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  Summary

The results of PERILIP are highly integrated but, for the purposes of this summary, they are presented as the original 10 workpackages (WPs).

 

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.

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).

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.

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.

 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.

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.

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.

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.

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.)