SERUM ZINC, COPPER AND IRON STATUS OF CHILDREN
WITH NEWLY DIAGNOSED CELIAC DISEASE ON 3 MONTHS
OF GLUTEN FREE DIET WITH OR WITHOUT FOUR WEEKS
OF ZINC SUPPLEMENTS - A RANDOMIZED CONTROLLED
TRIAL
PROTOCOL FOR SUBMISSION OF THESIS TO
UNIVERSITY OF DELHI
FOR THE DEGREE OF
DOCTOR OF MEDICINE
(M.D. PEDIATRICS)
Dr . Kanika Negi
Lady Hardinge Medical College and Associated Hospitals
New Delhi- 110001
(2012-2014)
PROTOCOL FOR THE PLAN OF SUBMISSION OF THESIS FOR
THE AWARD OF DEGREE OF DOCTOR OF MEDICINE (PEDIATRICS)
UNIVERSITY OF DELHI, SESSION 2012-2015
Title of Thesis
:
“SERUM ZINC, COPPER AND IRON STATUS
OF CHILDREN WITH NEWLY DIAGNOSED
CELIAC DISEASE ON 3 MONTHS OF GLUTEN
FREE DIET
WITH OR WITHOUT FOUR
WEEKS
OF
ZINC
SUPPLEMENTS-A
RANDOMIZED CONTROLLED TRIAL”
Name of the Institution
:
LADY HARDINGE MEDICAL COLLEGE AND
ASSOCIATED HOSPITALS, NEW DELHI.
:
Dr. KANIKA NEGI
:
Dr. PRAVEEN KUMAR
Professor, Dept. of Pediatrics
LHMC & Associated Hospitals,
New Delhi
:
Dr. MONISHA CHOUDHARY
Director-Professor, Dept. of Pathology
LHMC & Associated Hospitals,
New Delhi
:
DR S. ANEJA
Director-Professor & Head
Dept. of Pediatrics
LHMC & Associated Hospitals,New Delhi.
SIGNATURE
Name of the Candidate
SIGNATURE
Name of the Supervisor
SIGNATURE
Name of the
Co-Supervisor
SIGNATURE
Head of the Department
SIGNATURE
Head of the Institution
:
Dr. ATUL MURARI
Director
LHMC & Associated Hospitals,
New Delhi
CERTIFICATE FROM THE INSTITUTION
We hereby declare that to the best of our knowledge no study has been carried out on the thesis
topic “SERUM ZINC, COPPER AND IRON STATUS OF CHILDREN WITH NEWLY
DIAGNOSED CELIAC DISEASE ON 3 MONTHS OF GLUTEN FREE DIET WITH OR
WITHOUT
FOUR
WEEKS
OF
ZINC
SUPPLEMENTS-A
RANDOMIZED
CONTROLLED TRIAL” over the past 5 years in the Delhi University.
PLACE: New Delhi
Signature:
DATE :
Name of Candidate: Dr. Kanika Negi
PG Student (Pediatrics)
Signature:
Name of Supervisor:
Dr. Praveen Kumar
Professor, Dept. of Pediatrics
LHMC & Associated Hospitals,
New Delhi.
Signature:
Name of Co-Supervisor: Dr. Monisha Choudhary
Director-Prof, Dept of Pathology
LHMC & Associated Hospitals, New Delhi.
LADY HARDINGE MEDICAL COLLEGE & SMT. S.K. HOSPITAL, NEW DELHI.
UNDERTAKING
I/We agree to abide by the ethical guidelines for biomedical research on human subjects (As per
the ICMR guidelines) while conducting the research project being submitted for Ethical
Committee consideration:
1. Project is considered to be absolutely essential for the advancement of knowledge and for
the benefit of all.
2. Only subjects, who volunteer for the project will be included. Their informed consent
shall be obtained prior to commencement of the research project, and subjects will be
kept fully appraised of all the consequences.
3. Privacy and confidentiality of the subjects shall be maintained and without the consent of
the subject no disclosure will be made.
4. Proper precautions shall be taken so as to minimize the risk and prevent irreversible
adverse effects.
5. Research will be conducted by the professionally competent persons.
6. Research will be conducted in a fair, honest, impartial and transparent manner.
Researcher will be accountable for maintaining proper records.
