Diet and nutrient status in infants and children with cow's milk protein allergy

127 Pages·2015·2.02 MB·English

by  Mari Borge Eskerud

Diet and nutrient status in infants and
children with cow’s milk protein
allergy

Results from a cross sectional study with
emphasis on vitamin B12 and iron status

Mari Borge Eskerud

Master Thesis
Department of Nutrition
Institute of Basic Medical Sciences
Faculty of Medicine
© Mari Borge Eskerud
2015
Diet in nutrient status in infants and children with cow’s milk protein allergy.
Results from a cross sectional study with emphasis on vitamin B12 and iron status
Mari Borge Eskerud
http://www.duo.uio.no/
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II
Acknowledgements
This work was conducted at the Department of Nutrition, Faculty of Medicine, at the
University of Oslo and at the Department for Paediatrics, Ullevål, Oslo University Hospital
between June 2014 and May 2015.
I would like to thank my supervisors Christine Henriksen and Janne Anita Kvammen for
giving me the opportunity to be a part of this project. Since this study and field of nutrition
research is so important to both of you it has been a great pleasure to be trusted with this
project.
I would also like to thank Rut Anne Thomassen for working so closely with me this year. I’ve
felt included in the work place, you’ve answered all my questions no matter how silly they
were and I’ve learned so much from you this year. I’ve had a really great time this year.
Without the participating families this work would not have been possible. I would therefore
like to thank the parents who genuinely care about their children and their nutrition status
enough to put them through the unpleasant experience of the blood sampling and who are
generous enough with their own time to spend it doing the dietary registration and visiting the
hospital. Your efforts will hopefully benefit other families and infants with cow’s milk protein
allergy in the future.
And last but not least, thanks to my family for always believing that I can do anything I set
my mind to. Because of you, I can.

