Exploratory study into the relation between plasma phospholipid fatty acid status and cognitive performance.

Previous research found a negative association between DHA status and selective attention in pregnant women. Goal of the present exploratory study is to investigate the potential relationship between essential fatty acid status and cognitive performance in a healthy non-pregnant population. Cognitive performance of 54 non-pregnant women was determined at baseline, 3, 15, and 22 weeks later with an objective neurocognitive test battery covering different brain domains. Plasma phospholipid fatty acid status was determined at baseline and at 22 weeks. The fatty acids of primary interest (arachidonic acid, adrenic acid, Osbond acid, eicosapentaenoic acid, and docosahexaenoic acid) were no significant predictors of cognitive performance at baseline or 22 weeks later. However, they attributed significantly (26.3%) to the amount of explained variance of the learning effect on the Stroop task, measuring general speed of information processing. Higher docosahexaenoic acid levels were associated with a slower learning curve. For arachidonic acid the opposite was found. In conclusion, this study provides a preliminary indication that a higher DHA status might be associated with slower learning curves. However, additional studies are necessary.

Relationship between DHA status at birth and child problem behaviour at 7 years of age.

Animal studies have demonstrated behavioural effects of long-chain polyunsaturated fatty acid (LC-PUFA) deficiencies and in humans, several psychiatric disorders have been linked to abnormal essential fatty acid metabolism. The aim of this study was to examine the relationship between LC-PUFA status at birth and the later development of problem behaviour. In a sample of 393 children, higher levels of docosahexaenoic acid (DHA) at birth were associated with lower levels of internalising problem behaviour at age 7 years. The association was markedly present in the infants fed with artificial formula (n=215, Beta=-0.32, P=0.000), but absent in the infants fed with human milk (n=170, Beta=0.11, P=0.325). The associations between arachidonic acid and internalising or externalising behaviour were neither large nor significant. The results suggest that perinatal DHA status may have long-term behavioural consequences. Therefore, we suggest to include measures of problem behaviour in future trials of LC-PUFA supplementation of mothers and/or infants.

Association between prenatal and current exposure to selected LCPUFAs and school performance at age 7.

INTRODUCTION: Long-chain polyunsaturated fatty acids (LCPUFAs) are important for brain functioning and might, thus, influence cognition and school performance. However, research investigating LCPUFAs relationships with school performance is limited. The objective of this study was to determine the association between levels of the LCPUFAs docosahexaenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and n-6 docosapentaenoic acid (Osbond acid, ObA) at study entry, 22 weeks of pregnancy, 32 weeks of pregnancy, at partus, in umbilical cord plasma and child's plasma at age 7 and school performance scores at age 7. METHODS: Data from the Maastricht Essential Fatty Acid Birth cohort (MEFAB) were used for this study. Fatty acid levels of plasma phospholipids were measured in maternal blood plasma at study entry, 22 weeks of pregnancy, 32 weeks of pregnancy and partus. Childs fatty acid levels of plasma phospholipids were measured a in umbilical cord blood plasma, and in blood plasma of the child at age 7. Scores on national standardised tests for spelling, reading and arithmetic at age 7 were obtained via the school (scores were available for 149, 159 and 155 children, respectively). Associations between LCPUFA levels and school performance scores were analysed with categorical regression analyses with correction for covariates (smoking, maternal education, sex, breastfeeding, maternal intelligence, birth weight and BMI at age 7). RESULTS: Significant (p<0.001) associations between DHA level at age 7 and both reading (ß=0.158) and spelling (ß=0.146) were found. Consistent significant negative associations were observed between all maternal DHA plasma levels and arithmetic scores at age 7 (all p<0.001, all ß<-0.019). Additional significant negative associations were observed between maternal LCPUFA plasma levels at study entry and both reading and spelling scores at age 7; these associations were less consistent. CONCLUSION: Plasma DHA levels at age 7 were positively associated with reading and spelling scores at age 7. Consistent significant negative associations between maternal plasma DHA levels and arithmetic scores of the child at age 7 were found. Although this is an observational study, which cannot proof causality, the consistent negative associations observed between maternal plasma DHA levels and the arithmetic scores of the children at age 7 calls upon prudence when considering DHA supplementation during pregnancy.

