Predictors of anaemia in mothers and children in Uttar Pradesh, India.

OBJECTIVE: Anaemia affects more than half of Indian women and children, but the contribution of its causes remains unquantified. We examined interrelationships between Hb and nutritional, environmental, infectious and genetic determinants of anaemia in non-pregnant mothers and children in Uttar Pradesh (UP). DESIGN: We conducted a cross-sectional survey of households in twenty-five districts of UP between October and December 2016. We collected socio-demographic data, anthropometry and venous blood in 1238 non-pregnant mothers and their children. We analysed venous blood samples for malaria, Hb, ferritin, retinol, folate, Zn, vitamin B12, C-reactive protein, α1-acid glycoprotein (AGP) and ß-thalassaemia. We used path analysis to examine pathways through which predictors of anaemia were associated with Hb concentration. SETTING: Rural and urban households in twenty-five districts of UP. PARTICIPANTS: Mothers 18-49 years and children 6-59 months in UP. RESULTS: A total of 36·4 % of mothers and 56·0 % of children were anaemic, and 26·7 % of women and 44·6 % of children had Fe deficiency anaemia. Ferritin was the strongest predictor of Hb (ß (95 % CI) = 1·03 (0·80, 1·27) g/dL in women and 0·90 (0·68, 1·12) g/dL in children). In children only, red blood cell folate and AGP were negatively associated with Hb and retinol was positively associated with Hb. CONCLUSIONS: Over 70 % of mothers and children with anaemia had Fe deficiency, needing urgent attention. However, several simultaneous predictors of Hb exist, including nutrient deficiencies and inflammation. The potential of Fe interventions to address anaemia may be constrained unless coexisting determinants are jointly addressed.

Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial.

INTRODUCTION: Approximately 40% of children aged 6-59 months worldwide are anaemic. Iron-containing multiple micronutrient powders (MNPs) and iron supplements (syrup/drops) are used to combat anaemia in children in different parts of the world. However, evidence for functional benefits of iron supplementation in children is scarce, and potential risks remain poorly defined, particularly concerning diarrhoea and malaria. This trial aims to determine if: (1) the efficacy of iron supplements or MNPs (containing iron) given with malaria chemoprevention is superior to malaria chemoprevention alone, or (2) if the efficacy of malaria chemoprevention alone is superior to placebo on child cognitive development. METHODS AND ANALYSIS: IRMA is a four-arm, parallel-group, double-blinded, placebo-controlled, triple-dummy, randomised trial in Southern Malawi. The study recruits 2168 infants aged 6 months, with an intervention period of 6 months and a post-intervention period of a further 6 months. Children are randomised into four arms: (1) No intervention (placebo); (2) malaria chemoprevention only; (3) MNPs and malaria chemoprevention; and (4) iron syrup and malaria chemoprevention. The primary outcome, cognitive development (Cognitive Composite Score (CogCS)), is measured at the end of the 6 months intervention. Secondary outcomes include CogCS at a further 6 months post-intervention, motor, language and behavioural development, physical growth and prevalence of anaemia and iron deficiency. Safety outcomes include incidence of malaria and other infections, and prevalence of malaria parasitaemia during and post-intervention period. ETHICS AND DISSEMINATION: The trial is approved by the National Health Sciences Research Committee (#19/01/2213) (Malawi) and the Human Research Ethics Committee (WEHI: 19/012) (Australia). Written informed consent in the local language is obtained from each participant before conducting any study-related procedure. Results will be shared with the local community and internationally with academic and policy stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12620000386932.

Prevalence of early postpartum depression and associated risk factors among selected women in southern Malawi: a nested observational study.

