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HAEMATOLOGICAL PROFILE AND FERRITIN LEVELS IN CHILDREN
WITH PROTEIN ENERGY MALNUTRITION IN UNIVERSITY OF ILORIN
TEACHING HOSPITAL ILORIN
A DISSERTATION SUBMITTED TO THE NATIONAL POSTGRADUATE
MEDICAL COLLEGE OF NIGERIA IN PART FULFILLMENT OF THE
REQUIREMENT FOR THE FELLOWSHIP OF THE COLLEGE in
PAEDIATRICS
BY
DR AISHAT OLUWATOYIN SAKA
NOVEMBER, 2009
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Declaration
I, DR. AISHAT OLUWATOYIN SAKA, hereby declare that this dissertation is
original unless otherwise acknowledged. The dissertation has not been presented to
any College for Fellowship examination nor has it been submitted elsewhere for
publication.
---------------------------------------- -------------------------
Dr. Aishat Oluwatoyin Saka Date;
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Certification
We hereby certify that Dr. Aishat Oluwatoyin Saka of the Department of Peadiatrics
and Child Health, University of Ilorin Teaching Hospital, Ilorin, prepared this
dissertation under our close supervision.
First Supervisor Prof. Ayodele Ojuawo -------------------------------------------
Signature
Second Supervisor Dr Aishat Abdulkarim ---------------------------------------
Signature
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Dedication
This dissertation is dedicated to Almighty Allah, the author and giver of knowledge
and to the millions of children in the developing world struggling to survive
malnutrition.
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Acknowledgements
I am sincerely grateful to my teacher and supervisor, PROFESSOR AYODELE
OJUAWO, who did not only supervise this project work but ensured that I had a
sound and firm training as a Resident in Paediatrics, thank you sir, may God bless and
reward you.
To my second supervisor Dr Aishat Abdulkarim, thank you for taking time to
supervise the work. I am especially grateful to DR O.T ADEDOYIN, I appreciate
your mentorship and critical review of this project.
I wish to wholeheartedly show profound gratitude to Prof Adeoye Adeniyi (Baba) for
his advices and encouragement at each stage of my residency training.
To all consultants in Department of Paediatrics, PROF WBR JOHNSON, DR OA
MOKUOLU, DR SK ERNEST, DR ADEGBOYE, DR O ADESIYUN, DR
ADEBOYE MAN, DR JK AFOLABI and DR O V ADEBARA, I appreciate you all.
I am grateful to the authorities of University of Ilorin Teaching Hospital, Ilorin for
giving the approval for the study. Many thanks to my colleagues, the nursing staff
and all staff in the department of Paediatrics and Child Health, UITH Ilorin, thanks
for your support.
DR OLAWUMI (HOD) and MR LUQMAN LATUBOSUN of Haematology
Department UITH, Ilorin, DR BILAMIN of the Chemical Pathology Department
UITH, Ilorin, DR FOWOTADE of the Department of Microbiology, UITH Ilorin. I
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am grateful for your kind and immense assistance in the laboratory component of this
work.
Many thanks to Dr Aderibigbe of the Department of Community Health and
Epidemiology UITH Ilorin for your assistance in statistical analysis.
Special thanks and regards to my husband DR M J SAKA who has displayed real
friendship, sacrifice and support in ensuring I attain a comfortable height
academically. May the good lord bless and reward you. To my children, thanks for
your little prayers and enormous support. I love you all.
Above all, my sincere appreciation goes to the Almighty God for seeing me through
in the pursuit of my career so far.
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Table of Contents
Title i
Declaration ii
Certification iii
Dedication iv
Acknowledgement v-vi
Table of Contents vii-viii
Appendices ix
List of abbreviations x-xi
List of Tables xii-xiii
List of Figures xiv
Summary xv-xvii
Introduction 1-6
Literature Review 7-48
Justification 49
Aims and Objectives 50
Materials and Methods 51-67
Results 68-85
Discussion 86-90
Conclusion 91
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Recommendations 92
Limitations of the study 93
References 94-110
Appendices 111-121
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Appendices
i Information Sheet
ii Informed Consent Form
iii Study Proforma
iv Socio Economic Classification Scheme
v Serum Ferritin Absorbance Curve
vi Ethical approval, U.I.T.H Ilorin
vii National Postgraduate Medical College approval
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Abbreviations
EDTA Ethylene diamine tetra acetate
ELISA Enzyme linked immunosorbent assay
EPU Emergency Paediatric Unit
FBC Full Blood Count
Hb Haemoglobin
Hct Haematocrit
MCH Mean Corpuscular Haemoglobin
MCV Mean Cell Volume
MCHC Mean Corpuscular Haemoglobin Concentration
nm nanometer
Nos Numbers
PEM Protein Energy Malnutrition
PCV Packed Cell Volume
11
RBC Red blood cell
SEC Socio Economic Class
UITH University of Ilorin Teaching Hospital
WBC White blood cell
RDW Red blood cell distribution width
12
List of Tables
I : The Wellcome Classification of PEM
II: Modified Wellcome Classification of PEM
III: Gomez classification of PEM.
IV: Gomez and modified Gomez weight-for-age classification of
malnutrition
V: Mclaren and Read classification of nutritional status in early Childhood.
VI: The World Health Organization Classification of PEM.
VII: The socio-demographic characteristics of the subject and controls.
VIII: Anthropometric measurements of the study population
IX: Distribution of types of protein energy malnutrition according to the age.
X: Haematologic profile of the study population
XI: Haematolgic Profile of children according to the types of PEM and
controls.
XII: Red Cell Morphology and Prevalence Of Anaemia In Children With
PEM.
XIII: Stool RBC in PEM and Controls.
X IV: Relationship between stool RBC and serum ferritin in PEM .
XV: Serum Ferritin Level according to the Age and Sex in the total Study
population
13
XVI: The Levels of Serum Ferritin according to the types of PEM and
Controls
XVII: Prevalence of Iron Deficiency And Iron Deficiency Anaemia Amongst
PEM.
XVIII: Relationship between clinical features and serum ferritin levels in PEM
14
List of Figures
Figure 1: Picture of the peripheral blood smear prepared.
Figure 2: Comparisons of normal peripheral blood smear with smear of
microcytic, hypochromic anaemia.
.
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Summary
This is a case control study carried out at the University of Ilorin Teaching Hospital
to determine the haematologic profile and serum ferritin levels of children with
Protein Energy Malnutrition compared to that of controls. It also determined the
prevalence of anaemia and iron deficiency anaemia in children with Protein Energy
Malnutrition
The socio demographic characteristics, anthropometry, clinical and laboratory
parameters of children with Protein Energy Malnutrition were studied. The
haematologic profile was analyzed by the auto analyzer, serum ferritin was analyzed
by Nova Path TM Ferritin kit. Stool was analyzed for red blood cells. Data entry and
analysis were carried out with a micro-computer using the Epi info version 3.5 (2008)
software packages.
A total of 180 children 90 with Protein Energy Malnutrition and 90 controls were
studied. Fifty Nine(65%) were males and 31 (34.4%) were females with a male to
female ratio of 1.9:1.0. The mean age of the children with Protein Energy
Malnutrition was 22.7 + 14.4 months (Range of 9-59months) compared to 29.3 + 16.9
months (Range 6-59 months) for the controls and the difference was not significant
(p=0.08).
The children with Protein Energy Malnutrition had lower mean values for
haemoglobin, haematocrit and mean corpuscular haemoglobin (p<0.05). The subjects
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also had higher mean values of total white cell count, neutrophil and lower
lymphocytes counts (p<0.05). The highest lymphocyte count was seen in children
with Kwashiokor. Platelet counts were comparable in the two groups.
No significant differences were observed in the haematologic profile of the various
types of PEM, except for the mean corpuscular haemoglobin concentration which was
higher in children with Marasmic-Kwashiokor. Children with Kwashiokor had the
highest mean for haemoglobin, (31.6±1.6g/dl) and haematocrit (10.7±0.4%), while
subjects with marasmus had the lowest mean for haematocrit (27.6±5.8%),
haemoglobin (9.1±2.1g/dl) and mean corpuscular haemoglobin (22.9±2.3pg/cell).
The subjects had a lower mean serum ferritin compared to the controls. Serum ferritin
increased with age and females had a higher serum ferritin levels compared to males
(p=0.00001).
The prevalence of anaemia among the children with PEM was 74.4% of which 75%
had microcytic hypochromic anaemia. The prevalence of iron deficiency among
subjects was 24.4%, while 16.6% of these subjects had iron deficiency anaemia.
In conclusion, children with Protein Energy Malnutrition had lower red cell indices
and higher white cell count the controls. Serum ferritin level was lower in the
subjects than in the controls. A high prevalence of anaemia and iron deficiency
anaemia with microcytic hypochromic anaemia was observed in children with PEM.
17
It is recommended that anaemia and iron deficiency should be sought for in children
with Protein Energy Malnutrition and such should be treated. There is the need to
improve nutrition education among mothers and health workers. Food fortification as
well as supplementation of the important micronutrient especially iron should be
enhanced, as a good nutritional status remains the bedrock for good health and
prevention of diseases.
1
Introduction
Malnutrition refers to a group of pathological disorders resulting from imbalance
between intake of essential nutrients and body requirement for these nutrients.1
In other words, malnutrition results from not eating enough food or from intake
of food that although adequate in amount, lack the essential nutrients necessary
for normal growth and development.1
Protein Energy Malnutrition (PEM), is defined as a spectrum of diseases arising
as a result of an absolute, or relative deficiency of calories and or protein in the
diet.2,3 It is globally the most important risk factor for illness and death, with
hundreds of millions of young children affected.4
Malnutrition, with its two constituents of protein–energy malnutrition and
micronutrient deficiencies, continues to be a major health burden in developing
countries.4Apart from marasmus and kwashiorkor (the 2 forms of protein–
energy malnutrition), deficiencies in iron, iodine, vitamin A and zinc are the
main manifestations of malnutrition in developing countries.4Also,nutritional
deficiency contributes to a high rate of morbidity and mortality in Nigeria
especially among infant and young children.5
According to UNICEF in 2005, malnutrition was associated with approximately
50% of child deaths worldwide6. Protein Energy Malnutrition is estimated to
affect every fourth child in the developing world,6 with the regional prevalence
for the severe forms ranging from 1-7%.7 PEM is associated with 49% of the 10
million deaths occurring in children in the developing world and 52% of all
2
under five deaths in Nigeria.8 with 24% and 16% of the total under-5 Nigerian
population estimated to have suffered from mild-moderate and severe
malnutrition respectively from 1973 to 19839,10 .The hospital based incidence of
severe Protein Energy Malnutrition in Nigeria varies from 3.18% in Ilorin,11
4.39% in ibadan10 and 4.5% in Ife.12
Many classifications of malnutrition have been used over the past 30 years. The
choice of classification depends on the purpose or the type of study for which it
is to be used.13 There are classification for clinical studies and for community
survey. Classifications for clinical studies are based on the presence or absence
of edema, and are the severe forms. These severe forms of PEM are Marasmus,
Kwashiorkor and Marasmic Kwashiorkor.2,3 Community survey classification is
based on deficit in weight for age and 90% of Harvard standard is taken as cut
off point for separating normal from malnourished children.7 WHO published a
new classification for PEM called the Z-score or standard deviation classification
of malnutrition. 14 In this classification, protein–energy malnutrition is defined
by measurements that fall below 2 standard deviations. Z-scores classification
include height for age (HAZ) Z-score, weight-for-age Z-scores (WAZ), weight-
for-height Z-scores (WHZ) and body-mass- index for- age Z-scores (BMIZ).
Malnutrition is then defined as value below the normal weight for age
(underweight), height for age (stunting) and weight for height (wasting).15
Protein Energy Malnutrition is caused by low intake of food, which contains
macro and micronutrients. PEM results in various changes in the body including
3
changes in haematologic profile of the body. Anaemia has always been a
constant feature of protein energy malnutrition and may be normochromic
normocytic, microcytic hypochromic, or, macrocytic.20, 21.
The anaemia of malnutrition may be attributable to various factors such as iron
deficiency, and /or reduced red cell production in adaptation to a smaller lean
body mass.3,21 Erythropoietin deficiency, deficiencies of vitamins (folic acid,
B12,) or trace elements (copper, zinc), infection and chronic diseases may also
be implicated as causes of anaemia in malnutrition.3,21-22
Iron deficiency is the most widespread nutrition problem in the world.16-18 Iron is
a nutritionally important mineral whose function includes structure of
haemoglobin and myoglobin, which are important for oxygen and carbon
dioxide transport and as an oxidative enzyme in cytochrome c and catalase. Lack
of iron impairs the normal cognitive development of 40 % to 60 % of the
developing world’s young children.7
Ferritin is an iron storage protein, the level provides a relatively accurate
estimate of the body‘s iron stores in the absence of inflammatory disease and so
it very useful in assessing body iron status .19
Despite the extensive knowledge of iron metabolism, diagnosis of iron
deficiency often remains a difficult problem, whatever methods are used,
especially in children with protein malnutrition.3.112 Estimation of haematologic
changes such as haemoglobin alone is not completely representative of iron
deficiency. Other methods such as the use of serum ferritin , serum iron, Total
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iron binding capacity and Transferrin receptors all have their limitations.
Diminished stainable iron in a bone marrow aspirate is generally accepted as the
reference standard for iron status. 3, 58,112
Several stidies12, 24-27 have attempted to evaluate iron status and the haematologic
changes in children with protein energy malnutrition.
