|Year : 2019 | Volume
| Issue : 1 | Page : 39-44
Assessment of iron deficiency in malnutrition: the value of serum ferritin
AishatOluwatoyin Saka1, Ayodele I Ojuawo1, Mohammed Jimoh Saka2, S. Abayomi Biliaminu3, Lukman Olatunbosun4
1 Department of Paediatrics and Child Health, Faculty of Basic Science, College of Health Sciences, University of Iorin, Ilorin Kwara State, Nigeria
2 Department of Epidemiology and Community Health, Faculty of Clinical Science, College of Health Sciences, University of Iorin, Ilorin Kwara State, Nigeria
3 Department of Chemical Pathology & Immunology, Faculty of Basic Science, College of Health Sciences, University of Iorin, Ilorin Kwara State, Nigeria
4 Department of Heamatology and Blood Transfusion, Faculty of Basic Science, College of Health Sciences, University of Iorin, Ilorin Kwara State, Nigeria
|Date of Web Publication||17-Sep-2019|
Dip. Gastroenterology and Nutrition, Department of Pediatrics and Child Health, Faculty of Clinical Science, College of Health Sciences. University of Iorin, Ilorin Kwara State
Background Iron deficiency is the most common micronutrient deficiency seen in protein energy malnutrition (PEM) and a common cause of morbidity and mortality in this condition.
Aim The aim of the study was to assess the value of serum ferritin among PEM patients with iron deficiency.
Patients and methods It was a case–control study in which the participants were children diagnosed of PEM and the controls were children with normal nutrition. Ninety participants and controls each participated in the study with informed consent obtained from caregivers. Full blood count and examination of peripheral blood smear and serum ferritin concentration was analyzed by enzyme-linked immunosorbent assay.
Statistical analysis Data entry and analysis were carried out with a microcomputer using the SPSS, version 16, software packages.
Results The mean age of the children with PEM was 22.7±14.4 months. In the participants, the prevalence of iron deficiency was 24.4%, while that of iron-deficiency anemia was 16.6%. The mean serum ferritin levels were significantly lower in the patients compared with controls (P=0.000). The sensitivity and specificity of serum ferritin was 100.0% (95% confidence interval). The likelihood ratio was 0.00 (95% confidence interval).
Conclusion Patients with PEM were found to have high prevalence of iron-deficiency anemia and low serum ferritin levels. The sensitivity and specificity of serum ferritin levels were found to be high among PEM patients with iron-deficiency anemia.
Keywords: iron-deficiency anemia, protein energy malnutrition, serum ferritin
|How to cite this article:|
Saka A, Ojuawo AI, Saka MJ, Abayomi Biliaminu S, Olatunbosun L. Assessment of iron deficiency in malnutrition: the value of serum ferritin. Tanta Med J 2019;47:39-44
|How to cite this URL:|
Saka A, Ojuawo AI, Saka MJ, Abayomi Biliaminu S, Olatunbosun L. Assessment of iron deficiency in malnutrition: the value of serum ferritin. Tanta Med J [serial online] 2019 [cited 2020 Apr 8];47:39-44. Available from: http://www.tdj.eg.net/text.asp?2019/47/1/39/267021
| Introduction|| |
Iron deficiency is the most common micronutrient deficiency seen in children in Nigeria and worldwide. It affects more than two billion people including children with protein energy malnutrition (PEM) worldwide . PEM is a leading cause of morbidity and mortality among children in the developing countries carrying the highest burden . PEM is usually an outcome of both macronutrient deficiency and micronutrient deficiency coexisting . Iron is the most common of the micronutrient deficiency seen in PEM ,. Being the most common, nutritional anemia is usually invariable in children with PEM thus it has to be anticipated and managed. However, the laboratory diagnosis of iron deficiency among PEM for various previous studies has been inconclusive. Different modalities have been suggested based on the sensitivity and specificity of the various available diagnostic tools. Laboratory test such as serum ferritin, red cell protoporphyrin, transferring saturation, mean cell volume, or red cell distribution have been used severally to determine iron deficiency . A systematic overview of the diagnostic values used in the evaluation of iron-deficiency anemia showed that serum ferritin was by far the most powerful test for the diagnosis of iron deficiency, outperforming red cell protoporphyrin, transferring saturation, mean cell volume, or red cell distribution . Serum ferritin, which indirectly reflects total body iron stores, is routinely ordered in the evaluation of anemia . Low serum ferritin is highly specific for iron-deficiency anemia, and is much less invasive than the gold standard . However, test properties differs for populations of patients with inflammatory, liver, or neoplastic disease, because serum ferritin is an acute-phase reactant . PEM is also a condition in which acute-phase reaction such as serum ferritin are in circulation because of the presence of infection and other inflammatory response. Furthermore, in severe PEM despite the fact that dietary deficiency of iron is prevalent among children with PEM, hepatic iron and bone marrow free iron are usually elevated, as there is a reduction in the concentration of serum protein especially the transport protein thereby increasing the circulation of free iron, therefore making the use of serum ferritin as a diagnostic tool of limited value  Test properties of serum ferritin in other conditions such as neoplasms to aid appropriate interpretation of values have been determined in a previous study . However, the value of serum ferritin of severe PEM is still inconclusive.