BACKGROUND: The birth of a child should be a time of celebration. However, for many women, childbirth represents a time of great vulnerability to becoming mentally unwell, a neglected maternal morbidity. This study aimed to determine the prevalence of early postpartum depression (PPD) and its associated risk factors among women giving birth at health facilities in southern Malawi. Identifying women vulnerable to PPD will help clinicians provide appropriately targeted interventions before discharge from the maternity ward. METHOD: We conducted a nested cross-sectional study. Women were screened for early PPD using a locally validated Edinburgh Postpartum Depression Scale (EPDS) as they were discharged from the maternity ward. The prevalence of moderate or severe (EPDS ≥ 6) and severe (EPDS ≥ 9) PPD was determined, including 95% confidence intervals (CI). Data on maternal age, education and marital status, income source, religion, gravidity, and HIV status, among others, were collected during the second trimester of pregnancy, and obstetric and infant characteristics during childbirth were examined as potential risk factors for early PPD using univariable and multivariable logistic regression analyses. RESULTS: Data contributed by 636 women were analysed. Of these women, 9.6% (95% CI; 7.4-12.1%) had moderate to severe early PPD using an EPDS cut-off of ≥ 6, and 3.3% (95% CI; 2.1-5.0%) had severe early PPD using an EPDS cut-off of ≥ 9. Multivariable analyses indicated that maternal anaemia at birth (aOR; 2.65, CI; 1.49-4.71, p-value; 0.001) was associated with increased risk for moderate and/or severe early PPD, while live birth outcome (aOR; 0.15, 95% CI; 0.04-0.54, p-value; 0.004), being single compared to divorced/widowed (aOR; 0.09, 95% CI; 0.02-0.55, p-value; 0.009), and lower education level (aOR; 0.36, 95% CI; 0.20-0.65, p-value; 0.001) were associated with decreased risk. Being HIV positive (aOR; 2.88, 95% CI; 1.08-7.67, p-value; 0.035) was associated with severe PPD only. CONCLUSION: The prevalence of early PPD was slightly lower in our selected sample compared to previous reports in Malawi and was associated with maternal anaemia at birth, non-live birth, being divorced/widowed and HIV-positive status. Therefore, health workers should screen for depressive symptoms in women who are at increased risk as they are discharged from the maternity ward for early identification and treatment.

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.

BACKGROUND: Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. METHODS: In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. FINDINGS: Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). INTERPRETATION: In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. FUNDING: Bill & Melinda Gates Foundation (INV-010612).

Supplementation With Iron Syrup or Iron-Containing Multiple Micronutrient Powders Alters Resting Brain Activity in Bangladeshi Children.

BACKGROUND: Anemia and iron deficiency have been associated with poor child cognitive development. A key rationale for the prevention of anemia using supplementation with iron has been the benefits to neurodevelopment. However, little causal evidence exists for these gains. OBJECTIVES: We aimed to examine effects of supplementation with iron or multiple micronutrient powders (MNPs) on brain activity measures using resting electroencephalography (EEG). METHODS: Children included in this neurocognitive substudy were randomly selected from the Benefits and Risks of Iron Supplementation in Children study, a double-blind, double-dummy, individually randomized, parallel-group trial in Bangladesh, in which children, starting at 8 mo of age, received 3 mo of daily iron syrup, MNPs, or placebo. Resting brain activity was recorded using EEG immediately after intervention (month 3) and after a further 9-month follow-up (month 12). We derived EEG band power measures for delta, theta, alpha, and beta frequency bands. Linear regression models were used to compare the effect of each intervention with that of placebo on the outcomes. RESULTS: Data from 412 children at month 3 and 374 at month 12 were analyzed. At baseline, 43.9% were anemic and 26.7% were iron deficient. Immediately after intervention, iron syrup, but not MNPs, increased the mu alpha-band power, a measure that is associated with maturity and the production of motor actions (iron vs. placebo: mean difference = 0.30; 95% CI: 0.11, 0.50 µV2; P = 0.003; false discovery rate adjusted P = 0.015). Despite effects on hemoglobin and iron status, effects were not observed on the posterior alpha, beta, delta, and theta bands, nor were effects sustained at the 9-month follow-up. CONCLUSIONS: The effect size for immediate effects on the mu alpha-band power is comparable in magnitude with psychosocial stimulation interventions and poverty reduction strategies. However, overall, we did not find evidence for long-lasting changes in resting EEG power spectra from iron interventions in young Bangladeshi children. This trial was registered at www.anzctr.org.au as ACTRN12617000660381.

