Comparison of Anemia Screening Methods Using Paired Venous Samples in Women of Reproductive Age in Southern India

Amy Fothergill, Krista S Crider, Christina B Johnson, Mical P Raj, Heather M Guetterman, Beena Bose, Charles E Rose, Yan P Qi, Jennifer L Williams, Rebecca Kuriyan, Wesley Bonam, Julia L Finkelstein, Amy Fothergill, Krista S Crider, Christina B Johnson, Mical P Raj, Heather M Guetterman, Beena Bose, Charles E Rose, Yan P Qi, Jennifer L Williams, Rebecca Kuriyan, Wesley Bonam, Julia L Finkelstein

Abstract

Background: Anemia is an important public health problem, and accurate estimates may inform policy and programs. Although hemoglobin (Hb) assessment of venous blood via automated hematology analyzers (AHAs) is recommended, most population-based surveys estimate anemia prevalence based on analysis of capillary blood via portable hemoglobinometers.

Objectives: We aimed to evaluate screening methods for hemoglobin and anemia assessment using paired venous samples.

Methods: Participants were women 15-40 y who were not pregnant or lactating. Paired venous whole blood samples (n = 896) were analyzed for hemoglobin (Hb) via portable hemoglobinometer (HemoCue 301) and Coulter Counter AHA. Anemia and severe anemia were defined as Hb <12.0g/dL and <8.0 g/dL, respectively. Bland-Altman methods were used to assess the level of agreement for Hb results (mean difference, SD of differences, limits of agreement). Diagnostic accuracy parameters (sensitivity, specificity, positive predictive value, negative predictive value, accuracy) were calculated to evaluate HemoCue performance compared to the AHA reference, overall and by sociodemographic, nutritional, and metabolic characteristics.

Results: The estimated anemia prevalence was significantly lower via HemoCue vs. AHA (36.3% compared with 41.6%; P value < 0.0001). The HemoCue had 84.4% accuracy for anemia screening and 98.8% for severe anemia, compared to the AHA reference. The HemoCue had 74.8% sensitivity and 91.2% specificity, compared to AHA. HemoCue sensitivity was higher in women with iron deficiency [serum ferritin (SF) <15.0 μg/L: 81.6% compared with SF ≥15.0 μg/L: 41.3%], and lower in women with metabolic risk factors, including overweight [BMI ≥25.0 kg/m2: 63.9% vs. BMI <25.0 kg/m2: 78.8%], or elevated CRP (>1.0 mg/L: 67.2% vs. ≤1.0 mg/L: 82.9%), trunk fat (>35%: 62.7% vs. ≤35%: 80.1%), or whole-body fat (>35%: 63.9% vs. ≤35%: 80.3%).

Conclusions: Findings suggest that women with anemia may be incorrectly identified as not anemic via portable hemoglobinometer, and anemia prevalence may be underestimated at the population level.This study was registered at clinicaltrials.gov as NCT04048330.

Keywords: India; anemia; hemoglobin; iron; screening; women of reproductive age.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Participant flowchart. AHA, automated hematology analyzer; AMC, Arogyavaram Medical Center; NTD, neural tube defect; WRA, women of reproductive age.
FIGURE 2
FIGURE 2
Distribution of hemoglobin concentrations (g/dL) assessed via HemoCue and AHA. AHA, automated hematology analyzer.
FIGURE 3
FIGURE 3
Bland–Altman plot of differences in Hb concentrations as evaluated by HemoCue and AHA methods (HemoCue – AHA) compared with the mean Hb concentrations. The solid line represents the mean difference (HemoCue – AHA; 0.2 g/dL) and dashed lines represent the limits of agreement (±2 SD of the difference: −1.8, 2.3 g/dL). AHA, automated hematology analyzer; Hb, hemoglobin.