Alemnji G A, Thomas K D, Durosinmi M A e tal24 in Ife studied twenty
malnourished children’s haemotogram and iron status in the acute phase and
during rehabilitation and concluded that the iron status was low in malnutrition
and that none of the haematological parameters was significantly different after
rehabilitation for all the four types of PEM. However, detailed changes in the
blood profile of the PEM children studied were not emphasized in the study and
the study population was small to make any logic conclusion.
Said A, El-Hawary M F, Sakr R et al25 in another study used haematological as
well as biochemical parameter to study anaemia in PEM found and out that
hypochromic anaemia was predominant in 83.3% of moderate Kwashiorkor with
50% being normocytic and 33.3% microcytic. In severe kwashiorkor, anaemia
was normocytic in 51.7% and microcytic in 19.2%. Macrocytosis was found in
38.8% in severe kwashiokor. In marasmus, normocytic anaemia was revealed in
74% and microcytic in 40%. Macrocytic anaemia was detected in 26%. In the
mild cases, normocytic normochromic anaemia occurred in 70% of the cases
while macrocytosis was encountered among 30% of the cases. Serum iron and
transferrin level dropped in both kwashiokor and marasmus, the extent of
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decrease was greater in the former. The percent transferrin saturation was
elevated in severe cases, particularly severe kwashiokor and marasmic
kwashiokor .In this study serum ferritin which is the best indicator of iron stores
was not utilized and the other details about the haematologic changes in
malnutrition was not addressed by the study .24,25
Another study by Wickramasinghe S N, Gill D S, Broon D N et al26 described
the limited value of serum ferritin in evaluating iron status in PEM. Twenty five
underweight and stunted infants and young children, during recovery from
malnutrition were studied. Many were iron-deficient and, as judged by ESR
values, all but four had evidence of infection or inflammation, or conditions
known to be associated with elevated values for plasma ferritin concentration
and erythrocyte protoporphyrin content and for decrease in the iron saturation of
transferrin .The finding that a number of the plasma ferritin concentrations were
quite high (11 of 48 children had more than 100g/L) was perhaps not surprising
because even in presumably normal subjects in the age range of the
malnourished subjects, concentrations greater than 100g/L was sometimes found.
The study could not conclude whether this instability of serum ferritin in these
malnourished children is related to inflammation or to other factors.The study
did not include haematologic changes in malnutrition.
In another study that looked at the haematologic profile as well as serum ferritin
level of PEM children matched with controls, red cell count, mean corpuscular
haemoglobin and reticulocyte index were significantly lower in PEM than in
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controls. While serum ferritin was significantly higher and total iron-binding
capacity was significantly lower in PEM children than in controls. The anaemia
was attributed to mixed deficiencies resulting in ineffective erythropoiesis. 27The
contribution of iron deficiency to the anaemia seen in PEM was not addressed in
this study.
Laditan in another study on PEM children reported that pack cell values were
within the lower limits of normal values for healthy Nigerian children. This
study however did not highlight other haematologic parameters in PEM.12
Relevance Of The Study To The Practice Of The Discipline
The outcome of this study would provide evidence for the magnitude of iron-
ferritin depletion in children with PEM. It would also provide information about
the contribution of malnutrition to the prevalence of iron deficiency anaemia in
children. It would also provide baseline information on the prevalence of iron
deficiency anaemia in malnourished children in the North-central zone of
Nigeria and thus a template for future research in the future. Clinical finding
related to iron deficiency would provide information for early identification of
iron deficiency so that early identification and treatment would be instituted.
This would go a long way to decrease morbidity and mortality from iron
deficiency especially in the malnourished child.
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Literature Review
Introduction
Malnutrition refers to a group of pathological disorders resulting from imbalance
between intake of essential nutrients and body requirement for these nutrients. In
other words, malnutrition results from not eating enough food or from intake of
food that although adequate in amount, lack the essential nutrients necessary for
normal growth and development. Protein Energy Malnutrition (PEM), is defined
as a spectrum of diseases arising as a result of an absolute, or relative deficiency
of calories and or protein in the diet.28-30
Malnutrition continues to be a major public health problem throughout the
developing world, particularly in southern Asia and sub-Saharan Africa.28-32
Diets in populations are frequently deficient in macronutrients (protein,
carbohydrates and fat, leading to protein–energy malnutrition), micronutrients
(electrolytes, minerals and vitamins, leading to specific micronutrient
deficiencies) or both.30, 33, 34, 35
In children, protein–energy malnutrition is defined by measurements that fall
below 2 standard deviations under the normal weight for age (underweight),
height for age (stunting) and weight for height (wasting).33 Wasting indicates
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recent weight loss, whereas stunting usually results from chronic malnutrition.33
Of all children under the age of 5 years in developing countries, about 31% are
underweight, 38% have stunted growth and 9% show wasting.30 Protein– energy
malnutrition usually manifests early, in children between 6 months and 2 years of
age and is associated with early weaning, delayed introduction of complementary
foods, a low-protein diet and severe or frequent infections.33,36,37
Historical Perspective
Severe malnutrition used to be known by several names such as infantile
atrophy, arthrepsia, inanition and Marasmus (Marasmos in Greek means to
“wither away” or “wasting away”), 2,38the later term being the one that has
survived common usage.
Kwashiorkor was recognized and described early in the turn of this century. In
Germany,39 where it was noticed in German children weaned on a diet of cereal
flour, the condition was called Mehlnarschaden (German for flour
dystrophy).40,41 In 1908 the Spanish literature described it as Syndrome
Policarencial Infantil42 .In that same year it was described as Culebrilla in
Yucatan,43 Mexico. The French literature described it in 1913 as Boufissure d’
Annam44 (meaning the swelling disease of Vietnam). More reports were made in
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temperate regions in 191345 and 192146while a report was made in Kenya in
1926.47
Cicely Williams, in 1933 while working in the Gold Coast (present day Ghana)
among the Ga people described the same disease entity using the native Ga word
“kwashiorkor” (Ga for disease of the weanling).2,47 It was with this report that
this disease in children acquired its present name.31
In 1956 Fredico Gomez and his colleagues described the clinical picture
preceding death and the apparent cause of death in malnourished children
admitted to the nutrition department of the children’s hospital in Mexico.47, 48.
His paper was a landmark of achievement because it used a single anthropometry
measurement (weight) to develop an indicator. Weight for age was related to the
severity of PEM and the risk for mortality.4
Prevalence of PEM
PEM is highly prevalent in almost all developing countries.2,13 It is estimated to
affect every fourth child in the developing world6,8 and approximately 6.6
million of the 12.2 million under -5 deaths occurring annually in 3rd world
countries are attributed to malnutrition.6,9 About 1-7% of under -5 children
suffer from the severe forms of malnutrition like kwashiorkor and marasmus.6,7
This small percentage of severe forms identified is an indication that larger
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number of mild and moderate malnutrition occurred unrecognized. The
prevalence range from 0.5 - 20% for severe form and 3.5 to 40.4% for moderate
forms world wide. In Africa, the prevalence for the severe form range from 1.7 -
9.8% and 5.4- 44.9% for moderate forms .7,54
Geographical variation is seen in the frequency of the different forms of PEM
.7,54 Breast feeding and weaning practices have been shown to play an important
role in the determination of the age distribution and types of malnutrition
observed.13 In Africa kwashiorkor was more common but a changing pattern is
now being experienced, marasmus is becoming more prevalent. This change has
been attributed to changes in feeding practices. Weaning is a common
precipitating factors in Latin America where infantile marasmus is common.
Kwashiorkor and marasmus are common in Asia where prolong breastfeeding
has been implicated as a major contributor to PEM.7-8,12-13.
Aetiology
PEM is an outcome of interplay of several factors that affect a child. These
diverse factors range from inadequate diet, infections, socio-cultural and
economic factors. Infectious causes and inadequate diet have been identified as
the most important.7,78
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Diet
PEM was being thought to result from in adequate protien calorie ratio in the
habitual diet. Kwashiorkor resulted from deficiency in protein predominately
while marasmus was from a deficiency in calorie in the diet with adequate
protein. Weaning with diluted milk formulae resulted in infantile marasmus
while kwashiorkor was common in young children fed on diet low in protein. In
some situation where protein intake is adequate but calorie intake is not, some
protein will be used for energy leading to continue protein deficiency. Hence
protein-energy malnutrition is used to describe the condition.3,7
Some studies have found no difference in dietary pattern of children who
develop kwashiorkor and those with marasmus.2,3,35 Other studies suggest that
PEM does not result from isolated deficiency of protein or calorie ,but rather
PEM results from the body’s adaptation to nutritional stress.18,54Successful
adaptation results in marasmus while mis adaptation results in kwashiorkor.2
Infection
Infection such as diarrhea, measles and acute respiratory tract infection have
been known to be associated with increase incidence of PEM. Kwashiorkor is
often preceded by an episode of infection with diarrhea or respiration tract
infection. Measles is another common infectious disease affecting children in
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developing world. Its impact is more because of the secondary complications and
prolonged illness associated with it. Mechanism by which infection leads to
malnutrition include, reduced food intake, malabsorption of nutrient and
metabolic losses during infection.2, 54
Socioeconomic Factors
Several socioeconomic factors have been implicated in the etiology of PEM.13,60
Inadequate diet, poor housing, increase incidence of infection all result from
poverty. Poverty, infection and malnutrition are related by a vicious cycle.
Insufficient house hold food security, inappropriate care for mother and child
and inadequate health care services provision by the government are some of the
numerous causes of PEM in the developing world. Cultural belief, superstition
and taboos about food belief also influence nutrient intake.13,60,77
Types of Malnutrition
There are various classifications of malnutrition
On the basis of the particular nutrient(s) implicated in the balance between
supply and body requirement, malnutrition can be broadly classified into.1,30:
A Macronutrient malnutrition (relating to energy and protein)
1 Protein – Energy malnutrition
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2 Over nutrition and obesity (effect of nutrient excess)
B. Micro nutrient malnutrition
1 Vitamin nutritional disorder
2 Minerals and trace elements nutritional disorders
Classification of Protein Energy Malnutrition
As a nutritional deficiency disorder, PEM results in growth failure, poor
nutritional status and, in due course, may also result in distinctive clinical
manifestations. These characteristic changes produced by PEM constitute the
main features for classifying the disorder into the various types and severity.51
In all cases, anthropometric indicators of nutritional status (weight-for-age,
height-for-age, and weight-for-height) usually form the basis for the
determination of the extent and severity of the nutritional deprivation and when
combined with certain clinical signs that are of high prognostic significance, for
example nutritional edema further allows differentiation into various types of
severe forms.51
There are classifications for clinical studies and for community survey.
Classification for clinical studies is based on the presence or absence of edema,
and are the severe forms. 2,3 These severe forms of PEM are Marasmus,
14
Kwashiorkor and Marasmic Kwashiorkor. Community survey classification is
based on deficit in weight for age and weight for height.2,30-33
Clinical Classification
An International Working Party convened in 1969 agreed to a simple
classification of PEM which was published in 1970 as the Wellcome
classification2,50 in an attempt to bring orderliness to the classification of the
disorder.
In the Wellcome classification only two criteria were used to classify the
malnourished child; these are presence or absence of edema and the deficit in the
body weight for age.
The initial classification gave rise to four groups. Children with edema whose
weight was between 60 & 80% of expected weight for age were classified as
kwashiorkor, while those without edema in this weight range were classified as
underweight. Children without edema whose weight was below 60 % of
expected for age were classified marasmus or as Marasmic Kwashiokor in the
presence of edema.
15
Table I : The Wellcome Classification of PEM2,50
Weight (% of standard) Edema Present Edema Absent
60-80 Kwashiorkor Underweight
<60 Marasmic-
kwashiorkor
Marasmus
Modified Wellcome Classification of PEM
It was noticed that the Wellcome classification excluded children who either had
weights above 80 per cent of the standard weight -for –age or even those with
normal weight-for –age and who still had overt kwashiokor .This exclusion
promoted the misconception that kwashiokor was invariably associated with
overt weight loss, thus implying dietary deficiency. This conception is not true as
kwashiokor can and sometimes arise in children who by any anthropometric
criteria cannot be classified as malnourished. This further explains the fact that
dietary deficiency is not a prerequisite for the development of kwashiorkor.2,50
Thus this called for the modification of the classification which takes account of
this and seem more appropriate.
16
Table II: Modified Wellcome Classification of PEM 2,50
Weight (% of standard)* Edema Present Edema Absent
>80 Kwashiorkor Normal nutrition
60-80 Underweight-kwashiorkor Underweight
<60 Marasmic-kwashiorkor Marasmus
Classification for Community Survey
Classification on the basis of weight for age is used to assess the magnitude of
the problem in the community. This classification does not indicate the duration
or type of malnutrition.54 The joint FAO/WHO32 expert committee on nutrition
emphasized that weight deficit in relation with age may be negative as a measure
of the duration of malnutrition. Weight in relation to height gives rise to a
measure of current nutritional status, while height for age gives rise to a picture
of past nutritional history. The former is referred to as wasting while the latter is
stunting. Most community surveys used 80% of weight for age as level below
which malnutrition is defined and 90% height for age as a level below which
stunting is defined.54
17
Gomez classification is the most widely used. It is based on deficit in weight for
age. In this classification, malnutrition is classified as first, second and third
degree.47
Table III: Gomez classification of PEM.