The effects of purified eicosapentaenoic and docosahexaenoic acids on arterial thrombosis tendency and platelet function in rats.

Dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were compared for their effects on arterial thrombus formation in vivo using a well validated rat model. Platelet aggregation (triggered by collagen or adenosine diphosphate in whole hirudinized blood), thromboxane formation (TxB2) and platelet phospholipid fatty acid composition were measured also. Animals fed diets containing hydrogenated coconut oil or sunflower seed oil served as pro- and anti-thrombotic controls, respectively. In a first study, rats were fed a mixture of EPA and DHA ethyl esters (MIX) in increasing amounts and results indicated that 4% of n-3 fatty acids had an optimum reducing effect on thrombosis tendency. Dietary administration of MIX further resulted in a dose-dependent promotion of disaggregation after collagen-induced aggregation, which significantly correlated with the reduction in platelet TxB2 formation. In a subsequent comparative study, both EPA and DHA ethyl esters affected thrombosis tendency, platelet aggregation and TxB2 formation to a similar extent. In addition, both polyenes increased the apparent thromboxane A2-sensitivity of platelets, which appeared negatively related to arterial thrombosis tendency. We conclude that EPA and DHA have similar reducing effects on arterial thrombogenesis in vivo in rats and have comparable effects on the selected platelet functions in vitro.

Membrane fluidity of non-activated and activated human blood platelets.

The steady-state fluorescence anisotropy of membranes labeled with 1,6-diphenyl-1,3,5-hexatriene (DPH) or its 4'-trimethylammonio derivative, TMA-DPH, is generally considered a measure for the lipid order and, hence, inversely related to membrane fluidity. We now report that anisotropy values of DPH- and TMA-DPH-labeled human platelets are considerably influenced by experimental conditions like the platelet concentration, which do not affect membrane fluidity. Activation of platelets with thrombin increases, but activation with ionomycin decreases anisotropy values with both labels. Such anisotropy changes are not detected in platelet membranes or platelet lipids, when isolated after activation of the intact platelets. We present evidence that the anisotropy changes of intact platelets are not a consequence of modified lipid composition (e.g., as would be induced by phospholipase A2 activity) but are, at least partially, caused by changed optical properties of the cell suspension. Measurement of membrane fluidity of platelets by fluorescence polarization is severely hindered by a high turbidity of the platelet suspension and also by changes in the turbidity and platelet morphology during the activation process.

Influence of dietary fatty acids on membrane fluidity and activation of rat platelets.

The apparent steady-state fluorescence anisotropy of DPH- or TMA-DPH-labeled washed rat platelets is strongly affected by factors that also influence the turbidity by these platelet suspensions. Sonicated preparations from platelet lipids have a low turbidity and give anisotropy values which are hardly affected by the experimental conditions. We studied the effect of four high-fat diets on membrane fluidity, lipid composition and activation tendency of washed platelets. The diets contained 50 energy% of oils with different levels of saturated and (poly)unsaturated fatty acids. Only small diet-induced differences in DPH fluorescence anisotropy were found, which were comparable for intact platelets and platelet lipids. These differences were unrelated to the degree of saturation of the dietary fatty acids. Platelets from rats fed mainly saturated fatty acids differed significantly from other diet groups in a higher unsaturation degree of phospholipids and a lower cholesterol/phospholipid ratio, but this was not detected by DPH in terms of decreased anisotropy. These platelets aggregated less than other platelets in response to thrombin or collagen. The lower response to collagen persisted in indomethacin-treated platelets activated with the thromboxane A2 mimetic U46619, indicating a different sensitivity of these platelets for thromboxane A2. We conclude that in rat platelets: (a) the overall membrane fluidity and phospholipid unsaturation degree are subject to strong homeostatic control; (b) steady-state anisotropy with DPH or TMA-DPH label is inadequate to reveal subtile changes in lipid profile; (c) changes in platelet responsiveness to thrombin and thromboxane A2, rather than (plasma) membrane fluidity, determine the effect of dietary fatty acids on platelet aggregation.

Effects of dietary fatty acids on signal transduction and membrane cholesterol content in rat platelets.

