University of Groningen
Prenatal and early postnatal long-chain polyunsaturated fatty acid status
Bouwstra, Hylco
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2007
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Bouwstra, H. (2007). Prenatal and early postnatal long-chain polyunsaturated fatty acid status: do they
affect neurodevelopmental outcome in healthy term infants? s.n.
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Prenatal and early postnatal
long-chain polyunsaturated fatty
acid status
Do they affect neurodevelopmental outcome in
healthy term infants?
Hylco Bouwstra
“Verwondering is een authentiek menselijke eigenschap, die bij
volwassenen helaas bedreigd wordt door ‘gezond realisme’. In de
realistische maatschappij van volwassenen is verwondering meer
en meer gereduceerd geraakt tot het terrein van de kunsten en
(soms) van de wetenschap.”
Nico Smit, lector Hogeschool van beeldende kunsten, muziek en
dans te Den Haag
2
RIJKSUNIVERSITEIT GRONINGEN
Prenatal and early postnatal long-chain
polyunsaturated fatty acid status
Do they affect neurodevelopmental outcome in healthy term infants?
Proefschrift
ter verkrijging van het doctoraat in de
Medische Wetenschappen
aan de Rijksuniversiteit Groningen
op gezag van de
Rector Magnificus, prof. dr. F. Zwarts,
in het openbaar te verdedigen op
woensdag 3 oktober 2007
om 16:15 uur
door
Hylco Bouwstra
geboren op 30 juli 1980
te Heerenveen
3
Promotores
Prof.dr. M. Hadders-Algra
Prof.dr. F.A.J. Muskiet
Copromotores
Prof.em.dr. E.R. Boersma
Dr. D.A.J. Dijck-Brouwer
Beoordelingscommissie
Prof.dr. A.F. Bos
Prof.dr. B. Koletzko
Prof.dr. H.N. Lafeber
4
Paranimfen
Geert van den Bogaart
Durk-Rein Lolkema
5
Correspondence to:
Hylco Bouwstra
University Medical Center Groningen (UMCG)
Developmental Neurology
PO-Box 30.001
9700 RB Groningen
The Netherlands
Email: [email protected]
© H. Bouwstra, 2007
Prenatal and early postnatal long-chain polyunsaturated fatty acid status. Do they affect
neurodevelopmental outcome in healthy term infants?
Thesis University Medical Center Groningen. Summary in Dutch.
ISBN no: 9789036730389
No part of this thesis may be reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopy, recording, or any information storage and
retrieval system, without permission of the copyright owner.
The publication of this thesis was financially supported by Numico Research B.V.
The support is gratefully acknowledged.
Lay-out: H. Bouwstra
Cover: illustration by Luna Tjeerdsma, 2006
Printed by Gildeprint Drukkerijen, Enschede, The Netherlands
6
Table of Contents
Foreword……. ........................................................................................................ 9
List of abbreviations............................................................................................. 10
Chapter 1
General Introduction ................................................................. 13
Essential fatty acid status..................................................................................................... 15
Essential fatty acid deficiency ............................................................................................. 27
Overview of evidence of the effect of LCPUFA supplementation ...................................... 29
Theoretical considerations about neurodevelopmental assessments.................................... 39
Specific questions addressed in this thesis........................................................................... 49
Chapter 2
Effect of early postnatal feeding on neurodevelopment.......... 63
Long-chain polyunsaturated fatty acids have a positive effect on the quality of
general movements of healthy term infants ......................................................................... 65
Exclusive breastfeeding of healthy term infants for more than 6 weeks improves
neurological condition ......................................................................................................... 81
Long-chain polyunsaturated fatty acids and neurological developmental outcome
at 18 months in healthy term infants.................................................................................... 89
Chapter 3
Neonatal fatty acid status and neurological development .... 103
Relationship between umbilical cord essential fatty acid content and the quality
of general movements of healthy term infants at 3 months ............................................... 105
Neurological condition of healthy term infants at 18 months: positive association
with venous umbilical DHA status and negative association with umbilical
trans-fatty acids ................................................................................................................. 121
Chapter 4
Chapter 5
Chapter 6
Chapter 7
Chapter 8
General discussion.................................................................... 139
Summary ................................................................................... 149
Dankwoord................................................................................ 155
Samenvatting ............................................................................ 159
Curriculum vitae & list of publiciations................................. 168
7
8
Foreword
This thesis describes the main findings of the longitudinal LCP-project that was started
in 1997. The LCP-project is an international multidisciplinary collaboration between
the departments of Neurology and Pathology and Laboratory Medicine of the
University Medical Center Groningen, the department of Pediatrics of the University of
Pécs, Hungary, and Numico Research Germany, Friederichsdorf, Germany. Numico
Research sponsored the project. Initially the project leaders were prof. dr. E.R.
Boersma, and prof. dr. M. Hadders-Algra, later on the role of prof Boersma was taken
over by prof. dr. F.A.J. Muskiet. Between 1997 – 2002 two investigators, Mrs. J.A.L.
Wildeman and Mrs H.M. Tjoonk have investigated 472 enrolled infants and gathered
all infant follow-up data of the LCP-project. They started data-analysis, but at the end
of their employment period, major part of the data-analyses still had to be carried out.
At the end of 2002 the author of this thesis took part in the analyses of the follow-up
data of the project as a medical student which ultimately resulted in the writing of the
present thesis. The MD/PhD program of the ‘Junior Scientific Masterclass’ enabled
him to complete his PhD thesis. A major aim of the LCP-project was to evaluate the
effects of long-chain polyunsaturated fatty acid (LCPUFA) supplementation on
neurodevelopment of healthy term infants. A secondary objective was to compare the
developmental outcome of formula fed infants with breastfed infants. In addition, the
prenatal fatty acid status measured at birth was correlated with the neurodevelopmental
outcome at 3 and 18 months.
9
Abbreviations
AA
arachidonic acid
ALA
alpha-linolenic acid
DHA
docosahexaenoic acid
EFA
essential fatty acids
GMs
general movements
OOS
obstetrical optimality score
PDI
psychomotor developmental index
LCPUFA
long-chain polyunsaturated fatty acids
MND
minor neurological dysfunction
MDI
mental developmental index
MUFA
monounsaturated fatty acids
NOS
neurological optimality score
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