|Year : 2018 | Volume
| Issue : 3 | Page : 999-1004
Relationship between serum vitamin D and iron level in children with attention-deficit hyperactivity disorder
Fahima M Hassan1, Mohamed A Soliman2, Sameh A Abd El-Nabi1, Ghada A Elgazzar3
1 Department of Pediatrics, Menoufia University, Shebeen El-Kom, Egypt
2 Department of Clinical Pathology, Menoufia University, Shebeen El-Kom, Egypt
3 Department of Pediatrics, Menouf General Hospital, Shebeen El-Kom, Menoufia Governorate, Egypt
|Date of Submission||29-Jan-2017|
|Date of Acceptance||09-Apr-2017|
|Date of Web Publication||31-Dec-2018|
Ghada A Elgazzar
Department of Pediatrics, Menouf General Hospital, Sers Ellayan, Shebeen El-Kom, El Menoufia
Source of Support: None, Conflict of Interest: None
The aim of this study was to determine the association between iron, ferritin, and vitamin D deficiency with attention-deficit hyperactivity disorder (ADHD) and the effect of their deficiency on the development of ADHD in children.
ADHD is one of the most prevalent mental health disorders. It has been reported that iron, ferritin, and vitamin D deficiency may be related to the pathophysiology of ADHD.
Patients and methods
Our study includes 60 children with ADHD aged 3–18 years and 20 controls aged 3–18 years. Sociodemographic and clinical data were collected. The health status of the patients was assessed by symptoms and clinical presentations, family history, Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-V), and laboratory investigations, including serum level of iron, ferritin, and 25-hydroxyvitamin D.
Mean age (SD in years) for ADHD and control children was (7.13 ± 1.89 vs. 7.95 ± 1.84). There were statistically significant differences between ADHD versus control children for serum iron (44.05 ± 25.28 vs. 91.15 ± 33.83 μg/dl), ferritin (15.76 ± 18.06 vs. 98.2 ± 52.37 ng/ml), and vitamin D (13.1 ± 5.66 vs. 32.9 ± 9.12 ng/ml). There were many factors that were sought to be associated with increased risk of developing ADHD.
The study indicates that low serum iron, ferritin, and vitamin D deficiency may be related to ADHD pathophysiology.
Keywords: attention-deficit hyperactivity disorder, iron deficiency, risk factors, vitamin D
|How to cite this article:|
Hassan FM, Soliman MA, Abd El-Nabi SA, Elgazzar GA. Relationship between serum vitamin D and iron level in children with attention-deficit hyperactivity disorder. Menoufia Med J 2018;31:999-1004
|How to cite this URL:|
Hassan FM, Soliman MA, Abd El-Nabi SA, Elgazzar GA. Relationship between serum vitamin D and iron level in children with attention-deficit hyperactivity disorder. Menoufia Med J [serial online] 2018 [cited 2019 Jun 17];31:999-1004. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/999/248768
| Introduction|| |
Attention-deficit hyperactivity disorder (ADHD) is one of the most prevalent mental health disorders that affect ~5.3–7.1% of children and adolescents. Attention deficiency, hyperactivity, and impulsivity are three main symptoms that help diagnose the disorder before the age of 12 years. There are three major subtypes of the disorder: predominantly inattentive (ADHD-PI or ADHD-I), predominantly hyperactive impulsive (ADHD-HI or ADHD-H), or a combination of these two subtypes (ADHD-C). Despite being one of the most studied psychiatric disorders, the exact cause of ADHD is still unknown; both genetic and environmental risk factors contribute to the development of ADHD. Iron deficiency is considered a potent cause of poor cognitive impairment, learning disabilities, and psychomotor instability, which also supports the hypothesis that iron deficiency may play a role in the pathophysiology of ADHD. The most useful single laboratory value for the diagnosis of iron deficiency may be plasma ferritin. Recent studies have reported a significant relationship between ADHD and low serum ferritin levels. Vitamin D is essential for the brain as it promotes normal brain development. Studies demonstrate that vitamin D deficiency could be a risk factor for developing ADHD. This study aimed to clarify the association between iron, ferritin, and vitamin D deficiency and ADHD among children.
| Patients and Methods|| |
This study was carried in Pediatric Department, Menoufia University Hospital; it follows the ethical standards of our institution. Informed consents from all subjects were obtained in accordance with the local ethical committee from the period of April 2016 till November 2016. This study was carried on 80 patients. They were classified into the following groups.