Previously, we have reported that dietary fatty acids can modify the thromboxane A2-dependent activation of rat platelets. Here, we present evidence that this dietary effect is part of a more general effect on platelet signal transduction, putatively involving structural changes in the platelet membranes. Four experiments were performed, where Wistar rats were fed with a high-fat diet enriched in either saturated, n-6 polyunsaturated or n-3 polyunsaturated fatty acids, or with a low-fat diet enriched in n-6 polyunsaturated fatty acids. The type of diet hardly influenced mean number of double bonds in the major platelet phospholipids. Platelet membranes from the rats fed with the saturated-fat diet had phospholipids with relatively high levels of arachidonate, but were low in cholesterol/phospholipid ratio. When compared to this diet group, platelets from other groups had an arachidonate content that was 21 to 47% lower and a cholesterol/phospholipid ratio 3 to 5% higher. The saturated-fat diet resulted in platelets that, in general, were less responsive to agonists than the platelets from other groups: with thrombin, collagen and thromboxane A2 analogue U46619, both early (shape change and phospholipase C-dependent rise in [Ca2+]i) and late (exocytosis and aggregation) responses were relatively low. However, platelet activation evoked by ADP was not influenced by diet type. When the cholesterol content of rat platelets was modified in vitro, it appeared that the early and late responses to thrombin and U46619 increased with the cholesterol/phospholipid ratio. Taken together, these results suggest that in rat platelets (i) the membrane cholesterol/phospholipid ratio can be modulated by a diet rich in saturated fatty acids, explaining, at least in part, the dietary effect on phospholipase C-mediated platelet activation, and (ii) relatively small changes in cholesterol content can have a more profound effect on platelet activation than substantial changes in arachidonate level.

Membrane fatty acid composition and endothelial cell functional properties.

In order to study the influence of endothelial cell fatty acid composition on various membrane related parameters, several in vitro methods were developed for manipulating the fatty acid content of human endothelial cell membranes. Changes in membrane fatty acid profile were induced by using fatty acid modified lipoproteins or free fatty acids. The largest changes in endothelial fatty acid composition were obtained by culturing the cells in media supplemented with specific free fatty acids. An increase in arachidonic acid content of endothelial phospholipids was induced by supplementation with saturated fatty acids or with arachidonic acid itself. A decrease in arachidonic acid content was obtained by supplementation with other unsaturated fatty acids. Under the experimental conditions used endothelial cells showed a low desaturase activity and a high elongase activity. Considerable alterations in membrane fatty acid composition did not greatly influence certain membrane related parameters such as polymorphonuclear leukocyte adherence and endothelial cell procoagulant activity. In general, for fatty acid modified endothelial cells an association between endogenous arachidonic acid content and total production of eicosanoids was found. This study demonstrates that considerable changes in membrane fatty acid profile affect endothelial cell arachidonic acid metabolism, but it also illustrates homeostasis at the level of endothelial cell functional activity.

Formation of prostanoids and hydroxy fatty acids by stimulated peritoneal mast cells: role of the dietary fat type in rat.

To study the influence of membrane fatty acid composition on the formation of prostanoids and hydroxy fatty acids by rat peritoneal mast cells (MC), animals were fed three different types of fatty acids: mackerel oil (MO), abundant in n-3 fatty acids; sunflower seed oil (SO), rich in linoleic acid; and hydrogenated coconut oil (HCO), mainly containing saturated fatty acids. The presence of n-3 fatty acids in the diet resulted in the incorporation of 20:5(n-3), 22:5(n-3) and 22:6(n-3) in MC phospholipids. A decrease of arachidonic acid, 20:4(n-6), was observed in MC-phospholipids of the MO-fed animals. Furthermore, increasing the relative amounts of 18:2(n-6) in the diet (SO group) led to an increased incorporation of linoleic acid, 18:2(n-6) in MC phospholipids when compared to both other dietary groups. The changes in MC phospholipid fatty acid composition were (partly) reflected in the formation of prostanoids and hydroxy fatty acids upon stimulation with the calcium ionophore A23187. The decrease in arachidonic acid content in MC phospholipids of MO-fed rats resulted in a decreased formation of PGD2 when compared to both other groups. Also, the increased amounts of 18:2(n-6) in MC phospholipids of SO-fed rats resulted in an increased formation of 9- and 13-HODE upon stimulation. The results show that modifications in the fatty acid composition of the diet influences MC membrane fatty acid composition which ultimately results in changes in prostanoid and hydroxy fatty acid synthesis by MC upon stimulation with the calcium ionophore A23187.

