|Year : 2020 | Volume
| Issue : 2 | Page : 87-91
Sociodemographic and clinical determinants of folate deficiency among sickle cell anemia patients in Kano, North Western Nigeria
Ibrahim Abdulqadir MBBS, FMCPath 1, Aisha A Galadanci2, Mujtaba I Mashi3, Sagir A Gumel2, Aisha K Gwarzo2
1 Department of Haematology and Blood Transfusion, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria
2 Department of Haematology and Blood Transfusion, Aminu Kano Teaching Hospital/Bayero University, Kano, Nigeria
3 Department of Haematology and Blood Transfusion, Federal Medical Centre, Katsina, Nigeria
|Date of Submission||18-Dec-2019|
|Date of Acceptance||19-Apr-2020|
|Date of Web Publication||29-Dec-2020|
Department of Haematology and Blood Transfusion, Usmanu Danfodiyo University Teaching Hospital, Sokoto, P.M.B. 2370, Postal Code: 840232
Source of Support: None, Conflict of Interest: None
Context Folate deficiency is common among sickle cell anemia (SCA) patients and could be influenced by factors such as clinical and social conditions. Sociodemographic and clinical determinants of folate deficiency have not been previously investigated among SCA patients in this environment.
Aims The aim was to determine the sociodemographic and clinical factors associated with folate deficiency in SCA patients accessing care at Aminu Kano Teaching Hospital, Kano.
Settings and design This was a cross-sectional study involving 110 SCA participants at steady state.
Patients and methods Sociodemographic and clinical data of the participants were collated, while their folate status was determined using Roche Elecsys 2010.
Statistical analysis Data were analyzed with SPSS version 21.0 and level of significance was set at P less than or equal to 0.05.
Results The mean age of the participants was 14.9±7.1 years and the majority of them were men (58, 52.7%), students (96, 87.3%), and jaundiced (66, 60.0%). Age, sex, occupation of the participants, and mother’s level of education were significantly associated with folate deficiency (P<0.05). Female gender [odds ratio (95% confidence interval) for red blood cells 2.6 (1.2–5.7) and serum 2.8 (1.3–6.1)] and mothers with less than secondary education [odds ratio (95% confidence interval) for red blood cells 5.3 (1.0–27.6) and serum 4.2 (1.0–18.1)] were independent predictors of folate deficiency.
Conclusion Sociodemographic and clinical characteristics are important determinants of folate deficiency in SCA. We therefore recommend periodic assessment of folate status as part of the standard care to SCA patients to prevent complications of folate deficiency.
Keywords: clinical determinants, folate deficiency, Kano, sickle cell anemia, sociodemographics
|How to cite this article:|
Abdulqadir I, Galadanci AA, Mashi MI, Gumel SA, Gwarzo AK. Sociodemographic and clinical determinants of folate deficiency among sickle cell anemia patients in Kano, North Western Nigeria. Egypt J Haematol 2020;45:87-91
|How to cite this URL:|
Abdulqadir I, Galadanci AA, Mashi MI, Gumel SA, Gwarzo AK. Sociodemographic and clinical determinants of folate deficiency among sickle cell anemia patients in Kano, North Western Nigeria. Egypt J Haematol [serial online] 2020 [cited 2021 Jul 31];45:87-91. Available from: http://www.ehj.eg.net/text.asp?2020/45/2/87/305404
| Introduction|| |
It is a common hypothesis that increased erythropoietic activity in sickle cell anemia (SCA) will increase the risk for folate deficiency and has even formed the basis of routine folic acid supplementation in people with sickle cell disease (SCD) . This hypothesis can be true for patients in low-resource countries owing to several studies that reported higher folate deficiency in SCD patients compared with their non-SCD counterparts [2-4]. However, there is no convincing evidence pointing to increased risk of folate deficiency in SCD patients living in high-resource settings [5-9]. This is despite the fact that excessive cellular turnover, due to increased erythropoietic activity meant to compensate for the shortened red cell survival in hemolytic anemias, is at least relevant to all SCA patients in both high-resource and low-resource nations ,,,. So, the high folate deficiency reported among SCA patients in low-resource setting may be related to sociodemographic factors of the environment, such as inadequate dietary intake arising from poor socioeconomic standing, recurrent febrile infections like malaria and lack of food fortification. Understanding the individual and environmental factors that could influence folate status among SCA patients domicile in low-resource countries will form a basis for evidence-based interventions to prevent its complications. There is no study in the country that previously evaluated the role of sociodemographic and clinical factors in relation to folate status of SCA patients; hence, we seek to study the sociodemographic and clinical determinants of folate deficiency among SCA patients in Kano, Nigeria.