Group I included 60 patients with ADHD. Group II included 20 matched healthy individuals, excluding children with seizures, mental retardation, and children with chronic systemic diseases.
All participants underwent full history taking and thorough clinical examination and laboratory investigations, which included the following: (a) complete blood pictures, (b) serum iron, (c) serum ferritin, and (a) serum 25-hydroxy vitamin D [25(OH) D].
Specimen collection and preparation were done under sterile aseptic techniques. Venous blood samples were collected, and serum separated and stored at −70°C until analysis. A blood test was carried out for the patient group and the control group.
25(OH) D, a vitamin D metabolite, was measured using a commercially available kit (Sun Red Biotechnology Company, Shanghai, China). The treated samples were then assayed using competitive binding radioimmunoassay technique.
Ferritin was measured using commercially available kits (Immunospec Corporation, CanogaPark, California, USA).
Serum levels of these biochemical parameters were determined according to standard laboratory procedures and expected values as follow: serum iron (37–158 μg/dl), serum ferritin (15–150 ng/ml), and serum vitamin D (30–80 ng/ml).
The data collected were tabulated and analyzed by Statistical Package for the Social Science Software, version 20 (IBM corp., Armonk, N.Y., USA), on IBM compatible computer. Quantitative data were expressed as mean ± SD and analyzed by applying test for comparison between two groups of normally distributed variables, whereas for comparison between two groups of not normally distributed variables, Mann–Whitney test was applied. Qualitative data were expressed as n (%) and analyzed by applying χ2 for comparison between two or more independent qualitative variables normally distributed.
| Results|| |
Our study showed sociodemographic characteristics of patients with ADHD and the controls. Prevalence of ADHD was higher in male (71.7%) than female, with ratio of 2.5: 1 and more prevalent in school age than preschool age, as in school age was 83.3% whereas in preschool was 16.7%. Moreover, prevalence of ADHD in urban areas was 61.7% and was higher than prevalence in rural areas, which was 38.3%. There was significant statistical difference between ADHD and healthy children control subjects with respect to mother education (P = 0 03) and father education (P = 0.02). ADHD was statistically significantly higher in low socioeconomic status children and consanguineous marriages of parent (P = 0.04) [Table 1].
|Table 1: Distribution of sociodemographic characteristics in studied groups|
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We found that there was significant statistical difference between ADHD and healthy control children regarding large family size (>4 children), among single parent children, and family history of ADHD. Moreover, we found no significant difference according to birth order [Table 2].
|Table 2: Distribution of the studied children according to family risk factors|
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According to the maternal risk factors, which were sought to be associated with ADHD, our result revealed that there was a statically significant difference between ADHD and healthy control children regarding the duration of pregnancy, as preterms represented 41.7% of ADHD group and 15% of control group. Moreover, our study found that no significant statistical difference was found between studied groups regarding low-birth-weight children. There was a significant statistical difference between the studied groups regarding type of feeding, as bottle feeding represented 51.6% of ADHD group and 25% of control group [Table 3].
|Table 3: Distribution of the studied children according to maternal risk factors|
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Moreover, our result found that there were statistically highly significant differences between studied groups regarding iron level, as mean iron level in ADHD group was 44.05 ± 25.28 μg/dl, whereas in control group was 91.15 ± 33.83 μg/dl. There were statistically highly significant differences between studied groups regarding ferritin level, as mean ferritin level in ADHD group was 15.76 ± 18.06 ng/ml, whereas in control group was 98.2 ± 52.37 ng/ml, and there were statistically highly significant differences between studied groups regarding vitamin D level, as mean vitamin D level in ADHD group was 13.1 ± 5.66 ng/ml, whereas in control group was 32.9 ± 9.12 ng/ml [Table 4] and [Figure 1].
