Parminder S. Suchdev

Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE)

An increasing recognition has emerged of the complexities of the global health agenda—specifically, the collision of infections and noncommunicable diseases and the dual burden of over- and undernutrition. Of particular practical concern are both 1) the need for a better understanding of the bidirectional relations between nutritional status and the development and function of the immune and inflammatory response and 2) the specific impact of the inflammatory response on the selection, use, and interpretation of nutrient biomarkers. The goal of the Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE) is to provide guidance for those users represented by the global food and nutrition enterprise. These include researchers (bench and clinical), clinicians providing care/treatment, those developing and evaluating programs/interventions at scale, and those responsible for generating evidence-based policy. The INSPIRE process included convening 5 thematic working groups (WGs) charged with developing summary reports around the following issues: 1) basic overview of the interactions between nutrition, immune function, and the inflammatory response; 2) examination of the evidence regarding the impact of nutrition on immune function and inflammation; 3) evaluation of the impact of inflammation and clinical conditions (acute and chronic) on nutrition; 4) examination of existing and potential new approaches to account for the impact of inflammation on biomarker interpretation and use; and 5) the presentation of new approaches to the study of these relations. Each WG was tasked with synthesizing a summary of the evidence for each of these topics and delineating the remaining gaps in our knowledge. This review consists of a summary of the INSPIRE workshop and the WG deliberations.

Selling Sprinkles micronutrient powder reduces anemia, iron deficiency, and vitamin A deficiency in young children in Western Kenya: a cluster-randomized controlled trial

BACKGROUND Although the efficacy of micronutrient powders [MNPs; eg, Sprinkles MNP (Sprinkles Global Health Initiative)] in the reduction of anemia has been established, the effectiveness of these powders in real-world programs has seldom been assessed. OBJECTIVE In this study, we evaluated the effect of community-based marketing and distribution of Sprinkles MNP on childhood rates of anemia and iron and vitamin A deficiency. DESIGN In a cluster-randomized trial in children aged 6-35 mo in Western Kenya, 60 villages were randomly assigned to either intervention or control groups. Community vendors marketed and sold sachets of Sprinkles MNP in intervention villages. Biweekly household visits monitored the use of Sprinkles MNP. Hemoglobin, ferritin, retinol binding protein, malaria, and anthropometric measures were assessed at baseline (n = 1063) and 12 mo of follow-up (n = 862). Data were analyzed by using an intention-to-treat analysis and generalized linear mixed models. RESULTS On average, 33% of households in intervention villages purchased Sprinkles MNP; the average weekly intake per child was 0.9 sachets (∼11.3 mg Fe and ∼328 μg vitamin A). Compared with control subjects, intervention children had greater improvements in hemoglobin concentrations (increase of 0.9 compared with 0.6 g/dL, respectively; P = 0.02), iron deficiency (decrease of 19.3% compared with 5.3%, respectively; P = 0.001), and vitamin A deficiency (decrease of 7.5% compared with an increase of 2.5%, respectively; P = 0.01). Results adjusted for age, sex, socioeconomic status, and maternal education showed a significant association between the hemoglobin, iron, and vitamin A concentrations of children and the number of Sprinkles MNP sachets the children consumed. The prevalence of malaria, wasting, and stunting did not change significantly in either group. CONCLUSION Even with relatively low and infrequent use, Sprinkles MNP sales through community vendors were associated with decreased rates of anemia and iron and vitamin A deficiency in children in a resource-poor setting. This trial was registered at clinicaltrials.gov as NCT01088958.

