 6.4%, respectively). Starting use of FA, IFA, or MMN supplements before the 12th week of gestation produced a 41%-45% reduction in risk of SPB. Early prenatal enrollment and micronutrient use during the first trimester of pregnancy appeared to be of particular importance for prevention of SPB, regardless of supplement group.

Modifying effects of maternal Hb concentration on infant birth weight in women receiving prenatal iron-containing supplements: a randomised controlled trial.

Concerns have been raised about the benefits of Fe-containing supplements on infant birth weight among women with normal/high Hb levels at baseline. Thus far, no clinical trials have examined whether the effects of prenatal Fe-containing supplements on birth weight vary by maternal Hb levels. We compared the effects of Fe-folic acid (IFA) or multiple micronutrients (MMN) with folic acid (FA) supplements on birth weight among pregnant women with mild/no anaemia or high Hb levels. A double-blind randomised controlled trial was conducted in 2006-2009. In total, 18 775 pregnant women with mild/no anaemia (145 g/l) baseline Hb levels, IFA and MMN supplements increased birth weight by 91·44 (95% CI 3·37, 179·51) g and 107·63 (95% CI 21·98, 193·28) g (P<0·05), respectively, compared with the FA group. No differences were found between the IFA and the MMN group, regardless of maternal Hb concentration. In conclusion, the effects of Fe-containing supplements on birth weight depended on baseline Hb concentrations. The Fe-containing supplements improved birth weight in women with very high Hb levels before 20 weeks of gestation.

C-reactive protein increases with gestational age during pregnancy among Chinese women.

OBJECTIVE: To examine the concentration of C-reactive protein (CRP) in relation to gestational weeks during pregnancy among Chinese women. METHODS: From a randomized control trial of prenatal supplementation with folic acid, iron-folic acid, and multiple micronutrients in China, we examined 834 pregnant women with CRP measured initially between 5 and 20 weeks and at follow-up between 28 and 32 weeks gestation. We calculated and plotted CRP geometric means by gestational weeks. The same analysis was repeated for women who had normal pregnancies (624 women) by excluding women with stillbirth, preterm, small for gestational age, body mass index <18.5 kg/m(2) or >30 kg/m(2) at enrollment, and hypertension or anemia during pregnancy. RESULTS: We observed a significant positive trend between log-transformed CRP and gestational age from 5 to 20 weeks and from 28 to 32 weeks both in the full sample and in the subset of women who had normal pregnancies. CRP geometric mean was 0.81 mg/l at 5-7 weeks of gestation, 2.85 mg/l at 19-20 weeks of gestation, and 3.89 mg/l at 32 weeks of gestation. A similar increasing trend in the CRP median or percentage of elevated CRP were also observed. CONCLUSION: We concluded that CRP increased with gestational age among healthy Chinese women who delivered healthy infants. Am. J. Hum. Biol. 28:574-579, 2016. © 2016 Wiley Periodicals, Inc.

Iron-containing micronutrient supplementation of Chinese women with no or mild anemia during pregnancy improved iron status but did not affect perinatal anemia.

Universal prenatal daily iron-folic acid (IFA) and multiple micronutrient (MM) supplements are recommended to reduce the risk of low birth weight, maternal anemia, and iron deficiency (ID) during pregnancy, but the evidence of their effect on iron status among women with mild or no anemia is limited. The aim of this study was to describe the iron status [serum ferritin (SF), serum soluble transferrin receptor (sTfR), and body iron (BI)] before and after micronutrient supplementation during pregnancy. We examined 834 pregnant women with hemoglobin > 100 g/L at enrollment before 20 wk of gestation and with iron measurement data from a subset of a randomized, double-blind trial in China. Women were randomly assigned to take daily 400 µg of folic acid (FA) (control), FA plus 30 mg of iron, or FA, iron, plus 13 additional MMs provided before 20 wk of gestation to delivery. Venous blood was collected in this subset during study enrollment (before 20 wk of gestation) and 28-32 wk of gestation. We found that, at 28-32 wk of gestation, compared with the FA group, both the IFA and MM groups had significantly lower prevalence of ID regardless of which indicator (SF, sTfR, or BI) was used for defining ID. The prevalence of ID at 28-32 wk of gestation for IFA, MM, and FA were 35.3%, 42.7%, and 59.6% by using low SF, 53.6%, 59.9%, and 69.9% by using high sTfR, and 34.5%, 41.2%, and 59.6% by using low BI, respectively. However, there was no difference in anemia prevalence (hemoglobin < 110 g/L) between FA and IFA or MM groups. We concluded that, compared with FA alone, prenatal IFA and MM supplements provided to women with no or mild anemia improved iron status later during pregnancy but did not affect perinatal anemia. This trial was registered at clinicaltrials.gov as NCT00137744.

Physiologically based trimester-specific serum ferritin thresholds for iron deficiency in US pregnant women.