7. Research will be conducted keeping in view the public interest at large.
8. Research reports, materials and data will be preserved (as per institutional guidelines).
9. Result of research will be made known through scientific publications.
10. Professional and moral responsibilities will be of the researchers, directly or indirectly
connected with the research.
11. Only those drugs which are approved by the Drug Controller of India for a specific
purpose will be used in the research project.
Supervisor :
Dr. Praveen Kumar
Professor, Dept. of Pediatrics
Co-Supervisor
Dr. Monisha Choudhury
Director-Prof , Dept. of Pathology
Investigator:
Dr Kanika Negi
PG Student (Pediatrics)
CONSENT FORM
I, _____________________________________, S/D/of ________________________________,
R/o___________________________________________________________________________
hereby declare that I give my informed consent in the thesis entitled ““SERUM ZINC,
COPPER AND IRON STATUS OF CHILDREN WITH NEWLY DIAGNOSED CELIAC
DISEASE ON 3 MONTHS OF GLUTEN FREE DIET WITH OR WITHOUT FOUR
WEEKS OF ZINC SUPPLEMENTS-A RANDOMIZED CONTROLLED TRIAL”” which
will be used to treat me/my relative.
Dr. Kanika Negi has informed me to my full satisfaction in language I understand about the
purpose, nature of the treatment and various laboratory investigations for the study to be carried
out. I have been informed about the duration of the study and instructions to be followed during
this study period. I have been informed that blood investigations will be carried out at the start
and at the end of three months of study and I give my consent for it. I will also followup at two –
four week interval during this study period. I understand that the treatment is known to be
effective in the treatment of the disorder. I realize that this is being done for the sake of knowing
the relative merits of this procedure and I give my full consent for the same. I have also been
explained the side effects of the treatment to be used. I give full consent for being enrolled in the
above study and I reserve my rights to withdraw from the study whenever I wish without
prejudice of my rights to undergo treatment at Kalawati Saran Children Hospital, New Delhi.
Patient/Patient’s relative Signature
or thumb impression :
Name:
Date :
We have witnessed that the patient signed the above form in the presence of his/her freewill after
understanding its contents.
Signature of Witness:
Name:
Signature of the Investigation
Name:
Designation:
INTRODUCTION
Celiac disease (CD), also known as Gluten Sensitive Enteropathy is a reversible autoimmune
enteropathy caused by permanent sensitivity to gluten in wheat and related proteins in barley and
rye. It has genetic basis, associated with presence of specific HLA alleles that encode for DQ2 &
DQ81.From India, CD was first reported in 1966, in children by Walia et al and in adults by
Misra et al2. Many of the subsequent reports on CD are from North-West India (Punjab,
Haryana, Delhi, Rajasthan, Uttar Pradesh) where wheat is the staple cereal in the diet 3. Celiac
disease now has emerged as most common cause of chronic diarrhea in north & central India 4.
CD predominantly affects the proximal small intestine and is characterized by partial or total
villous atrophy of mucosa 5. The small intestine has a central role in maintaining nutrients like
zinc, copper and iron, vitamin B12 and folic acid homeostasis. In patients with CD, zinc
deficiency may result from a cumulative loss of insoluble zinc complexes with fat and
phosphate, exudation of zinc protein complexes into the intestinal lumen and massive loss of
intestinal secretions or impaired zinc absorption because of damaged intestinal epithelial cell
membrane. Some of the symptoms of CD (e.g. anorexia and reduced growth rate) may be
related, in part, to zinc deficiency.
Solomons et al. found that conditioned zinc deficiency may develop in patients with celiac sprue,
zinc therapy greatly enhances the healing of both the intestinal and skin lesions 6. In recent years
zinc has emerged as a very important micronutrient for maintaining the integrity of intestinal
mucosa, immunity and growth in children
7
.
However, the effect of Zinc therapy on iron is not
consisitent8,9.Studies also have shown that although rise in plasma Zinc is better in zinc
supplemented group, it is also satisfactory in children on GFD without supplementation
10
.Comparative data about the effects of GFD with or without zinc supplementation on intestinal
mucosal healing and normalization of plasma zinc and other micronutrient levels is scanty. With
these backgrounds we are proposing to evaluate the effects of GFD with or without zinc
supplementation on plasma zinc, copper and iron levels in newly diagnosed CD patients.
TITLE:
Serum zinc ,copper and iron status of children with newly diagnosed celiac disease on 3months
of gluten free diet with or without four weeks of zinc supplements-A randomized controlled trial.