Effects of iron supplementation on neural indices of habituation in Bangladeshi children.

BACKGROUND: Iron deficiency and anemia have been associated with poor cognition in children, yet the effects of iron supplementation on neurocognition remain unclear. OBJECTIVE: We aimed to examine the effects of supplementation with iron on neural indices of habituation using auditory event-related brain potentials (ERPs). METHODS: This substudy was nested within a 3-arm, double-blind, double-dummy, individual randomized trial in Bangladesh, in which 3300 8-mo-old children were randomly selected to receive 3 mo of daily iron syrup (12.5 mg iron), multiple micronutrient powders (MNPs) (including 12.5 mg iron), or placebo. Children were assessed after 3 mo of intervention (mo 3) and 9 mo thereafter (mo 12). The neurocognitive substudy comprised a randomly selected subset of children from the main trial. Brain activity elicited during an auditory roving oddball task was recorded using electroencephalography to provide an index of habituation. The differential response to a novel (deviant) compared with a repeated (standard) sound was examined. The primary outcome was the amplitude of the mismatch response (deviant minusstandard tone waveforms) at mo 3. Secondary outcomes included the deviant and standard tone-evoked amplitudes, N2 amplitude differences, and differences in mean amplitudes evoked by deviant tones presented in the second compared with first half of the oddball sequence at mo 3 and 12. RESULTS: Data were analyzed from 329 children at month 3 and 363 at mo 12. Analyses indicated no treatment effects of iron interventions compared with placebo on the amplitude of the mismatch response (iron syrup compared with placebo: mean difference (MD) = 0.07µV [95% CI: -1.22, 1.37]; MNPs compared with placebo: MD = 0.58µV [95% CI: -0.74, 1.90]) nor any secondary ERP outcomes at mo 3 or 12, despite improvements in hemoglobin and ferritin concentrations from iron syrup and MNPs in this nested substudy. CONCLUSION: In Bangladeshi children with >40% anemia prevalence, iron or MNP interventions alone are insufficient to improve neural indices of habituation. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12617000660381.

Effectiveness of the Eggs Make Kids demand-creation campaign at improving household availability of eggs and egg consumption by young children in Nigeria: A quasi-experimental study.

Using a quasi-experimental design, our study aimed to determine the effectiveness of the 'Eggs Make Kids Sharp & Bright and Strong & Active' demand-creation campaign in Nigeria. The intervention arm received emotionally compelling radio and television advertisements about eggs, and was exposed to promotional activities and advertising about eggs at points of purchase, schools and health facilities; the comparison arm received no intervention. Children 6-59 months of age (intervention: n = 1359; comparison: n = 1485) were assessed 14 months apart. Intent-to-treat analyses with analysis of covariance method assessed the impact of the intervention on caregivers' behaviour towards eggs, caregivers' willingness to pay for eggs, availability of eggs in households, and consumption of eggs by children 6-59 months of age. Analyses were adjusted for possible confounders and perceived effects of COVID-19 on finances and food consumption. Compared to the comparison arm, the intervention arm showed a greater prevalence of household egg acquisition (odds ratio = 1.34, p < 0.0001), and larger improvements in caregiver self-efficacy (ß = 0.242, p = 0.004) and intent to feed eggs to children (ß = 0.080, p = 0.021). No effects were found on children's egg consumption or caregivers' reported willingness to pay for eggs. The lack of impact on child egg consumption despite increased acquisition of eggs and caregiver self-efficacy suggests that other barriers to child consumption may exist. Additional research should further investigate factors that may influence intrahousehold distribution of eggs and whether these may also influence other nutritious foods.

Reliability and validity of depression anxiety stress scale (DASS)-21 in screening for common mental disorders among postpartum women in Malawi.