|Figure 1: Mean values of serum iron, ferritin, and vitamin D of the studied groups.|
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| Discussion|| |
ADHD is defined as a neurodevelopmental disorder characterized by persistent pattern of inattention and/or hyperactivity–impulsivity that interferes with functioning or development, has symptoms presenting in two or more settings, and negatively affects directly social, academic, or occupational functioning of the child.
Iron deficiency in early life likely affects brain regions that are rapidly developing at the time of insufficiency as well as connections to areas with more prolonged development, such as the frontal lobe, which explains the diverse effects of iron deficiency.
The effects of vitamin D on brain development and function, as a neuroimmunomodulatory, leading to behavioral and neuropsychiatric diseases have been reviewed by de Fernandes Abreu et al..
The aim of our work was to determine the relationship between iron and vitamin D deficiency with ADHD in children aged from 3 to 18 years. According to sociodemographic data, the prevalence of ADHD was higher in male (71.7%), than female, with ratio of 2.5 : 1. This was in agreement with Nafi, who found a significant sex difference in demographic data, with male to female ratio of 2.9 : 1. This can be explained by boys with ADHD have more externalizing symptoms (running, impulsivity, and hitting), whereas girls with ADHD have more internalizing symptoms and adverse effects (depression, anxiety, and low self-esteem).
Prevalence of ADHD in school age was more than in preschool age children, as in school age children, it was 83.3%, whereas in preschool age children, it was 16.7%. This was in agreement with Bener et al.. This may be explained by the fact that young children are expected to be inattentive–hyperactive, as these symptoms are considered normal at that age, and as the child grows, comorbid disorders start to appear, which results in greater impairment such as decrease in school performance.
Prevalence of ADHD in urban areas was 61.7% and was higher than prevalence in rural areas, which was 38.3%. This agreed with Bishry et al., who found that the prevalence of ADHD in urban area (6.3%) was higher than prevalence in rural areas (4.4%) in delta Egypt. This may be explained by different culture and environmental factor between two areas, which contributes to appearance of symptoms.
Regarding parents' education, our study showed significant association between low parents' education level and ADHD; this agrees with Bener et al.. This may be explained by parents with low level of education had poor knowledge of how to deal with children having ADHD, and might be treating children having ADHD violently, which may reflect negatively on them and lead to increased symptoms of ADHD.
Regarding the socioeconomic status of children, our study showed a significant association between low socioeconomic status of the family and ADHD; this agrees with Akinbami et al.. This may explained by higher rates of ADHD in groups with greater socioeconomic disadvantage are mediated through differential exposure. Such exposures could be perinatal, prenatal, or occur during childhood. There was a significant statistical difference between the studied groups regarding the presence of positive consanguinity, as it presents in 45% of the ADHD patient group and 20% of the control healthy group. This result was in agreement with Bener et al., who found that positive consanguinity was present in 39% of patients with ADHD. This suggests that consanguinity is a major risk factor in the development of ADHD.
Regarding the family risk factors, our study found significant statistical difference between the studied groups regarding family size and prevalence of ADHD, which was high in children with large family size (>4 children). This agrees with Jenahi et al., who showed the association of ADHD symptoms with large family size.
The larger the family size, the lesser care the child receives and the greater the behavioral problems observed, with ADHD being one of those problems. There was a significant statistical difference between the studied groups regarding family history of ADHD, as it was present in 35% of ADHD group and 10% of control group.
Our result was in agreement with Banerjee et al., who supported a strong familial nature in ADHD. Family studies have identified a 2–8-fold increase in the risk for ADHD in parents and siblings of children with ADHD.