Mari Borge Eskerud
Oslo, May 2015
III
Abstract
Background: Cow’s milk protein allergy is the most common food allergy in early life. The
diet is restrictive and is known to pose a risk of malnutrition. Recent studies have proposed a
higher prevalence of B12 deficiency in Norwegian infants than previously thought. Dairy
products are the most important sources of B12 in this population so it is possible that
excluding cow’s milk poses a risk of deficiency. Vitamin B12 and iron have many similar
food sources and a lack of both nutrients affects hematologic parameters.
Objectives: The main objective of this thesis was to investigate diet, B12 and iron status in a
group of cow’s milk allergic infants and children aged less than two years old. The link
between dietary habits and nutrient status were also investigated.
Subjects and methods: Forty nine infants with cow’s milk allergy and primarily
gastrointestinal symptoms were included in this cross sectional study at Oslo University
Hospital, the Children’s Department, Ullevål. The participants had been attending a milk free
diet course and inclusion was set after at least three weeks on the milk free diet. Participants
were weighed and measured, blood samples were drawn for nutrient status, questionnaires
about diet and background information were filled out and a three-day dietary registration was
performed by the parents.
Results: B12 deficiency was present in 17% of the infants and iron deficiency was present in
24%. The non-breastfed infants met their nutritional requirements from their diet and had a
adequate B12 and iron status. Partially breastfed infants past the age of six months were
identified as a high risk group of B12 and iron deficiency. The median intake of iron was
below the recommended level for the partially breastfed infants. Extensively hydrolyzed
infant formula (eHF) was found to be an important source of nutrients in this population and
intake correlated with higher blood levels of B12 and iron.
Conclusion: Infants on a cow’s milk protein free diet who have received guidance from a
pediatric dietitian generally have a sufficient intake of energy and nutrients. B12 and iron
deficiency were prevalent in partially breastfed infants and children. Infants and children that
are not given an eHF and have a breast milk based diet after the age of six months have an
increased risk of deficiency.
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Contents
List of figures and tables ................................................................................................... VIII
Abbreviations ........................................................................................................................ X
List of appendices ................................................................................................................. XI
1 Introduction ........................................................................................................................ 1
1.1 Cow’s milk protein allergy in infants and toddlers ..................................................... 1
1.1.1 Etiology, prevalence and symptoms ..................................................................... 1
1.1.2 Diagnosis .............................................................................................................. 2
1.1.3 Treatment ............................................................................................................. 2
1.1.4 Cow milks importance in the diet ........................................................................ 3
1.1.5 Nutrition status in cow’s milk protein allergy ...................................................... 3
1.2 Vitamin B12 ................................................................................................................ 3
1.2.1 Structure and function .......................................................................................... 3
1.2.2 Absorption and metabolism ................................................................................. 5
1.2.3 Recommended intake ........................................................................................... 5
1.2.4 Food sources ......................................................................................................... 6
1.2.5 B12 deficiency ...................................................................................................... 7
1.2.6 Groups at risk of deficiency ................................................................................. 8
1.2.7 B12 status in Norway ........................................................................................... 8
1.3 Iron............................................................................................................................... 9
1.3.1 Function ................................................................................................................ 9
1.3.2 Absorption and metabolism ................................................................................. 9
1.3.3 Recommended intake ......................................................................................... 10
1.3.4 Food sources ....................................................................................................... 10
1.3.5 Iron deficiency .................................................................................................... 11
1.3.6 Groups at risk of deficiency ............................................................................... 12
2 Objectives ......................................................................................................................... 14
3 Subjects and methods ....................................................................................................... 15
3.1 Study design .............................................................................................................. 15
3.2 Subjects ...................................................................................................................... 16
3.2.1 The milk free diet course .................................................................................... 17
3.3 Data collected ............................................................................................................ 17
V
3.3.1 Dietary record ..................................................................................................... 18
3.3.2 Growth and development ................................................................................... 19
3.3.3 Blood samples .................................................................................................... 20
3.3.4 B12-status ........................................................................................................... 21
3.3.5 Iron status ........................................................................................................... 22
3.3.6 Urine samples ..................................................................................................... 24
3.3.7 Additional information ....................................................................................... 24
3.4 Follow-up................................................................................................................... 25
3.5 Statistical analysis...................................................................................................... 25
3.6 My contribution to the research project ..................................................................... 25
4 Results .............................................................................................................................. 27
4.1 Subject characteristics ............................................................................................... 27
4.1.1 Background information on the participants and parents ................................... 27
4.2 Biomarkers of nutrient status ..................................................................................... 30
4.2.1 B12 status ........................................................................................................... 30
4.2.2 Iron status ........................................................................................................... 33
4.3 Nutrient and food intake ............................................................................................ 37
4.3.1 Intake of macronutrients ..................................................................................... 38
4.3.2 Intake of micronutrients ..................................................................................... 39
4.4 Associations between nutrient status, feeding patterns and nutrient intake .............. 42
4.5 Dietary sources of iron and B12 ................................................................................ 43
4.5.1 B12 sources ........................................................................................................ 43
4.5.2 Iron sources ........................................................................................................ 44
4.6 Characteristics of the nutrient deficient infants and children .................................... 45
4.6.1 B12-deficient infants .......................................................................................... 45
4.6.2 Iron deficient infants .......................................................................................... 47
4.6.3 Association between the B12 and iron deficient participants ............................ 48
5 Discussion ........................................................................................................................ 49
5.1 Subjects and methods ................................................................................................ 49
5.1.1 Subjects and study design .................................................................................. 49
5.1.2 Strengths and limitations of the method ............................................................. 50
5.1.3 Statistics ............................................................................................................. 52
5.2 Discussion of results .................................................................................................. 52
VI
5.2.1 B12-status ........................................................................................................... 52
5.2.2 Iron status ........................................................................................................... 57
5.2.3 Nutrient intake .................................................................................................... 59
5.2.4 Dietary habits affecting B12 and iron status ...................................................... 61
5.2.5 Who are the infants at risk of deficiency? .......................................................... 63
5.2.6 Clinical implications .......................................................................................... 65
6 Conclusions ...................................................................................................................... 67
7 Future perspectives ........................................................................................................... 68
8 References ........................................................................................................................ 69
Appendices ............................................................................................................................... 75