BACKGROUND: Approximately one in five women who have recently given birth suffer from common mental disorder (CMD), particularly depression and/or anxiety. Most available CMD screening tools in most low- and middle-income countries do not screen for more than one mental health problem. Having a screening tool that is free to use, short in assessment time, and used to screen for more than one CMD is appealing in a resource-constrained setting. METHOD: We conducted a criterion validation study of the Chichewa translated and adapted DASS-21 instrument against gold standard diagnoses of depression and anxiety disorders using an independently administered Structured Clinical Interview for DSM-IV (SCID). We compared the performance of the DASS-depression subscale with the Edinburgh Postpartum Depression Scale (EPDS). Internal reliability was reported using both Cronbach's alpha and ordinal alpha. The DASS-21 and EPDS ability to discriminate cases from non-cases was assessed by receiver operating characteristics (ROC) analysis. We selected cut-off points for DASS-21 and EPDS that maximise both sensitivity and specificity. RESULTS: One hundred fifteen participants were administered all the measures. Approximately 11.3% and 14.8% had depression and anxiety diagnoses respectively using SCID. The overall Cronbach's alpha for the DASS-21 scale was 0.74. The DASS-21 subscales had Cronbach's alpha values of 0.66, 0.29 and 0.52 for depression (DASS-D), anxiety (DASS-A) and stress (DASS-S), respectively. The ordinal alpha for DASS-D, DASS-A and DASS-S subscales were 0.83, 0.74 and 0.87, respectively. The area under the ROC curve was 0.76 (95% CI: 0.61; 0.91) for DASS-D and 0.65 for DASS-A. At a cut-off point of one or more, the sensitivity and specificity for DASS-D were 69.2% and 75.5%, whilst DASS-A was 52.9% and 75.5%, respectively. Pearson correlation coefficient for the association between DASS-D and EPDS was r = 0.61, p < 0.001. CONCLUSION: The DASS-21 had good internal reliability (Cronbach's alpha), and its ordinal alpha demonstrated good internal reliability for all its sub-scales. Regarding the criterion validation, only the DASS-D and EPDS demonstrated a satisfactory ability to discriminate cases from non-cases. Our findings suggest that health practitioners can use DASS-D as an alternative tool in screening depression as it has fewer questions than EPDS.

Benefits and Risks of Iron Interventions in Infants in Rural Bangladesh.

BACKGROUND: Universal provision of iron supplements (drops or syrup) or multiple micronutrient powders to young children in low-to-middle-income countries where anemia is prevalent is recommended by the World Health Organization and widely implemented. The functional benefits and safety of these interventions are unclear. METHODS: We conducted a three-group, double-blind, double-dummy, individually randomized, placebo-controlled trial to assess the immediate and medium-term benefits and risks of 3 months of daily supplementation with iron syrup or iron-containing multiple micronutrient powders, as compared with placebo, in 8-month-old children in rural Bangladesh. The primary outcome was cognitive development, as assessed by the cognitive composite score on the Bayley Scales of Infant and Toddler Development, third edition, immediately after completion of the assigned 3-month regimen; scores range from 55 to 145, with higher scores indicating better cognitive performance. Secondary outcomes included the cognitive composite score at 9 months after completion of the assigned regimen; behavioral, language, and motor development, as well as growth and hematologic markers, immediately after completion and at 9 months after completion; and safety. RESULTS: We randomly assigned 3300 infants to receive iron syrup (1101 infants), multiple micronutrient powders (1099), or placebo (1100) daily. After completion of the assigned 3-month regimen, no apparent effect on the cognitive composite score was observed with iron syrup as compared with placebo (mean between-group difference in change in score from baseline, -0.30 points; 95% confidence interval [CI], -1.08 to 0.48) or with multiple micronutrient powders as compared with placebo (mean between-group difference in change in score from baseline, 0.23 points; 95% CI, -0.55 to 1.00). No apparent effect on any other developmental or growth outcome was observed immediately after completion of the assigned regimen or at 9 months after completion. At 9 months after completion of the assigned regimen, the prevalences of anemia, iron deficiency, and iron deficiency anemia increased in all three trial groups but remained lower among the children who received iron syrup or multiple micronutrient powders than among those who received placebo. The risk of serious adverse events and incidence of symptoms of infection were similar in the three trial groups. CONCLUSIONS: In this trial involving infants in Bangladesh, 3 months of daily supplementation with iron syrup or multiple micronutrient powders did not appear to have an effect on child development or other functional outcomes as compared with placebo. (Funded by the National Health and Medical Research Council of Australia; BRISC Australian New Zealand Clinical Trials Registry number, ACTRN12617000660381.).