ABSTRACT: Serum ferritin (SF) concentration is the most widely used indicator for iron deficiency (ID). During pregnancy, the World Health Organization recently recommended SF thresholds for ID of <15 µg/L for the first trimester of pregnancy, based on expert opinion, and made no recommendations for the second and third trimesters. We examined the relationship of SF with 2 independent indicators of the onset of iron-deficient erythropoiesis, hemoglobin and soluble transferrin receptor 1, in cross-sectional data from US National Health and Nutrition Examination Survey for 1999 to 2010 and 2015 to 2018. We included 1288 pregnant women aged 15 to 49 years and excluded women with inflammation or potential liver disease. We used restricted cubic spline (RCS) regression analysis to determine SF thresholds for iron-deficient erythropoiesis. SF decreased during pregnancy; geometric mean SF was higher during the first and lower during the second and third trimesters. Using RCS analysis, the SF thresholds identified during pregnancy were <25.8 µg/L (18.1-28.5) during first trimester, <18.3 µg/L (16.3-22.9) during second trimester, and <19.0 µg/L (14.4- 26.1) during third trimester. These SF threshold levels track concentrations of hepcidin, the iron-regulatory hormone controlling the mobilization of iron stores. An SF concentration of <15 µg/L as the criterion for ID may underestimate the true prevalence of ID throughout pregnancy. In our study, an additional 1 of every 10 pregnant women would be recognized as iron deficient by using the physiologically based thresholds at SF of ∼25 µg/L during the first and ∼20 µg/L during the second and third trimesters.

Accuracy of a handheld 3D imaging system for child anthropometric measurements in population-based household surveys and surveillance platforms: an effectiveness validation study in Guatemala, Kenya, and China.

BACKGROUND: An efficacy evaluation of the AutoAnthro system to measure child (0-59 months) anthropometry in the United States found 3D imaging performed as well as gold-standard manual measurements for biological plausibility and precision. OBJECTIVES: We conducted an effectiveness evaluation of the accuracy of the AutoAnthro system to measure 0- to 59-month-old children's anthropometry in population-based surveys and surveillance systems in households in Guatemala and Kenya and in hospitals in China. METHODS: The evaluation was done using health or nutrition surveillance system platforms among 600 children aged 0-59 months (Guatemala and Kenya) and 300 children aged 0-23 months (China). Field team anthropometrists and their assistants collected manual and scan anthropometric measurements, including length or height, midupper arm circumference (MUAC), and head circumference (HC; China only), from each child. An anthropometry expert and assistant later collected both manual and scan anthropometric measurements on the same child. The expert manual measurements were considered the standard compared to field team scans. RESULTS: Overall, in Guatemala, Kenya, and China, for interrater accuracy, the average biases for length or height were -0.3 cm, -1.9 cm, and -6.2 cm, respectively; for MUAC were 0.9 cm, 1.2 cm, and -0.8 cm, respectively; and for HC was 2.4 cm in China. The inter-technical errors of measurement (inter-TEMs) for length or height were 2.8 cm, 3.4 cm, 5.5 cm, respectively; for MUAC were 1.1 cm, 1.5 cm, and 1.0 cm, respectively; and for HC was 2.8 cm in China. For intrarater precision, the absolute mean difference and intra-TEM (interrater, intramethod TEM) were 0.1 cm for all countries for all manual measurements. For scans, overall, absolute mean differences for length or height were 0.4-0.6 cm; for MUAC were 0.1-0.1 cm; and for HC was 0.4 cm. For the intra-TEM, length or height was 0.5 cm in Guatemala and China and 0.7 cm in Kenya, and other measurements were ≤0.3 cm. CONCLUSIONS: Understanding the factors that cause the many poor scan results and how to correct them will be needed prior to using this instrument in routine, population-based survey and surveillance systems.

Physiologically based serum ferritin thresholds for iron deficiency in women of reproductive age who are blood donors.

Our objective is to develop a physiologically based method to determine serum ferritin thresholds for iron deficiency in healthy individuals. The current World Health Organization threshold of <15 µg/L for iron deficiency in women is based on expert opinion. We examined the relationship between serum ferritin and 2 independently measured indicators of iron-deficient erythropoiesis, soluble transferrin receptor (sTfR) and hemoglobin, in baseline data from 286 women, 20 to 49 years, who were first-time or reactivated donors in the Retrovirus Epidemiology Donor Study-II Donor Iron Status Evaluation (REDS-RISE) study. At lower serum ferritin concentrations, median sTfR increased as hemoglobin decreased. Using restricted cubic spline regression analysis to determine thresholds for iron-deficient erythropoiesis, the thresholds identified by sTfR (serum ferritin < 25.4 µg/L) and hemoglobin (serum ferritin < 25.3 µg/L) did not differ significantly. The thresholds found in the REDS-RISE study do not differ from those identified by sTfR (serum ferritin < 25.5 µg/L) and hemoglobin (serum ferritin < 26.6 µg/L) in a previous study of 5442 women, 20 to 49 years, in the US National Health and Nutrition Examination Survey 2003 to 2018 (P = .98 and 0.83, respectively). Although international comparisons are needed, these results with US data provide additional evidence for the potential usefulness of a physiologically based method to identify serum ferritin thresholds for iron deficiency.

