The
results of PERILIP are highly integrated but, for the
purposes of this summary, they are presented as the original
10 workpackages (WPs).
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| WP1: |
Measurement
of fatty acid profile of mother, foetus and placenta in normal
and IUGR pregnancies |
Blood samples were taken from
mothers with normal pregnancies or with IUGR pregnancies of
different severities, and from their babies. They were analysed
for fatty acid composition as well as hormone concentrations
(WP8) and antioxidant status (WP9). Growth-restricted (or IUGR)
babies, when compared to normal babies, showed clear differences
in their ability to take up essential fatty acids via the placenta.
The results suggest
that it may be possible to ameliorate the effects of the
placental insufficiency by providing supplements of the affected
fatty acids to affected mothers. Further experiments would
be necessary to test this conclusion.
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| WP2: |
Placental
structure and function as it relates to the lipid content
in the maternal diet and to IUGR |
Key genes associated with placental
development have been identified in normal rat placentas. Diets
rich in fish oil appear to promote early growth and to slow
later degradation of the placenta. The techniques, at this
stage, are not sensitive enough to assess differences between
term placentas from normal and IUGR pregnancies. A cultured
cell line has been developed for the study of environmental
(e.g. dietary components) effects on proliferation trophoblast
(the important cell
type of placentas).
The results from
the dietary experiments add to the weight of evidence supporting
the use of fish oil in the
diets of pregnant women. (See WP10).
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| WP3: |
Placental
transfer of fatty acids in pregnant women and in an animal
model |
The fatty acid profiles in
plasma, adipose tissue and placenta in women and rats and from
the placental transfer studies both show that the placenta
preferentially transports the long chain polyunsaturated fatty
acids (LC-PUFA), typically derived from fish oils, to the foetus.
The development of a rat model was successful.
Again, these experiments support the contention that such (fish oil) fatty acids
are important in the development of the foetus. Future work may try to derive
actual mass fluxes of the fatty acids across the placenta, rather than just tracers,
but the difficulty of the techniques or the cost may prove prohibitive.
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| WP4: |
Relationship
between maternal dietary fatty acids, adipose tissue composition
and fatty acid availability to the foetus and mammary gland |
Maternal adipose tissue helps
to maintain the availability of important essential fatty acids
to the foetus (see also WP6). In rats, fish oil, in excess
especially during lactation, impairs the growth and development
of the offspring. This results from an inhibition of the pathway
leading to the long chain omega-6 fatty acids by the omega-3
fatty acids of the fish oil and can be overcome by providing
an
alternative source of the omega-6 acids.
The results suggest
that care is necessary not to recommend excessive intake
of fish oils as it is clearly important
to maintain a balance between the “omega-3” and “omega-6” acids.
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| WP5: |
Effects
of modifying fatty acid composition of lipids used in total
parenteral nutrition on the growth and metabolism of preterm
infants |
Total parenteral nutrition (i.e. intravenous feeding)
studies in human babies of very low birth-weight suggest
that lipid emulsions currently available are not optimum
for nutrition of the neonate. A piglet model of such treatments
has been successfully developed and has enabled the effects
of the treatments on
tissue composition to be determined.
The
piglet experiments, which suggest that an emulsion containing
some fish oil may offer an improved treatment,
need to be carefully checked in controlled clinical
trials with premature human babies. |
| WP6: |
An
examination of the effects of modifying the lipid content
of maternal diets at defined stages of pregnancy or during
lactation |
In
pigs, altering the maternal diet by enrichment with different
oils produced distinct effects
when restricted to the first half of pregnancy; supplementing
during the second half produced smaller differences between
the supplements. The effects of the oils were complex and
no single supplement was “all-good” or “all-bad”.
The experiment
emphasises the importance of diet during the first trimester
of pregnancy. Further, more sophisticated,
experiments will be necessary to determine
an optimum mixture of fatty acids to benefit maternal, foetal and neonatal
health.
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| WP7: |
Milk
fat composition and neonatal growth |
As expected, the fatty acid
profile in milk reflected the diet of the mother; more unexpected
was the observation in pigs that it reflected the diet given
only during the first half of pregnancy (at least 55 days earlier).
This was particularly so in the case of the fish oil derived
fatty acids.
The results emphasise
the importance as adipose tissue as a store for particular
fatty acids required later
(see WP4), support the importance of fish oil acids,
and again show that diet in early pregnancy is of great importance (see WP6).
Further experiments might be designed to see whether these effects might
be extended
by altering the maternal diet prior to conception.
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| WP8: |
Effects
of maternal dietary fatty acid composition on the plasma
concentration of maternal and placental hormones |
Some placental hormones, such
as human placental lactogen (HPL) and insulin-like growth factor
1 (IGF 1) are related to the pathology, i.e. they have significantly
reduced concentrations in maternal plasma of IUGR pregnancies.
In pigs, several hormones showed distinctive patterns during
the course of a pregnancy, but there appeared to be no major
effects on these patterns of any of the dietary treatments.
The results
suggest that changes (decreases) of particular hormones compared
to “normal” values may be an early predictor of growth restricted
pregnancies; prospective studies need to be established to test this hypothesis.
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| WP9: |
Role
of changes in dietary fatty acids during pregnancy and lactation
on
oxidative stress |
All the measures of oxidation
indicate that growth restricted babies have an impaired ability
to combat oxidative damage. In rats, fish oil diets clearly
put more stress on anti-oxidation mechanisms but was not the
cause of poor development in the pups of rats fed fish oil
during lactation (see WP4).
The results with
rats suggest that it may be worthwhile to check antioxidant
status as a precaution in pregnant
women, especially those that have been recommended
to increase their intake of fish oil. Supplementing the diets of women
who have
(early diagnosed) growth-restricted pregnancies with anti-oxidant vitamins
could only be recommended after further research.
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| WP10: |
Formulation
of recommendations on the fatty acid content of diets to
provide for improved foetal and neonatal growth |
A
consensus conference has been held. Many world and European
experts in foetal nutrition
attended and current knowledge was reviewed in the light
of recent results from elsewhere and the new results generated
by PERILIP.
Specific dietary recommendations for pregnant and lactating
women have been proposed. (See recommendations.)
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