Preanalytic and analytic factors affecting the measurement of haemoglobin concentration: impact on global estimates of anaemia prevalence.

The accuracy of haemoglobin concentration measurements is crucial for deriving global anaemia prevalence estimates and monitoring anaemia reduction strategies. In this analysis, we examined and quantified the factors affecting preanalytic and analytic variation in haemoglobin concentrations. Using cross-sectional data from three field studies (in children, pregnant and nonpregnant women), we examined the difference in haemoglobin concentration between venous-drawn and capillary-drawn blood measured by HemoCue (ie, preanalytic) and modelled how the bias observed may affect anaemia prevalence estimates in population surveys and anaemia public health severity classification across countries. Using data from an international quality assurance programme, we examined differences due to instrumentation from 16 different haematology analyzers (ie, analytic). Results indicated that capillary and venous haemoglobin concentrations are not in agreement (bias +5.7 g/L (limits of agreement (LoA) -11.2, 22.6) in preschool age children; range from -28 g/L to +20 g/L in pregnant women; bias +8.8 g/L (LoA -5.2, 22.9) in non-pregnant women). The bias observed could introduce changes in population survey estimates of anaemia of up to -20.7 percentage points in children and -28.2 percentage points in non-pregnant women after venous adjustment. Analytic variation was minimal and unlikely to influence the diagnosis of anaemia. These findings suggest that global estimates of anaemia prevalence derived from capillary haemoglobin, as they often are, may be inaccurate and lead to erroneous public health severity classification, but that point-of-care, or other, instruments should not introduce variation if properly used.

Home Fortification of Complementary Foods Reduces Anemia and Diarrhea among Children Aged 6-18 Months in Bihar, India: A Large-Scale Effectiveness Trial.

BACKGROUND: Home fortification of complementary foods with multiple micronutrient powders (MNPs) is recommended to reduce child anemia in resource-poor settings. However, evidence of program effectiveness in India to guide policies and programs is lacking. OBJECTIVES: We implemented a large-scale intervention of MNPs in Bihar, India. The primary outcome was MNP consumption and change in hemoglobin concentration among children aged 6-18 mo between baseline and endline (12 mo). Secondary outcomes were change in child weight and length and infant and young child feeding (IYCF) practices (initiation, diversity, and feeding frequency). Ad hoc analyses included changes in anemia; stunting; underweight; wasting; and reported diarrhea, fever, and hospitalization. METHODS: We conducted a cluster-randomized, effectiveness trial in >4000 children within the context of ongoing health and nutrition programs implemented by CARE, India. Seventy health subcenters were randomly assigned to receive either MNPs with IYCF counseling (intervention) or IYCF counseling only (control). We used an adjusted difference-in-difference approach using repeat cross-sectional surveys at baseline and endline to evaluate impact. RESULTS: At baseline, 75% of intervention and 69% of control children were anemic and 33% were stunted. By endline, 70% of intervention households reported their child had ever consumed MNPs, and of those, 64% had consumed MNPs in the past month. Relative to control, hemoglobin concentration increased (0.22 g/dL; 95% CI: 0.00, 0.44 g/dL) and anemia declined by 7.1 percentage points (pp) (95% CI: -13.5, -0.7 pp). There was no impact on anthropometry nor IYCF practices. However, there was a decline of 8.0 pp (95% CI: -14.9, -1.1 pp) in stunting among children aged 12-18 mo. Diarrhea prevalence in the past 2 wk was reduced by 4.0 pp (95% CI: -7.6, -0.4 pp). CONCLUSIONS: Home fortification of complementary foods within a government-run program in Bihar had moderate compliance and caused modest improvements in hemoglobin and reductions in anemia and diarrhea prevalence.