References

    1. Chaparro CM, Suchdev PS. Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries. Ann N Y Acad Sci. 2019;1450(1):15–31.
    1. The Global Health Observatory . WHO global anemia estimates, 2021 edition. Geneva, Switzerland: WHO; 2021.
    1. WHO . The global prevalence of anaemia in 2011. Geneva, Switzerland: WHO; 2015.
    1. WHO . Nutritional anaemias: tools for effective prevention and control. Geneva, Switzerland: WHO; 2017.
    1. WHO . Global anaemia reduction efforts among women of reproductive age: impact, achievement of targets and the way forward for optimizing efforts. Geneva, Switzerland: WHO; 2020.
    1. Rahman MM, Abe SK, Rahman MS, Kanda M, Narita S, Bilano Vet al. . Maternal anemia and risk of adverse birth and health outcomes in low- and middle-income countries: systematic review and meta-analysis. Am J Clin Nutr. 2016;103(2):495–504.
    1. Geelhoed D, Agadzi F, Visser L, Ablordeppey E, Asare K, O'Rourke Pet al. . Maternal and fetal outcome after severe anemia in pregnancy in rural Ghana. Acta Obstet Gynecol Scand. 2006;85(1):49–55.
    1. Rahman A, Khan N, Rahman M. Maternal anaemia and risk of adverse obstetric and neonatal outcomes in South Asian countries: a systematic review and meta-analysis. Public Health Pract. 2020;1:100021.
    1. Anand T, Rahi M, Sharma P, Ingle GK. Issues in prevention of iron deficiency anemia in India. Nutrition. 2014;30(7–8):764–70.
    1. Lone FW, Qureshi RN, Emanuel F. Maternal anaemia and its impact on perinatal outcome. Trop Med Int Health. 2004;9(4):486–90.
    1. Brabin BJ, Hakimi M, Pelletier D. An analysis of anemia and pregnancy-related maternal mortality. J Nutr. 2001;131(2):604S–15S.
    1. Daru J, Zamora J, Fernández-Félix BM, Vogel J, Oladapo OT, Morisaki Net al. . Risk of maternal mortality in women with severe anaemia during pregnancy and post partum: a multilevel analysis. Lancet Glob Health. 2018;6(5):e548–54.
    1. International Institute for Population Sciences (IIPS), ICF International . National Family Health Survey (NFHS-5) 2019–2020. Mumbai, India: IIPS; 2021.
    1. WHO . Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva, Switzerland: WHO; 2011.
    1. Prakash N, Banerji HN. Evaluation of cyanmethaemoglobin method for haemoglobin estimation. Indian J Chest Dis. 1972;14(2):102–5.
    1. Whitehead RD Jr, Mei Z, Mapango C, Jefferds MED. Methods and analyzers for hemoglobin measurement in clinical laboratories and field settings. Ann N Y Acad Sci. 2019;1450(1):147–71.
    1. Srinivasan B, Lee S, Erickson D, Mehta S. Precision nutrition—review of methods for point-of-care assessment of nutritional status. Curr Opin Biotechnol. 2017;44:103–8.
    1. Neufeld LM, Larson LM, Kurpad A, Mburu S, Martorell R, Brown KH. Hemoglobin concentration and anemia diagnosis in venous and capillary blood: biological basis and policy implications. Ann N Y Acad Sci. 2019;1450(1):172–89.
    1. Garcia-Casal MN, Pasricha S-R, Sharma AJ, Peña-Rosas JP. Use and interpretation of hemoglobin concentrations for assessing anemia status in individuals and populations: results from a WHO technical meeting. Ann N Y Acad Sci. 2019;1450(1):5–14.
    1. Sharma AJ, Addo OY, Mei Z, Suchdev PS. Reexamination of hemoglobin adjustments to define anemia: altitude and smoking. Ann N Y Acad Sci. 2019;1450(1):190–203.
    1. Karakochuk CD, Hess SY, Moorthy D, Namaste S, Parker ME, Rappaport AIet al. . Measurement and interpretation of hemoglobin concentration in clinical and field settings: a narrative review. Ann N Y Acad Sci. 2019;1450(1):126–46.
    1. Addo OY, Yu EX, Williams AM, Young MF, Mei Z, Jefferds MEet al. . Evaluation of hemoglobin cutoffs for defining anemia in a multinational sample of healthy individuals: the BRINDA project (OR07-07-19). Curr Dev Nutr. 2019;3(Supplement_1):nzz034.OR07–07-19.