Malnutrition Body weight(% of standard)
First degree 75-90
Second degree 60-75
Third degree <60
The classification developed by Gomez F, Galvan R R, Frenk S et al47 was based
on three prior selections, an anthropometric indicator, a reference population
with which to compare the index child or community41 and cut off points to
classify children according to varying degrees of malnutrition. All classifications
developed after Gomez have all relied on these elements.48
18
Table IV: Gomez and modified Gomez weight-for-age classification of
malnutrition2,47,48
Nutritional status Gomez classification
(%)
Modified Gomez
classification
(%)
‘Normal’ nutrition > 90 weight for age > 80 weight for age
Mild or grade I PEM 75-90 weight for age 70-80 weight for age
Moderate of grade II
PEM
60-75 weight for age 60-70 weight for age
Severe or grade III PEM < 60 weight for age <60 weight for age
Nutritional edema
Following the publication by Gomez in 1956, 1st degree, 2nd degree and 3rd
degree malnutrition became common place terminology among nutritionist’s and
medical personnel. Within the spectrum of PEM, three broad clinical types were
recognized, namely kwashiorkor, Marasmus and marasmic-kwashiorkor.
However, the criteria to distinguish these three conditions were based on clinical
observations, which are subjective, and ill-defined.51
19
In, the same year, Waterlow, while trying to establish guidelines for rational
action or intervention, recommended a classification based on weight and height
to determine the nutritional status of children in a community. This was based on
the fair relationship that existed between weight and height.53
In 1972, Mclaren and Read proposed a classification of nutritional status in early
childhood based on observed weight as a percentage of ideal weight.51,52
Table V:Mclaren and Read classification of nutritional status in early
Childhood52
Classification observed weight as % of ideal
Obesity 120%
Overweight 110-120%
Normal range 90-110%
Mild PEM 85-90%
Moderate PEM 75-85%
Severe PEM <75%
20
The World Health Organization Classification of PEM
In 1990 the WHO proposed a new classification of Protein Energy Malnutrition
based on the weight for height and the height for age Z-scores and the presence
or absence of symmetrical edema of the feet.55
Table VI: The World Health Organization Classification of PEM
Mild
Malnutrition
Moderate
Malnutrition
Severe Malnutrition
Weight-for-
Height
<-1 to >-2 Z-score
(90%-80%)
<-2 to >-3 Z-Score
(70%-79%)
<-3 Z-Score (70%)
Height-for-
Age
<-1 to >-2 Z-score
(90%-95%)
<-2 to >-3 Z-Score
(85%-89%)
<-3 Z-Score (<85%)
Symmetrical
Edema
No No Yes(Edematous
Malnutrition)
21
Pathological Changes
Pathological changes have been noted in the body of a child with PEM. These
changes can be categorized as 3,7,54
(i) The organs.
(ii) Haematology.
(iii) Biochemical.
Changes in the organs
Liver- Fatty infiltration, seen in kwashiorkor first noticed in the periphery then
spread towards the portal tract and cortical level until it affects the parenchyma.
Changes can be reversed with treatment.3,7
Pancreas-children with PEM show marked atrophy of the pancreas. Pancreatic
calcification may ensue. Changes are reversible with treatment.3,7
Kidney-kidney size is reduced in severe PEM; Pyelonephritics changes with
scaring of the medulla and focal areas of calcification are common. Glomerular
changes, thickening of basement membrane and increased cellularity of capillary
tuft also is present. Changes are reversible with treatment.3,7
Gastro intestinal tract- Mucosal atrophy of the small intestine. The villous
atrophy decreases the absorptive surface. Villous shortens, crypts /villous ratio
22
increase. Histology of gastrointestinal mucosa changes from columnar shapes to
cuboidal shapes and brush borders are lost. Inflammation cell infiltrations are
seen in laminar propria.3,7.
Thymolymphatic system-Thymus is greatly reduced in children during severe
PEM. Degree of thymic atrophy correlates closely with depletion of lymphocytes
.Tonsil sizes are significantly smaller with PEM, size of spleen is also decreased.
There is decrease in thymic dependent lymphocyte associated with impaired cell
Mediated immunity. However, B –lymphocytes responsible for humoral
immunity are not affected.3,7.
Muscle- There is marked reduction both in bundle and fibers of the muscle.3
Heart;- Heart size is usually reduced. ECG changes suggest non specific
myocardial damage. Reversal of changes occurs following full treatment.3,7
Haematological changes;
Some degree of anaemia is always found in children with PEM. Moderate
anemia with peripheral blood film showing normocytic or microcytic, hypo
chromic cell occur in PEM. Haemoglobin levels are reduced as a consequence of
low levels of plasma protein. Reticulocytes increase in response to anaemia with
increase erythroid activity. Anaemia may be due to associated deficiency of iron,
folate riboflavin and vitamin E.3,7,59.
23
Biochemical changes
Low levels of serum sodium, potassium, magnesium copper and zinc have been
reported in PEM.7
TYPES OF PEM
There are various forms of protein energy malnutrition , various distinctions
have been made between the various forms based on the clinical presentation,
such as the presence or absence of edema and weight loss . Some workers feel
that this distinction between the various forms of severe PEM need not be
emphasized as they are different facets of the same disease. 2,7 58For the purpose
of classification and management , the following are the clinical presentation and
features of the severe forms of protein energy malnutrition.
Marasmus
It is characterized by progressive wasting of the subcutaneous tissue and the
muscle. Marasmus is diagnosed when subcutaneous fat and muscle are lost
because of endogenous mobilization of all available energy and nutrients.28 This
condition is a consequence of inadequate food intake. It is often precipitated or
preceded by failure of breast feeding, infection or congenital abnormalities.
When an infant develops this condition, it is described as infantile Marasmus and
when seen in older children it is called late marasmus.28 Marasmus is defined as
a weight of <60%of the expected weight for age without edema.2,28
24
There are many mechanisms responsible for marasmus but in global terms,
marasmus results from a negative energy balance.3,7 It can result from decreased
intake, increased energy expenditure, or both as it may occur in either acute or
chronic disease states.56 Reasons why a continuous nutritional food deficit leads
to Marasmus rather than kwashiorkor are unclear but theories have shown that
Marasmus is a successful adaptation to continuous nutritional deficits, while
kwashiorkor is a dysadaptation. 2,3. The adaptations to energy deficit include
reduced activity, lethargy, decrease in basal energy metabolism slowing of
growth and then weight loss.56
Clinical presentation of marasmus include prominent bones and joint, hanging
skin folds over the buttocks and thighs, disappearance of buccal fat pads and
distended abdomen. There are also changes in the skin and in the hair. The skin
becomes loose and may eventually hang in folds; this is common in the buttocks
and thighs. It may also be wrinkled, dry or scaly.2-3 The buccal fats in the cheeks
of young infants may persist long after the subcutaneous tissue of other part of
the body have disappeared. Its disappearance is a poor prognostic sign. The
abdomen may be scaphoid or distended. Anal or rectal prolapse (from loss of
perianal fat) can also occur. Diarrhea is sometimes present with accompanying
dehydration. Anaemia is usually present.2-3,7.
25
Marasmic children are usually unhappy and irritable but usually respond
normally to attention and feed more hungrily. Edema is usually absent. There
are no constant biomedical derangements associated with marasmus.3,28, 56
Kwashiokor
Kwashiorkor usually manifests with edema, changes to hair and skin color,
anaemia, hepatomegaly, lethargy, severe immune deficiency and early death. It is
common in children between one and three years old. The physical findings in
kwashiorkor include poor growth, edema, muscle wasting, and mental changes.
These are the four cardinal signs which are always present in kwashiorkor. Other
features include skin changes, hair changes, and moon face appearance, signs of
micronutrient deficiency, hepatomegaly and intractable diarrhea. Anaemia is a
usual feature. Anaemia is usually moderate and when severe is usually due to
iron and/or folate deficiency.
Marasmic- Kwashiorkor
They are children that have both clinical features of kwashiorkor and marasmus.
In this condition, edema appears in a clinically undernourished child who has not
been growing for weeks or months. The degree of stunting is significantly
greater in them suggesting that the duration of illness is longer in marasmic–
kwashiorkor than in kwashiokor . Features like psychosocial, skin and hair
changes as well as other feature of kwashiorkor are also present.56
26
Complications
Infection
Infections are common complications of severe PEM. It is often severe and
reflects impaired immunological status of these children. It might be difficult to
diagnose because the typical features such as fever and leucocytosis might be
absent. Children with kwashiorkor are susceptible to gram negative organisms
such as Escherichi. coli, Proteus species and Pseudomonas Aeruginosa. Viruses
like measles, herpes simplex may cause serious infections and HIV/AID is also a
common infections. Severe candidaisis are frequently seen. Tuberculosis being
aggressive are usually difficult to identify in these children. Intestinal parasitic
infections (especially ascaris) are high in PEM. Hookworm infection is less
common in the malnourished children because they are too weak to walk around
to contract the infection. Malaria is common and it does appear to be less severe
in the malnourished.3,7,47
Hypoglycemia and Hypothermia
Fasting blood sugar may be decreased but symptomatic hypoglycemia is
uncommon and may develop if feeding is infrequent. Hypoglycemia is common
in marasmus while energy store are depleted often in association with
septicemia. It can present as twisting convulsion and unconsciousness.7,60
27
Hypothermia is manifestation of impairment of thermoregulatory center and
energy stores. It occurs often in severely wasted children.
Cardiac failure
Cardiac failure is commonly seen in the treatment phase and sometimes
associated with anaemia.3,7 During recovery, the heart size increases rapidly
owing to chamber enlargement, and left ventricle increase in proportion to
increasing weight. However if dietary repletion is rapid, especially with a high
sodium load, heart failure may develop and sudden death may occur.3
Investigation and Treatment of PEM
There are some investigations required for the diagnosis and treatment of PEM
these include1-3,7,.
1 Complete blood count-Haemoglobin and packed cell volume usually are
lower than normal .There might be leucocytosis or leucopenia in the
prescence of infection. Platelet count is usually within normal limits.2
2 Random blood sugar-blood sugar might be low or normal. Children with
PEM have an increase susceptibility to low blood sugar because of the
increase cortisol level which occurs in response to the severe malnutrition
and concomitant infection present in these children.1,3
28
3 Blood electrolyte, urea and creatinine –evidence of derangement of these
parameters can be present. High sodium as well as low potassium is
typical of malnutrition because of active transport of sodium out of the
cell as a result of increase permeability of the cells.3-4
4 Serum lipids and protein levels –changes seen in serum protein in
malnutrition include low serum albumin, transferin and apolipoprotien B .
PEM. This is as a result of changes in the liver where these proteins are
synthesized in severe malnutrition. 3 Plasma free fatty acids are raised
while the level of triglycerides and phospholipids are reduced with a low
ratio of esterified fatty acids to free cholesterols.7
5 Microbiological cultures -culture of blood and other body fluids such as
urine and cerebrospinal fluid can be done to know the organisms
responsible for any infection and their sensitivity patterns to antibiotics.
6 Stool for ova of parasite and occult blood to identify parasite if present.
7 Tuberculin skin test - for diagnosing tuberculosis even though it might be
negative because of immune suppression present in severe PEM despite
the presence of an active tuberculosis infection. Clinical presentation
along side with other investigations would be useful in making a diagnosis
in suspected cases.
29
8 Radiological chest x ray this is important because of the higher association
of malnutrition with tuberculosis.
9 HIV screening – this is important because of the common association of
PEM with HIV/AIDS.
10 Hormone; - increased serum levels of corticosteroid , cortisol and growth
hormones are common manifestation of PEM.
Treatment
Treatment is divided into phases;
(i) Stabilization phase (2-6 wks)
(i) Rehabilitation phase
(ii) Follow up between -6 months
Main stay of treatment has been elucidated by several workers 65,77. This includes
A Dietary management . These involve improving the nutritional level of the
child as soon as possible. Dietary management should follow stated protocol
such as the one provided by WHO.14 This should be adapted for the particular
locality where it is to be used. The protocol entails that what ever diet is chosen,
the energy density should be between 75-100kcal /100ml, the osmolarity should
30
be lower than 350-400mOsmol/L and 6-12% of the calories should come from
protein.3,14. Vitamin and other micronutrients should also be provided.
B Management of complication
Anaemia-Iron deficiency is the commonest cause of anaemia. It can be treated
with oral forms of iron. Associated folate deficiency can be treated with oral
dose of folic acid. Severe anaemia can be managed with blood transfusion of
packed cells to prevent heart failure.
Hypoglycemia; Treated with intravenous glucose and early monitored and
quantified feeding.
Infection; Gastro intestinal respiratory and urinary tract infection are common in
children with severe PEM. Rationale antibiotics use including the use of broad
spectrum antibiotics initially such as a combination of an aminoglycoside and a
penicillin compound to cover for both such gram positive and gram negative
organism. This can be changed to the sensitive antibiotic as soon a result of
sensitivity is out.
Parasitic infection, such as malaria and other intestinal infestation should be
managed appropriately.
Hypothermia; Child should be kept warm and temperature monitored regularly.
Shock and electrolyte derangements; Prompt and proper fluid and electrolyte
management should be instituted especially when diarrhea and vomiting are
present.
31
Long Term Care
Follow up care for nutritional rehabilitation and growth monitoring is required
for children with PEM. This can be done at health centers or domiciliary visit if
the situations permit. Nutritional education, immunization and growth
monitoring should be offered60,83.