| Patients and methods|| |
This was a cross-sectional study conducted among 110 SCA patients in steady state recruited at the adult and pediatric hematology clinics of Aminu Kano Teaching Hospital, Kano, Nigeria from April to August, 2017.
Sickle cell patients with non-SS hemoglobin phenotype, sickle cell-related complications (stroke, hypertension, liver, or renal diseases), and pregnancy as well SCA patients who were breastfeeding mothers were excluded from the study. Additional exclusions were SCA patients with chronic viral infections (HIV, hepatitis B or C) and those on hydroxyurea and any other drug outside routine folic acid, Proguanil and Penicillin prophylaxis.
Patients were examined for evidence of pallor, jaundice, and hypertension. Relevant sociodemographic and clinical data were obtained with interviewer-administered questionnaire and hospital case note of the patients, while 2.5 ml each of venous blood was collected into plain and K2- EDTA sample bottles.
For serum folate, sample in a plain bottle was allowed to form a clot undisturbed at room temperature, centrifuged at 2500 rpm for 15 min; serum was then harvested with a Pasteur pipette and stored at −20°C pending the folate assay.
For red cell folate, 0.1 ml of EDTA anticoagulated blood was added to 2 ml of 0.2 g/dl ascorbic acid solution to obtain 1 : 20 dilution. The mixture was then gently mixed, allowed to stand undisturbed in a dark environment at room temperature for 90 min, and then stored at −20°C ,.
Folate assay was done through ElectroChemiLuminescence Technology on Elecsys 2010 (Roche Diagnostics, Bellport, NY, USA) and analytical control specimens (Universal pericontrol I and II) were included with each batch of test. Human immunodeficiency virus, hepatitis B and C were screened with Determine (Shanghai, China), Ascon (Hangzhou, China), and Healgen, respectively, while serum pregnancy test was carried out with LabACON (Hong Zhou, China) for all sexually active women participants.
Definition of terms
Steady state is the absence of febrile illness, sickle cell-related crisis in the preceding 6 weeks, and blood transfusion in the last 3 months .
Folate deficiency is implicated when red cell and/or serum folate level is less than 100 and 6 ng/ml, respectively. .
Informed written consent was obtained from adult participants while parental/guardian consent and child assent were obtained from pediatric participants. Ethical approval was obtained from Aminu Kano Teaching Hospital Ethics Review Board.
Data were analyzed with the Statistical Package for the Social Sciences (SPSS) version 21.0 (IBM Corp., Armonk, New York, USA) and the result is presented as proportion and percentage. χ2 was used to test for association, while logistic regression analysis at 95% confidence interval was used to estimate risk and statistically significant relationship was set at P less than 0.05.
| Results|| |
The mean age of the participants was 14.9±7.1 years and majority were men (58, 52.7%), students (96, 87.3%), and jaundiced (66, 60.0%). Folate deficiency was more common among women [red blood cells (RBC) 32 (61.5%) and serum 31 (59.6%)], students [RBC 52 (54.2%) and serum 47 (49.0%)] and children of mothers with no formal education [RBC 10 (83.3%) and serum (9, 75.0%)] than their SCA counterpart who were men [RBC 22 (37.9%); P=0.01 and serum 20 (34.5%); P=0.01], civil servants [both RBC and serum 0 (0.0%); P=0.01], and children of mothers with tertiary education [both RBC and serum 4 (25.0%); P=0.01], respectively ([Table 1]).
