Brain, Behaviour, and Iron in the Infant Diet

203 Pages·1990·5.708 MB·English

by  John Dobbing (auth.), John Dobbing DSc, FRCP, FRCPath (eds.)

John Dobbing (Ed.)
Brain, Behaviour,
and Iron in the
Infant Diet
With 27 Figures
Springer-Verlag London Ltd.
John Dobbing, DSc, FRCP, FRCPath
Emeritus Professor of Child Growth and Development,
Department of Child Health, University of Manchester,
Oxford Road, Manchester M13 9PT, UK
ISBN 978-1-4471-1768-1 ISBN 978-1-4471-1766-7 (eBook)
DOI 10.1007/978-1-4471-1766-7
British Library Cataloguing in Publication Data
Dobbing, John, 1922-
Brain behaviour and iron in the infant diet.
1. Man. lron
1. Title
612.3924
Library of Congress Cataloging-in-Publication Data
Brain, behaviour, and iron in the infant dietlJohn Dobbing (ed.),
p. cm.
IncIudes bibliographical refereilces.
1. lron deficiency diseases in infants. 2. Brain-Growth. 3. Infants-Development.
1. Dobbing, John.
[DNLM: 1. Brain--<lrug effects. 2. Child Behavior--<lrug effects. 3. Child
Nutrition. 4. Infant Nutrition. 5. Iron--<leficiency. WS 120 B8135]
RJ399.175B73 1990
618.92'8--<lc20
DNLMlDLC
for Library of Congress 90-9577
CIP
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© Springer-Verlag London 1990
Originally published by Springer-Verlag London Limited in 1990
Softcover reprint of the hardcover 1s t edition 1990
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Preface
This monograph is concerned with the important question whether a
reduced supply of dietary iron in infancy may result in impaired or
altered brain growth, or in temporary or permanent deficits in higher
mental function. The evidence that this may be so is not complete,
but it already seems to be sufficiently good to make preventive action
desirable.
Iron deficiency is very widespread in the world, in both privileged
and underprivileged societies, often independently of general nutri
tional status. The means of prevention are readily available and
cheap. In such circumstances, which have many parallels in clinical
practice, doctors will rightly decide not to wait for complete proof
before acting in what they believe to be the best interests of their
patients and their community.
It will be surprising for some that the proposition is so resistant to
absolute proof, but in the laboratory, in experimental animals, and,
much more importantly, in field investigations in human communi
ties, it is exceptionally complex, multifactorial and multidisciplinary.
As will be seen, it is in the nature of such subjects that there may
never be total proof.
We have compiled the present monograph in a rather unusual way
which is particularly suitable for such difficult questions. The result
makes no attempt to arrive at a clear answer, since that quite simply
is not available to us. Neither does it attempt a consensus, something
which is still equally elusive. What we have done is to set out the
available evidence, and to discuss it extensively with the help of
experts from the many disciplines concerned, so that you, the reader,
will be able to come to an informed, personal opinion.
Each Chapter was sent to each of the other eight authors as well as
to four other participating scientists. All were given the task of
writing considered Commentaries on every Chapter. These were
then sent to everyone else taking part. We then met together for
three days of open-ended, informal argument and discussion of the
outstanding points.
vi Preface
As a result the authors of the Chapters made modifications to their
manuscripts, sometimes quite extensively, but in such a way that the
author remained the sole judge of what would eventually be pub
lished under his or her name. Thus is can be said that all the Chapters
have been reviewed by no fewer than 12 peers: a trial which was far
more testing than the normal procedure for judging contributions to
the usual scientific journals, and infinitely more so than is applied to
Chapters in the customary "books of meetings". The resulting
Chapters have therefore been refined to an extent which is not
revealed to the reader, although it will be readily acknowledged by
the authors.