This article examines serum ferritin levels of children with PEM with specific objectives to determine the prevalence of iron deficiency and iron-deficiency anemia in PEM, the sensitivity as well as the specificity of serum ferritin in the diagnosis of iron deficiency in PEM.
| Patients and methods|| |
The study was a case–control study in which the participants were children diagnosed of PEM and the controls were children with normal nutritional status without hematological or infectious conditions. It was conducted in the emergency Pediatric ward of the University of Ilorin Teaching Hospital where inpatient care of children (6–59-month old) with malnutrition was routinely done. All consecutive admissions into the Emergency Pediatric Unit with a diagnosis of PEM based on the Wellcome classification were enrolled, while PEM patients with underlying hemotological conditions such as sickle cell disease, or chronic disease or PEM patients on iron supplements are excluded. Controls were healthy children attending the routine clinic without hematologic or infectious condition and not on iron supplement. Consent of care giver were sought.
The study was approved by the Ethics and Research Committee of the University of Ilorin Teaching Hospital.
Using a prevalence of 10% from a previous study , the minimum calculated sample size was 70 participants; 90 participants each were selected for the study and the control groups included a total of 180 participants for the study.
Under strict aseptic conditions, after cleaning the blood collection site thoroughly with 70% alcohol, 5 ml of venous blood was collected by venepucture using a fixed hypodermic needle. Three milliliters of the withdrawn blood was decanted into a sample bottle containing EDTA and was gently mixed to prevent clotting while the remaining 2 ml was decanted into a heparinized bottle which was left to stand for 2 h and the serum was separated by centrifuging and the serum was decanted into another bottle and frozen at −20°C. Automated blood analyzer model/Symax KX 21 was used to analyze the full blood count while a low power examination of a peripheral blood smear, the 50× or 100× objective of the microscope was selected and the area of morphology was examined.
Serum ferritin assay
Serum ferritin concentrations were analyzed by enzyme-linked immunosorbent assay using the Nova Path Ferritin kit . Serum was prepared from the whole blood specimen collected under aseptic conditions into an EDTA bottle. Serum was capped and stored at −20°C.
Iron deficiency was defined as serum ferritin levels of below 31 ng/ml, while iron-deficiency anemia was defined as hemoglobin of less than 11 g/dl and serum ferritin of less than 31 ng/ml ,. Anemia was defined as hemoglobin of less than 11 g/dl. MCV 70–74 fl was taken as the normal range. Values of less than 70 fl was taken as microcytosis and more than 74 fl as macrocytosis.
Data entry and analysis were carried out with a microcomputer using the SPSS Epi info, version 3.5, software packages.
| Results|| |
The mean age of the children with PEM was 22.7±14.4 months (range, 9–59 months) compared with the mean age of 29.3±16.9 months (range, 6–59 months) in the controls and the difference was not significant (P=0.08) ([Table 1]). Fifty-six percent of the children with PEM belong to the low socioeconomic class (IV and V). The participants were of a lower socioeconomic class compared with the controls (P=0.00001).
Sixty-five (72.2%) of the PEM children were not exclusively breastfed while the mean age for the start of complementary feeds was 5.1±1.93 months in children with PEM compared with 5.6±2.4 months in the controls, and the difference was not significant (P=0.126).
More than 75% of the PEM cases were fed with guinea corn gruel, 11.1% with fortified gruel, 10% with maize gruel, and only 1.1% added milk to the feeds. The children with PEM were fed more with nonnutritive feeds when compared with the controls (P=0.02).
The mean values for weight, height, BMI, mean arm circumference and the Z scores for weight for age and weight for height were all significantly higher in the controls compared with the PEM children ([Table 2]).
The overall prevalence of anemia in PEM was 74.4% with the underweight children having the highest prevalence. The prevalence of iron deficiency was 24.4% in children with PEM, while that for iron-deficiency anemia was 16.6% in these children. Microcytic-hypochromic anemia was the most common anemia as it accounts for 84.4% of the type of anemia seen ([Table 3]).
The mean serum ferritin levels was higher in the controls compared with PEM cases (P=0.000) ([Table 4]). The mean serum ferritin was significantly higher in women (P=0.00001).