RESEARCH QUESTION
Do children(<18yrs) with newly diagnosed celiac disease receiving GFD and four weeks of
zinc supplementation have higher rise in mean serum zinc, copper and better iron status at 3
months after diagnosis as compared to children receiving only GFD ?
HYPOTHESIS
Children (<18yrs) with newly diagnosed celiac disease receiving GFD and four weeks of zinc
supplementation will have 10% higher increase in serum zinc as compared to children receiving
GFD alone and higher proportion of children (<18yrs) with celiac disease receiving GFD and
four weeks of zinc supplementation will have normal serum zinc, copper and iron status
compared to children receiving GFD alone.
as
AIMS AND OBJECTIVES
PRIMARY
1.
To compare mean rise of serum zinc at 3 months after diagnosis in children with Celiac
disease
receiving
GFD and four weeks of zinc supplementation as compared to
children on GFD without zinc supplements.
SECONDARY
1. To compare the proportion of children with normal serum zinc level at 3 months after
diagnosis in children with Celiac disease
receiving
GFD and four weeks of zinc
supplementation as compared to children on GFD without zinc supplements.
2. To compare the proportion of children with normal serum copper and iron status at 3
months after diagnosis in children with Celiac disease receiving GFD and four weeks
of zinc supplementation as compared to children on GFD without zinc supplements.
3. To compare weight gain at 3 months after diagnosis in children with Celiac disease
receiving
GFD and four weeks of zinc supplementation as compared to children on
GFD without zinc supplements.
REVIEW OF LITERATURE
Celiac disease (CD) also known as Celiac sprue or Gluten Sensitive Enteropathy is an autoimmune gastrointestinal disorder triggered by the ingestion of wheat, barley and rye in
genetically susceptible persons and characterized by chronic inflammation of the small intestine.
Grains and genes are the two basic elements in the pathogenesis of celiac disease. The gliadin
fraction of Gluten found in cereals triggers a T cell mediated immune response initiating a
damaging inflammatory process in the lining of small intestine that blunts or destroys intestinal
villi reducing the surface area for absorption, limiting absorption of nutrients 11.
Epidemiology of Celiac Disease
A few decades ago, celiac disease was considered an uncommon disorder, present mainly in
Europe. From India, CD was first reported in 1966, in children by Walia et al and in adults by
Musra et al12. Many of the subsequent reports on CD are from North West India (Punjab,
Haryana, Delhi, Rajasthan, Uttar Pradesh) where wheat is the staple cereal in the diet. There are
limited data on prevalence of CD from India 13-16.
Celiac Disease: Clinical presentation and micronutrient deficiency
Classically, children with celiac disease children present within first 2 years of life with failure to
thrive, chronic diarrhea, vomiting abdominal distension, muscle wasting, anemia and irritability.
Occasionally there is constipation, rectal prolapse or intussusceptions. The onset of symptoms
is gradual and follows the introduction of cereals into the diet; patients with severe, untreated
celiac spruce may present with short stature, delayed puberty, iron and folic acid deficiency with
anemia and rickets 17.
Most of the Indian studies have also reported a delayed diagnosis of CD 18, which could be due
to delayed weaning, a late introduction of gluten, delayed referral and lack of awareness about
the disease. Due to delayed diagnosis most of the children have moderate to severe malnutrition
and anemia. It is also postulated that they will have co-existent other micronutrient deficiencies.
Zinc Deficiency And Health Implications:
It has been known for many years that zinc deficiency in experimental animal’s results in
atrophy of thymic and lymphoid tissue. The deprivation of zinc, caused by malnutrition or
disease, strongly affects immune cell functions, causing higher frequency of infections. Among
other effects, an increased production of reactive oxygen species (ROS) and proinflammatory
cytokines has been observed in zinc-deficient patients 19.
Zinc supplementation trials carried out among children have produced variable results,
depending on the specific outcomes considered and the initial characteristics of the children who
were enrolled. In a meta-analyses to study the health benefits of zinc supplementation it was
found that zinc supplementation reduced the incidence of diarrhea by approximately 20%, and
reduced the incidence of acute lower respiratory tract infections by approximately 15%. Zinc
supplementation had a marginal 6% impact on overall child mortality, but there was an 18%
reduction in deaths among zinc-supplemented children older than 12 months of age. Zinc
supplementation increased linear growth and weight gain by a small, but highly significant,
amount. The interventions yielded a consistent, moderately large increase in mean serum zinc
concentrations, and they had no significant adverse effects on indicators of iron and copper
status20.