Risk Factors for Protein Energy Malnutrition in Nigeria
Protein-energy malnutrition is still highly prevalent in Nigeria as a result of
many factors which include faulty weaning practices, poverty, poor sanitary
conditions, minimal medical attention, and endemic childhood infections.60
Inadequate production or shortage of food is no longer thought to be the usual
cause of malnutrition. Instead the problem develops from, and are maintained by,
a complex network of socio-economic and health determinants.3,7 Studies have
shown that in developing countries, the nutritional status of children has a
significant direct relationship with household income. 12,13,75 Other socio-
economic factors such as educational level of parents, distribution of food in the
family, demographic data, immunization status, childhood illness, intestinal
parasitoses, and childhood nutrition also have significant association with the
nutritional status of children.83,98-100.
32
Prevention of Malnutrition
Protein Energy Malnutrition can be prevented by improving maternal diet and
health, and providing good antenatal care. Other modalities of prevention include
appropriate infant feeding practice which include, practice of exclusive breast
feeding and good complementary feeding practice. Prevention of infections and
diseases by immunization, diarrheal management, growth monitoring and
sustenance of other child survival strategies will also prevent malnutrition.8,14,60.
Haematologic Changes In Protein Energy Malnutrition
In children with protein energy malnutrition, the haemoglobin concentration is
usually low ,it may fall to 8g/dl of blood.57,58 However, some PEM children with
features of acute complication who are admitted to the hospital, a normal
haemoglobin levels may initially be present . This can be attributed to a
reduction in plasma volume present at this stage of the illness.
The mechanism of anaemia in PEM has been attributed to various causes such as
protein deficiency which leads to an increased oxygen consumption and
erytropoitein production. This invariably results in a drop in erythropoiesis and
reticulocyte counts.59 Red cell maturation is blocked at the erythrocyte level
and the erythropoietin-sensitive stem cell pool is slightly decreased57-59. The
production of red blood cells (RBCs) is governed by various growth factors. Of
all the factors stimulating erythropoiesis has a more important regulatory role
33
than erythropoietin. Erythropoietin binds to specific receptors on the erythroid
bone marrow precursors [colony forming unit-erythroid (CFU-E) and burst
forming unit-erythroid (BFU-E)], thus stimulating their differentiation and clonal
maturation into mature RBCs 59,76. Other requirements for normal erythropoiesis
are protein, iron for haemoglobin synthesis, vitamin B12 and folate for DNA
synthesis, as well as other vitamins such as pyridoxine, riboflavin, thiamine,
vitamins C and E, and trace elements such as cobalt 59,77.
Some investigators, who have also found normal erythropoietin production in
PEM, have suggested that the impairment of erythropoiesis in PEM could be due
to an abnormality in the erythroid progenitor cell pool or ineffective
erythropoiesis82. It has also been shown that in anaemia of some chronic diseases
there could be a blunted serum erythropoietin response to anaemia83, which was
not the situation in the anaemia of PEM infants in a study27, where the
erythropoietin response to anaemia was preserved.
Another possible etiology of anaemia in PEM is a reduction in the plasma
volume to a variable degree seen especially in children with Kwashiokor, the
total red cell mass also decreases in proportion to the decrease in the lean body
mass as a result of protein deficiency which reduces metabolic needs of the
body.57
34
The anaemia in PEM is usually normocytic normochromic, but there is a
considerable variation in size and shape of the red cell on the blood film.58
The white cell count and platelets counts are usually normal.3 The marrow is
most often normally cellular or slightly hypocellular, with a reduced erythriod-
myeloid ratio.3 Erythroblastopenia, reticulocytopenia, and a marrow containing a
few giant pronormoblast may be seen in the presence of infection.58
During repletion in the recovery phase an increase in plasma volume may occur
before an increase in red cell mass, anaemia may then become more severe
despite reticulocytosis. Also during this stage of repletion, occult deficiencies of
iron, folic acid, riboflavin, vitamins E and B12 may occur and thus worsen the
anaemia in these children .57-59
35
Nutritional Anaemia
Anaemia is defined as a reduction of the red blood cell volume or haemoglobin
concentration below the range of values occurring in healthy persons.61 It results
in a reduction in circulating red cells, haemoglobin and haematocrit. A reduction
in haemoglobin concentration usually reduces oxygen carrying capacity of the
blood but this is usually apparent when the haemoglobin Concentration fall
below 7-8g/dl.84 When anaemia occurs as a consequence of a nutritional
deficiency, any of these pathologic processes may be involved either singly or
combined . This is referred to as nutritional anaemia.
Nutritional anaemia may be due to iron deficiency (inadequate iron intake, poor
iron absorption, or excess iron losses), vitamin deficiency such as vitamin A,
vitamin B group(pyridoxine B6, riboflavin B2, folate B9,and cyanocobalamin
B12), vitamin C and vitamin E deficiencies.58,62 Nutritional disturbances such as
protein and calorie deficiency states can also result in anaemia.
Prevalence of iron deficiency anaemia in PEM
Nutritional anaemia is a common problem in Nigeria among children with iron
deficiency being the commonest micronutrient deficiency, affecting more than 2
billion people world wide. Iron deficiency anaemia (IDA) is reported to be the
most common nutritional anaemia in the world. It affects 20% to 50% of the
world's population and it is common in young children.5 In the United states ,
36
data from the National Health and Nutrition Examination survey found the
prevalence of iron deficiency to be 9% among children 1-2 years. Despite this
fact the prevalence of iron in vulnerable groups such as children with protein
energy malnutrition is extremely variable.25-26 In Nigeria, the Prevalence of iron
deficiency anaemia has been reported to be as high as 20-25% among children, 5
while the prevalence of iron deficiency anaemia in children with PEM in Nigeria
was 10% .75
Normal term infants are born with sufficient iron stores to prevent iron
deficiency for the first 4-5 months of life. Thereafter, enough iron needs to be
absorbed to keep pace with the demands of rapid growth. For this reason,
nutritional iron deficiency is most common between 6 and 24 months of life. A
deficiency earlier than age 6 months may occur if iron stores at birth are reduced
by prematurity, neonatal anaemia, small birth weight, or perinatal blood loss.65A
significant body of evidence indicates that iron deficiency, in addition to causing
anaemia, has adverse effect on multiple organ systems. Thus, the importance of
identifying and treating iron deficiency extends past the resolution of any
symptom directly attributable to a decreased hemoglobin concentration.64,66
Anaemia is classified according to the red cell on peripheral blood film and the
mean corpuscular volume (MCV). The primary classification includes;84
Hypochromic microcytic (small pale red cells and low MCV).
37
Macrocytic (large red cell with large MCV).
Normocytic normochromic (cells of normal size and normal MCV).
History of Iron deficiency Anaemia
A disease believed to be iron deficiency anaemia was described in about 1500
B.C. in the Egyptian Ebers papyrus, it was termed chlorosis or green sickness in
Medieval Europe, and iron salts were used for its treatment in France by the mid-
17th century.68 Thomas Sydenham recommended iron salts as treatment for
chlorosis, but treatment with iron was controversial until the 20th century, when
its mechanism of action was more fully elucidated.68
Etiology of Iron Deficiency Anaemia In PEM
Iron deficiency anaemia is the most common type of anaemia, and is also known
as sideropenic anaemia. It is the most common cause of microcytic anaemia. The
causes of iron deficiency anaemia are numerous. 69Dietary deficiency,
malnutrition, infection and infestation are the leading cause of iron deficiency
ananemia.68,84
Iron deficiency anaemia occurs when the dietary intake or absorption of iron is
insufficient, and haemoglobin, which contains iron, cannot be formed.68 Also,
the popular complementary food given to infants in developing countries like
Nigeria such as corn pap which are very low in protein, energy, and other vital
38
nutrients such as iron that support optimal growth can contribute to iron
deficiency.101 Besides, the traditional method of preparing corn pap permits
nutrients losses especially iron loss.102 This popularly used Corn pap (gruel)
contains 3.8 to 7.9% protein, grossly deficient vitamins and minerals and fat
content less than 2% .
Iron deficiency anaemia in PEM can be caused by parasitic infections, such as
hookworms. Intestinal bleeding caused by hookworms can lead to fecal blood
loss and haemoglobin/iron deficiency. Chronic inflammation caused by parasitic
infections as well as diversion of iron to fetal erythropoiesis, intravascular
haemolysis and haemoglobinuria contributes to anaemia in most developing
countries.
Iron deficiency occurs in three stages and this include.69-70,112
Stage 1 characterized by a reduction in serum iron and mobilization of storage
iron. Levels of transport iron and haemoglobin are reduced.
Stage 2 characterized by iron-deficient erthropoiesis involving a decrease in
transport iron (low serum ferritin, serum Transferrin receptor and free
erythrocyte protophyrin). This stage is referred to as iron deficiency without
anaemia as haemoglobin concentration is within normal limit.
39
Stage 3 Iron deficiency anaemia is the final stage of iron deficiency. It develops
when the supply of transport iron decreases to the point where haemoglobin
synthesis is restricted. Thus there is low haemoglobin and low iron stores
Clinical features of iron deficiency
Iron deficiency anaemia is characterized by pallor (reduced amount of
oxyhaemoglobin in skin or mucous membrane), fatigue and weakness. Because
it tends to develop slowly, adaptation occurs and the disease often goes
unrecognized for some time. In severe cases, dyspnea can occur. Unusual
obsessive food cravings, known as pica can occur. Geophagia, and pagophagia
may also develop. Hair loss and lightheadedness can also be associated with iron
deficiency anaemia. Other symptoms include sore tongue, fainting and
breathlessness. Nails may become weak, brittle and koilonychia occurs with
severe anaemia.68
Effect of Iron deficiency anaemia in PEM
Iron deficiency is a condition which there is a lack of cellular iron to the tissues.
It represent a spectrum of mild to severe forms characterized by the presence or
absence of physiologic, biochemical, haematologic and functional changes in the
body.65,112
40
Clinical consequences of iron deficiency anaemia include poor cognitive
performance, anaemia, poor immune function and decreased work output. 112
Iron deficiency anaemia for infants in their earlier stages of development may
have significantly greater consequences than it does for adults. It affects the
neurological development by decreasing learning ability, altering motor
functions, and permanently reducing the number of dopamine receptors and
serotonin levels. Iron deficiency occurring during development can lead to
reduced myelination of the spinal cord, as well as a change in myelin
composition. Several studies have proven these facts.65,69,112 Additionally, iron
deficiency anaemia has a negative effect on physical growth. Growth hormone
secretion is related to serum transferrin levels, suggesting a positive correlation
between iron-transferrin levels and an increase in height and weight.71
Diagnosis
Anaemia may be diagnosed from symptoms and signs, but when anaemia is mild
it may not be diagnosed from mild non-specific symptoms. Anaemia is often
first shown by routine blood tests, which generally include a complete blood
count (CBC). A sufficiently low haemoglobin or haematocrit value is
characteristic of anaemia, and further studies will be undertaken to determine its
cause and the exact diagnosis.19,56.
41
In progressive iron deficiency, sequences of biochemical and haematologic
events occur. First, the tissue iron stores represented by bone marrow
haemosiderin disappear. The level of serum ferritn, an iron storage protein,
provides a relatively accurate estimate of the body iron stores in the absence of
inflammatory disease. Normal ranges are age dependent, and decreased levels
accompany iron deficiency. Next the serum iron level decreases, iron binding
capacity (TIBC), serum transferrin increases and the percentage saturation falls
below normal and free erythrocyte protoporphyrins accumulate. As deficiency
progresses, the red blood cells(RBC) becomes smaller than normal and their
hemoglobin content decreases .This can be determined by changes in the mean
corpuscular hemoglobin (MCH) and mean corpuscular volume(MCV). With
increasing deficiency the red blood cells become deformed and misshapened and
present with characteristic microcytosis, hypochromic poikilocytosis, and
increased red cell distribution width. The reticulocyte may be normal or
moderately elevated, nucleated red blood cells are seen in the peripheral blood if
anaemia is severe. White blood cell counts are normal, sometimes
thrombocytosis occurs though thrombocytopenia may occur in severe forms.
There will be a high red blood cell distribution width (RDW), reflecting a varied
size distribution of red blood cells. In about a third of cases, occult blood can be
detected in the stools19,90.
42
Treatment of Iron Deficiency Anaemia
If the cause is dietary iron deficiency, iron supplements, usually with iron (II)
sulfate, ferrous gluconate, or iron amino acid chelate NaFeEDTA, will usually
correct the anaemia. The recommended daily oral dose of elemental iron is 3-
6mg/kg/day. Mild cases may be treated with 3 mg/kg/day before break fast.
Parental administration is rarely required. Iron therapy results in an increased
reticulocyte count within 3-5 days and maximal between 5 and 7 days. The
hemoglobin level begins to increase thereafter. The rate of haemoglobin
increases is inversely related to the haemoglobin level at diagnosis. In moderate
cases an elevated reticulocyte count 1 week after initiation of therapy confirms
the diagnosis and documents compliance. When iron deficiency is the only cause
of anaemia, adequate treatment usually results in resolution of anaemia in 4-6
weeks. Treatment is continued for a few months to replenish stores. While
adequate medication is given, family must be educated about child’s diet, which
should contain iron fortified diet.65,68.
Assessment Of Iron Status
There is a wide variety of laboratory methods that can be used to assess iron
status in the body. These methods include ; Haemoglobin , haematocrit, mean
corpuscular volume(MCV), mean corpuscular haemoglobin concentration
43
(MCHC); and mean corpuscular haemoglobin(MCH).Others include serum Iron,
total iron binding capacity, serum Ferritin and serum Transferrin receptor.65
Haemoglobin Concentration; The amount of hemoglobin in the blood. The
hemoglobin concentration is measured in grams per deciliter (g/dL) of whole
blood. It measures the presence of anaemia but can not distinguish between
anaemia of iron deficiency and other causes. It is interpreted according to age
and sex-specific references.