Differential release of histamine and prostaglandin D2 in rat peritoneal mast cells: roles of cytosolic calcium and protein tyrosine kinases.

We studied how the release of histamine and prostaglandin D2 (PGD2) were connected in stimulated rat peritoneal mast cells, and to what extent these processes were controlled by the cytosolic Ca2+ concentration, [Ca2+]i, and protein tyrosine kinases. In the presence of 1 mM CaCl2, the G-protein activating compound 48/80 (10 micrograms/ml) evoked a transient rise in [Ca2+]i and a relatively high secretion of histamine, but only a low release of PGD2. In contrast, 5 microM thapsigargin (an inhibitor of endomembrane Ca(2+)-ATPases) and 5 microM ionomycin evoked high and prolonged rises in [Ca2+]i, and stimulated the cells to release relatively small amounts of histamine and high amounts of PGD2. Stimulation of the cells with CaCl2 and 10 microM ATP4- gave only minor quantities of histamine and PGD2, despite of the micromolar level of [Ca2+]i reached. When CaCl2 was replaced by EGTA, rises in [Ca2+]i as well as release of histamine and PGD2 were reduced with each agonist, but the preference of agonists to release more histamine or PGD2 remained unchanged. In mast cells with depleted Ca2+ stores, the addition of CaCl2 stimulated the store-regulated Ca2+ entry resulting in a prolonged rise in [Ca2+]i. However, simultaneous addition of compound 48/80 and CaCl2 was required for release of histamine and PGD2. In cells with full stores, PGD2 release evoked by compound 48/80 was greatly reduced by genistein and methyl-2,5-dihydroxycinnamate, two structurally unrelated inhibitors of protein tyrosine kinases, whereas histamine secretion was not influenced by these inhibitors. Similarly, with thapsigargin or ionomycin as agonist, PGD2 release was more sensitive to the tyrosine kinase inhibitors than histamine secretion. We conclude that in activated rat peritoneal mast cells: (i) the influx of extracellular Ca2+ potentiates agonist-evoked rises in [Ca2+]i as well as histamine secretion and PGD2 release; (ii) the amplitude of the [Ca2+]i rise does not determine the preferential effect of agonists to release more histamine or more PGD2; (iii) the relatively high PGD2 release evoked by thapsigargin and ionomycin is probably due to their potency to evoke a prolonged rise in [Ca2+]i and to activate protein tyrosine kinases.

Dietary plant stanol esters reduce VLDL cholesterol secretion and bile saturation in apolipoprotein E*3-Leiden transgenic mice.

Dietary plant stanols lower serum cholesterol levels in humans and in hyperlipidemic rodents, mainly by inhibition of the intestinal cholesterol absorption. We used female apolipoprotein E*3-Leiden transgenic mice to investigate the consequences of this effect on serum lipid levels and hepatic lipid metabolism. Five groups of 6 or 7 mice received for 9 weeks a diet containing 0.25% cholesterol and 0.0%, 0.25%, 0.5%, 0.75%, or 1.0% (wt/wt) plant stanols (sitostanol 88% [wt/wt], campestanol 10% [wt/wt]) esterified to fatty acids. Compared with the control diet, plant stanol ester treatment dose-dependently reduced serum cholesterol levels by 10% to 33% (P<0.05), mainly in very low density lipoproteins (VLDLs), intermediate density lipoproteins, and low density lipoproteins. Furthermore, 1.0% of the dietary plant stanols significantly decreased the liver contents of cholesteryl esters (-62%), free cholesterol (-31%), and triglycerides (-38%) but did not change the hepatic VLDL-triglyceride and VLDL-apolipoprotein B production rates. However, plant stanol ester feeding significantly decreased the amounts of cholesteryl esters and free cholesterol incorporated in nascent VLDLs by 72% and 30%, respectively, resulting in a net 2-fold decreased VLDL cholesterol output. Liver mRNA levels of low density lipoprotein receptors, 3-hydroxy-3-methylglutaryl coenzyme A synthase, cholesterol 7alpha-hydroxylase, and sterol 27-hydroxylase were not changed by plant stanol ester feeding. Nevertheless, the serum lathosterol-to-cholesterol ratio was significantly increased by 23%, indicating that dietary plant stanol esters increased whole-body cholesterol synthesis. Plant stanol esters also significantly decreased the cholesterol saturation index in bile by 55%. In conclusion, in apolipoprotein E*3-Leiden transgenic mice, plant stanol ester feeding dose-dependently lowered serum cholesterol levels as a result of a reduced secretion of VLDL cholesterol. This was caused by a decreased hepatic cholesterol content that also resulted in a lowered biliary cholesterol output, indicative of a reduced lithogenicity of bile in these mice.