Can Double Fortification of Salt with Iron and Iodine Reduce Anemia, Iron Deficiency Anemia, Iron Deficiency, Iodine Deficiency, and Functional Outcomes? Evidence of Efficacy, Effectiveness, and Safety.

BACKGROUND: Anemia, iron deficiency, and iodine deficiency are problems of important public health concern in many parts of the world, with consequences for the health, development, and work capacity of populations. Several countries are beginning to implement double fortified salt (DFS) programs to simultaneously address iodine and iron deficiencies. OBJECTIVE: Our objective was to summarize the evidence for efficacy and effectiveness of DFS on the full range of status and functional outcomes and across different implementation and evaluation designs essential to successful interventions. METHODS: We conducted a systematic review and meta-analysis of published and gray literature examining the effects of DFS on nutritional status, cognition, work productivity, development, and morbidity of all population groups. We searched for articles in Medline, Embase, CINAHL, Cochrane Central Register, and ProQuest for randomized trials, quasi-randomized trials, and program effectiveness evaluations. RESULTS: A total of 22 studies (N individuals = 52,758) were included. Efficacy studies indicated a significant overall positive effect on hemoglobin concentration [standardized mean difference (95% CI): 0.33 (0.18, 0.48)], ferritin [0.42 (0.08, 0.76)], anemia [risk ratio (95% CI): 0.80 (0.70, 0.92)], and iron deficiency anemia [0.36 (0.24, 0.55)]. Effects on urinary iodine concentration were not significantly different between DFS and iodized salt. The impact on functional outcomes was mixed. Only 2 effectiveness studies were identified. They reported programmatic challenges including low coverage, suboptimal DFS quality, and storage constraints. CONCLUSIONS: Given the biological benefits of DFS across several populations in efficacy research, additional evaluations of robust DFS programs delivered at scale, which consider effective implementation and measure appropriate biomarkers, are needed.

Variability in haemoglobin concentration by measurement tool and blood source: an analysis from seven countries.

OBJECTIVE: We explore factors such as the blood sampling site (capillary vs venous), the equipment (HemoCue vs automated haematology analyser) and the model of the HemoCue device (201+ vs 301) that may impact haemoglobin measurements in capillary and venous blood. METHODS: Eleven studies were identified, and bias, concordance and measures of diagnostic performance were assessed within each study. FINDINGS: Our analysis included 11 studies from seven countries (Cambodia, India, The Gambia, Ghana, Laos, Rwanda and USA). Samples came from children, men, non-pregnant women and pregnant women. Mean bias ranged from -8.7 to 2.5 g/L in Cambodian women, 6.2 g/L in Laotian children, 2.4 g/L in Ghanaian women, 0.8 g/L in Gambian children 6-23 months and 1.4 g/L in Rwandan children 6-59 months when comparing capillary blood on a HemoCue to venous blood on a haematology analyser. Bias was 8.3 g/L in Indian non-pregnant women and 2.6 g/L in Laotian children and women and 1.5 g/L in the US population when comparing capillary to venous blood using a HemoCue. For venous blood measured on the HemoCue compared with the automated haematology analyser, bias was 5.3 g/L in Gambian pregnant women 18-45 years and 11.3 g/L in Laotian children 6-59 months. CONCLUSION: Our analysis found large variability in haemoglobin concentration measured on capillary or venous blood and using HemoCue Hb 201+ or Hb 301 or automated haematology analyser. We cannot ascertain whether the variation is due to differences in the equipment, differences in capillary and venous blood, or factors affecting blood collection techniques.

Balancing Safety and Potential for Impact in Universal Iron Interventions.