Haematocrit; The haematocrit is a test that measures the volume of blood in
percentage that is comprised of the red blood cells.
Mean Corpuscular Volume (MCV); This is haematocrit divided by the red
blood cell count. It is a measurement of the volume occupied by a single red
blood cell and it is an indication of individual red cell size. Normal value is
between 73-93fl. Decreases values indicates microcytic anaemia while raised
value indicates microcytic anaemia.
Mean Corpuscular Haemoglobin Concentration (MCHC); This is
haemoglobin concentration divided by haematocrit. It represents the average
concentration of haemoglobin in the red blood cell. It is expressed as a
percentage. Increased values indicate spherocytosis while decreased value
indicates iron deficiency. Normal value is between 13-31g/dl.
44
Mean corpuscular Haemoglobin (MCH); This is haemoglobin concentration
divided by the red cell count. It represents the average haemoglobin contained in
each red cell. It is influenced by the size of the cell and haemoglobinization.
Normal values are between 27-34pg. increased values occur in microcytic
anaemia while decreased values are seen in microcytic anaemia.
Serum Ferritin
Structure: Ferritin is a large protein shell (MW 450,000) comprised of 24
subunits, covering an iron core containing up to 4000 atoms of iron. In normal
condition it may represent 25% of total iron found in the body.73
Function: Ferritin acts as the soluble storage form of iron in tissue . It may serve
other functions as well although these are controversial. It is found in most cells
of the body, especially macrophages, hepatocytes and erythrocytes. Its synthesis
occurs in the liver and the rate correlates directly with the cellular iron content.
Control of ferritin synthesis occurs post-transcriptionally (at the mRNA level).
There are iron- and cytokine-responsive elements in ferritin mRNA. Increased
iron or cytokines (such as IL-1, IL-6) promotes ferritin translation, resulting in
increased iron storage. This is one of the causes of iron "sequestration" that
occurs in animals with chronic or inflammatory disease and will lead to reduced
serum iron values. The function of serum ferritin is not known, but the
concentration correlates well with the amount of stored iron in normal (and most
45
diseased) subjects. Serum ferritin concentrations are quite stable from day-to-
day, in contrast to serum iron73,74.
Measurement: Sensitive methods are needed, since serum levels are very low.
Immunologic assays requiring species-specific reagents, such as RIA and
ELISA, have been employed. Canine and feline-specific ferritin assays are also
available74.
Variation in disease: Low serum ferritin: A decrease in the amount of stored
iron is the only known cause for low serum ferritin result. This is the strong point
of this test. Increased stored iron (overload) is associated with raised serum
ferritin levels. Unfortunately, ferritin is an acute phase reactant protein, so liver
disease, infection, inflammation, or malignancy will result in high serum ferritin
levels. The concurrent presence of these conditions in an iron-deficient subject
may raise serum ferritin concentration to a level not clearly indicative of iron
deficiency; or raise the level in a subject with normal iron stores to an extent
suggestive of iron overload.74
46
Overview of PEM and Iron (Serum Ferritin)
PEM is a generalized disorder affecting the structure and function of the entire
body. According to various reports the incidence of iron deficiency in PEM is
extremely variable.5,79 Iron deficiency in PEM might arise from dietary
deficiencies. This can arises from reduced dietary iron and/or low bioavailability
of dietary iron. Despite the high bioavailability of iron in human milk, it contains
a low iron store. This might result in iron deficiency anaemia in children
exclusively breast fed after 6 months. The choices of complementary foods
usually further increase the risk of iron deficiency as most complementary foods
in the developing world are poor sources of iron. 3,99,101
Despite the fact that dietary deficiency of iron is prevalent among children with
PEM, hepatic iron and bone marrow free iron might also be elevated in severe
PEM, as there is a reduction in the concentration of serum protein especially the
transport protein. Iron is usually tightly bound to proteins during storage and
transport to prevent free iron forming the extremely damaging hydroxyl radical.
Reduced serum transport proteins such as transferrin will result in a reduction in
total iron binding capacity and an increase in concentration of free iron.3
47
Low serum transferin in PEM has been associated with increase mortality in
severe PEM131, 132 while free iron has been implicated in the etiology of PEM
especially kwashiokor.131, 132
Several studies on haematologic and biochemical parameters have revealed low
iron stores in children with Protein Energy Malnutrition25, 26, 97. Some of these
studies demonstrated high serum ferritin levels despite the low iron stores.
Intestinal absorption of iron is maintained in PEM children with high serum
ferritin while those with low ferritin levels have impaired absorption.134 In the
acute phase of PEM ferritin level might be elevated as ferritin serves as an acute
phase reactant26 and iron supplements at this stage has been found to be
associated with increased mortality135. However during the recovery phase of
PEM, with accompanying increase in the lean body and red cell mass, iron is
required, and stores are quickly exhausted so that classic iron deficiency features
occur.136 At this stage iron supplements would be required.
Prevention and control of iron deficiency anaemia in PEM
Interventions to prevent protein– energy malnutrition range from promoting
breast-feeding to food supplementation schemes. Micronutrient deficiencies
would best be addressed through food-based strategies such as dietary
48
diversification through home gardens and small livestock. To be effective, all
such interventions require accompanying nutrition-education campaigns and
health education interventions. To achieve the hunger- and malnutrition-related
Millennium Development Goals, we need to address poverty, which is clearly
associated with the insecure supply of food and nutrition22,4
49
Justification
Protein-energy malnutrition is still highly prevalent in Nigeria. Malnutrition can
be due to macro or /and micronutrient deficiency. Micro nutrient deficiency is
becoming increasingly common with iron deficiency being the commonest. The
impact of iron deficiency is enormous especially on the developing child’s
growth, developmental, cognitive and intellectual abilities. Despite this fact the
prevalence of iron in vulnerable groups such as children with protein energy
malnutrition is extremely variable.25-26 Iron deficiency results in nutritional
anaemia thus there is a need to assess the haematologic profile of the group in
question(PEM) to properly asses this important trace element.
Generally and especially in these part of the country there a paucity of literatures
on the hematological profile and ferritin levels of children with Protein Energy
Malnutrition. Majority of the studies carried out on hematological profile in
malnutrition were done several decades ago, many of such were not in this
environment. Thus, there is paucity of data on this subject and a hence the need
for this study. This will enable us to predict the status of this essential
micronutrient in this group of children, as well as their haematological profile.
Iron deficiency and its attendants consequences would thus be prevented in this
already compromised group of children. This would in turn reduce childhood
mortality, and further enhance child survival in this part of the world.
50
Aims and Objectives
General objectives
To assess the haematological profile and serum ferritin levels in children with
PEM in UITH, Ilorin.
Specific Objectives
To determine;
1. The haematological profile of children with PEM
2. The serum ferritin levels of children with PEM.
3. The prevalence of anaemia in children with PEM
4. The prevalence of iron deficiency anaemia in children with PEM in Ilorin
5. The relationship between the clinical feature and serum ferritin levels in
PEM.
51
Materials and Methods
Study Design
The study was a case control study in which subjects were children diagnosed
for PEM and controls were children with normal nutritional status without
haematological or infectious conditions.
Background of study site
The University of Ilorin Teaching hospital is located in Ilorin West Local
Government Area of Kwara State. This lies in the North Central zone and serves
as a gateway between the Northern and Southern parts of the country. The state
population stands at 2.4million,85 Ilorin west local government area is populated
by 36,466.86 people and the vegetations is largely Guinea Savannah.25 – 28 The
hospital serves as a referral center for Kogi, Niger, Osun, and Ekiti states. It has
an Emergency Pediatrics Unit that treats children on referral and also renders
consultation to outpatients. The Emergency Pediatrics Unit is a 30 bedded unit
with a functional side laboratory. The Hospital also offers efficient laboratory
services.
52
Study population
This survey was conducted in the Emergency Paediatric ward of UITH Ilorin
among children (6 -59 months old) with malnutrition.
Sampling techniques
All consecutive admissions into the Emergency Paediatric Unit with a diagnosis
of PEM based on the Wellcome’s classification that fulfilled the inclusion
criteria were enrolled. Controls were well children attending the routine clinic
without haematologic or infectious condition.
Inclusion criteria
1. Children between the ages 6 months and 59 months diagnosed with PEM
according to Wellcome classification.
2. Patients whose parents consent.
Exclusion criteria
1. Patients on drugs containing iron
2. History of blood transfusion in the last 3 months
3. History suggestive of on going haemolysis, such as haematuria, and other
indices of chronic blood loss, malignancy and peptic ulcer disease.
53
4. Children with haemoglobinopathies such as Sickle cell anaemia,
thalassemia, and patients with HIVs Positive status.
Research Instruments
Interviewer administered semi-structured questionnaire.
Stadiometer, tape rule, and weighing machine.
Proforma (Questionnaire)
A semi–structured questionnaire (proforma) was used to collect information
from the subjects using interview method. The questionnaire was translated into
other languages such as Yoruba, and Nupe and used for respondents (mothers
and care givers) who do not understand the English language. Relevant
information on the child’s socio-demographic characteristics, nutritional indices
and laboratory findings were obtained.
Pre- Testing of instrument
The research instrument was pre-tested among mothers of children with Protein
Energy Malnutrition in the children’s ward at children specialist hospital Ilorin.
This was to ensure validity and reliability of the instrument. It also gave an idea
of the level of difficulty and complexity, which could hinder the administration
of the instrument. The pre-tested instrument was then analyzed and necessary
modification was effected.
54
Validity of the profoma (questionnaire)
Senior Laboratory Scientist and Lecturers in the Department of Pediatrics,
Chemical Pathology and Hematology were consulted for a careful vetting of the
initial items in the proforma. The correction and suggestions on the tool lead to
the modification of some of the items of the instrument all of which were
incorporated into the final copy of the proforma.
Institution/College approval
The study was approved by the Ethics and Research Committee of the University
of Ilorin Teaching Hospital (Appendix vi), and also by the National Post
Graduate Medical College of Nigeria (Appendix vii)
Consent
The caregiver were interacted with and were provided with adequate
explanations about the study as contained in the information sheet (Appendix i)
with a view to obtaining their consent by signing or thumb printing on the form
for that purpose.
All the patients received standard treatment for the primary conditions. The
study pro forma used is as displayed in Appendix ii.
55
Method of data collection
The researcher along side with research assistants made up of Paediatrics
residents that were trained, were involved in sample collections and
administration of questionnaires. The researcher and the Laboratory Scientist in
hematology, chemical pathology and microbiology were involved in sample
analysis and interpretation of laboratory results.
Sample size determination
The minimum sample size was determined using the formula (29,30)
N=2z2pq
d2
Where
N= desire sample size
Z = the standard normal deviate usually set at 1.96 (or simply at 2.0) which
corresponds to 95% confidence interval.
P = the proportion in the target population estimated to have a particular
characteristics (malnutrition) The prevalence from a previous study is put at 10
%( 0.10)75
q=1-p
56
= 1.0 – 0.10=0.90
d =observed difference of 10% or more taken as being significant.
N = 2 x (1.96)2 x 0.10 x0.90
(0.10)2
= 69
The minimum calculated sample size was 69; making allowance for at least 10%
attrition rate, the calculated sample size was 76. To obtain an equal distribution
for statistical analysis, 90 subjects each were selected for the study and control
groups with a total of 180 participants for the study.
Data Collection /analysis
Structured questionnaire was used to obtain information’s on;
1. Socio-demographic characteristic.
2. Clinical profile of sign and symptoms.
3. Anthropometric measurements.
4. Laboratory parameters.
57
Socio-Economic Index Score
Socio-economic index scores were awarded to the occupations and educational
attainments of their parents or caregivers using the Oyedeji socio –economic
classification scheme13 (Appendix IV). The mean of four scores (two for the
father and two for the mother) approximated to the nearest whole number was
the social class assigned to the child as proposed by oyedeji.13 For example, if
the mother was a junior school teacher (score = 3) and father a senior teacher
(score=2) and the educational attainment of the mother was primary six
(score=4), and the father was a school certificate holder(score=2), the socio-
economic index score for this child
was; 3+2+4+2/4=2.75 to the nearest whole number 3.Socio economic class I
and II are the upper socio-economic class, class III is the middle class while
socio economic class IV and V are the lower socio-economic class.13
Clinical Examination; Clinical examination and anthropometric measurements
such as weight and height were carried out among the subjects by the
investigator. The weight was measured to the nearest 0.1kg using standardized
scales while the length was measured to an accuracy of 0.1m using an
infantometer for children less than 2 years and a stadiometer for height among
children older than 2 years children. The body mass index (BMI) were calculated
using the WT(kg)/HT(m)2 formula.6 The Z scores for height/age, weight/age
58
were calculated for each child by comparing the height and weight of the
subjects to the reference values 15 for the age and sex expressed as a ratio of the
standard.
Blood specimen collection; Under strict aseptic conditions, after cleaning the
blood collection site thoroughly with 70% alcohol, 5ml of venous blood was
collected by venepucture using a fixed hypodermic needle. Three milliliters of
the withdrawn blood was decanted into a sample bottle containing ethylene
diamine tetra acetate (EDTA) and gently mixed to prevent clotting while the
remaining 2ml was decanted into a heparinized bottle which was left to stand for
2 hours and the serum was separated by centrifuging and serum was decanted
into another bottle and frozen at -20˚C.