MICRONUTRIENT DEFICIENCIES IN CELIAC DISEASE:
In a recently conducted cross-sectional study among 109 individuals deficiency of micronutrients
was found both in typical as well as in typical cases 21. In patients with CD, zinc deficiency may
result from a cumulative loss of insoluble zinc complexes with fat and phosphate, exudation of
zinc protein complexes into the intestinal lumen and massive loss of intestinal secretions or
impaired zinc absorption because of damaged intestinal epithelial cell membrane.
In another study the nutritional status and micronutrient levels of 22 children aged 2 to 14 years
diagnosed as Celiac disease on the basis of typical intestinal biopsy findings were studied
before and after GFD. 15 healthy children served as controls. Anthropometric measurements and
serum Zinc Copper Magnesium and Iron along with albumin were done for both patients and
controls initially and repeated after 6 months while patients were receiving strict GFD and
controls receiving normal diet. There was a statistically significant increase in serum zinc, iron
and magnesium levels (p value< 0.05) while serum copper and albumin did not show any
significant rise after Gluten free diet. The authors concluded that celiac children receiving strict
Gluten free diet and showing good clinical response probably do not need mineral
supplementation 22.
Singhal et al in another study evaluated serum zinc level at inclusion and zinc supplementation
for 3 months. The serum zinc levels of newly diagnosed CD cases (0.64+/-0.34 microg/mL)
versus controls (0.94+/-0.14 microg/mL) were significantly lower (95% CI -0.44 to -1.4). No
significant difference in serum zinc was seen with increasing grades of villous atrophy. The
study has limitation of small sample size and comparison of supplemented group with controls
and old cases 23.
Kapur et al studied the effect of iron supplementation in 21 children with celiac disease who
completed at least one year of regular follow up on GFD (mean 1.5 years, range 1-2 years).At the
time of enrolment all the children had hemoglobin level <11 gm%, 78% had microcytic
hypochromic anemia and 22% had dimorphic anemia, with lower mean MCV, MCH and serum
ferritin levels, and a significantly higher mean TIBC as compared to controls (p<0.001). In the
follow up evaluation of these cases on GFD, mean hemoglobin levels were comparable with
controls but the cases continued to have lower mean MCV, MCH serum ferritin levels (p<0.05)
and higher mean TIBC (p<0.05) suggesting iron deficiency state continues for a longer time even
after iron supplementation. Serum ferritin levels showed a negative correlation with the grade of
villous atrophy and lamina propria infiltrate 24.
Hallert et al carried out a double blind placebo controlled multicentre trial in which 65 coeliac
patients (61% women) aged 45-64 years on a strict gluten-free diet for several years were
randomized to a daily dose of 0.8 mg folic acid, 0.5 mg cyanocobalamin and 3 mg pyridoxine or
placebo for 6 months. The outcome measures were psychological general well-being (PGWB)
and the plasma total homocysteine (tHcy) level, marker of B vitamin status. The tHcy level was
baseline median 11.7 micromol/L (7.4-23.0), significantly higher than in matched population
controls [10.2 micromol/L (6.7-22.6) (P < 0.01)]. Following vitamin supplementation, tHcy
dropped a median of 34% (P < 0.001), accompanied by significant improvement in well-being (P
< 0.01), notably Anxiety (P < 0.05) and Depressed Mood (P < 0.05) for patients with poor wellbeing. They concluded that adults with longstanding coeliac disease taking extra B vitamins for 6
months showed normalized tHcy and significant improvement in general well-being, suggesting
that B vitamins should be considered in people advised to follow a gluten-free diet 25.
In a study done at PGI, Chandigarh, a total of 134 patients underwent plasma zinc estimation at
baseline and after a four week period. Zinc-deficient patients were randomly assigned to two
groups. Group G (n=48) received GFD without zinc supplementation, Group G+Z (n=48)
received GFD with zinc supplementation for 4 weeks. The rise in plasma Zinc levels although
higher in supplemented group was statistically similar to children managed on GFD alone. In this
other micronutrients were not studied26.