Correcting for Inflammation Changes Estimates of Iron Deficiency among Rural Kenyan Preschool Children

The assessment of iron status where infections are common is complicated by the effects of inflammation on iron indicators and in this study we compared approaches that adjust for this influence. Blood was collected in 680 children (aged 6-35 mo) and indicators of iron status [(hemoglobin (Hb), zinc protoporphyrin (ZP), ferritin, transferrin receptor (TfR), and TfR/ferritin index)] and subclinical inflammation [(the acute phase proteins (APP) C-reactive protein (CRP), and α-1-acid glycoprotein (AGP)] were determined. Malaria parasitemia was assessed. Subclinical inflammation was defined as CRP >5 mg/L and/or AGP >1 g/L). Four groups were defined based on APP levels: reference (normal CRP and AGP), incubation (raised CRP and normal AGP), early convalescence (raised CRP and AGP), and late convalescence (normal CRP and raised AGP). Correction factors (CF) were estimated as the ratios of geometric means of iron indicators to the reference group of those for each inflammation group. Corrected values of iron indicators within inflammation groups were obtained by multiplying values by their respective group CF. CRP correlated with AGP (r = 0.65; P < 0.001), ferritin (r = 0.38; P < 0.001), Hb (r = -0.27; P < 0.001), and ZP (r = 0.16; P < 0.001); AGP was correlated with ferritin (r = 0.39; P < 0.001), Hb (r = -0.29; P < 0.001), and ZP (r = 0.24; P < 0.001). Use of CF to adjust for inflammation increased the prevalence of ID based on ferritin < 12 μg/L by 34% (from 27 to 41%). Applying the CF strengthened the expected relationship between Hb and ferritin (r = 0.10; P = 0.013 vs. r = 0.20; P < 0.001, before and after adjustment, respectively). Although the use of CF to adjust for inflammation appears indicated, further work is needed to confirm that this approach improves the accuracy of assessment of ID.

Overview of the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) Project

Anemia remains a widespread public health problem. Although iron deficiency is considered the leading cause of anemia globally, the cause of anemia varies considerably by country. To achieve global targets to reduce anemia, reliable estimates of the contribution of nutritional and non-nutritional causes of anemia are needed to guide interventions. Inflammation is known to affect many biomarkers used to assess micronutrient status and can thus lead to incorrect diagnosis of individuals and to overestimation or underestimation of the prevalence of deficiency in a population. Reliable assessment of iron status is particularly needed in settings with high infectious disease burden, given the call to screen for iron deficiency to mitigate potential adverse effects of iron supplementation. To address these information gaps, in 2012 the CDC, National Institute for Child Health and Human Development, and Global Alliance for Improved Nutrition formed a collaborative research group called Biomarkers Reflecting Inflammation and Nutrition Determinants of Anemia (BRINDA). Data from nationally and regionally representative nutrition surveys conducted in the past 10 y that included preschool children and/or women of childbearing age were pooled. Of 25 data sets considered for inclusion, 17 were included, representing ∼30,000 preschool children, 26,000 women of reproductive age, and 21,000 school-aged children from all 6 WHO geographic regions. This article provides an overview of the BRINDA project and describes key research questions and programmatic and research implications. Findings from this project will inform global guidelines on the assessment of anemia and micronutrient status and will guide the development of a research agenda for future longitudinal studies.

Monitoring the marketing, distribution, and use of Sprinkles micronutrient powders in rural western Kenya.

Background In 2007, the US Centers for Disease Control and Prevention partnered with local Kenyan institutions to implement the Nyando Integrated Child Health and Education Project, an effectiveness study that used social marketing and a community-based distribution program to promote the sale of Sprinkles and other health products. Objective To describe monitoring of wholesale sales, household demand, promotional strategies, and perceived factors influencing Sprinkles sales among vendors. Methods Ongoing quantitative and qualitative monitoring of Sprinkles sales began in May 2007 in 30 intervention villages. Data sources included baseline and follow-up cross-sectional surveys; office records of Sprinkles sales to vendors; biweekly household monitoring of Sprinkles use; and qualitative data collection, including vendor focus groups and key informant interviews. Results A total of 550 children aged 6 to 35 months were enrolled at baseline, and 451 were available at 12-month follow-up. During this period, nearly 160,000 sachets were sold wholesale to vendors, with variability in sales influenced by the social, political, and economic context. Vendors living closer to the wholesale office purchased more Sprinkles, so a second office was opened closer to remote vendors. On average, 33% of house-holds purchased Sprinkles during household monitoring visits. Training sessions and community launches were important for community support and raising awareness about Sprinkles. Vendor incentives motivated vendors to sell Sprinkles, and consumer incentives promoted purchases. Conclusions Sprinkles program monitoring in Kenya was critically important for understanding sales and distribution trends and vendor perceptions. Understanding these trends led to strategic changes to the intervention over time.