Stool collection and analysis; Freshly passed stool was collected using pre
coded specimen bottles. Some of the stool samples were analyzed by the
researcher under the supervision of a Senior Laboratory Technologist within an
hour of collection or preserved using 10% formol saline when immediate
analysis was not possible. Each stool sample was subjected to macro and
microscopic examinations using saline and iodine preparation to assess red blood
cells.90,91
59
Laboratory Analysis;
Full blood count
Under close supervision of senior lab scientists, pathologists and other members
of staff in the laboratory an automated blood analyzer model/Symax KX 21®
was used to analyse the full blood count. This works on the principle of
electronic gating. The passage of cells through charged orifices result in voltage
changes whose magnitude and pulse frequency suggests cell size and count
respectively.
The machine was used to analyse composition and concentration of the cellular
components of blood such as: red blood cell (RBC) count, hemoglobin,
haematocrit and red blood cell indices (mean corpuscular volume (MCV), mean
corpuscular haemoglobin (MCH), and mean corpuscular haemaoglobin
concentration (MCHC)); white blood cell (WBC) count, classification of White
Blood Cells (WBC differential);and Platelet Count. The limitation of the use of
this procedure is its inability to differentiate between monocyte, eosinophils and
basophils.
60
Peripheral blood film preparation for cell morphology
A small drop of venous blood was placed on a glass microscope slide, using a
glass capillary pipette. A spreader slide was positioned at an angle 45˚and slowly
drawn toward the drop of blood. The spreader slide was brought in contact with
the drop of blood and was drawn away. The spreader slide was further pulled
out, leaving a thin layer of blood behind glass slide with a well-formed blood
film. After drying for about 10 minutes, the slide was stained manually using the
Wrights’ stain.
A low power examination of a peripheral blood smear, the 50X or 100X
objective of the microscope was selected and the area of morphology was
examined in a consistent scanning pattern to avoid counting the same cell(s)
twice. A differential count of at least 100 red blood cells (200, 500, or 1000) was
performed, and any abnormal morphology of RBCs observed during the
differential count was recorded. Each morphologic abnormality observed was
quantified ("graded") separately as to severity ("slight to marked" or "1+ to 4+").
61
Figure 1: Picture of the peripheral blood smear prepared. The arrow points
to the zone of morphology.
Serum ferritin assay
Serum Ferritin concentrations was analyzed by enzyme—linked immuno
adsorbant assay using the Nova Path TM Ferritin kit.93 Serum was prepared from
whole blood specimen collected under aseptic condition into an EDTA bottle.
Serum was capped and stored at -20 oC.95
Principle of the assay; The ferritin quantitative test is based on the principle of
a solid phase enzyme linked immunosorbent assay. The assay system utilizes
rabbit anti-ferritin for the solid phase (micro titer wells) immobilization and
mouse monoclonal anti-ferritin in the antibody–enzyme (horseradish peroxidase)
conjugate solution. The serum was allowed to react simultaneously with anti
62
bodies, resulting in the ferritin molecules being sandwiched between the solid
phase and enzyme linked antibodies. After 45 minutes incubation at room
temperature, the wells were washed with water to remove the unbound labeled
antibodies. A solution of 3, 3, 5, 5’- Tetramethylbenzidine (TMB) was added and
incubated for 20 minutes, resulting in the development of a blue color. The color
development was stopped with the addition of 1N HCl, and the resulting yellow
colors measured spectrophotometrically at 450nm. The concentration of ferritin
is directly proportional to the color intensity of the test sample.95, 96
Standardization and quality control; The reference standards are calibrated
against the international committee for standardization in Hematology (ICSH)
Expert panel on iron, human liver standard (NIBSC_WHO80/602). Good
laboratory practice requires that quality control specimens (controls) be run with
each calibration curve to verify assay performance. To assure proper
performance, a statistically significant number of controls were assayed to
establish mean values and acceptable ranges.96, 96
Calculation of Serum ferritin level
In constructing the standard curve, the ferritin standard value was checked on
each vial. The absorbance for ferritin standard (vertical line) was plotted against
the Ferritin standard concentration (horizontal) line on a linear graph paper. The
63
absorbance for the controls and each unknown sample was read from the
curve.(Appendix V)
Normal mean serum ferritin level for children in this age group was 31ng/ml65,
low serum ferritin was defined as levels below 31ng/ml. Iron deficiency was
defined as serum ferritin levels below 31ng/ml, while iron deficiency anaemia
was defined as haemoglobin less than 11g/dl and serum ferritin < 31ng/ml.64,75,97
Methods for assessing iron deficiency
Haemoglobin; The level falls in the third stage of iron deficiency and the degree
of fall reflects the severity of the iron deficiency. Anaemia was defined as
haemoglobin <11g/dl.
Haematocrit; The estimation of packed cell volume has the advantages of
simplicity, accuracy, few technical errors and can be done in capillary samples.
Mild anaemia was haematocrit =26-29%, moderate anaemia was haematocrit
=21-25% and Severe anaemia, was haematocrit of <20%. 110
Red blood cell count; the estimation of the red cell count is a simple and
accurate test if an electronic counter is available.
Mean corpuscular Volume (MCV) This is the haematocrit divided by the red
blood cell count. It is a measurement of the spacies occupied by a single red
blood cell and it is an indication of individual cell size. Decreased values
64
indicate microcytic anaemia (as seen in iron deficiency anaemia, thalasemia ),
while increased values indicate differentials that encompass macrocytic anaemia
(for example Vitamin B12 deficiency, folate deficiency). MCV 70-74fl was
taken as normal range. Values less than 70fl was taken as microcytosis and
>74fl as macrocytosis.
Mean corpuscular haemoglobin (MCH).The MCH is the haemoglobin
concentration per cell (haemoglobin mass/red blood cell), expressed in
picograms per cell (pg, 10-12 g). The MCH is calculated from the haemoglobin
and RBC by the following formula:
The MCH is decreased in patients with anaemia caused by impaired
haemoglobin synthesis. The MCH may be falsely elevated in blood specimens
with turbid plasma (usually caused by hyperlipidemia) or severe leukocytosis.
Mean corpuscular haemoglobin concentration (MCHC); The MCHC is the
average haemoglobin concentration per total red blood cell volume (ratio of
haemoglobin mass to RBC volume), as determined from the following equation:
65
The MCHC is decreased in microcytic anaemias where the decrease in
haemoglobin mass exceeds the decrease in the size of the red blood cell. It is
increased in hereditary spherocytosis and in patients with haemoglobin variants,
such as sickle cell disease and hemoglobin C disease).
Red cell morphology
Normocytic normochromic Normal red blood cells ("normocytes,"
"discocytes") are round to very slightly ovoid cells with a mean diameter of
approximately 7 mm and a central pale area ("area of central pallor")
approximately 1/3 the diameter of the cell that gradually fades towards the more
deeply stained periphery.
Hypochromia
Hypochromia is a decreased amount (MCH) and concentration (MCHC) of
haemoglobin in red blood cells. In the peripheral blood smear, hypochromic cells
have an expanded central zone of pallor. Small hypochromic red blood cells
(microcytes) are usually present, and the mean corpuscular volume (MCV) is
decreased. Microcytosis and hypochromia are characteristic of iron deficiency
anaemia and other microcytic, hypochromic anaemias [anaemia of chronic
disease, hereditary haemoglobinopathies with diminished globin synthesis
(thalassemias, haemoglobin E, haemoglobin H), red blood cell enzyme
66
deficiencies (sideroblastic anaemias, lead poisoning, and pyridoxine
deficiency)].
Figure 2 : Comparisons of normal peripheral blood smear with smear of
microcytic, hypochromic anaemia.
Microcytes
Microcytes are small red blood cells (MCV < 70 fL) with decreased amounts of
haemoglobin formed as a result of iron deficiency and defective haemoglobin
synthesis, imbalance of globin chains, or defective porphyrin synthesis. Possible
clinical causes of microcytosis include iron deficiency anaemia, thalassemia, the
anaemia of chronic disease, lead poisoning, and sideroblastic anaemia.
67
Benefit of study to participants.
The children that participated benefited from the study by knowing their blood
profile and ferritin level. Children with anaemia depending on its severity were
treated. Those with iron deficiency also had treatment commenced. Nutritional
education was given to the parents or care giver. The children were followed up
in the nutrition clinic.
Data analysis
Data entry and analysis were carried out with a micro-computer using the Epi
info version 3.5 (2008) software packages.94 Chi-square test and student t-test
were used to test for statistical significance of the difference for discreet and
continuous variable respectively. A p value of < 0.05 was regarded as
significant. Analysis of variance (ANOVA) was used for some comparisons
when indicated. Kruskal-Wallis One Way Analysis Of variance – a non
parametric test was used for some variables when indicated.
68
Results
The Socio-Demographic Characteristics of The Subject and Controls
A total of 90 children with Protein Energy Malnutrition (PEM) admitted into the
Emergency Paediatiric Unit were studied, 90 apparently well children attending
the Well-Child Clinic served as controls.
Table VII shows that of the 90 children with PEM, 59 (65.6%) were males and
31 (34.4%) were females, with a male to female ratio of 1.9:1.0. The mean age
of the children with Protein Energy Malnutrition was 22.7 + 14.4 months (Range
of 9-59months) compared to the mean age of 29.3 + 16.9 months (Range 6-59
months) in the controls and the difference was not significant (p=0.08).
Forty two percent(38) of the children with Protein Energy Malnutrition were in
socio-economic class (SEC) IV, 26 (28.8%) in SEC III, 18(20%) in SEC V and
only 2(2.2%) in SEC I. The subjects were of a lower socioeconomic class
compared to the controls (p=0.00001).
Of the 90 mothers interviewed, 29(32.2%) had primary education, 25(27.8%)
had no form of education, while 21(23.3%) and 15(16.7%) had secondary and
tertiary education respectively. The educational status of mothers of children
with PEM were lower compared to that of controls (p=0.0002).
69
TABLE VII: The socio-demographic characteristics of the subject and
controls
Variable PEM
(n=90)
Controls
(n=90)
χ2 p
Age (month)
Range
Mean S.D
Gender
Male
Female
Social Economic Class
I
II
III
IV
V
Maternal Educational Status
None
Primary
Secondary
Post secondary
Exclusive Breast Feeding
Practices
Yes
No
Age of introduction of
complementary food (Months)
MeanS.D
Type of complementary feeds
Guinea corn gruel
Maize gruel
Infant formula
Fortified gruel
Milk
9.0-59.0
22.714.4
59(65.6%)
31(34.4%)
2(2.2)
6(6.8)
26(28.8)
38(42.2)
18(20.0)
25(27.8)
29(32.2)
21(23.3)
15(16.7)
25(27.8%)
65(72.2%)
5.11.93
68(75.6%)
9(10%)
2(2.2%)
10(11.1%)
1(1.1%)
6.0-59.0
29.316.9
53(58.9%)
37(41.1%)
4(4.4)
27(30.0)
35(38.9)
16(17.8)
8(8.9)
9(10)
20(22.2)
23(25.6)
38(42.2)
33(36.7%)
57(63.4%)
5.62.4
56(62.2%)
11(2.2%)
2(2.2%)
16(17.8%)
5(5.6%)
t=7.95
0.85
28.17
19.025
1.63
t=2.35
12.93
0.08
0.356
0.000012
0.0002
0.2019
0.26
0.024
70
The percentage of PEM children exclusively breast fed (27.8%) was lower than
36.7% found in the controls. However the difference did not reach statistical
significant difference (p=0.02).The mean age for the commencement of
complementary feeds was 5.1±1.93 months in children with Protein Energy
Malnutrition compared to 5.6±2.4 months in the controls, and the difference was not
significant (p=0.126) .
Over 68% of the PEM cases were fed with guinea corn gruel, 11.1% with
fortified gruel, 10% with maize gruel and only 1.1% added milk to the feeds.
The children with PEM were fed more with non nutritive feeds when compared
to the controls (p=0.02).
71
Anthropometric Measurements Of the Study Population
Table VIII shows that the mean weight of PEM children was 7.9 + 3.2 kg while
that of the controls was 13.9 + 13.6kg and the difference was significant
(p=0.0001). The mean height was 0.75 + 0.11m for PEM and 0.94±25.3m for
controls, the difference was significant (p=0.0001).
The mean for the mid upper arm circumference was 11.9 + 3.4cm and 16.4 +
2.6cm for the subjects and controls respectively. The mean BMI for the controls
(15.2±3.4kg/m2) was significantly higher than the BMI for the subjects
(13.3±4.5kg/m2), (p=0.001). Occipito frontal circumference was similar in both
groups (p=0.03). The mean Z score of weight for age was -3.2±1.8 for PEM and
-5.03± 1.0 for controls, there was a statistically significant difference ( p=0.001).
The mean weight for height Z score was -2.0±3.45 and 0.01±4.2 in subjects and
controls respectively, there was a statistically significant difference in these
values.