There was a significant statistical difference between the studied groups regarding living with single parent, as it was present in 40% of ADHD group and 15% of control group. Deault reported that separation of the child from one or both parents early in life was associated with increase prevalence of ADHD. This may be explained by parental separation and divorce, which had been shown to have negative effects on the child behavior such as inconsistent parenting, more punishment, and violence.
According to the maternal risk factors, there was a statistical significant difference between studied groups regarding duration of pregnancy, as preterms represent 41.7% of ADHD group and 15% of control group. This agrees with Johnson et al..
Goldenberg et al. reported that preterm labor is thought to be initiated by multiple mechanisms, including infection or inflammation, utero-placental ischemia or hemorrhage, stress, and other immunologically mediated processes. Moreover, our study reaveled no significant statistical difference in prevalence of ADHD regarding low-birth-weight children.
Regarding the type of feeding, our result demonstrated a significant statistical difference between the studied groups regarding the type of feeding, as bottle feeding represents 5.6% of ADHD group and 25% of control group. This agrees with Mimouni-Bloch et al., who found that lack of breastfeeding increases the likelihood of ADHD and attention problem of children, which decreases the child's IQ.
Regarding the serum levels of iron and ferritin, our results revealed that there was a significant statistical difference (P value of less than 0.001) between ADHD group and control group regarding iron and ferritin levels, as mean values of iron were 44.05 ± 25.28 μg/dl and 91.15 ± 33.83 μg/dl among ADHD group and control children, respectively, and also regarding ferritin mean values, which were 15.76 ± 18.06 ng/ml and 98.2 ± 52.37 ng/ml in ADHD group and control children, respectively. This result was in agreement with Bener et al., who revealed that there was a significant statistical difference between ADHD and control groups regarding iron and ferritin levels.
Regarding serum vitamin D level, our result revealed that there was a significant statistical difference (P value of less than 0.001) between patient group and control regarding vitamin D level, as mean values of vitamin D were 13.1 ± 5.66 ng/ml in ADHD group and 32.9 ± 9.12 ng/ml in the control children. This is in agreement with Sharif et al..
Our results also go with the results of Bener et al., who found that mean value of vitamin D in ADHD children was much lower than the normal controls, and there was a significant difference found in the mean values of vitamin D betwee n ADHD (16.8 ± 7.8) and control children (22.1 ± 9) (P < 0.01).
| Conclusion|| |
In view of this study, we concluded that serum iron, ferritin, and vitamin D level were lower in children with ADHD than in normal control, which were significant, and these may play a prominent role in the pathogenesis of ADHD. So serum analysis of iron, ferritin, and vitamin D could be considered in the workup of ADHD, and this may suggest alternative therapeutic approach (iron and vitamin D supplementation) in prevention and treatment of ADHD.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Arnold LE, Hodgkins P, Caci H, Kahle J, Young S. Effect of treatment modality on long-term outcomes in attention deficit/hyperactivity disorder: a systematic review. PLoS ONE 2015; 10
Matthews M, Nigg JT, Fair DA. Attention deficit hyperactivity disorder. Curr Top Behav Neurosci 2014; 16
Ramsay JR. Cognitive behavioral therapy for adult ADHD. Routledge 2007; 4
Thapar A, Cooper M, Eyre O, Langley K. Practitioner review: what have we learnt about the causes of ADHD. J Child Psychol Psychiatry 2013; 54
Konofal E, Lecendreux M, Deron J, Marchand M, Cortese S, Zaïm M. Effects of iron supplementation on attention deficit hyperactivity disorder in children. Pediatr Neurol 2008; 38
Cortese S, Angriman M, Lecendreux M, Konofal E. Iron and attention deficit/hyperactivity disorder: what is the empirical evidence so far? A systematic review of the literature. Exp Rev Neurother 2012; 12
Abdel-Rasoul G, El Bahnasy R, El Shazly H, Gabr H, Abdel-Aaty N. Epidemiology of iron-deficiency anemia among primary school children (6–11 years), Menoufia governorate, Egypt. Menoufia Med J 2015; 28
Bener A, Kamal M, Bener H, Bhugra D. Higher prevalence of iron deficiency as strong predictor of attention deficit hyperactivity disorder in children. Ann Med Health Sci Res 2014; 4
Eyles DW, Feron F, Cui X, Kesby JP, Harms LH, Ko P. Developmental vitamin D deficiency causes abnormal brain development. Psychoneuroendocrinology 2009; 34
Goksugur SB, Tufan AE, Semiz M, Gunes C, Bekdas M, Tosun M, et al
. Vitamin D status in children with attention deficit hyperactivity disorder. Pediatr Int 2014; 56:
Kirkpatrick LA, Feeney BC. A simple guide to IBM SPSS Statistics for version 20.0
Student ed. Belmont, CA and Wadsworth, OH: Cengage Learning; 2013.