    1. Pasricha S-R, Colman K, Centeno-Tablante E, Garcia-Casal M-N, Peña-Rosas J-P. Revisiting WHO haemoglobin thresholds to define anaemia in clinical medicine and public health. Lancet Haematol. 2018;5(2):e60–2.
    1. WHO . WHO methods and data sources for mean haemoglobin and anaemia estimates in women of reproductive age and pre-school age children 2000–2019. Geneva, Switzerland: WHO; 2021.
    1. Sawant RB, Bharucha ZS, Rajadhyaksha SB. Evaluation of hemoglobin of blood donors deferred by the copper sulphate method for hemoglobin estimation. Transfus Apher Sci. 2007;36(2):143–8.
    1. Jaggernath M, Naicker R, Madurai S, Brockman MA, Ndung'u T, Gelderblom HC. Diagnostic accuracy of the HemoCue Hb 301, STAT-Site MHgb and URIT-12 point-of-care hemoglobin meters in a central laboratory and a community based clinic in Durban, South Africa. PLoS One. 2016;11(4):e0152184.
    1. Jain A, Chowdhury N. Comparison of the accuracy of capillary hemoglobin estimation and venous hemoglobin estimation by two models of HemoCue against automated cell counter hemoglobin measurement. Asian J Transfus Sci. 2020;14(1):49–53.
    1. Neogi SB, Sharma J, Pandey S, Zaidi N, Bhattacharya M, Kar Ret al. . Diagnostic accuracy of point-of-care devices for detection of anemia in community settings in India. BMC Health Serv Res. 2020;20(1):468.
    1. Hinnouho G-M, Barffour MA, Wessells KR, Brown KH, Kounnavong S, Chanhthavong Bet al. . Comparison of haemoglobin assessments by HemoCue and two automated haematology analysers in young Laotian children. J Clin Pathol. 2018;71(6):532–8.
    1. Rappaport AI, Karakochuk CD, Hess SY, Whitehead JRD, Namaste SML, Dary Oet al. . Variability in haemoglobin concentration by measurement tool and blood source: an analysis from seven countries. J Clin Pathol. 2021;74(10):657–63.
    1. Young MF, Raines K, Jameel F, Sidi M, Oliveira-Streiff S, Nwajei Pet al. . Non-invasive hemoglobin measurement devices require refinement to match diagnostic performance with their high level of usability and acceptability. PLoS One. 2021;16(7):e0254629.
    1. Finkelstein JL, Fothergill A, Johnson CB, Guetterman HM, Bose B, Jabbar Set al. . Anemia and vitamin B-12 and folate status in women of reproductive age in southern India: estimating population-based risk of neural tube defects. Curr Dev Nutr. 2021;5(5):nzab069.
    1. Finkelstein JL, Fothergill A, Johnson CB, Guetterman HM, Bose B, Jabbar Set al. . Periconceptional surveillance for prevention of anaemia and birth defects in Southern India: protocol for a biomarker survey in women of reproductive age. BMJ Open. 2020;10(10):e038305.
    1. Ruth CJ, Huey SL, Krisher JT, Fothergill A, Gannon BM, Jones CEet al. . An electronic data capture framework (ConnEDCt) for global and public health research: design and implementation. J Med Internet Res. 2020;22(8):e18580.
    1. Lynch S, Pfeiffer CM, Georgieff MK, Brittenham G, Fairweather-Tait S, Hurrell RFet al. . Biomarkers of Nutrition for Development (BOND)—iron review. J Nutr. 2018;148(suppl_1):1001S–67S.
    1. Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood. 2003;101(9):3359–63.
    1. Flowers CH, Skikne BS, Covell AM, Cook JD. The clinical measurement of serum transferrin receptor. J Lab Clin Med. 1989;114(4):368–77.
    1. Pfeiffer CM, Cook JD, Mei Z, Cogswell ME, Looker AC, Lacher DA. Evaluation of an automated soluble transferrin receptor (sTfR) assay on the Roche Hitachi analyzer and its comparison to two ELISA assays. Clin Chim Acta. 2007;382(1–2):112–16.
    1. WHO . WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations. Geneva, Switzerland: WHO; 2020.