Almost 300 million children under 5 years of age are anemic worldwide. International policymakers recommend universal distribution of iron-based interventions - either iron supplements or iron-containing multiple micronutrient powders - to alleviate the burden of anemia in young children. When considering whether to implement universal iron interventions, it is essential to balance the putative benefits with possible risks. The key rationale for deploying universal iron interventions to reduce anemia in young children is to improve development, growth, and well-being. While plausible, few randomized controlled trials (RCTs) of iron interventions have carefully assessed these outcomes and there is currently inadequate evidence to support the hypothesis that universal iron interventions provide benefits on functional child health outcomes. Conversely, several important RCTs have found that when iron interventions are given to all children in a population, they may increase infection risk. Other possible risks of iron interventions have not yet been extensively described but include a risk of iron overdose and long-term iron loading in high-risk individuals. Identifying whether these interventions provide a net benefit or harm to populations is challenging. Until the quality of evidence for benefits improves, implementation of universal iron interventions in young children should be undertaken with caution.

Global Landscape of Malnutrition in Infants and Young Children.

Malnutrition during the first years of life has immediate adverse health consequences, including increased mortality risk, and impaired long-term health and capacities. Undernutrition is an important contributor to poor linear growth, stunting, which affects over 149 million children <5 years of age worldwide, one-third of whom live in India. Over 49 million children are wasted; yet globally, there are also 40 million overweight children. Up-to-date data on the magnitude and distribution of micronutrient malnutrition globally and in many countries are lacking. Anemia has been used as a proxy for micronutrient malnutrition; yet anemia, like stunting, has a complex etiology and numerous nonnutritional as well as nutritional causes. Undernutrition, specifically stunting, wasting, and micronutrient deficiency increasingly coexist with overweight, but accurate data to assess the extent to which these co-exist in countries, households, and individuals and the factors that predict it are scarce. Recent analyses in several countries suggest that there is substantial variability within and among regions in the prevalence and determinants of malnutrition. More and better data that can be used to tailor policies and programs to local contexts are urgently needed if we are to accelerate progress toward addressing malnutrition in all its forms.

The global effect of extreme weather events on nutrient supply: a superposed epoch analysis.

BACKGROUND: To date, the effects of extreme weather events on nutrient supply within the population have not been quantified. In this study, we investigated micronutrient, macronutrient, and fibre supply changes during 175 extreme weather events within 87 countries in the year that a major extreme weather event occurred, with a targeted focus on low-income settings. METHODS: We collected data from the International Disasters Database and the Global Expanded Nutrient Supply model for the period 1961-2010, and applied superposed epoch analysis to calculate the percentage change in nutrient supply during the year of an extreme weather event relative to its historical context. We composited globally and by subgroup (EU, landlocked developing countries, least developed countries, low-income food deficit countries, and net food-importing developing countries). Lastly, we reported nutrient supply changes in terms of recommended dietary allowance for children aged 1-3 years. FINDINGS: Globally, all micronutrient supplies had a modest negative percentage change during the year of an extreme weather event; of these effects, those that reached an α=0·05 significance level included calcium, folate, thiamin, vitamin B6, and vitamin C, with nutrient supply changes ranging from -0·40 to -1·73% of the average supply. The effect of an extreme weather event was especially magnified among landlocked developing countries and low-income food deficit countries, with significant nutrient supply changes ranging from -1·61 to -7·57% of the average supply. Furthermore, the observed nutrient supply deficits in landlocked developing countries constituted a large percentage (ranging from 1·95 to 39·19%) of what a healthy child's sufficient average dietary intake should be. INTERPRETATION: The global effects of extreme weather events on nutrient supply found in this study are modest in isolation; however, in the context of nutrient needs for healthy child development in low-income settings, the effects observed are substantial. FUNDING: Australian-American Fulbright Commission.

Do effects of early life interventions on linear growth correspond to effects on neurobehavioural development? A systematic review and meta-analysis.