Children with marasmus had the highest mean serum ferritin level of 600.5±392.6 ng/ml, while those with Kwashiorkor had the lowest level of 165.5±6.2 ng/ml and the difference was statistically significant (P=0.009) ([Table 5]).
|Table 5 Serum ferritin distribution for the various classes of protein energy malnutrition|
Click here to view
The sensitivity of serum ferritin was 100.0% (95% confidence interval), while specificity was 100.0% (95% confidence interval). The likelihood ratio was 0.00 (95% confidence interval) and the positive predictive value was 100.0%, negative predictive value 100.0%, while the disease prevalence was for the predictive value 16.67% ([Table 6] and [Table 7]).
|Table 6 Sensitivity and specificity of serum ferritin in diagnosing iron deficiency in protein energy malnutrition|
Click here to view
| Discussion|| |
Majority of the participants belong to families of low socioeconomic class and mothers with low level of education. The practice of exclusive breastfeeding was very low among the participants as well as the controls and about 85% of the participants were fed with a common staple food such as the unfortified maize gruel. These findings are major risk factors for the development of malnutrition and nutritional anemia in PEM as found in several other studies ,.
A high prevalence of anemia (74.4%) among children with PEM was found in this study, and was in consonance with previous studies where anemia was said to be a common feature of PEM ,,. Microcytic-hypochromic red cells were most commonly observed in PEM in this study. This is in contrast with previous studies where anemia seen in PEM was normocytic normochromic ,. Several factors have been implicated in the etiology of anemia in PEM and these include deficiencies of iron, folate, vitamin B12; infections, blood loss, hemolysis, erythroid hypoplasia, and adaptation to lower metabolic oxygen requirements and decrease in lean body mass . Microcytic-hypochromic anemia found to be the most common in this study can be attributed to deficiency of iron which is a common cause of microcytic-hypochromic anemia. This finding strongly supports the fact that iron deficiency is the most common cause of nutritional anemia in this part of the world . Iron-deficiency anemia seen in these children from this study can be attributed to several factors such as inadequate intake, problems of absorption, and utilization. The type of food eaten by majority of the PEM children in this study can also be a factor for the high evidence of iron-deficiency anemia recorded in this study. Eighty-five percent of PEM children were fed with a common staple food such as maize gruel with a low iron content of 0.02 mg and guinea corn and millet, which does not contain any iron at all . These provisions are quite below the recommended daily requirement of elemental iron which is 3–6 mg/kg/day .
The prevalence of iron-deficiency anemia is 16.6% in this study. This finding is higher than values documented in previous studies ,. This higher prevalence of iron-deficiency anemia in this study can result from early age of introduction of complementary feeds, and nutritionally poor complementary feeds given to the children as well as low practice of exclusive breastfeeding recorded in the study population.
The study has shown a lower mean serum ferritin level among the malnourished in the acute phase compared with controls. This is in contrast to previous studies where a higher serum ferritin value was observed in PEM as compared with controls , even though the participants studied were in the recovery phase of PEM. However, this study is in conformity with other studies that assessed the serum ferritin levels in PEM in the acute phases and found that serum ferritin was lower in the children with malnutrition ,,. Its level are expected to be elevated in the phase of an acute ongoing infection or inflammation. The studied population were in the acute phase of the illness and the prescience of ongoing infection cannot be excluded and so the expectation was an elevation in the serum ferritin which is an acute-phase reactant in these patients. However, because there is a real depletion in the store of these acute-phase reactant iron, the expected response cannot be observed; thus for PEM, this low serum ferritin level is a true reflection of iron deficiency in these children, as serum ferritin is the best indicator for iron deficiency because a decrease in the amount of stored iron is the only known cause for low serum ferritin results .
The diagnosis or establishment of iron-deficiency anemia in children with PEM usually brings about diagnostic challenges. The choice of the type of appropriate investigative tool depends on many factors. Some other study on the usefulness of serum ferritin in the diagnosis of iron status concluded that serum ferritin has a limited value as an indicator of iron status in participants with PEM, presumably because of the frequency of infections and of hepatocellular damage in such participants , while most others have been inconclusive . The use of serum ferritin for the diagnosis of iron-deficiency anemia in PEM from this study however shows that serum ferritin has a very high sensitivity in establishing the presence of iron-deficiency anemia in these groups of children. The chances or probability that serum ferritin alone will pick iron deficiency in children with PEM is very high. This has been found in another study though not in children with PEM where serum ferritin was by far the most powerful test for the diagnosis of iron deficiency, outperforming the other methods ,.A high specificity was also found from these studies; this implies that the probability of serum ferritin to identify iron deficiency correctly in PEM was high. This further corroborates previous studies and documentation that serum ferritin is highly specific for iron deficiency ,,. Furthermore, a high positive predictive value also indicates that the probability that low serum ferritin will identify iron-deficiency anemia if present is high.
| Conclusion|| |
Our study concluded that anemia particularly microcytic anemia was common in children with PEM and this finding is more attributed to the poor feeding practice seen in this study. The study also found a low serum ferritin in children with PEM compared with controls and also concluded that serum ferritin has a very high sensitivity and specificity in detecting iron-deficiency anemia in children with PEM.