The Commentary sections after each Chapter are not mere
transcripts of our discussions, which were unrecorded and private to
us. Instead they are well-considered, written, referenced Commen
taries, dealing mostly with aspects of the subject which remained
open. These Commentaries are often as important as the Chapters
they accompany.
The "physical" development of the human brain continues at
considerable speed well beyond the sixth postnatal month, the time
when it used to be thought it was reasonably mature. Some of its
most important features, for example the astonishing increase in
dendritic complexity and the achievement of synaptic connectivity,
continue very rapidly at least until the second human birthday. Its
most distinctively human functions, those concerned with intellect
and personality, continue to develop for many childhood years
beyond that. All these aspects of development, both physical and
behavioural, are particularly vulnerable to environmental depriva
tion or hostility at that time; but, what is even more important, the
periods during which such growth and development are taking place
are times of immense opportunity for us to promote good brain
growth and to lay sound intellectual foundations. This is a much
more positive "take home" message than that of mere vulnerability;
and, as will be seen in our book, promotion of continuous good iron
nutritional status, by very cheap and simple means, as well as the
ensuring of optimum general nutrition throughout these early
months and years, may well be an important part of this policy of
wanting to do the best for our children.
We would like to acknowledge the enormous help we have
received from Ross Laboratories, without which our endeavour
would not have been possible. The Editor would also like to express
his profound gratitude to all those who have contributed to the book.
They had to work much harder than for most other comparable
ventures. They responded valiantly to the many, sometimes impor
tunate, demands made on them, and I hope they are happy with the
result. He also acknowledges the efforts and continuous support
throughout of his wife, Dr Jean Sands.
St Julien de Cenac, November 1989 John Dobbing
Contents
List of Contributors .................................................... xi
Chapter 1. Vulnerable Periods in Developing Brain
John Dobbing ........................................................... I
Possible Effects of Undernutrition on the Developing Brain... 3
Vulnerability of Particular Brain Structures .................... 10
Cross-Species Extrapolation ....................................... II
Human Field Studies ............................... ................. 13
Conclusions.............................................................. 14
References ............................................................... IS
Commentary ............................................................ 17
Chapter 2. The Epidemiology of Childhood Iron Deficiency:
Evidence for Improving Iron Nutrition among US Children
Ray Yip ................................................................... 27
Introduction ............................................................. 27
How Iron Nutritional Status Is Defined ............................ 27
Defining Iron Deficiency ........................................... 27
Defining Anemia .................................................... 28
Defining the Spectrum of Iron Nutritional Status ............. 28
The Relationship between Iron Deficiency and Anemia ..... 29
Declining Prevalence of Anemia among US Children:
Evidence to Support Improvement of Infant Iron Nutrition. 31
Evidence of Improved Iron Nutritional Status among
Low-Income Children ............ ........ ........ ............... 31
Evidence for a Generalized Improvement of Childhood
Iron Nutritional Status in the US .............................. 33
Evidence for Increased Iron Intake among US Infants and
Children ............................................................ 35
Evidence of Improved Infant Feeding Patterns in the US .... 36
The Public Health Significance of Childhood Iron Deficiency. 37
viii Contents
References ............................................................... 39
Commentary ............................................................ 40
Chapter 3. Importance of Fetal and Neonatal Iron:
Adequacy for Normal Development of Central Nervous System
Edward C. Larkin and G. Ananda Rao ............................ 43
Hypertriglyceridemia .................................................. 44
Fatty Liver ............................................................... 46
Fatty Acid Composition of Liver Lipids............................ 47
Hypomyelination ....................................................... 48
Fatty Acid Oxidation by Cerebral Tissue .......................... 52
Conclusions .............................................................. 53
References ............................................................... 54
Commentary ............................................................ 57
Chapter 4. Neurochemical Basis of Behavioural Effects of
Brain Iron Deficiency in Animals
Shlomo Yehuda ......................................................... 63
Animal Models.......................................................... 63
Learning Capacity ...................................................... 64
Dopamine-Mediated Behaviours.................................... 66
Pain Threshold ....................................................... 66
Stereotypy ............................................................. 68
Motor Activity ....................................................... 68
Thermoregulation ................................................... 69
Specific Brain Lesions .............................................. 70
Iron Deficiency and Neuroleptic Drugs ............................ 71
Iron in the Brain ........................................................ 72
Development and Iron Deficiency .................................. 73
Iron Deficiency and the Immune System ........................... 74
Conclusion ............................................................... 74
References ............................................................... 75
Commentary ............................................................ 76
Chapter S. Neuropharmacological and Neurobiochemical
Aspects of Iron Deficiency
Moussa B. H. Youdim ................................................. 83
Introduction ............................................................. 83
Neurochemical and Neuropharmacological Aspects............. 86
Biochemical Basis of Learning Deficit in Iron Deficiency ...... 90
Blood-Brain Barrier and Iron Deficiency.... . . ... . . . . . .... . . . . .... 94
Conclusion and Future Perspectives ................................ 96
References ............................................................... 97
Commentary ............................................................ 99
Contents ix
Chapter 6. Has Iron Deficiency Been Shown to Cause Altered
Behavior in Infants?