Determinants of Anemia among Preschool Children in Rural, Western Kenya

Although anemia in preschool children is most often attributed to iron deficiency, other nutritional, infectious, and genetic contributors are rarely concurrently measured. In a population-based, cross-sectional survey of 858 children 6–35 months of age in western Kenya, we measured hemoglobin, malaria, inflammation, sickle cell, α-thalassemia, iron deficiency, vitamin A deficiency, anthropometry, and socio-demographic characteristics. Anemia (Hb < 11 g/dL) and severe anemia (Hb < 7 g/dL) prevalence ratios (PRs) for each exposure were determined using multivariable modeling. Anemia (71.8%) and severe anemia (8.4%) were common. Characteristics most strongly associated with anemia were malaria (PR: 1.7; 95% confidence interval [CI] = 1.5–1.9), iron deficiency (1.3; 1.2–1.4), and homozygous α-thalassemia (1.3; 1.1–1.4). Characteristics associated with severe anemia were malaria (10.2; 3.5–29.3), inflammation (6.7; 2.3–19.4), and stunting (1.6; 1.0–2.4). Overall 16.8% of anemia cases were associated with malaria, 8.3% with iron deficiency, and 6.1% with inflammation. Interventions should address malaria, iron deficiency, and non-malarial infections to decrease the burden of anemia in this population.

A proposed model curriculum in global child health for pediatric residents

OBJECTIVE In response to the increasing engagement in global health (GH) among pediatric residents and faculty, academic GH training opportunities are growing rapidly in scale and number. However, consensus to guide residency programs regarding best practice guidelines or model curricula has not been established. We aimed to highlight critical components of well-established GH tracks and develop a model curriculum in GH for pediatric residency programs. METHODS We identified 43 existing formal GH curricula offered by U.S. pediatric residency programs in April 2011 and selected 8 programs with GH tracks on the basis of our inclusion criteria. A working group composed of the directors of these GH tracks, medical educators, and trainees and faculty with GH experience collaborated to develop a consensus model curriculum, which included GH core topics, learning modalities, and approaches to evaluation within the framework of the competencies for residency education outlined by the Accreditation Council for Graduate Medical Education. RESULTS Common curricular components among the identified GH tracks included didactics in various topics of global child health, domestic and international field experiences, completion of a scholarly project, and mentorship. The proposed model curriculum identifies strengths of established pediatric GH tracks and uses competency-based learning objectives. CONCLUSIONS This proposed pediatric GH curriculum based on lessons learned by directors of established GH residency tracks will support residency programs in creating and sustaining successful programs in GH education. The curriculum can be adapted to fit the needs of various programs, depending on their resources and focus areas. Evaluation outcomes need to be standardized so that the impact of this curriculum can be effectively measured.

Identification, Prevention and Treatment of Iron Deficiency during the First 1000 Days

Iron deficiency is a global problem across the life course, but infants and their mothers are especially vulnerable to both the development and the consequences of iron deficiency. Maternal iron deficiency during pregnancy can predispose offspring to the development of iron deficiency during infancy, with potentially lifelong sequelae. This review explores iron status throughout these “first 1000 days” from pregnancy through two years of age, covering the role of iron and the epidemiology of iron deficiency, as well as its consequences, identification, interventions and remaining research gaps.

