Abstract
Iron deficiency anemia (IDA) is a persistent public health challenge in India, particularly among adolescent girls. Despite the use of Iron–Folic Acid (IFA) intervention, the IDA prevalence remains high due to variability in the degree of hemoglobin (Hb) response to supplementation. This study aimed to investigate whether the baseline levels of vitamin-A and pro-inflammatory cytokines influence the Hb increase following IFA supplementation in adolescent girls with IDA. Blood samples were collected from girls aged 15–19 y at baseline (day-0) and after 3 months of supplementation (day-90). The Hb was estimated using an analyzer, serum levels of ferritin, TfR, hepcidin, IL-6, TNF-α were measured using ELISA and vitamin A was estimated using HPLC. Based on the change in Hb (day-0–day-90), the response was categorized as good (≥ 1.0 g/dL) and inadequate (< 1.0 g/dL). Nearly 50% IDA subjects exhibited inadequate Hb increment. This group had elevated IL6 levels and decreased vitamin-A levels compared to the good Hb response at baseline (p < 0.05). Logistic regression demonstrated a significant association between lower baseline vitamin A levels and increased odds of inadequate Hb response, particularly in moderate IDA subjects (OR = 1.28, p < 0.05). A direct association was observed between baseline retinol and Hb, this relationship likely to be dependent on IL-6 levels. In conclusion, low vitamin A status is a significant limiting factor contributing to the inadequate Hb increment during IFA supplementation, which may be particularly relevant in regions where vitamin-A deficiency is still a public health concern.
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References
Safiri S, Kolahi A-A, Noori M, Nejadghaderi SA, Karamzad N, Bragazzi NL, et al. Burden of anemia and its underlying causes in 204 countries and territories, 1990–2019: results from the Global Burden of Disease Study 2019. J Hematol OncolJ Hematol Oncol. 2021;14:185.
Scott S, Lahiri A, Sethi V, de Wagt A, Menon P, Yadav K, et al. Anaemia in Indians aged 10–19 years: prevalence, burden and associated factors at national and regional levels. Matern Child Nutr. 2022;18: e13391.
Wiafe MA, Ayenu J, Eli-Cophie D. A review of the risk factors for iron deficiency anaemia among adolescents in developing countries. Anemia. 2023;2023:6406286.
Ministry of Health and Family Welfare. Intensified national iron plus initiative (I-NIPI) [Internet]. Government of India; 2018. Available from: https://resources.anemiamuktbharat.info/Awareness_Generation/Anemia-Mukt-Bharat-Brochure_English+(1).pdf
Chakrabarty M, Singh A, Singh S, Chowdhury S. Is the burden of anaemia among Indian adolescent women increasing? Evidence from Indian Demographic and Health Surveys (2015–21). PLOS Glob Public Health. 2023;3: e0002117.
Beaton GH, McCabe GP. Efficacy of intermittent iron supplementation in the control of iron deficiency anaemia in developing countries—an analysis of experience: final report to the micronutrient initiative.
Rai RK, Fawzi WW, Barik A, Chowdhury A. The burden of iron-deficiency anaemia among women in India: How have iron and folic acid interventions fared? WHO South-East Asia J Public Health. 2018;7:18–23.
Cappellini MD, Comin-Colet J, de Francisco A, Dignass A, Doehner W, Lam CS, et al. Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management. Am J Hematol. 2017;92:1068–78.
Gernand AD, Xu X, West KP. Vitamin A in Nutritional Anemia. Nutr Anemia. 2022. https://doi.org/10.1007/978-3-031-14521-6_12.
Kyaw Htet M, Fahmida U, Dillon D, Akib A, Utomo B, Thurnham DI. Is Iron Supplementation Influenced by Sub-Clinical Inflammation?: A randomized controlled trial among adolescent schoolgirls in Myanmar. Nutrients. 2019;11:918.
Palika R, Dasi T, Ghosh S, Peter R, Parasannanavar DJ, Pradhan AS, et al. Efficacy of iron–folic acid treatment for reducing anemia prevalence and improving iron status in women of reproductive age: A one-year longitudinal study. Clin Nutr ESPEN. 2022;49:390–7.
Wang M. Iron deficiency and other types of anemia in infants and children. Am Fam Physician. 2016;93:270–8.
Gupta A, Kant S, Ramakrishnan L, Pandey RM, Khandelwal R, Kapil U, et al. Impact of daily-supervised administration of a package of iron and folic acid and vitamin B12 on hemoglobin levels among adolescent girls (12–19 years): A cluster randomized control trial. Eur J Clin Nutr. 2021;75:1588–97.