Betsy Lozoff ............................................................. 107
Proving that Iron Deficiency Causes Alteration in Infant
Behavior............................................................... 107
Is Iron Deficiency Associated with Altered Infant
Behavior? .......................................................... 107
Does Iron Deficiency Precede Altered Behavior? ............ 113
Is the Relationship between Iron Deficiency and Altered
Behavior Non-spurious? ......................................... 114
Relating Research on Iron Deficiency to Research on Other
Risk Factors .......................................................... 123
References ............................................................... 124
Commentary ............................................................ 126
Chapter 7. Iron Deficiency and BehaviolH' in IRfancy:
A Critical Review
Tomas Walter ............................... ............................. 133
Use of Developmental Scales ........................................ 134
Recent Research ........................................................ 135
Summary .............................................................. 141
Conclusions .............................................................. 147
References ............................................................... 148
Commentary ............................................................ 150
Chapter 8. Iron Deficiency and the Brain:
Clinical Significance of Behavioural Changes
Yvonne A. Parks and Brian Wharton ............................... 157
Introduction ............................................................. 157
How Might Iron Deficiency Affect Behaviour? ................... 158
What Degree of Iron Deficiency Affects Behaviour? ......... 159
Iron Status ............................................................ 159
Behavioural Tests. . . .... . . .... . . .... . . . ... . . . . .... . . . ..... . . .... . . . .. 160
Cognitive Function .................................................. 160
Non-cognitive Function ............................................ 163
Does Iron Therapy Reverse Any Changes in Behaviour? ...... 164
Short-Term Effects on Cognitive Function ..................... 164
Short-Term Effects on Non-cognitive Function ...... ...... .... 165
Long-Term Effects of Treatment on Cognitive Function . ... 166
Are There Any Long-Term Effects on Behaviour? ..... ......... 167
What Are the Implications for the Clinician? ..................... 169
Conclusions .............................................................. 170
References ............................................................... 171
Commentary ............................................................ 172
x Contents
Chapter 9. Prevention of Iron Deficiency Anemia:
Iron Fortification of Infant Foods
Howard A. Pearson .................................................... 177
Iron Requirements of Infancy ........................................ 177
Content of Iron in Infant Food ....................................... 179
Prevalence of Iron Deficiency Anemia in Infants..... ............ 180
Fortification of Cows' Milk Formulas............................ 180
Fortification of Cereal Preparations .............................. 181
Epidemiological Effects of Iron Fortification of Infant
Food in the US ....................................................... 181
Possible Adverse Effects of Iron Fortification of Infant Foods. 182
Iron and Host Resistance ............................................. 184
Summary and Conclusions...... ........ ................ .......... .... 185
References ............................................................... 186
Commentary ............................................................ 187
Subject Index ............................................................ 191