Rat platelets are deficient in internal Ca2+ release and require influx of extracellular Ca2+ for activation.

Calcium fluxes were studied in fura-2-labeled rat platelets. Thrombin, ADP and ionomycin induced rapid mobilization of internally stored Ca2+, which resulted in only a moderate increase of cytosolic [Ca2+]i. Thrombin and ADP stimulated influx of extracellular Ca2+, which was monitored as uptake of 45Ca2+ and of Mn2+. With either agonist, the influx of Ca2+ magnified the initial increase of [Ca2+]i. Since responses of rat platelets were dependent on external [Ca2+], we conclude that Ca2+ influx complements the mobilization of internal stores to reach sufficiently high [Ca2+]i for full activation. A regulatory effect of protein kinase C modulators was observed on both agonist-induced elevation of [Ca2+]i and receptor-mediated Ca2+ entry.

Lipid peroxidation-associated oxidative stress during percutaneous transluminal coronary angioplasty in humans.

Animal studies suggest that myocardial ischemia/reperfusion causes oxidative stress. We, therefore, examined whether routinely performed percutaneous transluminal coronary angioplasty (PTCA) might be a human ischemia/reperfusion model for oxidative stress-induced lipid peroxidation. Fasting antecubital venous blood was sampled from 13 patients on the morning of PTCA, and 2 d after PTCA. Venous and coronary arterial blood were sampled just before and 10 min after the first balloon inflation. Samples were analyzed for plasma and LDL lipid hydroperoxide levels, in vitro oxidation of LDL, and LDL antioxidant levels. Lipid hydroperoxide levels in plasma and LDL remained unchanged throughout the study. During the first 10 min of PTCA, the lag time during oxidation of LDL in vitro did not change, but the maximum rate of oxidation decreased in venous and arterial samples (Wilcoxon signed rank test: p < .002). At the same time, total tocopherol levels in LDL significantly increased by 6.3% (p = .048) in arterial, but not in venous samples. Total carotenoid levels increased by 3.8% (p = .127) in arterial samples and decreased by 2.9% (p = .040) in venous samples. Forty hours after PTCA, LDL oxidation parameters and LDL antioxidant levels were similar to baseline, except for about 17% lower levels of delta-tocopherol (p = .037) and gamma-tocopherol (p = .014). Our results, therefore, do not support that PTCA in humans is associated with oxidative stress-induced lipid peroxidation.

Essential fatty acids in mothers and their neonates.

Essential fatty acids (EFAs) and their long-chain polyenes (LCPs) are indispensable for human development and health. Because humans cannot synthesize EFAs and can only ineffectively synthesize LCPs, EFAs need to be consumed as part of the diet. Consequently, the polyunsaturated fatty acid (PUFA) status of the developing fetus depends on that of its mother, as confirmed by the positive relation between maternal PUFA consumption and neonatal PUFA status. Pregnancy is associated with a decrease in the biochemical PUFA status, and normalization after delivery is slow. This is particularly true for docosahexaenoic acid (DHA) because, on the basis of the current habitual diet, birth spacing appeared to be insufficient for the maternal DHA status to normalize completely. Because of the decrease in PUFA status during pregnancy, the neonatal PUFA status may not be optimal. This view is supported by the lower neonatal PUFA status after multiple than after single births. The neonatal PUFA status can be increased by maternal PUFA supplementation during pregnancy. For optimum results, the supplement should contain both n-6 and n-3 PUFAs. The PUFA status of preterm neonates is significantly lower than that of term infants, which is a physiologic condition. Because the neonatal DHA status correlates positively with birth weight, birth length, and head circumference, maternal DHA supplementation during pregnancy may improve the prognosis of preterm infants. In term neonates, maternal linoleic acid consumption correlates negatively with neonatal head circumference. This suggests that the ratio of n-3 to n-6 PUFAs in the maternal diet should be increased. Consumption of trans unsaturated fatty acids appeared to be associated with lower maternal and neonatal PUFA status. Therefore, it seems prudent to minimize the consumption of trans fatty acids during pregnancy.