In a study conducted in non celiac children which was done to find out the efficacy of combined
iron and zinc supplementation on micronutrient status and growth, a total of 915 Vietnamese
breast-fed infants aged 4-7 months were included and 784 completed the study.The Fe-group
received daily and for a 6-month period 10 mg of iron, the Zn-group 10 mg zinc, the Fe-Zn
group 10 mg iron+10 mg zinc and the placebo group a placebo. Hemoglobin (Hb), serum ferritin
(SF) and zinc (SZn), and anthropometry were measured before and at the end of the intervention.
Morbidity was recorded daily.Changes of Hb and SF were higher in both Fe and Fe+Zn groups
(respectively 22.6 and 20.6 g/l for Hb; 36.0 and 24.8 microg/l for SF) compared to Zn and
placebo groups (Hb: 6.4 and 9.8 g/l; SF: -18.2 and -16.9 microg/l, P<0.0001). SZn Weight gain
was higher in the Zn group.. The authors concluded that combined iron-zinc supplementation
had a positive effect on iron and zinc status in infants27.
MATERIALS AND METHODS
STUDY DESIGN Randomized controlled trial
PERIOD OF STUDYThe study will be conducted during the period between November 2012 - March 2014.
PLACE OF STUDYThe study shall be conducted in the Department of Pediatrics, Department of Pathology, Lady
Hardinge Medical College, New Delhi and Indian Agriculture Research Institute (IARI), Pusa
Road, Delhi.
SAMPLE SIZE:
Following formula is used:
N = (Za + ZB)2*S2*2
D2
Where *=multiplication
Za =Z value for a error(a=alpha error)at 0.05=1.96
ZB=Z value for B error(B=beta error) at 0.20=0.842
S= common standard deviation between two treatment =24.2
D=clinically meaningful mean difference between two treatment =10
Using the above method, sample size will be 184 patients which is not feasible.
Therefore, a convenient sample size of 66 cases shall be enrolled for the study, considering
approximately 10percent drop out/loss to follow up .
STUDY POPULATION:
A child <18 years of age diagnosed as a case of celiac disease based on positive celiac serology
and modified ESPGHAN criteria (suggestive duodenal biopsy histopathology in the form of
either partial or total villous atrophy along with increased intra epithelial lymphocytes &/or
crypt hyperplasia ).
Participation shall be voluntary and informed written consent will be taken from the participants
or the parents, in the case of a minor.
INCLUSION CRITERIA:
1. Newly diagnosed cases of
CD as per revised ESPGHAN criteria (Positive celiac serology
along with partial or total villous atrophy)
2. Age less than 18 years
EXCLUSION CRITERIA:
1. Refusal of informed consent.
2. Newly diagnosed CD patients who has received GFD or zinc supplements in last 3 months
3. Clinical signs of acrodermatitis enteropathica.
RANDOMIZATION & BLINDING:
1. Computer generated block randomization of 4
2. Stratification according to age - < 5 year, 6-10 years and > 10 years
3. Allocation concealment by opaque envelope.
4. No blinding
INTERVENTION :
Group-A:
GFD plus supplements
Zinc- 2 mg/kg (maximum dose -20 mg) daily in single dose for initial 4 weeks,on the day of
starting GFD.
Group –B:
GFD
Both Groups will receive iron, calcium supplements as per clinical requirement.
DATA COLLECTION PROCEDURE:
All the newly diagnosed celiac disease cases shall be called for evaluation and enrollment in the
study. Selected study subjects shall be evaluated according to prestructured proforma.
Informed and written consent of all the subjects will be taken. Detailed history and physical
examination will be recorded on a prestructured proforma.5ml of venous blood will be drawn
under all aseptic conditions at the time of enrollment and 3 months thereafter. Blood for
Complete Blood Count will be collected in EDTA vial, along with peripheral smear and send for
analysis the same day. It will be measured by automatic blood cell (sysmex) analyser that is
based on flow cytometry.
Blood for serum iron ,ferritin ,copper and zinc will be collected in metal free vials. The samples
will be allowed to stand and clot and then centrifuged in a cold centrifuge at 3000rpm for
5minutes and stored at -20degree celcius until further analysis. Serum iron will be measured by
calorimeter. Serum Cu, Zn estimation will be done by atomic absorption spectrophotometry.
S. ferritin estimation will be done by sandwich enzyme immunoassay technique using a one step
capture or ‘sandwich type assay’.
