Level of Micronutrient [zinc] and its Association
with Seizures in Children: A Case Control Study
Bhat Jehangir Allam*, Kurmi Rajesh, Ara Roshan and Kumar Santosh
Kurji Holy Family Hospital, India
Submission: August 12, 2018; Published: October 09, 2018
*Corresponding author: Dr. Jehangir Allam, Kurji Holy Family Hospital, Patna, Bihar, India.
How to cite this article: Bhat J A, Kurmi R, Ara R, Kumar S. Level of Micronutrient [zinc] and its Association with Seizures in Children: A Case Control
Study. Acad J Ped Neonatol. 2018; 7(2): 555765. DOI: 10.19080/AJPN.2018.07.555765
Objective: To determine the levels of serum zinc in children with febrile seizures when compared to children with fever without seizures and compare the levels of serum zinc in children with seizure due to CNS with febrile seizures and febrile children without seizures.
Methods: This was an observational case control study. Total 150 children of age group 6-60 months were included in study. 2ml of blood from venipuncture within 24 hours of contact of patient in both the groups. Estimation of serum zinc was done within 6 hours of collection.
Results: Mean age of presentation in febrile seizures (GROUP A) was 22.14±15 months, 24.26±17.2 months in CNS infections (GROUP B) and 21.16±16.77 months control (GROUPC). Thus, most of the patients fall in age group < 2years. Males predominated in present study with male female ratio of 2.9:1. Mean serum zinc level in febrile seizure (case) was 37.31 ± 17.68μgm/dl with lowest 14.3μgm/dl and highest 98μgm/dl and in CNS infections was 55.54 ± 22.82μgm/dl was observed. Thus, febrile seizures cases n= 45(90%), CNS infections n=33(66 %) has biochemical hypozincemia i.e. serum zinc less than 65μgm/dl.
Conclusion: In febrile seizures and seizures due to CNS infection zinc deficiency could be a potential risk factor.
Brain consists of nerve cells that usually communicate with each other through electrical activity thus, controls and regulates all voluntary and involuntary responses in the body. When region(s) of brain receives a burst of abnormal electrical signals that temporarily interrupts normal electrical brain function a seizure occurs. Transient occurrence of signs and or symptoms resulting from abnormal excessive or synchronous neuronal activity in the brain is defined as seizure. Febrile seizures is defined as the seizure that occurs between the age of 6 and 60 months with a temperature of 38 0C or higher that are not the result of CNS infections or any metabolic imbalance, and that occur in the absence of a history of prior afebrile seizures. Febrile seizure is either simple or complex. Febrile seizure that is primary generalized, usually tonic-clonic attack associated with fever, lasting for a maximum of 15min, and not recurrent within a 24 hrs period is simple and febrile seizure that is more prolonged i.e., > 15min, is focal, and or reoccurs within 24 hrs is complex . Many children who have febrile seizures have genetic conditions . Various factors have been described in the pathophysiology of febrile seizures like infections (Bacterial and viral) , temperature Susceptibility of immature brain , interleukins, circulating toxins association , micronutrient deficiency and iron deficiency .
Role of micronutrients like copper, zinc, magnesium and selenium have been described in association with febrile seizures . Micronutrients appear to play a vital role by their ability to modulate neurotransmission by acting on ion channels as well as coenzyme activity . Zinc-containing glutaminergic neuron-rich areas i.e. the hippocampus and amygdala [limbic system] and the zinc homeostasis in this area of brain may be associated with the etiology and manifestation of epileptic seizures . Zinc homeostasis in the brain is important for prevention of seizure development because it can act either as proconvulsant  or anticonvulsant . Neuron terminals glutamate concentration(10Mm) in was estimated to be much higher than extracellular fluid(<1Mm) and vesicular zinc concentration(300Mm) . The degree and balance of inhibition–excitation, which is associated with the etiology and manifestation of seizures is varied by excessive excitation of zinc -containing glutaminergic neurons when released into the synaptic clefts. Inhibitory effect of zinc on N-Methyl-D aspartate receptorsis responsible for excitatory phenomenon after binding with glutamate. Thus, decreased Zinc levels may play a role in pathogenesis of febrile seizures .
Since most of the research on zinc association with seizures is on febrile seizures, our focus of research was to show its association with febrile seizures and seizures due to CNS infections
like meningitis and encephalitis.
In this observational case-control study, total 150 children
fulfilling the predefined inclusion criteria were studied during
the period of 2 years, from May 2014 to May 2016 in Kurji Holy
Family Hospital Patna Bihar. Ethical clearance was taken from
hospital ethical team and proper consent was taken from parents/
guardians of cases. Cases were divided into three equal groups.
I. GROUP A 50 febrile seizures (Cases)
II. GROUP B 50 (CNS infections)
III. GROUP C 50 Fever without seizures (Control)
Children aged six months to five years with simple febrile
seizures, complex febrile seizures, fever without seizures and
seizure due to CNS infections (meningitis and encephalitis) were
included in our study. Children having cerebral palsy, seizure
disorder, chronic diseases, dysmorphic and syndromic features,
children on zinc supplements and history of zinc supplementation
in last 3 months, on anti-convulsant, acute and chronic diarrhea&
past history of neonatal seizures and metabolic disorders and any
clinical feature thought to be due to zinc deficiency were excluded.
