controlling iron defecieny anemia and preventing calicum deficency in bangladeshi children

159 Pages·2011·2.76 MB·English

CONTROLLING IRON DEFICIENCY ANEMIA AND PREVENTING CALCIUM
DEFICIENCY IN BANGLADESHI CHILDREN: A NOVEL APPROACH USING A
MULTI-MICRONUTRIENT POWDER (MNP) FORMULATION

by

Waqas Ullah Khan

A thesis submitted in conformity with the requirements
for the degree of Masters of Science
Graduate Department of Nutritional Sciences
University of Toronto

© Copyright by Waqas Ullah Khan (2011)

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CONTROLLING IRON DEFICIENCY ANEMIA AND PREVENTING CALCIUM
DEFICIENCY IN BANGLADESHI CHILDREN: A NOVEL APPROACH USING A
MULTI-MICRONUTRIENT POWDER (MNP) FORMULATION

Master of Science, 2011
Waqas Ullah Khan
Graduate Department of Nutritional Sciences
University of Toronto

ABSTRACT
Iron deficiency anemia (IDA) and calcium deficiency affect millions of children globally.
Sprinkles is a multi-micronutrient powder (MNP) that has successfully treated anemic infants
and can be modified to include additional micronutrients. The efficacy for treating IDA and
preventing calcium deficiency requires evaluation due to potential nutrient interactions. We
assessed the efficacy of Sprinkles MNP including iron with and without calcium on
hemoglobin (Hb) response in 100 anemic rural Bangladeshi infants for 2 months. Sprinkles
MNP with and without calcium resulted in a significantly higher Hb concentrations in both
groups (P<0.0001 and P<0.0001). However, infants who received Sprinkles MNP without
calcium had a significantly higher change in Hb concentration (P=0.024) and rate of recovery
from anemia (P=0.008). No differences in socio-demographic or dietary characteristics were
documented between groups. Although both groups had an improvement in Hb status, the
antagonistic interaction between iron and calcium requires further study.

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To my mother (Shahida Khan), father (Rajab Khan), brother (Imran), sisters (Sofia, Saema,
and Shafia), Dr. Zlotkin, and the wonderful people of Bangladesh

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Acknowledgements
First, and foremost, I would like to thank God for blessing me with this life learning
experience and keeping me safe during my adventures.
I would like to acknowledge all of the infants and their mothers, fathers, and villages
who participated in our study. Without them, the work presented in this thesis would not
have been possible. With them, we were able to fill the knowledge gap on two global health
concerns plaguing not only millions of Bangladeshi children, but many others around the
world. I hope we have made a positive impact on the lives we touched just as they have
made on mine.
I would also like to thank my supervisor Dr. Stanley H. Zlotkin for all of his support
throughout my Masters career. He has been a source of inspiration, an excellent role model,
and I am extremely grateful to him for trusting and believing in me, and giving me this
opportunity to mature scientifically and otherwise. I would also like to express my deepest
gratitude to my thesis advisory committee: Dr. Daniel Sellen, Dr. Pauline Darling, Dr.
Harvey Anderson, and Dr. Zia Hyder for bringing their expertise and support to this project.
I am grateful to our colleagues at BRAC for their hospitality and support. I thank all
of the data collectors, community health workers, and field managers Azad Bhai and Bashir
Bhai for their extraordinary work throughout this study. It was truly an honour to be apart of
such a highly motivated, hard working, and sincere group of people. The warmth of their
faces will always be engrained in my memory. Also, I would like to thank the following
people at the BRAC head office: Jalal, Turjo, Raniya, Anindita, Rehnuma, and Sabia. One

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person whom I would especially like to thank at BRAC is Hasina Shikder (Aka “Super
Mohilla #2”) for the important role she played in this study. Her guidance and support
throughout my stay in Bangladesh are greatly appreciated and I am truly honoured to have
met such a wonderful, intelligent, and caring person.
To my colleagues and friends Sohana Shafique (aka “Super Mohilla #1”) and Yaseer
Shakur, your wisdom, intelligence, and kindness have truly been appreciated throughout
these past years. I look forward to seeing big things coming from the both of you in the
future and can’t wait to hear about your adventures! I would also like to thank my good
friends Greg Staios, Fawad Chughtai, Ali Shahzada, Kristy Hackett (aka “Super Mohilla
#3”), Kevin Ferreira, Paul E. Kwan, Laszlo Csampai, Andre Dos Santos, Bawa Prashar,
Brian Caceras, Adrian Nicolucci, Lilatool Shakur, and Heather Miller for being there for me
during the good, the bad, and the ugly times of my Masters career.
Lastly, I would like to extend my deepest thanks to my family for always supporting
and motivating me. To my siblings Sofia, Saema, Imran, and Shafia, although we all have
our own unique personalities, I don’t think I could get along with anyone better than you
guys. To my brother-in-law Sameel, your friendship has been appreciated, to many more
NHL and table tennis games to come! I would especially like to thank my parents for their
love and support, and sacrificing so much for my siblings and I. They have given us the
opportunity to pursue our dreams and I shall always be grateful to them. Mommy your
guidance, lessons, and warmth are always going to be apart of me. Likewise, Baba your
words of wisdom have always been appreciated.