The study recommends that the diagnosis of iron-deficiency anemia is common among malnourished and it should be sought for because of its long-time effects on cognition and development. Its diagnosis can be established by a combination of hematologic as well as biochemical parameters such as serum ferritin to enhance the diagnosis. Future studies for other possible sensitive tests that can be utilized for screening and diagnosis of iron-deficiency anemia in PEM especially in developing countries where the condition is prevalent is strongly advocated. Continuous nutritional education and campaign on exclusive breastfeeding and introduction of appropriate complementary feeds should also be intensified. These would help reduce the risk of both overt and obvious malnutrition and its attendant effects. Recommendation of iron supplementation and iron therapy would be of great value in the care of children with malnutrition.
The authors acknowledge the authority of the University for Ilorin Teaching Hospital where the study was carried out. The authors are also grateful to the parents and caregiver who accepted to participate in this study. Finally, they are grateful to the consultant, residents, and the nursing staff of the Pediatrics Department for their various contributions to the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Federal Ministry of Health guidelines for infant and young children feeding in Nigeria 2005; 25–30.
UNICEF State of the World’s children: Official publication of the United Nations. 2005. 85–88.
Mary EP. Protein energy malnutrition, path physiology, clinical consequences and treatment. In Walker AW, Christopher D, Watkim JB, eds. Nutrition in paediatrics. London: Blackwell Waterson; 2008. 171–184
Warrier RP. The anemia of malnutrition. In Suskind RM, Suskind LL eds. The malnourished child. New York: Lippincott-Raven 1990. 19: 61–72.
Guyatt GH, Oxman AD, Ali M, Willan A, McIlroy W, Patterson C. Laboratory diagnosis of iron-deficiency anemia: an overview. J Gen Intern Med 1992; 7:145–153.
Kratz A, Ferraro M, Sluss PM, Lewandrowski KB. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values. N Engl J Med 2004; 351:1548–1563.
Heath AL, Fairweather-Tait S, Worwood M. Reference limits for haemoglobin and ferritin. If it’s not broken, don’t fix it. BMJ 2001; 323:806–807.
Wickramasinghe SN, Gill DS, Broon DN, Akinyanju OO, Grange AO. Limited value of serum ferritin in evaluating iron status in children with protein-energy malnutrition. Scand J Haematol 1985; 35:292–298.
Koduri PR, Shah PC, Goyal V, Mehta P. Elevated serum ferritin levels: associated diseases and clinical significance, Am J Med 1996; 101:121–122.
Hammidu JL, Salami HA, Ekanem AL, Hamman L. Prevalence of protein energy malnutrition in Maiduguri, Nigeria. Afr J Bio Research 2003; 6:123–127.
Engvali E, Van Vunakis H, Langone JJ. eds. Method in Enz. New York: Academic press 1980. 70: 419–492.
Brady P. Iron deficiency anemia: a call for aggressive diagnostic evaluation. Southern Med J 2007; 10:967.
Ellen B, Paul H, Bertram L. Nutritional anaemias. In Walker AW, Christopher D, Watkim JB, eds. Nutrition in peadiatrics. London: Blackwell Waterson 2008. 701–711
Atair R, Mannan MA, Hamidu RMD. Influence of infection on iron profile in severely malnourished children. India J Paediatr 2007; 8:20–23.
Ojofeitimi EO. Principles and practice of nutrition for community health workers. Ibadan: None Publishers; 2008. 102–105
Bede C. Ibe; overview of complementary feeding. J Child Health 2007; 1:23–40.
El-Nawawy S, Barakat T, Elwalily A, Abdel-Moneim Deghady, Hussein M. Evaluation of erythropoiesis in protein energy malnutrition. East Med Health J 2002; 8:2–3.
Abidoye RO, Sikabofori. A study of prevalence of protein energy malnutrition among 0–5 years in rural Benue State, Nigeria. Nutr Health 2000; 13:235–247.
Alemnji GA, Thomas KD, Durosinmi MA, Taiwo O, Fakunle JB. Haematogram and serum iron status of malnourished Nigerian children. East Afr Med J 1995; 72:605–608.
Smith, Cipriano. Serum ferritin levels in Shetland Ponies with experimentally-induced acute inflammation (commencing day zero) compared to normal control animals. Vet Pathol 1987; 24:354–356.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]