VII
List of figures and tables
Figures
Figure 1 B12’s functions in human metabolism. ….………………….………………………4
Figure 2 Flowchart of the study population.…………………………………………....…....15
Figure 3 Number of the infants with increased homocysteine, >6,5 µmol/L, and low B12,
<300 pmol/L………………………………………………………………………………..…31
Figure 4 Number of infants with decreased hemoglobin (below 9 g/100 mL for infants aged
2-5 months, below 10 g/100 mL for infants aged 6-11 months and below 11 g/100 mL for
infants aged 12-23 months) and ferritin (<25 µg/L for infants aged 0-11 months and <10 for
children aged 12-23 months)……………………………………………………….…………36
Figure 5 Distribution of infants with increased soluble transferrin(s-TfR, >4,4 mg/L for girls
and >5,0 mg/L for boys) receptor and low ferritin(<25 µg/L for infants aged 0-11 months and
<10 for children aged 12-23 months)………………………………………………………....36
Figure 6 Supplement use among the participants…………………………………….……...37
Figure 7 Food sources of B12, except for breast milk, in partially breastfed infants………..43
Figure 8 Food sources of B12 in non-breastfed infants……………………………………...43
Figure 9 Food sources of iron, except for breast milk, in partially breastfed infants………..44
Figure 10 Food sources of iron in non-breastfed infants…………………………………….44

Tables
Table 1 Recommended daily intake of B12 in different age groups…………………….……6
Table 2 Recommended iron intake in different age groups……………………………...…..10
Table 3 Reference intervals B12 and Hcy in infants and children………………………...…21
Table 4 Reference intervals for iron parameters in infants and children…………………….23
Table 5 Characteristics of the population…………………………………………………….28
Table 6 Background characteristics on the infants’ parents………………………………….29
Table 7 Vitamin B12, folate and vitamin D status presented based on breastfeeding..……...31
Table 8 B12 and Hcy in infants aged 6-8 months by feeding status………………………....32
Table 9 Biomarkers of iron status according to breastfeeding status…………………...……34
VIII
Table 10 Intake of macronutrient from complimentary food in partially breastfed infants….38
Table 11 Total macronutrient intake in non- breastfed infants………………………………39
Table 12 Intake of micronutrients from complimentary foods in partially breastfed infants..40
Table 13 Total micronutrient intake in non-breastfed infants………………………………..41
Table 14 Factors correlated with s-B12……………………………………………………...42
Table 15 Factors correlated with s-ferritin…………………………………………………...42
Table 16 B12 deficient participants compared with the non-deficient participants………….46
Table 17 Characterization of the iron deficient participants and comparison with the non-
deficient………………………………………………………………………………………48

IX
Abbreviations
Abbreviations
AAF Amino acid based formula
B12 Vitamin B12
CALIPER Canadian Laboratory Initiative on Pediatric Reference Intervals
CMP Cow’s milk protein
CMPA Cow’s milk protein allergy
CMPFD Cow’s milk protein free diet
CNS Central nervous system
CRP C Reactive Protein
E % Energy percent
eHF Extensively hydrolyzed formula
ESPGHAN European Society for Paediatric Gastroenterology, Hepatology and Nutrition
G grams
GIT Gastrointestinal tract
Hb Hemoglobin
Hcy Homocysteine
IDA Iron deficiency anemia
IF Intrinsic factor
Ig Immunoglobulin
Kcal Calories
MFDC Milk free diet course
MMA Metylmalonic acid
NHANESIII The third National Health and Nutrition Examination Survey
NFCT Norwegian Food Composition Table
OUS Oslo University Hospital
PA Pernicious anemia
RCT Randomized Controlled Trial
sTfR Soluble Transferrin Receptor
USA United States of America
WHO World Health Organization

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