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This research was funded by a grant from the H.J. Heinz Company Foundation.
Personal support was from the Ontario Ministry of Training, Colleges, and Universities
Ontario Graduate Scholarship (OGS).

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Table of Contents
Abstract _________________________________________________________________ ii
Dedication _______________________________________________________________iii
Acknowledgements________________________________________________________iv
Table of Contents ________________________________________________________ vii
List of Tables_____________________________________________________________ x
List of Figures ___________________________________________________________ xii
List of Abbreviations _____________________________________________________ xii
Chapter 1.0 Introduction___________________________________________________ 1
Chapter 2.0 Review of the literatrue 4
2.1 Micronutrients_______________________________________________________ 4
2.1.1 Importance of Micronutrients ________________________________________ 4
2.1.2 Definition of Micronutrients _________________________________________ 4
2.1.3 Micronutrient Deficiency____________________________________________ 5
2.1.4 Populations at Risk of Developing Micronutrient Deficiencies ______________ 5
2.1.5 Global Burden of Micronutrient Deficiencies____________________________ 5
2.2 Anemia_____________________________________________________________ 6
2.2.1 Definition of Anemia_______________________________________________ 6
2.2.2 Global Burden of Anemia ___________________________________________ 7
2.2.3 Etiology of Anemia ________________________________________________ 8
2.3 Iron_______________________________________________________________ 10
2.3.1 The Importance of Iron in the Body __________________________________ 10
2.3.2 Iron in the Body__________________________________________________ 11
2.3.3 Regulation of Iron Metabolism ______________________________________ 11
2.3.4 Absorption, Uptake, and Transport of Iron _____________________________ 12
2.3.5 Cellular and Systemic Regulation of Iron Homeostasis ___________________ 13
2.3.6 Souces and Bioavailability of Iron ___________________________________ 13
2.3.7 Iron Status During Infancy _________________________________________ 14
2.3.8 Stages of Iron Deficiency __________________________________________ 14
2.3.9 Etiology of Iron Deficiency Anemia in Infants 6 months and Older _________ 15
2.3.10 Health and Socioeconomic Implications of Iron Deficiency Anemia _______ 17
2.3.11 Global Prevalence of Iron Deficiency Anemia _________________________ 20
2.3.12 Prevalence of Iron Deficiency Anemia in Bangladesh ___________________ 21
2.3.13 Screening Methods for Iron Deficiency Anemia _______________________ 21
2.3.14 Hemoglobin Cut-Off Value________________________________________ 22
2.4 Calcium ___________________________________________________________ 23
2.4.1 The Importance of Calcium in the Body _______________________________ 23
2.4.2 Calcium in the Body ______________________________________________ 24