2-3ml of blood from venous site using sterile needle, within
24 hours of contact of patient in both the groups after taking all
aseptic precautions. The sample was centrifuged for 3-4 minutes
at 3,000-4,000rpm, serum thus obtain and preserved in sterile
deionized vial. Estimation of serum zinc was done within 6
hours of collection. Method used was based on colorimetric test
kits, reagent used was 2-(5-bromo-2-pyridylazo)-5-(N-propyl-
N-sulphopropylamino) phenol. Zinc forms a red chelate with it.
Increase in the absorbance of wavelength 560nm can be measured
and is proportional to concentration of the zinc. As per WHO
recommendation the cut off value for hypozincemia has been
taken as 65μgm/dl . Hence 65μgm/dl was taken as cutoff for
Statistical Analysis of data was done using SPSS version 20.0
for windows. Zinc level presented as mean and standard deviation,
the difference in mean among the groups was assessed by use of
one-way ANOVA and t-test to analyze inter group difference. A pvalue
less than 0.05 was taken as statistically significant.
In our study as shown in Table 1. majority of the patients in
all groups were of age group < 2years and males predominated in
present study with male female ratio of 2.9:1 (Table 2).
A = febrile seizure group, GROUP B= CNS infection group, GROUP C= Controls
GROUP A = febrile seizure group, GROUP B= CNS infection group, GROUP C= Controls
GROUP A = febrile seizure group, GROUP B= CNS infection group, GROUP C= Controls
Table 3 shows mean serum zinc level in GROUP A (febrile
seizure) was 37.31±17.68 μgm/dl with lowest and highest levels
of 14.3μg/dl and 98.2μg/dl respectively. Mean serum zinc levels
in GROUP B (CNS infections) was 55.54 ±21.82μg/dl with lowest level of 17μg/dl and highest 122μg/dl. The mean serum zinc level
in control was 67.19± 20.6).
Statistically significant difference was observed between
mean serum zinc in GROUP A (febrile seizure group) and GROUP
C (Control group) with standard error of 3.98, mean difference of
29.88 and p value <0.001 and mean serum zinc level in GROUP
B (CNS infection group) and GROUP C (control group) with the
mean difference of 11.65, p value =0.011 and standard error of
3.98 (Table 4).
GROUP A = febrile seizure group, GROUP B= CNS infection group, GROUP C= Controls.
The present study was under taken in this context to study
the correlation of serum zinc level with Febrile seizures, CNS
infections presenting with seizures in comparison with febrile
children without seizures.
In our study most of the patients had purely biochemical
hypozincemia because as stated in methodology, patients having
any clinical feature of zinc deficiency were excluded from the
study. More than three fourth of the patients were below 24
months with mean age of 22.14±15 months in febrile seizures
(GROUP A), 24.26±17.2 months in CNS infections (GROUP B)
and 21.16± 16.77 months control (GROUP C). Mahyar et al. 
reported similar observation, mean age 27.13±15.12 months
in cases and 28.49±16.5 months control. Ganesh et al.  also
reported mean age of 23.8 months in cases. Thus, this study shows
febrile seizures are more common in age less than 24 months,
as 40(80%) patients in febrile seizure group was between 6-24
Males predominated in present study with male female ratio
of 2.9:1 in total 150 study population. In GROUP A (febrile seizures
cases) 40 (80%) patient was male, in GROUP B (CNS infections) 37
(74%) were male and 35 (70%) in control (GROUP C) were male
gender. Other studies were having gender ratio 1.4-1 as reported
by Park JR et al. . Thus, this indicates the male predominance
in febrile seizures.
In the present study, mean serum zinc level in febrile seizure
was 37.31±17.68μgm/dl and mean serum zinc level in control
was 67.19± 20.6. Thus, significant difference of 29.88μg/dl was
observed in mean serum zinc level in cases as compared to controls
with p value <0.001 and standard error 3.98. Similar findings have
been reported by other researchers Ganesh R et al. , Okposio
et al. , Mahyar et al. , Amiri et al. , Heydarian F et al.
, Gattoo et al. .
In the present study mean serum zinc levels in GROUP B
(CNS infections) of 55.54±21.82μg/dl was compared with mean
serum zinc level in control group (67.19±20.6μg/dl), the mean
difference of 11.65, p value =0.011 and standard error of 3.98
which is also statistically significant. Low serum zinc levels have
been observed in cases of pyogenic meningitis may be secondary
to disease process or it may be primary hypozincemia leading
to septic meningitis. The reasons are multifactorial. One is an
adaptive response intended to deprive invading pathogens of zinc.
Secondly, zinc may be utilized by the organisms for growth and
multiplication. Latitkumar et al.  also reported low serum zinc
in CNS infections (pyogenic meningitis) of 70.9816±59.39μg/dl
and control group 120.0±37.79μg/dl with p<0.01.
Serum Zinc level in febrile seizures and seizures due CNS
infections patients is low as compared to WHO normal level.
Hypozincemia is risk factor for seizures (both febrile seizures and
seizures due CNS infections). Thus, it appears that presence of
hypozincemia in presence of other risk factors may enhance the
occurrence of febrile seizures explaining a possible correlation
between low serum zinc levels and febrile seizures. However,
large randomized control trials are recommended to analyze
this association and if proven, the possibility of prophylactic zinc
supplementation in reducing the risk of febrile seizures in such
The authors are highly thankful to the hospital administration,
the paramedical staff of the paediatric department, hospital
statistician, and computer operators for helping in conducting this