Also, SCA who were erratic with folic acid supplementation had more folate deficiency [RBC 31 (73.8%) and serum 30 (69.8%)] than those who were regular [RBC 23 (33.8%); P=0.03 and serum 21 (31.3%); P=0.04], but neither history of blood transfusion [RBC 21 (45.7%) versus 33 (51.6%); P=0.47 and serum 27 (45.8%) versus 32 (47.1%); P=0.44] nor presence of jaundice [RBC 32 (48.5%) versus 22 (50.0%); P=0.47 and serum 29 (43.9%) versus 22 (50.0%); P=0.22] were associated with folate deficiency as depicted in [Table 2].
Age less than 18 years [odds ratio (OR) (95% confidence interval) for RBC 5.0 (2.0–12.5); P=0.01 and serum 2.8 (1.2–6.7); P=0.04], female gender [OR (95% CI) for RBC 2.6 (1.2–5.7); P=0.04 and serum 2.8 (1.3–6.1); P=0.03], and mothers with less than secondary education [OR (95% CI) for RBC 5.3 (1.0–27.6); P=0.02 and serum 4.2 (1.0–18.1); P=0.01] were independent predictors of folate deficiency ([Table 3]).
| Discussion|| |
The study showed that folate deficiency is more common among SCA patients who were women, students, children of mothers with no formal education, and those who were erratic with routine folic acid supplementation, while there is no difference with respect to folate deficiency on the basis of history of blood transfusion, presence of jaundice or annual frequency of bone pain crisis. Also, the study has identified age of less than 18 years, female sex, students, and mothers with less than secondary education as the only predictors of folate deficiency in SCA patients among all the sociodemographic and clinical factors tested.
The finding of high folate deficiency in female participants in this study was consistent with a study from India where they reported high folate deficiency among apparently healthy women . This could be related to the monthly menstrual bleeding demanding additional output from the bone marrow and/or repeated pregnancy within short intervals preventing replenishment of folate store, situations which can easily be complicated by folate deficiency especially if the dietary intake is inadequate ab initio. For women with SCA this can be further accentuated by repeated hemolysis that defines the course of the condition. Although, at variance with the finding of Kennedy et al. , when they reported decreased RBC folate with increasing age of sickle cell patients, our finding of high risk of folate deficiency using both serum and red cell folate among younger patients with SCA is not surprising and this was earlier highlighted by Sukla et al. , while evaluating causes of folate deficiency anemia in a population-based study. Children and teenagers in comparison to adults have higher demand for folate and other nutrients to support physical growth and body development. Also, individuals with SCA under the age of 18 years might not have gained all the necessary experience to live with the disorder compared with their adult counterparts and as such they may need assistance from caregivers in order to adequately comply with instructions from physicians such as protection from adverse weather conditions and mosquito bites as well as taking routine drugs as and when due. This can be further highlighted by higher risk of folate deficiency among children of mothers with less than secondary education reported in this study. This is probably because, mothers with low level of education may not be able to device conscious strategies of preventing folate deficiency in their children with SCA, as maternal education status has been reported to influence awareness of folate deficiency among pregnant women . These strategies include folate-rich meal, folate-fortified diet, folate supplementation, and good cooking practice since folate is a thermolabile vitamin and can be easily destroyed when overheated during the cooking process ,.
The finding of higher folate deficiency (using both serum and red cell folate) among SCA patients, who were erratic with routine folic acid supplementation is reasonable as previous studies have established a positive association between supplementation in the form of either oral folic acid or fortified food with the body’s folate status ,. However, the inability of the study to find an association between folate deficiency and blood transfusion, jaundice, or painful crises among SCA patients cannot readily be explained. We had expected folate deficiency to cause anemia and to increase the bilirubin load due to ineffective hemopoiesis that normally accompanies the megaloblastic process, situation that would have accentuated both anemia and jaundice much higher than what could arisen from hemolysis alone. For anemia, despite the reported association between anemia and folate deficiency , some studies have suggested anemia as a late event in the course of folate deficiency and others did not report association between folate status and hemoglobin concentration ,. So, it can be assumed that our participants were in the early phase of folate deficiency and as such have not yet developed anemia to warrant blood transfusions and this assumption underscores the need for regular folate assay for SCA patients living in low-resource settings. Also, the position of homocysteine in the metabolic pathway of folate means that folate deficiency invariably causes hyperhomocysteinemia which predisposes to thrombotic events and this will in turn lead to painful episodes ,.