Comparison of the effects of diets enriched in lauric, palmitic, or oleic acids on serum lipids and lipoproteins in healthy women and men.

The degree to which different saturated fatty acids exert their cholesterol-raising effects is still unknown. Therefore, we studied the effect on serum lipids and lipoproteins of diets rich in lauric, palmitic, or oleic acids. Eighteen women and 14 men consumed in random order three experimental diets, each for 6 wk. The diets consisted of solid foods and contained 40% of energy as fat, of which 28% was supplied by the experimental fats. The fat high in lauric acid was a mixture of palm kernel oil (75%) and a high-oleic acid sunflower oil (25%); the fat high in palmitic acid consisted of dairy fat (55%), palmstearin (36%), and sunflower oil (9%); and the fat high in oleic acid consisted of dairy fat (37%) and sunflower oil (63%). The calculated nutrient composition was the same in each diet except for approximately equal to 8.5% of energy, which was provided by lauric, palmitic, or oleic acids. With the lauric acid diet the subjects' serum total cholesterol concentration increased by 0.22 mmol/L (P = 0.0121; 95% CI: 0.02, 0.41 mmol/L) as compared with the palmitic acid diet and by 0.48 mmol/L (P < 0.0001; 95% CI: 0.29, 0.67 mmol/L) compared with the oleic acid diet. Total cholesterol concentrations with the palmitic acid diet were 0.26 mmol/L (P = 0.0012; 95% CI: 0.07, 0.46 mmol/L) higher than with the oleic acid diet. High-density-lipoprotein (HDL)-cholesterol concentrations increased by 0.12 mmol/L (P = 0.006; 95% CI: 0.04, 0.20 mmol/L) with the lauric acid compared with the palmitic acid diet and by 0.14 mmol/L (P < 0.001; 95% CI: 0.07, 0.22 mmol/L) compared with the oleic acid diet. HDL-cholesterol concentrations with the palmitic acid and the oleic acid diet were the same. No effects were seen in serum triacylglycerol and lipoprotein(a) concentrations. We conclude that both lauric and palmitic acids are hypercholesterolemic compared with oleic acid. Lauric acid raises total cholesterol concentrations more than palmitic acid, which is partly due to a stronger rise in HDL cholesterol.

Dietary-fish effects on serum lipids and apolipoproteins, a controlled study.

In Maastricht and Zeist, The Netherlands, and Tromsø, Norway, a well-controlled study was performed on the effect of a fish-enriched diet on serum lipids, apolipoproteins A-1 and B, and fatty acid compositions of serum triglycerides and cholesterol esters. For 6 wk healthy male volunteers were given a daily dietary supplement consisting of 135 g mackerel paste (experimental group, n = 42) or meat paste (control group, n = 42). Dietary adherence was calculated on the basis of urinary excretion of a standard amount of lithium added to the supplements. Average compliance was 80%. Low-density-lipoprotein (LDL) and total serum cholesterol concentrations were unaffected. High-density-lipoprotein (HDL) cholesterol increased to a comparable degree in both groups. Triglyceride content of serum decreased in the fish group. Apolipoproteins A-1 and B (both in Maastricht subjects only) were only slightly affected. In the mackerel group the n-3 fatty acids increased significantly in serum cholesterol esters and triglycerides; the n-6 fatty acids decreased in cholesterol esters only.

Evaluation of the relation between n-3 and n-6 fatty acid status and parity in nonpregnant women from the Netherlands.

