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.

Fetal learning and memory: weak associations with the early essential polyunsaturated fatty acid status.

To study the potential associations between fetal brain functions and the early essential polyunsaturated fatty acid (ePUFA) status, fetal learning and memory were assessed by repeated habituation rate measurements (HR) in fetuses of 30, 32, 34 or 36 weeks gestational age (GA). HR tests were repeated 10 min later. Both measurements were replicated in a second session at GA 38. Fetal short-term memory (STM) and long-term memory (LTM) were calculated from these habituation rates and related to concentrations of ePUFAs and their status markers, measured in umbilical artery wall phospholipids. The only relevant associations observed were positive trends (0.010

Relationship between long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age.

BACKGROUND/OBJECTIVES: Long-chain polyunsaturated fatty acids (LCPUFA) rapidly accumulate in the central nervous system (CNS) during the perinatal CNS growth spurt. This particularly concerns arachidonic acid (AA: 20:4n-6) and docosahexaenoic acid (DHA: 22:6n-3), which are thought to play important roles in CNS development and function. The aim of this study was to investigate the relation between motor function at 7 years of age and the levels of AA and DHA in umbilical venous plasma phospholipids, representing the prenatal availability of these fatty acids, and in plasma phospholipids sampled at age 7 years. SUBJECTS/METHODS: Motor function was assessed both quantitatively (the ability to perform a movement) and qualitatively (how the movement is performed) with the Maastricht Motor Test (MMT) in 306 children, born at term, at 7 years of age as part of a follow-up study. RESULTS: Backward stepwise multiple regression analyses revealed a significant, positive relation between umbilical plasma DHA concentrations (but not plasma DHA levels at 7 years) and the MMT total and quality score, corrected for the covariables gender, cognitive performance, gestational age and age at measurement (partial beta=0.13, P=0.01 and 0.14, P=0.01, respectively). The contributions of DHA and AA (both at birth and at 7 years of age) to quantitative movement scores were not significant. CONCLUSIONS: Our results suggest that prenatal DHA availability, which can be influenced by maternal dietary DHA intake during pregnancy, can have an effect on quality of movement in later life.

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.

Differences in cognitive performance during pregnancy and early motherhood.

BACKGROUND: Pregnancy has often been associated with cognitive deficits, but results are equivocal and little is known about how these deficits progress with time. METHOD: In the present study, the cognitive performance of 57 pregnant women was compared with that of 50 non-pregnant women matched for age and education, using a well-validated neurocognitive test battery at weeks 14, 17, 29, and 36 of pregnancy, and 32 weeks postpartum in the pregnant group and at comparable times in the non-pregnant group. RESULTS: Memory encoding and retrieval, as assessed with a word learning task, were significantly lower in the pregnant group than in the control group. This difference was still present at 32 weeks after delivery. The two groups did not differ in complex speed of information processing at any of the test moments; however, general speed of information processing was significantly compromised during early motherhood (week 32 postpartum). CONCLUSION: Thus, memory performance is poorer during pregnancy and early motherhood, and general speed of information processing is slower during early motherhood.

Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism.

Essential fatty acids (EFAs), and their longer-chain more-unsaturated derivatives (LCPUFAs) in particular, are essential for normal growth and cognitive development during childhood. Children with inborn errors of amino acid metabolism represent a risk population for a reduced LCPUFA status because their diet is low in EFAs and LCPUFAs. We have investigated the EFA and LCPUFA status of children with various amino acid metabolism disorders (not PKU) under treatment. Fatty acid profiles of plasma and erythrocyte phospholipids of 33 patients (aged 0-18 years) and 38 matched controls were determined by gas-liquid chromatography. Food-frequency questionnaires were used to assess the mean fatty acid intake. The dietary intake of the EFAs linoleic acid (LA) and alpha-linolenic acid (ALA) was comparable in both groups, while the LCPUFA intake was much lower in patients. This was associated with lower relative concentrations (% of total fatty acids) of n-3 docosahexaenoic acid (DHA) in plasma and erythrocyte phospholipids. Concentrations of arachidonic acid (AA) did not differ. The same was observed for the two EFAs LA and ALA. Thus, as compared to healthy controls, children with amino acid metabolism disorders have a lower intake of LCPUFAs and have lower concentrations of DHA but not of AA in plasma and erythrocyte phospholipids. This suggests that endogenous AA synthesis might guarantee an adequate AA status. The lower DHA status, however, warrants further investigations regarding the impact of DHA supplementation on growth and development of these children.

Essential fatty acids in erythrocyte phospholipids during pregnancy and at delivery in mothers and their neonates: comparison with plasma phospholipids.