Global prevalence of vitamin A deficiency in populations at risk 1995–2005 : WHO global database on vitamin A deficiency [Internet]. (2023). Available from: https://www.who.int/publications-detail-redirect/9789241598019
Ahmed F, Hasan N, Kabir Y. Vitamin A deficiency among adolescent female garment factory workers in Bangladesh. Eur J Clin Nutr. 1997;51:698–702.
Hashizume M, Chiba M, Shinohara A, Iwabuchi S, Sasaki S, Shimoda T, et al. Anaemia, iron deficiency and vitamin A status among school-aged children in rural Kazakhstan. Public Health Nutr. 2005;8:564–71.
West KP. Extent of vitamin A deficiency among preschool children and women of reproductive age. J Nutr. 2002;132:2857S-2866S.
Htet MK, Fahmida U, Dillon D, Akib A, Utomo B, Thurnham DI. The influence of vitamin A status on iron-deficiency anaemia in anaemic adolescent schoolgirls in Myanmar. Public Health Nutr. 2014;17:2325–32.
Ahmed F, Khan MR, Jackson AA. Concomitant supplemental vitamin A enhances the response to weekly supplemental iron and folic acid in anemic teenagers in urban Bangladesh123. Am J Clin Nutr. 2001;74:108–15.
Suharno D, West CE, Muhilal N, Karyadi D, Hautvast JG. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet Lond Engl. 1993;342:1325–8.
Kolsteren P, Rahman SR, Hilberbrand K, Dintz A. Treatment for iron deficiency anaemia with a combined supplementation of iron, vitamin A and zinc in women of Dinajpur. Bangladesh Eur J Clin Nutr. 1999;53:102–6.
Soekarjo DD, de Pee SS, Kusin JA, Schreurs WHP, Schultink W, Muhilal N, et al. Effectiveness of weekly vitamin A (10000 IU) and iron (60 mg) supplementation for adolescent boys and girls through schools in rural and urban East Java, Indonesia. Eur J Clin Nutr. 2004;58:927–37.
Leenstra T, Kariuki SK, Kurtis JD, Oloo AJ, Kager PA, ter Kuile FO. The effect of weekly iron and vitamin A supplementation on hemoglobin levels and iron status in adolescent schoolgirls in western Kenya. Eur J Clin Nutr. 2009;63:173–82.
Ministry of Health & Family Welfare, Govt. of India. Comprehensive National Nutrition Survey (2016–18) report [Internet]. (2023) Available from: https://nhm.gov.in/index1.php?lang=1&level=2&sublinkid=1332&lid=713
Semba RD, Bloem MW. The anemia of vitamin A deficiency: epidemiology and pathogenesis. Eur J Clin Nutr. 2002;56:271–81.
Camaschella C, Nai A, Silvestri L. Iron metabolism and iron disorders revisited in the hepcidin era. Haematologica. 2020;105:260–72.
Sipahi T, Akar N, Eğin Y, Cin S. Serum interleukin-2 and interleukin-6 levels in iron deficiency anemia. Pediatr Hematol Oncol. 1998;15:69–73.
Gutowska K, Formanowicz D, Formanowicz P. Interrelations between Iron and Vitamin A-Studied Using Systems Approach. Int J Mol Sci. 2022;23:1189.
Katagiri N, Hitomi H, Mae S-I, Kotaka M, Lei L, Yamamoto T, et al. Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells. Sci Rep. 2021;11:3936.
Pasricha S-R, Casey GJ, Phuc TQ, Mihrshahi S, Macgregor L, Montresor A, et al. Baseline Iron Indices as Predictors of Haemoglobin Improvement in Anemic Vietnamese Women Receiving Weekly Iron–Folic Acid Supplementation and De-Worming. Am J Trop Med Hyg. 2009;81:1114–9.
Acknowledgements
We thank all the adolescent girls, parents and teachers who participated in the study. We thank the Indian Council of Medical Research (ICMR), New Delhi, India for financial assistance. We also thank Dr. Geereddy Bhanuprakash Reddy, Dr. Ravindranadh Palika and Dr. Teena Dasi for their valuable suggestions.
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This study was funded by Indian Council of Medical Research, 5/9/1322/2020-Nut, Subrahamanyam Dantham
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SD: Conceptualization, Methodology, Writing–Reviewing and Editing, Funding acquisition; IG: Methodology Investigation and Original draft preparation; SSV: Investigation; NB: Investigation; RRC: Formal Analysis.
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Dantham, S., Gaddam, I., Vadakattu, S.S. et al. Low Vitamin A Status: A Potential Limiting Factor for Hemoglobin Improvement to Iron–Folic Acid Supplementation in Adolescent Girls with Iron Deficiency Anemia. Ind J Clin Biochem (2024). https://doi.org/10.1007/s12291-024-01228-6
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DOI: https://doi.org/10.1007/s12291-024-01228-6