Erskine HE, Ferrari AJ, Polanczyk GV, Moffitt TE, Murray CJ, Vos T. The global burden of conduct disorder and attention deficit/hyperactivity disorder in 2010. J Child Psychol Psychiatry 2014; 55
Georgieff MK. Long – term brain and behavioural consequences of early iron deficiency. Nutr Rev 2011; 69
de Fernandes Abreu DA, Eyles D, Feron F. Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology 2009; 34s:
Nafi OA. Prevalence of ADHD co-morbidities in children of South Jordan. Eur Sci J 2013; 9
El-Nemr FM, Badr HS, Salem MS. Prevalence of attention deficit hyperactivity disorder in children science. J Public Health (Bangkok) 2015; 3
Bishry Z, Elwan M, Rashed N, Al Hamrawy L, El-Sayed S, El-Bahy M. Prevalence of attention deficit hyperactivity disorders in primary school children in Shebin El Kom. Curr Psychiatry 2008; 15
Akinbami LJ, Liu X, Pastor PN, Reuben CA. Attention deficit hyperactivity disorder among children aged 5–17 years in the United States, 1998–2009. NCHS Data Brief 2011; 70
Reiss F. Socioeconomic inequalities and mental health problems in children and adolescents: a systematic review. Soc Sci Med 2013; 90
Jenahi E, Khalil MS, Bella H. Prevalence of attention deficit hyperactivity symptoms in female school children in Saudi Arabia. Ann Saudi Med 2012; 32
Hartung CM, Willcutt EG, Lahey BB, Pelham WE, Loney J, Stein MA, et al
. Sex differences in young children who meet criteria for attention deficit/hyperactivity disorder. J Clin Child Adolesc Psychol 2002; 3
Banerjee TD, Middleton F, Faraone SV. Environmental risk factors for attention-deficit hyperactivity disorder. Acta Pediatr2007; 96
Deault LC. A systematic review of parenting in relation to the development of comorbidities and functional impairments in children with attention-deficit/hyperactivity disorder (ADHD). Child Psychiatry Hum Dev 2010; 41
Counts CA, Nigg JT, Stawicki JA, Rappley MD, von Eye A. Family adversity in DSM-IV ADHD combined and inattentive subtypes and associated disruptive behavior problems. J Am Acad Child Adolesc Psychiatry 2005; 44
Johnson S, Wolke D. Behavioural outcomes and psychopathology during adolescence. Early Hum Dev 2013; 89
Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet2008; 371
Mimouni-Bloch A, Kachevanskaya A, Mimouni FB, Shuper A, Raveh E, Linder N. Breast feeding may protect from developing attention-deficit/hyperactivity disorder. Breastfeed Med 2013; 8
Sharif MR, Madani M, Tabatabaei F, Tabatabaee Z. The relationship between serum vitamin D levels and attention deficit hyperactivity disorder. Iran J Child Neurol Autumn 2015; 9
[Table 1], [Table 2], [Table 3], [Table 4]