BACKGROUND: Faltering in linear growth and neurobehavioural development during early childhood are often assumed to have common causes because of their consistent association. This notion has contributed to a global focus on the promotion of nutrition during pregnancy and childhood to improve both conditions. Our aim was to assess whether effects of interventions on linear growth are associated with effects on developmental scores and to quantify these associations. METHODS: In this systematic review and meta-analysis, we included randomised trials done during pregnancy and in children aged 0-5 years that reported effects of any intervention on length-for-age or height-for-age Z scores (LAZ or HAZ) and on any of the following outcomes: motor, cognitive or mental, language, and social-emotional or behavioural development. We searched MEDLINE (Ovid), CINAHL (EBSCO), and PsycINFO (EBSCO) from database inception to June 25, 2019. Study-level data were extracted and, when required, authors were contacted for missing information. We calculated weighted meta-regression coefficients of the association between standardised effect sizes of interventions on LAZ or HAZ and developmental outcome scores and calculated pooled effect sizes for different types of intervention. FINDINGS: Of the 7207 studies identified, we included 75 studies with 122 comparisons between intervention and control groups and outcomes reported for 72 275 children. Across all interventions, effect sizes on LAZ or HAZ were significantly associated with effect sizes on social-emotional scores (ß 0·23, 95% CI 0·05 to 0·41; p=0·02), but not on cognitive (0·18, -0·36 to 0·72; p=0·51), language (0·12, -0·07 to 0·31; p=0·21), or motor development scores (0·23, -0·05 to 0·50; p=0·11). In studies that provided nutritional supplements, we observed positive significant pooled effect sizes on all five outcomes of LAZ or HAZ (effect size 0·05, 95% CI 0·01-0·09; p=0·01; n=50), cognitive or mental (0·06, 0·03-0·10; p<0·01; n=38), language (0·08, 0·03-0·13; p=0·01; n=21), motor (0·08, 0·04-0·12; p<0·01; n=41), and social-emotional (0·07, 0·02-0·12; p=0·01; n=20) scores. The effect sizes of nutritional supplementation on LAZ or HAZ scores were significantly associated with effect sizes on cognitive (ß 0·40, 95% CI 0·04-0·77; p=0·049) and motor (0·43, 0·11-0·75; p=0·01) scores. In the 14 interventions promoting responsive care and learning opportunities, the pooled effect size on LAZ or HAZ score was not significant (-0·01, 95% CI -0·07 to 0·05; p=0·74), but pooled effect sizes on cognitive, language, and motor scores were 4 to 5 times larger (range 0·38-0·48) than the pooled effect sizes of nutritional supplementation (0·05-0·08). INTERPRETATION: In nutritional supplementation interventions, improvements in linear growth were associated with small improvements in child development, whereas nurturing and stimulation interventions had significant effects on child development but no effects on linear growth. The determinants of linear growth and neurodevelopment are only partly shared. To nurture thriving individuals and communities, interventions should specifically target determinants of neurodevelopment and not simply linear growth. FUNDING: University of California Davis, US Department of Agriculture National Institute of Food and Agriculture.

Hemoglobin concentration and anemia diagnosis in venous and capillary blood: biological basis and policy implications.

Anemia is an important public health challenge and accurate prevalence estimates are needed for program planning and tracking progress. While venous blood assessed by automated hematology analyzers is considered gold standard, most population-based surveys use point-of-care diagnostics and capillary blood to estimate population prevalence of anemia. Several factors influence hemoglobin (Hb) concentration, including human and analytic error, analysis method, and type of instrument, but it is unclear whether biological variability exists between venous and capillary blood. The objective of this paper was to systematically review sources of Hb variability and the potential biological basis for venous and capillary differences. We use data from a recent survey in the state of Uttar Pradesh, India, to illustrate the implications on anemia prevalence estimates. Significant differences in Hb concentration between capillary and venous blood samples are common. Most but not all find capillary Hb concentration to be higher than venous. Instrument/method variability and human error play an important role, but cannot fully explain these differences. A normative guide to data collection, analysis, and anemia diagnosis is needed to ensure consistent and appropriate interpretation. Further research is needed to fully understand the biological implications of venous and capillary Hb variability.