Pregnancy and Fetal Growth

Since World War II, the role of maternal nutrition in fetal growth and development has been extensively studied in the context of protein-calorie malnutrition. The role of n-3 fatty acids has only recently come into focus, despite the evidence of its importance having been demonstrated in a series of studies between 1928 and 1930 involving rats and primates. Lipid nutrition during pregnancy and lactation is of special relevance to human development, because brain development in the human takes place during fetal life and in the first 2 years after birth. DHA is found in larger amounts in the gray matter of the brain and in the retinal membranes, where it accounts for 30% or more of the fatty acids in the ethanolamine and serine phos-pholipid. DHA accumulates in the neurons of the brain between weeks 26 and 40 of gestation in humans.

During the third trimester of human development, rapid synthesis of brain tissue occurs in association with increasing neuromotor activity. The increase in cell size, number, and type requires de novo synthesis of structural lipids, leading to accumulation of DHA in the brain of the human infant during the last trimester. The levels of ALA and LA are low in the brain, whereas marked accretion of long-chain desaturation products, specifically DHA and AA, occurs. More recent data indicate that the main developmental changes in the brain seem to be an increase in DHA at the end of gestation and a decrease in oleic acid (18:1n-9) and AA in phospha-tidlyethanolamine (PE). Similar changes occur in the liver. Therefore, a premature infant (prior to 37 weeks' gestation) has much lower amounts of DHA in the brain and liver and is at risk of becoming deficient in DHA unless it is supplied in the diet. In the full-term newborn, about half of the DHA accumulates in the brain before birth and the other half after birth.

There is epidemiologic evidence that the birth weights of newborns in the Faroe Islands (where fish intake is high) are higher than those in Denmark, as is the length of gestation: 40.3 ± 1.7weeks for the Faroese versus 39.7 ± 1.8 weeks for the Danish pregnant women. The average birth weight of primiparas is 194 g higher for the Faroe Islands. The higher dietary n-3 fatty acid intake quite possibly influences endogenous prostaglandin metabolism. It is

Table 7 Effects of n-3 fatty acids on factors involved in the pathophysiology of atherosclerosis and inflammation

Factor

Function

Effect of n-3 fatty acid

Arachidonic acid Thromboxane A2 Prostacyclin (PGI2/3) Leukotriene (LTB4) Fibrinogen Tissue plasminogen activator Platelet activating factor (PAF) Platelet-derived growth factor (PDGF) Oxygen free radicals

Lipid hydroperoxides Interleukin 1 and tumor necrosis factor

Interleukin-6

C-reactive protein

(CRP) Endothelial-derived relaxation factor Insulin sensitivity VLDL HDL Lp(a)

Triglycerides and chylomicrons

Eicosanoid precursor; aggregates platelets; stimulates white blood cells Platelet aggregation; vasoconstriction; increase of intracellular Ca++ Prevent platelet aggregation; vasodilation; increase cAMP Neutrophil chemoattractant; increase of intracellular Ca++ A member of the acute phase response; and a blood clotting factor Increase endogenous fibrinolysis

Activates platelets and white blood cells

Chemoattractant and mitogen for smooth muscles and macrophages

Cellular damage; enhance LDL uptake via scavenger pathway; stimulate arachidonic acid metabolism Stimulate eicosanoid formation

Stimulate neutrophil O2 free radical formation; stimulate lymphocyte proliferation; stimulate PAF; express intercellular adhesion molecule-1 on endothelial cells; inhibit plasminogen activator, thus, procoagulants Stimulates the synthesis of all phase proteins involved in the inflammatory response: C-reative protein; serum amyloid A; fibrinogen; a1-chymotrypsin; and haptoglobin

An acute phase reactant and an independent risk factor for cardiovascular disease

Reduces arterial vasoconstrictor response

Decreases the risk for coronary heart disease

Lipoprotein(a) is a genetically determined protein that has atherogenic and thrombogenic properties Contribute to postprandial lipemia

Source: Updated and modified from Weber PC, Leaf A. Cardiovascular effects of omega-3 fatty acids. Atherosclerosis risk factor modification by omega-3 fatty acids. World Rev Nutr Diet 1991, 66: 218-32. With permission.

hypothesized that the dietary n-3 fatty acids inhibit the production of the dienoic prostaglandins, especially PGF2a and PGE2, because they are involved in the mediation of uterine contractions and the ripening of the cervix that lead to labor and delivery. These important observations need to be further investigated, as the prevention of prematurity is one of the most critical issues to be overcome in perinatal medicine.

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