| Conclusion|| |
Sociodemographics and clinical parameters of SCA patients at steady state are a valuable guide to folate deficiency and when judiciously harnessed can prevent complications associated with folate deficiency like megaloblastic anemia and growth stunting. To prevent these complications, we recommend periodic assessment of folate status as part of standard care to all SCA patients living in low-resource settings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dexit R, Nettem S, Madan SS, Soe HHK, Abas ABL, Vence LD et al.
Folate supplementation in people with sickle cell disease. Cochrane Database Syst Rev
Abbas SS, Abdul-Razak N, Mustafa N, Abd-Ali R. Homocysteine, folic acid, vitamin B12 and pyridoxine: effects on vaso-occlusive crisis in sickle cell anaemia and sickle thalasaemia. Iraqi Postgrad Med J
Raouf AA, Hamdy MM, Badr AM, Shalaan D, Sakr M, Rahman ARA. Effect of homocysteine and folic acid on vaso-occlusive crisis in children with sickle cell disease. Egypt J Haematol
Galadanci AA, Abdulqadir I, Kuliya AG, Ahmed SG. Relationship between folate status and complete blood count parameters in sickle cell anaemia at steady state in Aminu Kano Teaching Hospital, Kano, Nigeria. IJR2H
Louise S, Amy L, Kate LEP, Russel DK. Stopping folic acid supplementation in hydroxyurea treated children with sickle cell disease. Blood
Rodriguez-Cortes HM, Griener JC, Hyland K, Bottiglieri T, Bennett MJ, Kamen BA. Plasma homocysteine levels and folate status in children with sickle cell anemia. J Pediatr Hematol Oncol
Lowenthal EA, Mayo MS, Cornwell PE, Thornley-Brown D. Homocysteine elevation in sickle cell disease. J Am Coll Nutr
Dhar M, Bellevve R, Brar S, Carmel R. Mild hyperhomocysteinaemia in adult patients with sickle cell disease: a common finding unrelated to folate and cobalamin status. Am J Hematol
Nguyen GT, Lewis A, Goldener C, Reed B, Dulman RY, Yang E. Discontinuation of folic acid supplementation in young patients with sickle cell anaemia. J Pediatr Hematol Oncol
Kennedy TS, Fung EB, Kawchak DA, Zamel BS, Frempong KO, Stallings VA. Red blood cell folate and serum vitamin B12 status in children with sickle cell disease. J Pediatr Hematol Oncol
Liwenbaum J, Klipstein FA. Folic acid deficiency in sickle cell anemia. N Engl J Med
Kannan A, Tilak V, Rai M, Gupta V. evaluation of clinical, biochemical and hematological parameters in macrocytic anemia. Int J Res Med Sci
William EO, William LR. Comparison of five automated serum and whole blood folate assays. Am J Clin Pathol
Billon J, Zaman Z, Clueys G. Limited dynamic range of a new assay for serum folate. Clin Chem
Khanduri U, Sharma A, Joshi A. Occult cobalamin and folate deficiency in Indians. Natl Med J India
Sukla KK, Nagar R, Raman R. Vitamin −B12 and folate deficiency, major contributing factors for anemia: a population based study. E-SPEN Journal
Anzaku AJ. Assessing folic acid awareness and its usage for the prevention of neural tube defects among pregnant women in Jos, Nigeria. J Basic Clin Reprod Sci
Dugdale AE. Predicting iron and folate deficiency anaemias from standard blood testing: the mechanism and implications for clinical medicine and public health in developing countries. Theor Biol Med Model
Ndiaye NF, Idohou_Dossau N, Diouf A, Guiro AT, Wade S. Folate deficiency and anaemia among women of reproductive age (15–49 years) in Senegal: results of national cross sectional survey. Food Nutr Bull
Ballas SK, Baxter JK, Riddick G. folate supplementation and twinning in patients with sickle cell disease. Am J Hematol
[Table 1], [Table 2], [Table 3]