Evidence that the essential fatty acid (EFA) status during pregnancy and at birth may not be optimal is mainly based on fatty acid profiles of maternal and neonatal plasma phospholipids. However, erythrocyte phospholipids may be more reliable than plasma phospholipids to reflect the EFA status of an individual. Therefore, the present study compares the levels of EFA and of their derivatives (LCPUFA) in erythrocyte and plasma phospholipids collected during pregnancy and at delivery of 184 women and of their infants at birth. In general, the relative concentrations of erythrocyte and plasma phospholipid fatty acids (% of total fatty acids) were strongly correlated, but not at early pregnancy. The overall changes in fatty acid concentrations during pregnancy were qualitatively comparable between erythrocytes and plasma, although the comparability became less towards the end of pregnancy. The changes in absolute amounts (mg/l) of fatty acids in erythrocyte and plasma phospholipids also compare quite well till 32 weeks of gestation, but not thereafter. Most maternal-neonatal differences in relative fatty acid concentrations are qualitatively comparable for erythrocyte and plasma phospholipids. However, significant differences were observed for the absolute amounts of arachidonic and docosahexaenoic acids. No matter these differences, plasma and erythrocyte phospholipids seem equally suitable to reliably quantify the more functional EFA and LCPUFA status based on fatty acid ratios. Correlations between neonatal and maternal fatty acid values at delivery/birth are highly significant in erythrocyte as well as plasma phospholipids. Neonatal erythrocyte (but not plasma) values also correlated strongly with maternal values at early pregnancy. Therefore, the neonatal EFA and LCPUFA status might be predicted on the basis of EFA and LCPUFA concentrations of maternal erythrocyte phospholipids at early pregnancy.

Increased risk of postpartum depressive symptoms is associated with slower normalization after pregnancy of the functional docosahexaenoic acid status.

Observational studies suggest an association between a low docosahexaenoic acid (DHA, 22:6n-3) status after pregnancy and the occurrence of postpartum depression. However, a comparison of the actual biochemical plasma DHA status among women with and without postpartum depression has not been reported yet. The contents of DHA and of its status indicator n-6 docosapentaenoic acid (n-6DPA, 22:5n-6) were measured in the plasma phospholipids of 112 women at delivery and 32 weeks postpartum. At this latter time point, the Edinburgh Postnatal Depression Scale (EPDS) questionnaire was completed to measure postpartum depression retrospectively. The EPDS cutoff score of 10 was used to define 'possibly depressed' (EPDS score > or =10) and non-depressed women (EPDS score <10). Odds ratios (OR) were calculated using a multiple logistic regression analysis with the EPDS cutoff score as dependent and fatty acid concentrations and ratio's as explanatory variables, while controlling for different covariables. The results demonstrated that the postpartum increase of the functional DHA status, expressed as the ratio DHA/n-6DPA, was significantly lower in the 'possibly depressed' group compared to the non-depressed group (2.34+/-5.56 versus 4.86+/-5.41, respectively; OR=0.88, P=0.03). Lactating women were not more predisposed than non-lactating women were to develop depressive symptoms. From this observation it seems that the availability of DHA in the postpartum period is less in women developing depressive symptoms. Although further studies are needed for confirmation, increasing the dietary DHA intake during pregnancy and postpartum, seems prudent.

Memory performance, but not information processing speed, may be reduced during early pregnancy.

Several studies have investigated aspects of cognitive functioning during late pregnancy or in the period around delivery. The present paper describes a controlled study of neurocognitive functioning in an early phase of pregnancy (14 weeks). Seventy-one pregnant women and 57 control subjects matched for age and education were tested with a cognitive test battery. Intentional learning was tested with the Verbal Learning Test, retrieval from semantic memory with the Fluency Test, and speed of information processing with the Concept Shifting Test, the Stroop test, and the Letter Digit Substitution Test. Results show that performance on tests measuring intentional learning and retrieval from semantic memory were lower in the pregnant group during early pregnancy as compared to a closely matched nonpregnant group. In contrast, speed of information processing was not different between the two groups. The differences observed in memory performance were not large and further research is needed to establish their clinical significance. In addition, the results should be interpreted with care, because our study has a cross-sectional design, which has limitations concerning the fact that preexisting performance differences might be possible. Therefore, longitudinal studies are essential to ascertain clear associations between pregnancy and cognitive performance.

Selective attention deficits during human pregnancy.

Using a longitudinal design we provide evidence that selective attention - a key component of cognition concerned with selection and preparation - is compromised during pregnancy. Selective attention was operationalized by means of the finger precuing technique, which selectively prepares two of four finger responses. The precuing benefit was taken as a measure of selective attention. Pregnant women showed a significant smaller precuing benefit at week 36 of pregnancy than did the control women, indicating loss of selective attention. Thirty-two weeks after childbirth this performance decrement had vanished, reflecting a functional recovery.

Long-chain polyunsaturated fatty acids at birth and cognitive function at 7 y of age.

OBJECTIVE: During the central nervous system (CNS) growth spurt, rapid accretion of long chain polyunsaturated fatty acids (LCPUFA) takes place. This particularly concerns docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are thought to play important roles in CNS development and function. The aim of this study was to investigate the relationship between cognitive performance at 7 y of age and LCPUFA levels in umbilical venous plasma phospholipids, representing the prenatal fatty acid availability, and in plasma phospholipids sampled at 7 y. DESIGN: As part of a follow-up study, the cognitive performance of 306 children, born at term, was assessed at 7 y of age with the Kaufman Assessment Battery for Children. Backward stepwise regression analysis was used to study the relationship between the outcomes and LCPUFA status. Social class, maternal intelligence and parenting skills were included as covariables, among others. RESULTS: Results show no significant association with either DHA or AA at birth and the cognitive performance at 7 y of age. The LCPUFA levels at 7 y were not associated with these outcomes either. Consistent with the literature, significant relationships were found between cognitive outcome measures and maternal education, maternal intelligence and the child's birthweight. CONCLUSIONS: In conclusion, our results do not provide evidence for a positive association between cognitive performance at 7 y and LCPUFA status at birth or at 7 y of age.