OPERATIONAL DEFINITIONS:
Deficient Cu nutritional status:
S.cu
<70microgm/dl in males,
<70microgm/dl in girls<12yrs,
<80microgm/dl in girls>12yrs28.
Deficient Iron status:
Hb conc <11g/dl in children <5yrs,
<11.5g/dl in children 5-12 yrs
<13g/dl males,
<12g/dl females>12yrs 29
S.Iron
<70microG/dl in children<12yrs,
<70microg/dl in males
<60microg/dl in women>12yrs
S.Ferritin <12microg/L 30
Deficiency Zinc status:
S.Zn
<74microg/L in males
<70microg/L in females 31
FOLLOW UP PLAN:
Dietary counseling will be done at the time of diagnosis and each follow-up visits. Patients will
be followed up in PGN clinic at 2, 4, 8 and 12weeks.Also,the assessment of dietary compliance
and intake of supplements at each visit will be carried out.
STUDY INSTRUMENTS:
Pre-structured and pretest proforma.
Clinical history and physical examination.
Hematological and serological measurements.(S.Hb,S.Iron,S.Ferritin,S.Zinc,S.Copper)
.
FEASIBILITY :
In 2011 a total of 114 were diagnosed and 2012 (January to August) a total of 72 cases have
been diagnosed as Celiac disease. Serum iron status will be done at Department of Pathology and
Serum Zinc and Serum Copper will be done at Indian Agricultural Research Institute , Pusa ,
Delhi.
STATISTICAL ANALYSIS:
Statistical analysis will be performed with the Statistical Package
for the Social Sciences
(SPSS, version 13,Chicago,IL,USA).For continuous data from the entire study population Mean,
Standard deviation and Range will be calculated. For categorical data - Number and
Percentages will be calculated. The baseline parameters between the two randomized groups and
baseline and post-treatment plasma nutrients and percentage changes between the 2 groups will
be compared by - unpaired t-test. Pre- and post treatment changes in plasma nutrient levels
within the group will be done by paired t-test. For comparing categorical data between
randomized groups Chi-square test will be used. A p-value of- <0.05 will be taken as statistically
significant.
ETHICAL ISSUES :
Ethical clearance shall be taken from the Ethical Committee of the institute.A well –informed
written consent shall be taken from the study subjects.They shall be counselled for gluten free
diet by the trained physician. They shall receive iron and calcium supplements as per the
requirements and followed up in Gastoenterology Clinic at our institute.
Date
S.No
PROFORMA FOR CLINICAL EVALUATION OF CELIAC DISEASE
INDEX CASE
Name:
Age/Sex:
CR No.:
Father’s Name:
Address:
Phone No.:
Religion:
Clinical Details:
Age at diagnosis:
CLINICAL EXAMINATION:
GPE:
Gait:
Pallor/Clubbing/Pedal edema/Icterus/Lymphadenopathy:
Skin changes:
Dental changes:
Anthropometry:
Weight:
CNS Examination:
Per Abdomen (hepatomegaly):
CVS:
R/S:
Height:
Weight for Height:
SEROLOGY OF CELIAC DISEASE:
1.tTG:
2.Endoscopic Findings:
3.Histopathological Findings:
Investigations – Hemoglobin
S. Ferritin
S. Iron
S. Zinc
S.Copper
S. Calcium
BASELINE PARAMETERS [AT THE TIME OF DIAGNOSIS]:
GROUP(G/G+Z) S.Hb
(g/dl)
S.Ferritin
(microg/dl)
S. Iron
(microg/dl)
S.Zinc
(microg/dl)
S.Copper
(microg/dl)
FOLLOW UP:
AT THE
TIME OF
DIAGNOSIS
DIETARY
COMPLIANCE
(Y/N)
IRON
SUPPLEMENTS
CALCIUM
SUPPLEMENTS
2WEEKS
4WEEKS
8WEEKS
12WEEKS
AT THE END OF 3 MONTHS:
Clinical details:
GPE:
Gait:
Pallor/Clubbing/Pedal edema/Icterus/Lymphadenopathy:
Skin changes:
Dental changes:
Anthropometry:
Weight:
Height:
Weight for Height:
CNS Examination:
Per Abdomen (hepatomegaly):
CVS/RS:
GROUP(G/G+Z)
S.Hb
(g/dl)
S.Ferritin
(microg/dl)
S. Iron
(microg/dl)
S.Zinc
(microg/dl)
S.Copper
(microg/dl)
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