72
TABLE VIII: Anthropometric measurements of the study population
Anthropometry PEM
(n=90)
Controls
(n=90)
t p
Weight(kg)
Range
Means ± S.D
Height (m)
Range
Means ±S.D
Body Mass Index(kg/m2)
Range
Means± S.D
Mid Arm
Circumference(cm)
Range
Mean± S.D
Occipitofrontal
circumference(cm)
Range
Mean±
Weight For Age Z score
Mean± S.D
Weight For Height Z score
Mean± S.D
3.2-13.2
7.9±3.2
0.5-0.80
0.75±111
7.0-23.7
13.3±4.5
9.2-16.1
13.2±8.6
40.0-51.0
45.6±2.1
-3.2±1.8
-2.01±3.45
4.2-23.9
13.9±13.6
0.6-0.99
0.94±25.3
8.2-29.1
15.2±3.4
12.0-19.0
15.1±1.6
41.0-56.0
47.7±8.2
-5.03±1.0
-0.01±4.2
192.86
12.86
9.99
4.22
4.82
303.98
17699.4
0.0001
0.0001
0.001
0.04
0.03
0.001
0.001
73
Distribution of Types of Protein Energy Malnutrition According to the Age
in the Study Population
Table IX Shows that 50 (55.6%) children with PEM were Underweight,
21(23.3%) had Marasmus, 11 (12.2%) had Marasmic-Kwashiokor and 8 (8.8%)
had Kwashiorkor. Over a half of the children were in the 10 - 19 months age
bracket.
Table IX: Distribution of types of protein energy malnutrition according to
the age in the study population
Age range
(months)
Marasmus
(%)
Kwashiorkor(%) Marasmic-
kwashiokor(%)
Underweight Total
(%) (%)
0-9
10-19
20-29
30-39
40-49
50-59
60-69
Total
0
10
4
0
4
1
2
21(23.3)
0
8
0
0
0
0
0
8(8.8)
0
6
5
0
0
0
0
11(12.2)
4 4
26 50
4 13
10 10
2 6
2 3
2 4
50(55.6)90(100)
74
Haematologic Profile of the Study Population
Table X shows that the mean haematocrit values for the subjects and controls
were 30.4 ± 6.3% and 32.0 ± 6.1% respectively while the mean haemoglobin
values for the subject and controls were 10.1±2.1g/dl and 10.9±15.0g/dl
respectively and the difference was statistically significant (p=0.019 and 0.003
respectively) with the svalue for PEM being lower.
The mean values of the mean corpuscular volume were 72.4 ± 10.9fl and 72.6 ±
13.6fl in the subjects and controls respectively and the values were similar (p =
0.913).
The mean values for mean corpuscular haemoglobin concentration and mean
corpuscular haemoglobin in the subjects were 30.4±2.8g/dl RBC and
24.3±10.5fl.These values in the controls were30.3±1.8 and25.6±1.6,and were
similar in both the subjects and controls (p>0.05).
The mean value of platelets count were 291.8 ±131.7 and 326.4 ±133.9 for the
subjects and controls respectively and the difference was statistically significant
(p=0.0001) with PEM children having a lower platelet count compared to the
controls.
75
TABLE X Haematologic profile of the study population
Haematological
Parameters
PEM
mean±S.D
Controls
mean±S.D
t P
RBC (x100 cell/mm3)
Haemoglobin (gldl)
Haematrocrit (%)
MCV(fl)
MCH (pg/cell)
MCHC(gHbldl RBC)
Platelet count(x103
cell/mm3)
White cell count(x103
cell/mm3)
Neutrophils (%)
Lymphocyte (%)
Total protein(g/l)
Albumin(g/l)
4.0±0.9
10.1±2.1
30.4±6.3
72.4±10.9
24.3±10.5
30.4±2.8
291.8±131.7
12.8±11.6
49.5±12.3
52.7±12.3
3.24±1.36
2.11±0.87
4.2±0.9
10.9±15.0
32.0±6.1
72.6±13.6
25.6±10.6
30.3±1.8
326.4±133.9
5.9±8.7
43.8±5.9
59.4±7.5
3.90±1.03
2.94±0.65
2.39
18.58
2.97
0.01
0.68
0.68
180.18
20.38
15.64
23.80
12.83
4.50
0.123
0.019
0.003
0.091
0.41
0.411
0.0001
0.001
0.001
0.00002
0.0044
0.0352
76
The mean total white cell count of 12.8 ± 11.6×109 was higher in PEM than 5.9
± 8.7×109 in controls and the difference is significant (p=0.001) with the subject
having a higher white cell counts than controls. The Neutrophil value was 49.5 ±
12.3 % and 43.8 ± 5.9 % for PEM and controls respectively, the difference was
statistically significant. (p = 0.0001). The mean value for lymphocyte was 52.7 ±
12.3 % for PEM and 59.4 ± 7.5% for controls. It was statistically significant. (p
= 0.00002) with a lower count in the subjects compared with controls.
77
Haematolgic Profile According to the Types of PEM
Table XI shows that the mean values of red cell count, haemoglobin, and
haematocrit, MCV, MCH, and MCHC were similar in all the types of
malnutrition (p>0.05), however, the mean MCHC was significantly high in all
the types of PEM, with Marasmic- Kwashiokor having the highest mean.
Children with Kwashiokor had the highest levels of haemoglobin, (31.6±1.6g/dl)
and haematocrit (10.7±0.4%), while subjects with Marasmus had the lowest
values of haematocrit (27.6±5.8%), haemoglobin (9.1±2.1g/dl) and mean
corpuscular haemoglobin (22.9±2.3pg/cell).
Underweight children had the highest mean of white cell count (13.8±14.5×103
cell/mm3) while Marasmic –Kwashiokor had the lowest mean count, however,
the difference is not statistically significant (p=0.750). The neutrophils counts
were similar in all the types of Protein Energy Malnutrition (p=0.438).
Children with Kwashiokor had the highest lymphocyte count while underweight
had the lowest lymphocyte count with a statistical significant difference
(p=0.05).
The children with Marasmic-Kwashiokor had the lowest level of platelets
(226.5±48.7×103cell/mm3) though, there was no significant difference in the
platelets count in all the various types of Protein Energy Malnutrition (p=0.171).
78
Table XI: Haematolgic Profile Of Children According To The Types Of
PEM
Haematologic
Parameters
Marasmus
n=21
Mean±S.D
Kwashiokor
n=8
Mean±S.D
Marasmic-
kwashikor
n=11
Mean±S.D
Underweight
n=50
Mean±S.D
t p
RBC(×10 6
cell/mm3)
Haemoglobin
(g/dl)
Haematocrit (%)
MCH(pg/cell)
MCHC(hb/dlRBC)
MCV(fl)
Total WBC (x103
cell mm3)
Neutrophils%
Lymphocyte%
Platelet (x103 cell
mm3)
3.82±0.91
9.1±2.1
27.6±5.8
22.9±2.3
31.2±2.9
68.1±11.9
12.9±8.8
47.2±17.9
51.8±13.9
273.9±156.2
4.28±0.05
10.7±0.4
31.6±1.6
22.4±0.5
31.5±2.1
73.0±3.6
11.2±0.7
52.3±13.4
67±4.1
270.0±5852
4.28±0.05
10.4±1.7
31.1±5.1
23.5±1.3
33.1±1.5
74.4±6.2
9.9±1.3
44.7±7.4
59.9±4.2
226.5±48.7
4.08±9.5
10.3±2.4
31.08±21
25.2±13.9
29.4±2.9
73.3±2.1
13.8±14.5
51.2±9.8
49.1±7.1
316.8±137.6
0.85
1.89
1.77
0.36
4.43
1.231
0.405
0.915
11.62
1.7022
0.47
0.1575
0.157
0.7815
0.006
0.3015
0.750
0.438
0.0001
0.171
79
Red Cell Changes In Children With Protein Energy Malnutrition.
Table XII shows that all the children with Kwashiorkor had mild anaemia
8(100.0%). Moderate anaemia was found in 9(42.0%) children with Marasmus,
3(27.3%) with Marasmic-Kwashiorkor and 10(20.0%) children with
underweight .Severe anaemia was found in only 2(9.5%) of the Marasmic and
4(8.0%) of the underweight children.
All the subjects with Kwashiorkor and Marasmic –Kwashiokor had microcytic
cells whereas microcytosis and macrocytosis was seen in 66.0% and 23.8% of
subjects with marasmus. All the subjects with kwashiorkor and Marsmic –
Kwashiokor had microcytic hypochromic anaemia while it was observed in
90.5% and 76% of marasmus and Underweight children respectively.
The prevalence of anaemia in PEM was 74.4% as a total of 67 out of the 90
subjects had haemoglobin level below 11g/dl.
80
Table XII: Red Cell Morphology and Prevalence Of Anaemia In Children
With Protein Energy Malnutrition.
Red cell
Changes
marasmus
n=21
Kwashiokor
n =8
Marasmic-
kwashiokor
n=11
Underweight
n=50
Anaemia
Mild
Moderate
Severe
RBC size
Normocytic
Microcytic
Macrocytic
PBF*
appearance
Normochromic
Microcytic-
hypochromic
Prevalence of
Anaemia
Hb˚<11g/dl
2(9.5%)
9(42.9%)
2(9.5%)
2(9.5%)
14(66%)
5(23.8%)
2(9.5%)
19(90.5%)
19(21.1%)
8(100%)
Nil
Nil
Nil
8(100%)
Nil
Nil
8(100%)
8(8.9%)
3(27.3%)
3(27.3%)
Nil
Nil
6(54.6%)
Nil
Nil
11(100%)
6(6.6%)
6(12%)
10(20%)
4(8%)
12(24%)
12(24%)
26(52%)
12(24%)
38(76%)
34(37.8%)
*PBF -Peripheral blood film
˚Hb - Haemoglobin
81
Table XIII shows that only 3 of the PEM had RBC in their stool and there was
no statistical significant difference in stool RBC in subjects and
controls(p>0.05). There was also no significant difference in the serum ferritin
levels of PEM who had RBC in their stool and those who did not have RBC in
their stool. (Table XIV)
Table XIII : Stool RBC in PEM and Controls.
Stool RBC Present Stool RBC Absent χ2 p
PEM PEM 3 87
Controls Nil 90 2.48 0.478
Table XIV : Relationship between stool RBC and serum ferritin in PEM.
Stool RBC n Serum ferritin( Mean±SD) t p
Present 3 310.1±286.7
Absent 87 496.7±320.5 0.821 0.512
82
Serum Ferritin Levels In The Study Population
Table XV shows that the serum ferritin levels increased as age advanced in the
subjects, however, the mean ferritin levels were higher in the controls compared
to PEM cases (p=0.0001). The mean serum ferritin was significantly higher in
females (p=0.00001).
Table XV: Serum Ferritin Level (ng/ml)according to the Age and Sex in the
total Study Population.
Age
(months)
PEM
Serum ferritin
Mean
Controls
Mean
t p
Age(months)
0-19
20-39
40-59
Sex
Males
Females
Total
332.±26.5
496.5±36.7
630.±49.2
349±316.4
534±376.7
386.1±39.2
459.6±1.4
536.9±27.3
355.7±42.9
428±343.3
486.1±373.5
450.7±23.7
345.70 0.004
455.66 0.003
597.14 0.0001
46.06 0.0001
48.05 0.0002
41.60 0.003
83
Serum Ferritin Distribution Of The Various Classes Of PEM
Children with Marasmus had the highest mean serum ferritin level of
600.5±392.6ng/ml, while those with kwashiorkor had the lowest level of
165.5±6.2ng/ml and the difference was statistically significant (p=0.009).
Table XVI: The Levels Of Serum Ferritin According To The Types Of
PEM and Controls
Serum Marasmus Kwashiokor Marasmic- Under- Controls t p
Ferritin Kwashiokor weight
Range 4.5-1000 15.8-170 11.2-780 1.0-1000 67-1000
ng/ml
Mean±SD 600.5±392.6 165±6.2 320±252.7 395.2±340 450.7±23.7 4.010 0.09
Prevalence Of Iron Deficiency And Iron Deficiency Anaemia Amongst PEM
Table XVII shows that, the prevalence of iron deficiency was 24.4% in the
children with Protein Energy Malnutrition. It also shows that the prevalence of
iron deficiency anaemia was 16.6% in these children.
84
Table XVII: Prevalence of Iron Deficiency And Iron Deficiency Anaemia
Amongst PEM.
Clinical Profile and Serum Ferritin Levels
Table XVIII shows that those with fever had the highest mean value of serum
ferritin 455.22±365.42 and a significant relationship with serum ferritin
(p=0.03). while those with glossitis had lowest mean serum ferritin value but
was not statistically significant (p>0.05).
Iron Status Marasmus Kwashiokor
n=21 n=8
Marasmic-
kwashiokor
n=11
Underweight Total
n=50 Total (%)
Iron
deficiency
Iron
deficiency
anaemia
4(4.4%) 4(4.4%)
4(4.4%) 3(3.3%)
3(3.3%)
3(3.3%)
11(12.2%) 22(24.4%)
5(5.5%) 15(16.7%)
85
Table XVIII: Relationship between clinical features and serum ferritin
levels in PEM.