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2.4.3 Calcium Absorption, Uptake, and Transport____________________________ 24
2.4.4 Calcium Excretion _______________________________________________ 25
2.4.5 Regulation of Calcium Homeostasis __________________________________ 25
2.4.6 Sources and Bioavailability of Calcium _______________________________ 26
2.4.7 Calcium Status During Infancy ______________________________________ 27
2.4.8 Calcium Deficiency ______________________________________________ 27
2.4.9 Etiology of Calcium Deficiency _____________________________________ 28
2.4.10 Health and Economic Implications of Calcium Deficiency _______________ 29
2.4.11 Global Prevalence of Calcium Deficiency ____________________________ 31
2.4.12 Prevalence of Calcium Deficiency in Bangladesh ______________________ 32
2.4.13 Screening Methods for Calcium Deficiency ___________________________ 33
2.5 The Interaction between Iron and Calcium _____________________________ 34
2.5.1 Studies Examining the Interaction between Iron and Calcium ______________ 34
2.5.2 Mechanisms of Iron and Calcium’s Nutrient-Nutrient Interaction ___________ 37
2.5.3 Other Nutrient-Nutrient Interactions of Importance 38
2.6 Strategies for Preventing and Treating Micronutrient Deficiencies __________ 38
2.6.1 Strategies for Preventing and Treating Micronutrient Deficiencies __________ 38
2.6.2 Multiple Micronutrient Powder (MNP) Formulation – “Sprinkles Home-
Forticiation __________________________________________________________ 42
Chapter 3.0 Rationale, Objectives and Hypotheses_____________________________ 46
3.1 Rationale __________________________________________________________ 46
3.2 Objectives ________________________________________________________ 47
3.3 Hypotheses_________________________________________________________ 47
Chapter 4.0 Thesis Study___________________________________________________ 48
4.1 Introduction__________________________________________________________ 48
4.2 Methods _________________________________________________________ 50
4.2.1 Study Setting ____________________________________________________ 50
4.2.2 Study Collaborative Partner - BRAC_________________________________ 51
4.2.3 Study Subjects _______________________________________________ 51
4.2.4 Ethical Approval _______________________________________________ 52
4.2.5 Multi-Micronutrient Powder (MNP) Formulations 52
4.2.6 Sample Size ___________________________________________________ 53
4.2.7 Study Design ____________________________________________________ 54
4.2.8 Study Logistics, Data Collection, and Compliance_______________________ 54
4.2.9 Anthropometric and Biochemical Measurements ________________________ 57
4.2.10 Study Questionnaires ____________________________________________ 57
4.2.11 Statistical Analysis_______________________________________________ 60
4.3 Results __________________________________________________________ 61
4.3.1 Study Attrition _________________________________________________ 61
4.3.2 Infant Baseline Characteristics ______________________________________ 61
4.3.3 Household Socio-demographic Characteristics__________________________ 62

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4.3.4 Primary Outcome: Effects on Infants Hemoglobin Concentration ___________ 63
4.3.5 Infant Food Consumption with an Emphasis on Dietary Intake of Iron and
Calcium ____________________________________________________________ 64
4.3.6 Adherence and Side Effects_________________________________________ 65
4.3.7 End-line Anthropometric Characteristics ______________________________ 65
4.4 Discussion ________________________________________________________ 77
4.5 Study Limitations ___________________________________________________ 85
Chapter 5.0 Conclusions and Future Considerations 87
5.1 Conclusions 87
5.2 Future Considerations _____________________________________________ 88
References ____________________________________________________________ 90
Appendices ___________________________________________________________ 107
Appendix A: Baseline Questionnaires_____________________________________ 107
Appendix B: Morbidity, Monitoring, and Compliance Forms_________________ 135
Appendix C: Self-Coaching Material _____________________________________ 140
Appendix D: End-line Questionnaires ____________________________________ 144

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List of Tables
Table 2.2.1 Public health significance of anemia in populations based on the estimated
prevalence of anemia _______________________________________________________ 7

Table 4.2.5 Sprinkles MNP formulations used for the control and intervention treatments 53

Table 4.2.6 Sample size calculation using different parameters _____________________ 54

Table 4.3.2.1 Infant characteristics at baseline by treatment group __________________ 67

Table 4.3.3.1 Household socio-demographic characteristics by treatment group at baseline 69

Table 4.3.4.1 Hemoglobin concentration and the percentage of non-anemic children by
treatment group, at baseline, and after 2 months of treatment _______________________ 70

Table 4.3.4.5 Correlations between covariates and change in infants' hemoglobin_______ 73

Table 4.3.4.6 Univariate analysis of variables associated with change in infants’ hemoglobin
_________________________________________________________________________74

Table 4.3.4.7 Multivariate analysis of variables associated with change in infants’
hemoglobin______________________________________________________________ 74

Table 4.3.5.1 Mean baseline iron and calcium nutrient intakes from complementary foods
and breastmilk compared with recommended1 nutrient intakes for infants 6 to 11 months of
age _____________________________________________________________________ 75
Table 4.3.5.2 Mean end-line iron and calcium nutrient intakes from complementary foods
and breastmilk compared with recommended nutrient intakes for infants 6 to 11 months of
age_____________________________________________________________________ 75

Table 4.3.5.3 Proportion of infants who met the recommended dietary allowance for iron and
adequate intake for calcium based on treatment group ____________________________ 76

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