BACKGROUND: We previously observed an inverse relation between parity and docosahexaenoic acid (DHA) status in pregnant women in the Netherlands. This implies that maternal DHA status may not fully normalize after a mature pregnancy. OBJECTIVE: The objective was to investigate the relation between the essential fatty acid status (in particular the DHA status) of nonpregnant women and the number of completed pregnancies and whether the number of previous pregnancies is associated with a lower DHA status in women from the Netherlands. DESIGN: This was a cross-sectional study of 129 healthy nonpregnant women who completed 0, 1, 2, 3, or 4 mature, uncomplicated, singleton pregnancies. RESULTS: The relative amount of DHA in the plasma phospholipids of nulliparous women and of mothers who completed 1-4 pregnancies (duration since last pregnancy: 3.9 +/- 2.4 y) was not significantly different; a significant correlation between parity and the percentage of DHA in the phospholipids was not observed either. The percentage of DHA in the phospholipids of erythrocytes of mothers was significantly lower than the percentage in the erythrocytes of the nulliparas (P = 0.013), but no significant correlation between the percentage of DHA in the phospholipids of erythrocytes and parity was found. The time interval between the different pregnancies did not influence maternal DHA status. CONCLUSIONS: No relation was found between DHA status and parity in the nonpregnant Dutch women whose last pregnancy was completed > or = 1 y previously. Maternal DHA status, as reflected in plasma and erythrocyte phospholipids, probably normalized within 1 y after the last partus. Whether this is true for other tissues remains to be determined.

Essential fatty acid composition of plasma phospholipids and birth weight: a study in term neonates.

BACKGROUND: Essential fatty acids (EFAs) in umbilical cord blood samples are associated with attained birth weight in premature infants and low-birth-weight neonates. OBJECTIVE: The objective was to investigate relations between the EFA composition of cord and maternal plasma phospholipids and birth weight in term neonates. DESIGN: This was a cross-sectional study in 627 singletons born at term. The plasma phospholipid EFA composition of the mothers was determined by gas-liquid chromatography at study entry (< or = 16 wk gestation), at delivery, and in cord plasma at birth. Birth weights were normalized to SD scores. RESULTS: In cord plasma, the dihomo-gamma-linolenic acid concentration was positively related to weight SD scores. Both arachidonic acid (AA) and docosahexaenoic acid (DHA) were negatively related to weight SD scores. EFA-status indicators showed similar negative associations, whereas eicosatrienoic acid concentrations were positively related to neonatal size. In maternal plasma, proportions of n-3 long-chain polyenes (LCPs) and n-6 LCPs decreased during pregnancy. Larger decreases in AA, DHA, n-3 LCP, and n-6 LCP fractions were observed in mothers of heavier babies. Higher concentrations of LCPs in maternal plasma were, however, not related to a larger infant size at birth. CONCLUSIONS: A lower biochemical EFA status in umbilical cord plasma and a larger decrease in maternal plasma LCP concentrations are associated with a higher weight-for-gestational-age at birth in term neonates. Our findings do not support a growth-stimulating effect of AA or DHA; however, they do suggest that maternal-to-fetal transfer of EFAs might be a limiting factor in determining neonatal EFA status.

Long-chain polyunsaturated fatty acids, pregnancy, and pregnancy outcome.

During pregnancy, essential long-chain polyunsaturated fatty acids (LCPUFAs) play important roles as precursors of prostaglandins and as structural elements of cell membranes. Throughout gestation, accretion of maternal, placental, and fetal tissue occurs and consequently the LCPUFA requirements of pregnant women and their developing fetuses are high. This is particularly true for docosahexaenoic acid (DHA; 22:6n-3). The ratio of DHA to its status marker, docosapentaenoic acid (22:5n-6), in maternal plasma phospholipids decreases significantly during pregnancy. This suggests that pregnancy is associated with maternal difficulty in coping with the high demand for DHA. The DHA status of newborn multiplets is significantly lower than that of singletons; the same is true for infants of multigravidas as compared with those of primigravidas and for preterm compared with term neonates. Because the LCPUFA status at birth seems to have a long-term effect, the fetus should receive an adequate supply of LCPUFAs. Data from an international comparative study indicated that, especially for n-3 LCPUFAs, the fetus is dependent on maternal fatty acid intake; maternal supplementation with LCPUFAs, their precursors, or both increased LCPUFA concentrations in maternal and umbilical plasma phospholipids. However, significant competition between the 2 LCPUFA families was observed, which implies that effective supplementation requires a mixture of n-6 and n-3 fatty acids. Further research is needed to determine whether higher LCPUFA concentrations in plasma phospholipid will have functional benefits for mothers and children.