Clinical
feature
Present
Serum ferritin
N (mean±S.D)
Absent
Serum Ferritin
n(mean±S.D)
t p
Vomiting
Fever
Pallor
Diahorea
Cough
Failure to
gain
Edema
Skin
changes
Stomatitis
Glositis
54(408.44342.56)
71(455.22365.42)
25(408.44342.56)
60 (369.5330.4)
49 (429.1367.3)
63 (437.3356.4)
29 (384.1319.9)
28 (320.9301.4)
15 (431.4311.6)
2 (225.5317.5)
36(406.34347.18)
19(257.68±214.19)
64(406.3±347.18)
30(501.5±369.9)
41(394.9±326.20)
27(357.9±325.9)
59(422.5±357.4)
62(455.3±361.2)
75(409.9±356.3)
88(417.8±348.8)
0.026
2.249
0.026
1.715
0.046
0.992
0.441
1.716
0.217
0.7
0.980
0.027
0.980
0.090
0.644
0.323
0.660
0.089
0.828
0.4424
86
DISCUSSION
Majority of the children in all the four classes of Protein Energy Malnutrition
studied were in the age range of 10-19 months and Sixty five percent of the
subject were males. Sixty two percent of the subjects belong to families of low
socio economic class and mothers with low level of education. These are major
risk factors for the development of malnutrition and nutritional anaemia in PEM
as found in other studies. 99,101
In this study, haematologic changes observed include a significantly lower mean
values for MCH, MCV and RBC count in children with PEM as compared to
the controls. A lower mean values was also observed in the haematocrit and
haemoglobin values of children with PEM as compared to controls a finding
similar to previous studies.12, 27 Red cell changes observed among the various
classes of PEM in this study showed that there were no significant differences in
the red blood cells in the various types of PEM except for the MCHC. The
lowest red blood cell counts, haemoglobin and haematocrit values were observed
in marasmus while underweight had the highest of these values. These red cell
changes can be attributed to adaptation to lower metabolic oxygen requirements
ands decrease in lean body mass seen in PEM.78
This study found a significant leucocytosis and neutrophilia among children with
PEM as compared to controls, this is similar to a previous study where there was
87
a significant rise in leukocyte count in the patients with PEM compared to the
controls. despite the fact that children enrolled in that study had no apparent
infection.97 Leucocytosis in these children can be a result of infection which is
seen commonly in PEM:both PEM and infection, either clinical or subclinical
have been reported to act synergistically .81 This has been an important factor in
determining morbidity and mortality attributed to PEM.27 However, a lower
lymphocyte count was observed in the malnourished children compared to
controls. The lower lymphocyte count can be attributed to changes in the
Thymus which is greatly reduced in children during severe Protein Energy
Malnutrition. The degree of Thymic atrophy correlates closely with depletion of
lymphocytes and a decrease in the thymic dependent lymphocyte is also
associated with impaired immunity.74
The study also shows that the underweight children had the highest white cell
count; this can be attributed to their immune response to infection that is not so
severely compromised as compared to those of the more severe forms of PEM. A
significant difference in the lymphocyte count was seen in the various classes of
Protein Energy Malnutrition, this is in keeping with a previous study.24 No
significant changes was observed in the platelet of the various classes of PEM
but there was a significant difference in the controls compared to PEM. Children
with PEM had a significantly lower platelet count.
88
In this study, a lower mean serum ferritin level was observed in the
malnourished compared to controls. This is in contrast to previous studies where
a higher serum ferritin value was observed in PEM as compared to controls, 26
though the subjects studied were in the recovery phase of PEM. However, this
study is in conformity with other studies that assessed the serum ferritin levels in
PEM in the acute phases and found that serum ferritin was lower in the children
with malnutrition.24, 97 This low serum ferritin level is a true reflection of iron
deficiency in these children, as serum ferritin is the best indicator for iron
deficiency because a decrease in the amount of stored iron is the only known
cause for low serum ferritin result.74
There was a statistical significant difference in the serum ferritin level of the
various classes of malnutrition. The lowest mean value was seen in children with
kwashiorkor. Marasmus had the highest mean serum ferritin and this is not
surprising as the low serum protein seen in marasmus allows an increased free
unbound iron. Serum protein is necessary for the binding and transport of iron.66
The number of subjects that had red blood cell in the stool was not significant
and there was no significant difference in the serum ferritin of those that had
RBC in the stool compared to those who did not. This finding shows that iron
losses through stool was not common in these group of children studied. Thus
iron deficiency can be attributed to dietary deficiencies majorly in this study.
89
A high prevalence of anaemia (74.4%) among children with Protein Energy
Malnutrition found in this study, is in consonance with previous studies where
anaemia was said to be a common feature of Protein Energy Malnutrition.12,25-27
Mild to moderate anaemia with Microcytic hypochromic cells was the most
commonly observed in PEM in this study, this is in contrast with previous
studies where anaemia seen in Protein Energy Malnutrition was normocytic
normochromic.25, 27, 75 Several factors have been implicated in the aetiology of
anaemia in PEM and these include deficiencies of iron, folate, Vitamin B12 ,
infections, blood loss, haemolysis, erythroid hypoplasia and adaptation to lower
metabolic oxygen requirements and decrease in lean body mass.78 Microcytic
hypochromic anaemia found to be the commonest in this study can be attributed
to deficiency of iron which is a common cause of microcytic hypochromic
anaemia. This finding strongly support the fact that iron deficiency was
commonest cause of nutritional anaemia in this part of the world.57 Nutritional
anaemia among children in this study can be attributed to the type of food which
was eaten by majority of the PEM children in this study. Eighty five percent of
PEM children in this study were fed with common staple food such as maize
gruel with iron content of 0.02mg, guinea corn and millet, which do not contain
any iron at all. 101 These provisions are below the recommended daily
requirement of elemental iron which is 3-6mg/kg/day.
90
The prevalence of iron deficiency anaemia is 16.6% in this study, this finding is
higher than values documented in previous studies .27, 75 This higher prevalence
of iron deficiency anaemia in this study can result from a low practice of
exclusive breastfeeding (27.8%) reported in this study as, early age of
introduction of complementary feeds, and nutritionally poor complementary
feeds given to the children.
This study also shows that serum ferritin was highest in the children with PEM
that presented with fever, and there was a significant relationship between fever
and serum ferritin level.
91
Conclusion
It is concluded from this study that;
1. The subjects have a lower haemoglobin, heamtocrit, platelet count and
lymphocyte and a higher total white cell count and Neutrophils than the
controls.
2. Malnourished children had a lower serum ferritin levels than the controls.
3. The prevalence of anaemia was 74.4% in children with Protein Energy
Malnutrition
5. Microcytic hypochromic anaemia was found to be the commonest form of
anaemia in Children with Protein Energy Malnutrition.
6. The prevalence of iron deficiency anaemia in children with Protein Energy
Malnutrition is 16.6%
92
Recommendations
From this study it therefore recommended that,
1. Anaemia should be sought for and treated in children with Protein Energy
Malnutrition. Iron deficiency should be considered as a most likely cause
of anaemia in this group of children in this part of the world.
2. Efforts should be increased by health workers to promote exclusive breast
feeding in the first six months of life.
3. Adequate enlightenment of mothers and health workers on appropriate
energy dense and fortified complementary foods for children.
4. Food fortification as well as supplementation of the important
micronutrient especially iron should be enhanced as a good nutrition status
remains the bedrock for good health and prevention of diseases.
93
Limitation of study
1. The limitation in the use of the auto analyzer makes it impossible
to differentiate between monocyte, eosinophils and basophils.
2. Other biochemical tests of assessing the iron status of the
subjects and their relationship with serum ferritin could not be
carried out on account of inaccessibility of the reagents kits.
94
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Appendix I
Information Sheet
What Is The Study About
The study aims at documenting the hematological profile and ferritin levels of
children with PEM in UITH Ilorin.
What Is Expected Of You If You Agree To Participate
You will be expected to provide answers to simple questions like your child’s
age, sex, your level of education and occupation. Your child will then be
examined in detail and certain laboratory investigations shall be performed after
collection of blood and stool samples
Your Participation Is Voluntary
Your child’s participation is voluntary and you may withdraw him or her at any
time of the study without any repercussion.
Confidentiality
The information obtained will be treated in absolute confidence. No part or
whole of such information shall be divulged to anyone except the investigators.
We owe it a duty to keep your child’s records absolutely secret.
112
Benefit From Participation
Your child will benefit by knowing his or her blood profile and iron status and
knowing if he or she has occult blood in the stool in which case adequate
treatment instituted. In case of any abnormal incidental finding, adequate referral
shall be done to appropriate specialist.
113
Appendix ii
Informed Consent Form
Mr/Mrs/Chief/Alhaja/Dr.----------------------------------------------
Whose address is ----------------------------------------------------
Hereby give consent to---------------------------------------------
To carry out research on my child/ward as explained to me. I am aware the test
to be carried out will not harm my child/ward.
I have the right to withdraw at any point of the study if I so wish.
All the terms of this consent have been explained to me in a language that I
understand. I am also aware that the information on my child on my child shall
be kept in strict confidence.
Sign---------------------- Sign-----------------
Child’s Parent/Guardian Interviewer
Date-----------------------
Time----------------------
114
Appendix iii
Study Profoma
HEAMATOLOGICAL PROFILE AND FERRRTIN LEVELS IN CHILDREN
WITH PROTEIN ENERGY MALNUTRITIONIN UITH ILORIN
Hospital No------- Serial No -----
A) Sociodemographic data
1. Age---------
2. Sex 1)Male 2)Female
3. Mother’s Education level 1) Post 30 2) 30 3) 20 4)10 5
None
4. Father’s Education Level 1)Post 30 2) 30 3)20 4) 10 5) None .
5. Mother’s Occupation: ---------- 6. Father’s Occupation:--------
7. Family type 1)Monogamy 2)Polygamy
8. No of sibling(s) 1)1-2 2) 3-4 (3) ≥5
B) Feeding pattern;
9. Was the child Exclusively breastfeed yes No
10. At what age was complementary feeding commenced----------
115
11. What type of food is given---------?
12. How is the child given the food (1) cup & spoon (2) feeding bottle?
13. Who feeds the child (1) mother (2) care giver
14. How many times is the child fed in a day --------------------
(C) Any Associated illness Yes No
15. If yes what illness (1) Pneumonia (2) Tuberculosis (3) Diarrheal disease
(4) Others (specify) ------
116
D) Clinical Profile symptoms and Signs
S/N Symptoms and Signs Yes =1 No=2
16. Fever
17. Vomiting
18. Diarrhea
19. Cough
20. Failure to gain weight
21. Edema
22. Pallor
23 Skin changes dry peeling or hyper pigmentation
24. Angular stomatis
25. Glositis
26. Fissured nail
27. Papillary atrophy
117
(E) GROWTH MEASURE:
S/N Anthropometry Indicators Value
29. Weight for age
30. Height for age
31. Weight for height
32. BMI=W(kg)/HT(m)2
33. Mid Arm Circumference
34. Occipital frontal
circumference OFC
35. Percentage of expected
weight
(F) LABORATORY; HEMATOLOGICAL PARAMETERS
RBC (cells X l06.ccı) -----------------------
Hb (g/dl) --------------------------------------
Hct(%)-----------------------------------------
MCV (fl) --------------------------------------
118
MCH (pg/cell) -------------------------------
MCHC (%) -----------------------------------
PLATELET COUNT (cell/mm3)
WBC (per cells/ mm3)
Serum Protein (Total and albumin)
Peripheral blood film PBF---------------------------------------------
(G) Iron Status
Serum ferritin(ng/mL)
Stool examination for Red blood cell Present Absent
(H) Outcome Of The Patient
Well and discharge--------Yes Died
If yes, what is number of days in hospital-----------------
119
Appendix Iv
Socio-Economic Classification Scheme By Oyedeji
For Occupation
Class Occupation
I Senior Public Servants, Professionals, Managers,
large scale traders, businessmen and contractors.
II Intermediate grade public servants and senior school
teachers.
III Junior school teachers, drivers, artisans.
IV Petty traders, labourers, messengers .
V Unemployed, full-time housewife, students and
subsistence farmers.
For Educational Status
Class Educational Attainment
I University graduates or equivalents
II School certificate holders ordinary level (GCE) who
also had teaching or other professional training.
120
III School certificate or grade II teachers certificate
holders.
IV Modern three and primary six certificate holders.
V Those who could either just reads and write or were
illiterate.
121
Appendix v
Serum Ferritin Absorbance Curve
122
123
Table XI: Haematolgic Profile Of Children According To The Types Of
PEM and Controls
Haematologic
Parameters
Marasmus
n=21
Mean±S.D
Kwashiokor
n=8
Mean±S.D
Marasmic-
kwashikor
n=11
Mean±S.D
Underweight
n=50
Mean±S.D
T p Control
RBC(×10 6 cell/mm3)
3.82±0.91
4.28±0.05
4.28±0.05
4.08 ±9.5 0.85 0.47 42. ±0.9
Haemoglobin (g/dl)
9.1±2.1 10.7±0.4 10.4±1.7 10.3±2.4 1.89 0.1575 10.9±15.0
Haematocrit (%)
27.6±5.8 31.6±1.6 31.1±5.1 31.08±21 1.77 0.157 32.0±6.1
MCH (pg/cell) 22.9±2.3 22.4±0.5 23.5±1.3 25.2±13.9 0.36 0.7815 25.6±10.6
MCHC (hb/dlRBC) 31.2±2.9 31.5±2.1 33.1±1.5 29.4±2.9 4.43 0.006 30.3±1.8
MCV (fl) 68.1±11.9 73.0±3.6 74.4±6.2 73.3±2.1 1.231 0.3015 72.6±13.6
Total WBC (x103 cell
mm3)
12.9±8.8 11.2±0.7 9.9±1.3 13.8±14.5 0.405 0.750 5.9±8.7
Neutrophils% 47.2±17.9 52.3±13.4 44.7±7.4 51.2±9.8 0.915 0.438 43.8±5.9
Lymphocyte% 51.8±13.9 67±4.1 59.9±4.2 49.1±7.1 11.62 0.0001 59±7.5
Platelet (x103 cell mm3) 273.9±156.2 270.0±5852 226.5±48.7 316.8±137.6 1.7022 0.171 326.4±133