Acceptability and Experiences with the Use of 3D Scans to Measure Anthropometry of Young Children in Surveys and Surveillance Systems from the Perspective of Field Teams and Caregivers.

Background: Portable systems using three-dimensional (3D) scan data to calculate young child anthropometry measurements in population-based surveys and surveillance systems lack acceptability data from field workers and caregivers. Objective: The aim was to assess acceptability and experiences with 3D scans measuring child aged 0-59 mo anthropometry in population-based surveys and surveillance systems in Guatemala, Kenya, and China (0-23 mo only) among field teams and caregivers of young children as secondary objectives of an external effectiveness evaluation. Methods: Manual data were collected twice and 12 images captured per child by anthropometrist/expert and assistant (AEA) field teams (individuals/country, n = 15/Guatemala, n = 8/Kenya, n = 6/China). Caregivers were interviewed after observing their child's manual and scan data collection. Mixed methods included an administered caregiver interview (Guatemala, n = 465; Kenya, n = 496; China, n = 297) and self-administered AEA questionnaire both with closed- and open-ended questions, and 6 field team focus group discussions (FGDs; Guatemala, n = 2; Kenya, n = 3; China, n = 1). Qualitative data were coded by 2 authors and quantitative data produced descriptive statistics. Mixed-method results were compared and triangulated. Results: Most AEAs were female with secondary or higher education. Approximately 80-90% of caregivers were the child's mother. To collect all anthropometry data, 62.1% of the 29 AEAs preferred scan, while 31% preferred manual methods. In FGDs, a key barrier for manual and scan methods was lack of child cooperation. Across countries, approximately 30% to almost 50% of caregivers said their child was bothered by each manual and scan method, while ≥95% of caregivers were willing to have their child measured by scans in the future. Conclusions: Use of 3D scans to calculate anthropometry measurements was generally at least as acceptable as manual anthropometry measurement among AEA field workers and caregivers of young children aged <60 mo, and in some cases preferred.

Physiologically based serum ferritin thresholds for iron deficiency in children and non-pregnant women: a US National Health and Nutrition Examination Surveys (NHANES) serial cross-sectional study.

BACKGROUND: Serum ferritin concentrations are the most widely used indicator for iron deficiency. WHO determined that insufficient data are available to revise the serum ferritin thresholds of less than 12 µg/L for children and less than 15 µg/L for women, which were developed on the basis of expert opinion, to define iron deficiency. We aimed to derive new physiologically based serum ferritin concentration thresholds for iron deficiency in healthy young children and non-pregnant women using data from the US National Health and Nutrition Examination Survey (NHANES). METHODS: In this serial cross-sectional study, we examined the relationship of serum ferritin with two independent indicators of iron-deficient erythropoiesis, haemoglobin and soluble transferrin receptor (sTfR), in children (12-59 months) and non-pregnant women (15-49 years) using cross-sectional NHANES data from 2003-06, 2007-10, and 2015-18. NHANES is a US national stratified multistage probability sample that includes a household interview followed by a standardised physical examination in a mobile examination centre. We excluded individuals with missing serum ferritin, sTfR, haemoglobin, or white blood cell counts measurements; non-pregnant women with missing C-reactive protein (CRP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) data were also excluded. In addition, individuals with infection (white blood cell counts >10·0×109/L) and non-pregnant women with possible liver disease (ALT >70 IU/L or AST >70 IU/L) and inflammation (CRP >5·0 mg/L) were excluded. We examined distributions of haemoglobin and sTfR with serum ferritin and used restricted cubic spline regression models to determine serum ferritin thresholds for iron-deficient erythropoiesis. FINDINGS: 5964 children and 10 462 non-pregnant women had physical examinations and were screened for inclusion in the study, of whom 2569 (43·1%) children and 7498 (71·7%) non-pregnant women were included. At lower serum ferritin concentrations, median haemoglobin concentration decreased as sTfR concentration increased, with each varying in a curvilinear manner. Using restricted cubic spline plateau points to determine the onset of iron-deficient erythropoiesis, the serum ferritin thresholds identified by haemoglobin and sTfR concentrations were not different. For children, the haemoglobin identified serum ferritin threshold was 19·9 µg/L (95% CI 18·8-22·6) and the sTfR identified serum ferritin threshold was 20·0 µg/L (19·4-20·9; p=0·89). For women the haemoglobin identified serum ferritin threshold was 25·2 µg/L (24·2-26·2) and the sTfR identified serum ferritin threshold was 24·0 µg/L (23·3-24·6; p=0·05). INTERPRETATION: The association between two independent indicators of iron-deficient erythropoiesis, haemoglobin and sTfR, identified serum ferritin concentration thresholds of about 20 µg/L for children and 25 µg/L for non-pregnant women, providing physiological evidence of potential new thresholds for consideration when determining the prevalence and distribution of iron deficiency in populations. In healthy children and non-pregnant women, physiologically based thresholds for iron deficiency might be more clinically and epidemiologically relevant than those based on expert opinion. Validation of this physiologically based approach in non-US populations might help the international harmonisation of serum ferritin thresholds for iron deficiency. FUNDING: None.