    1. Backes JM, Howard PA, Moriarty PM. Role of C-reactive protein in cardiovascular disease. Ann Pharmacother. 2004;38(1):110–18.
    1. Dhingra R, Gona P, Nam B-H, D'Agostino RB, Wilson PWF, Benjamin EJet al. . C-reactive protein, inflammatory conditions, and cardiovascular disease risk. Am J Med. 2007;120(12):1054–62.
    1. Cordero AM, Crider KS, Rogers LM, Cannon MJ, Berry RJ. Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines. MMWR Morb Mortal Wkly Rep. 2015;64(15):421–3.
    1. Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF 3rd, Mills JLet al. . Biomarkers of Nutrition for Development—folate review. J Nutr. 2015;145(7):1636S–80S.
    1. Pfeiffer CM, Zhang M, Lacher DA, Molloy AM, Tamura T, Yetley EAet al. . Comparison of serum and red blood cell folate microbiologic assays for national population surveys. J Nutr. 2011;141(7):1402–9.
    1. Yetley EA, Pfeiffer CM, Phinney KW, Bailey RL, Blackmore S, Bock JLet al. . Biomarkers of vitamin B-12 status in NHANES: a roundtable summary. Am J Clin Nutr. 2011;94(1):313S–21S.
    1. Allen LH, Miller JW, de Groot L, Rosenberg IH, Smith AD, Refsum Het al. . Biomarkers of Nutrition for Development (BOND): vitamin B-12 review. J Nutr. 2018;148(suppl_4):1995S–2027S.
    1. Green R, Allen LH, Bjørke-Monsen A-L, Brito A, Guéant J-L, Miller JWet al. . Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3(1):17040.
    1. WHO Expert Consultation . Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363(9403):157–63.. Erratum in: Lancet 2004;363(9412):902.
    1. WHO . Waist circumference and waist-hip ratio. Report of a WHO expert consultation. Geneva, Switzerland: WHO; 2008.
    1. American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) Obesity Task Force . AACE/ACE position statement on the prevention, diagnosis, and treatment of obesity. Endocr Pract. 1998;4(5):297–350.
    1. American Diabetes Association . 2. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes—2020. Diabetes Care. 2020;43(Suppl 1):S14–S31.
    1. WHO . Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. Geneva, Switzerland: WHO; 2011.
    1. Namaste SM, Rohner F, Huang J, Bhushan NL, Flores-Ayala R, Kupka Ret al. . Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 2017;106(Suppl 1):359s–71s.
    1. Suchdev PS, Williams AM, Mei Z, Flores-Ayala R, Pasricha S-R, Rogers LMet al. . Assessment of iron status in settings of inflammation: challenges and potential approaches. Am J Clin Nutr. 2017;106(Suppl 6):1626S–33S.
    1. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Int J Nurs Stud. 2010;47(8):931–6.
    1. Westgard . CLIA requirements for analytical quality. Madison, WI: WestGard; 2018.
    1. Morris LD, Osei-Bimpong A, McKeown D, Roper D, Lewis SM. Evaluation of the utility of the HemoCue 301 haemoglobinometer for blood donor screening. Vox Sang. 2007;93(1):64–9.
    1. Singh S, Geddam JJB, Reddy GB, Pallepogula DR, Pant HB, Neogi SBet al. . Folate, vitamin B12, ferritin and haemoglobin levels among women of childbearing age from a rural district in South India. BMC Nutr. 2017;3(1):50.
    1. Chowdhury R, Taneja S, Dhabhai N, Mazumder S, Upadhyay RP, Sharma Set al. . Burden of preconception morbidity in women of reproductive age from an urban setting in North India. PLoS One. 2020;15(6):e0234768.
    1. Muñoz M, Romero A, Gómez JF, Manteca A, Naveira E, Ramírez G. Utility of point-of-care haemoglobin measurement in the HemoCue-B haemoglobin for the initial diagnosis of anaemia. Clin Lab Haematol. 2005;27(2):99–104.
    1. Abraham RA, Agrawal PK, Johnston R, Ramesh S, Porwal A, Sarna Aet al. . Comparison of hemoglobin concentrations measured by HemoCue and a hematology analyzer in Indian children and adolescents 1–19 years of age. Int J Lab Hematol. 2020;42(4):e155–e9.
