Influence of Dietary Fatty Acids on the Pathophysiology of Intrauterine Foetal Growth and Neonatal Development

OR:

PERILIP (for: Perinatal Lipid Nutrition)

Nutrition during pregnancy and during early life (or “perinatal nutrition”) is known to affect the health and development of the newborn child. A foetus that suffers intra-uterine growth restriction (IUGR) is more likely to suffer from heart problems or diabetes in later life, an effect known as “metabolic programming”. Dietary fats from different sources (fish oil, vegetable oils, animal fats) contain distinctive mixtures of the component fatty acids. Some particular fatty acids are required for development while others have roles in providing energy but the optimum composition of dietary fats remains contraversial.

The PERILIP project will compare normal and IUGR pregnancies in terms of maternal, new-born and placental fatty acid profiles. Transfer of fatty acids across a living placenta and the effects of different fatty acids on the ability of placental cells called “trophoblasts” to function in a culture dish will be measured. The effects of dietary fats on mothers’ hormones, ability to withstand damage from oxygen, the composition of their milk and placental function will be measured in humans, where possible, or in animal models. These results will be compared with assessments of the development of both IUGR and normal foetuses in the womb (or in an intensive care unit, in the case of the premature infants being fed intravenously).

The results will be used to help suggest improved dietary recommendations for mothers throughout pregnancy and while breast-feeding.

The collaboration will examine the roles played by different fatty acids in the pathophysiology of intrauterine growth restriction (IUGR). A multidisciplinary approach will be employed to examine placental physiology, maternal lipid biochemistry and foetal and neonatal development as they relate to lipid nutrition.

The project will begin by studying how the fatty acid profiles of maternal, foetal and placental compartments correlate with the existence and severity of IUGR. It will continue with investigations into the factors affecting fatty acid delivery to the foetus and neonate, and how the vital physiological functions respond to attempts to modify the fatty acid composition by dietary means. Particular attention will be paid to the differences occurring in the IUGR pregnancy. Placental transport of fatty acids by women in vivo using stable isotopes will be carried out and the disposition of the acids in the foetus evaluated in complementary studies in rats. The abilities of trophoblasts from IUGR and normal pregnancies to perform functions associated with differentiation and placentation, and the effects of modifying their fatty acid compositions will be studied in cell culture. The roles of dietary and adipose stores of fatty acids in the supply of fatty acids to the foetus, to the neonate in lactation, on maternal hormonal status and on indicators of oxidative stress will all be investigated using rats and pigs as models. The latter two may provide useful biomarkers. The study of very low birth weight preterm infants fed intravenously with formulations containing different fatty acid mixtures will give an insight into the final stages of foetal development and will be extended in a piglet model to test new experimental formulations.

A final workpackage is designed to produce improved dietary recommendations for pregnant and lactating women based on the total knowledge gained from the experimental phases of the project.