Comparison of indicators of iron deficiency in Kenyan children

BACKGROUND In the absence of a feasible, noninvasive gold standard, iron deficiency (ID) is best measured by the use of multiple indicators. However, the choice of an appropriate single iron biomarker to replace the multiple-criteria model for screening for ID at the population level continues to be debated. OBJECTIVE We compared ID defined as ≥ 2 of 3 abnormal ferritin (< 12 μg/L), soluble transferrin receptor (TfR; > 8.3 mg/L), or zinc protoporphyrin (ZP; > 80 μmol/mol) concentrations (ie, multiple-criteria model) with ID defined by abnormal concentrations of any of the independent candidate iron biomarkers (ferritin alone, TfR alone, or ZP alone) and TfR/ferritin index (ID, > 500). Values either were adjusted for inflammation [as measured by C-reactive protein (> 5 mg/L) and α(1)-acid glycoprotein (> 1 g/L) before applying cutoffs for ID] or were unadjusted. DESIGN In this community-based cluster survey, capillary blood was obtained from 680 children (aged 6-35 mo) for measurement of iron status by using ferritin, TfR, and ZP. RESULTS On the basis of the multiple-criteria model, the mean (±SE) prevalence of ID was 61.9 ± 2.2%, whereas the prevalences based on abnormal ferritin, TfR, or ZP concentrations or an abnormal TfR/ferritin index were 26.9 ± 1.7%, 60.9 ± 2.2%, 82.8 ± 1.6%, and 43.1 ± 2.3%, respectively, for unadjusted values. The prevalences of ID were higher for adjusted values only for low ferritin and an elevated TfR/ferritin index compared with the unadjusted values. The κ statistics for agreement between the multiple-criteria model and the other iron indicators ranged from 0.35 to 0.88; TfR had the best agreement (κ = 0.88) with the multiple-criteria model. Positive predictive values of ID based on the other iron indicators in predicting ID based on the multiple-criteria model were highest for ferritin and TfR. Receiver operating characteristic curve analysis indicated that TfR (AUC = 0.94) was superior to the other indicators in diagnosing ID based on the multiple-criteria model (P < 0.001). The inflammation effect did not appear to alter these observations appreciably. CONCLUSION TfR better estimates the prevalence of ID in preschoolers than do ferritin, ZP, and the TfR/ferritin index on the basis of multiple indexes in a high inflammation, resource-poor setting. This trial was registered at clinicaltrials.gov as NCT101088958.

Global health education in US pediatric residency programs

BACKGROUND AND OBJECTIVE: Despite the growing importance of global health (GH) training for pediatric residents, few mechanisms have cataloged GH educational opportunities offered by US pediatric residency programs. We sought to characterize GH education opportunities across pediatric residency programs and identify program characteristics associated with key GH education elements. METHODS: Data on program and GH training characteristics were sought from program directors or their delegates of all US pediatric residency programs during 2013 to 2014. These data were used to compare programs with and without a GH track as well as across small, medium, and large programs. Program characteristics associated with the presence of key educational elements were identified by using bivariate logistic regression. RESULTS: Data were collected from 198 of 199 active US pediatric residency programs (99.5%). Seven percent of pediatric trainees went abroad during 2013 to 2014. Forty-nine programs (24.7%) reported having a GH track, 66.1% had a faculty lead, 58.1% offered international field experiences, and 48.5% offered domestic field experiences. Forty-two percent of programs reported international partnerships across 153 countries. Larger programs, those with lead faculty, GH tracks, or partnerships had significantly increased odds of having each GH educational element, including pretravel preparation. CONCLUSIONS: The number of pediatric residency programs offering GH training opportunities continues to rise. However, smaller programs and those without tracks, lead faculty, or formal partnerships lag behind with organized GH curricula. As GH becomes an integral component of pediatric training, a heightened commitment is needed to ensure consistency of training experiences that encompass best practices in all programs.