    1. Monárrez-Espino J, Roos N. Comparison of the analytic performance between the B-HB and HB-201+ HemoCue® hemoglobinometers for venous and capillary blood under field work conditions. Ecol Food Nutr. 2008;47(2):159–69.
    1. Rudolf-Oliveira RCM, Gonçalves KT, Martignago ML, Mengatto V, Gaspar PC, dos Santos Ferreira Jet al. . Comparison between two portable hemoglobinometers and a reference method to verify the reliability of screening in blood donors. Transfus Apher Sci. 2013;49(3):578–82.
    1. Shahshahani HJ, Meraat N, Mansouri F. Evaluation of the validity of a rapid method for measuring high and low haemoglobin levels in whole blood donors. Blood Transfus. 2013;11(3):385–90.
    1. Nass SA, Hossain I, Sanyang C, Baldeh B, Pereira DIA. Hemoglobin point-of-care testing in rural Gambia: comparing accuracy of HemoCue and Aptus with an automated hematology analyzer. PLoS One. 2020;15(10):e0239931.
    1. Nkrumah B, Nguah SB, Sarpong N, Dekker D, Idriss A, May Jet al. . Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting. BMC Clin Pathol. 2011;11(1):5.
    1. de A Paiva A, Rondó PHC, de B Silva SS, do RDO Latorre M. Comparison between the HemoCue® and an automated counter for measuring hemoglobin. Rev Saude Publica. 2004;38(4):585–7.
    1. Boghani S, Mei Z, Perry GS, Brittenham GM, Cogswell ME. Accuracy of capillary hemoglobin measurements for the detection of anemia among U.S. low-income toddlers and pregnant women. Nutrients. 2017;9(3):253.
    1. Neufeld L, García-Guerra A, Sánchez-Francia D, Newton-Sánchez O, Ramírez-Villalobos MD, Rivera-Dommarco J. Hemoglobin measured by Hemocue and a reference method in venous and capillary blood: a validation study. Salud Publica Mex. 2002;44(3):219–27.
    1. Whitehead RD Jr, Zhang M, Sternberg MR, Schleicher RL, Drammeh B, Mapango Cet al. . Effects of preanalytical factors on hemoglobin measurement: a comparison of two HemoCue® point-of-care analyzers. Clin Biochem. 2017;50(9):513–20.
    1. Sanchis-Gomar F, Cortell-Ballester J, Pareja-Galeano H, Banfi G, Lippi G. Hemoglobin point-of-care testing: the HemoCue system. J Lab Autom. 2013;18(3):198–205.
    1. Baart AM, de Kort WL, van den Hurk K, Pasker-de Jong PC. Hemoglobin assessment: precision and practicability evaluated in the Netherlands—the HAPPEN study. Transfusion. 2016;56(8):1984–93.
    1. Sari M, de Pee S, Martini E, Herman S, Sugiatmi, Bloem MWet al. . Estimating the prevalence of anaemia: a comparison of three methods. Bull World Health Organ. 2001;79(6):506–11.
    1. Parker M, Han Z, Abu-Haydar E, Matsiko E, Iyakaremye D, Tuyisenge Let al. . An evaluation of hemoglobin measurement tools and their accuracy and reliability when screening for child anemia in Rwanda: a randomized study. PLoS One. 2018;13(1):e0187663.
    1. Sümnig A, Hron G, Westphal A, Petersmann A, Kohlmann T, Greinacher Aet al. . The impact of noninvasive, capillary, and venous hemoglobin screening on donor deferrals and the hemoglobin content of red blood cells concentrates: a prospective study. Transfusion. 2015;55(12):2847–54.
    1. da Silva Pereira A, de Castro IRR, Bezerra FF, Nogueira Neto JF, da Silva ACF. Reproducibility and validity of portable haemoglobinometer for the diagnosis of anaemia in children under the age of 5 years. J Nutr Sci. 2020;9:e3.
    1. WHO Obesity: preventing and managing the global epidemic. Report of a WHO consultation. Geneva, Switzerland: WHO; 2000.
    1. Snehaltha C, Viswanathan V, Ramachandran A. Cutoff values for normal anthropometric variables in Asian Indian adults. Diabetes Care. 2003;26(5):1380–4.
    1. WHO Physical status: the use and interpretation of anthropometry, report of a WHO expert committee. WHO Technical Report Series 854. Geneva, Switzerland: WHO; 1995.

Source: PubMed

3
Subskrybuj