Study of Role of Iron Deficiency Anaemia in Febrile Seizures in Children in a Tertiary Care Centre

Address for correspondence: Dr. Kumar GV Associate Professor, Department of Paediatrics Sri Siddhartha Medical College, Tumkur, Karnataka, India. PIN 572107 Email: kumargowripura@yahoo.co.in Tel: +919739306525 1Dr. Bheema Naik Sreenivasa, MBBS. MD, Associate Professor, Department of Paediatrics, Basaweshwara Medical College, Chithradurga, Karnataka, India. 2Dr. Gowripura Visweswaraiah Kumar, MBBS.DCH. DNB, Associate Professor, Department of of Paediatrics, Sri Siddhartha Medical College, Tumkur, Karnataka, India. 3Dr. Bheema Naik Manjunatha, MBBS. DCH, Senior Resident of Paediatrics, Basaweshwara Medical College, Chithradurga, Karnataka, India. Abstract


Introduction
T he world health organiza on es mates that anaemia largely caused by iron defi ciency, aff ec ng between 500 million and two billion people world wide 1,2 .It is the most common nutri onal defi ciency and haematological disease of infancy and childhood 3 .Iron is a nutri onal element not only needed for the synthesis of haemoglobin, but it is also essen al for enzymes involved in neurochemical reac ons 4 .To date, the pathophysiology of febrile seizure is unknown 5 .Age for peak incidence of febrile seizure is 14 to 18 months, which overlaps with that of iron defi ciency anaemia which is form 6 to 24 months 6,7 .Considering the age prevalence of iron defi ciency anaemia and febrile convulsion which are the same, the role of iron in the metabolism of neurotransmi er (such as GABA and serotonin) and some enzymes (such as monoaminoxidase and aldehidoxidase), the func on of hemoglobin in conveying oxygen to the brain and since fever can exacerbate symptoms that result from anaemia, a rela onship between iron defi ciency anaemia and febrile convulsions is probable 8,9,10 .Some studies have suggested iron defi ciency as a predisposing factor for febrile seizures, some described iron defi ciency anaemia is less frequent in children with febrile seizures 11 .Considering the confl ic ng results of the previous studies, we designed this case control study to evaluate the rela onship between iron defi ciency anaemia and febrile convulsions.

Material and Methods
A case control study was conducted from July 2010 to October 2014 in Basaveshwara Medical college hospital Chitradurga.One hundred children aged between 6 months to 6 years with febrile seizures were enrolled as cases.Sample size was based on Z formula and confi dence interval of 95% with 80% power, type one error of 5% to detect any signifi cant diff erence between the two groups with a level of 0.05.Febrile seizures were defi ned as a seizure occurring in associa on with a febrile illness, in the absence of CNS infec on or any other defi ned causes of seizures 12 .Children with a history of seizures, thalassaemia, central nervous system (CNS) infec ons, developmental delay and neurological defi cits, on iron therapy were excluded from the study.A control group of 100 children was selected from among children hospitalized for a febrile illness (such as upper and lower respiratory tract infec ons and gastroenteri s) but without seizures.Controls were group matched to cases on age and sex.An informed consent was obtained from parents or the guardian.Demographic data, seizure details, nature of febrile illness, the family history of epilepsy/febrile seizures, temperature at admission, and nutri onal status were recorded.Blood samples were collected from all par cipants for measurement of haemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), red cell distribu on width (RDW) and serum ferri n was done.Ethical commi ee clearance was sorted out.
Iron defi ciency anaemia was defi ned as Hb ˂11g/dl, MCV ˂70 fl , MCH ˂27 pg, RDW ˃15%, serum ferri n ˂12 ng/ml (WHO) 13 .In presence of fever, a higher cut-off value of serum ferri n (25-50ng/ml) was considered 14 .Cases and controls were compared with respect to blood indiciesand serum ferri n.Chisquare and ANOVA tests for discon nuous variable and unpaired t-test for con nuous variable at 5% signifi cance (p˂0.05) level were used for sta s cal analysis.

Results
100 cases (56 male, 44 female) and 100 controls (52 male, 48 female) were enrolled.The mean ages of pa ents in the febrile seizure and control groups were 1.5±1.2 and 1.9±1.5 year respec vely.Respiratory tract infec ons were the most common cause of fever in our study followed by gastroenteri s.

Discussion
Numerous studies have addressed the associa on between iron defi ciency anemia and febrile seizure in children.The results, however, have been controversial and even primary researches with high number of cases have failed to provide unequivocal results.We observed signifi cantly low serum ferri n levels in children with febrile seizures than in controls.Similar results were observed by Pisacame, etal 15 .But in contrast with these studies Mansourietal reported mean ferri n was higher in the convulsive group with no sta s cally signifi cant diff erence 16 .Kobrinsky et al deduced that iron defi ciency might have a protec ve eff ect on febrile convulsion 17.Iron has been found to act as a cofactor in a number of enzyma c reac ons at the cellular level and eff ects neurotransmi er produc on and func on, hormone func on and DNA replica on.Defi ciency of iron, therefore, results in disrup on of normal cell and organ func on.
Iron defi ciency is associated with neurological problems in young children, including developmental delay, stroke, and breath-holding spells.Screening for IDA should be considered in children with febrile seizures.Fever can worsen the nega ve eff ect of anaemia or for iron defi ciency on the brain and a seizure can occur as a consequence.Alterna vely, anaemia can be associated with the severity of a febrile illness, and more severe cases could be more likely to get seizures 17 .
Iron defi ciency anaemia may reduce the seizure threshold in the infancy and childhood.Low PF level is associated with and may play a role in febrile seizures. 17e study has some limita ons.Serum ferri n, a nonspecifi c acute phase reactant can rise in any infl ammatory condi ons, although both cases and controls were having fever at the me of enrollment.Iron defi ciency and lead poisoning may be associated.Blood lead levels could not be determined in our subjects.
Although serum ferri n levels rise in infl ammatory condi ons, MCV and RDW are not aff ected by acute infec on 18 .RDW has been shown to dis nguish between pa ents with lead poisoning and iron defi ciency in children with microcy c anaemia.Specifi cally the RDW is elevated in iron defi cient pa ents with lead poisoning and normal in children with lead poisoning alone 19 .

Conclusions
Iron defi ciency anaemia is a modifi able risk factor for febrile seizure in children.Early detec on and mely correc on of iron defi ciency may be helpful for preven on of febrile seizures in children.

Table 1 :
Peak temperature on admission, underlying causes of fever among cases and controls N.S = Not signifi cant sta s cally

Table 2 :
Haematological parameters of cases and controls