Red blood cell and plasma phospholipid arachidonic and docosahexaenoic acid levels at birth and cognitive development at 4 years of age.

OBJECTIVE: The long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) have biophysical properties that may mediate behavioral outcome, especially cognitive development. This study examined the relationship between the LCPUFA-status at birth and cognitive development at 4 years of age. METHODS: Cognitive development of 128 full-term neonates, whose umbilical venous plasma and/or red blood cell phospholipid DHA and AA levels were known, was assessed at 4 years of age. Pearson correlation coefficients were calculated between cognitive development and DHA, AA, maternal intelligence, birth weight, duration of breast-feeding and paternal educational attainment. Multiple linear regressions were employed with cognitive development as the dependent variable and whereby the above-mentioned covariables were entered in step one while each of the four LCPUFAs was entered in step two. RESULTS: In bivariate analysis, maternal intelligence, birth weight, maternal smoking habits during pregnancy, paternal education and duration of breast-feeding showed significant correlations with cognitive development (p<0.01). The association of cognitive development with DHA and AA measured zero in bivariate analysis (plasma levels: r=0.03 and r=-0.03, respectively; erythrocyte levels: r=0.01 and r=0.05) and in multiple regression analysis (plasma DHA r=0.01, p=0.88; plasma AA r=0.02, p=0.80; erythrocyte DHA r=-0.01, p=0.95) except for erythrocyte AA (r=0.15, p=0.09). CONCLUSION: No evidence was found for an association of the DHA or AA-status at birth with cognitive development at 4 years of age.

Components of the insulin resistance syndrome in seven-year-old children: relations with birth weight and the polyunsaturated fatty acid content of umbilical cord plasma phospholipids.

AIMS/HYPOTHESIS: According to the foetal origins hypothesis, there is a relation between foetal nutrition and adult glucose intolerance. In adults, insulin resistance has been associated with dietary polyunsaturated fatty acids. We examined whether the availability of polyunsaturated fatty acids during foetal life, as indicated by the fatty acid composition of cord blood samples, relates to childhood body composition and glycaemic control. METHODS: Fatty acid concentrations in umbilical cord blood were determined by gas-liquid chromatography in a birth-cohort of infants. When the children were seven years old, fasting glucose, insulin, proinsulin, and leptin levels were measured in 259 of these children, and relations with cord plasma fatty acid concentrations were studied. RESULTS: Cord plasma phospholipid gamma-linolenic acid and dihomo- gamma-linolenic acid concentrations were negatively related to insulin concentrations and calculated insulin resistance (homeostasis model assessment) at seven years of age. The gamma-linolenic acid concentrations were also negatively related to body fatness and proinsulin and leptin concentrations at seven years of age. No association was found for other polyunsaturated fatty acid concentrations at birth. Adjusted for age, sex, current weight, and gestational age, a lower birth weight related to higher values of insulin resistance variables. The highest insulin concentrations were found in children with a low birth weight and a low gamma-linolenic acid concentration at birth. The relations between gamma-linolenic acid concentration at birth and fasting insulin and calculated insulin resistance remained statistically significant when adjusted for birth weight. CONCLUSION/INTERPRETATION: These findings indicate that foetal availability or metabolism of gamma-linolenic acid could be involved in the early origins of insulin resistance.

Body composition and cardiorespiratory fitness indicators in prepubescent boys and girls.

Abstract. Relations between frequently used indicators of cardiorespiratory fitness, sex and body composition were studied in a birth-cohort based sample of young prepubescent children (age range: 6.8 - 8.2 years). The Bruce treadmill test was used to assess submaximal heart rate, endurance time (ET), calculated total work (W(total)) and maximal power output (P(max)) in 100 children (50 boys, 50 girls). Body composition was determined by skinfold measurements. In 17 children, maximal oxygen consumption was measured. Percent body fat was negatively associated with ET and relative oxygen uptake (ml x min(-1) x kg(-1)) and was positively related to submaximal heart rate at 6 minutes exercise (HR6). Fat-free mass was positively related to W(total), P(max) and absolute oxygen uptake (ml x min(-1)). Relative oxygen uptake (ml x min(-1) x kg(-1)) was related to ET. Absolute oxygen uptake (ml x min(-1)) was related to W(total) and P(max). The observed differences in indicators of cardiorespiratory fitness between boys and girls were largely attributable to a difference in body composition. The results further demonstrate that when oxygen uptake measurement is not feasible, W(total) or P(max) (expressed per kilogram fat-free mass) seem to provide better indicators of aerobic power than endurance time.

Interaction between a common variant of the cholesteryl ester transfer protein gene and the apolipoprotein E polymorphism: effects on plasma lipids and lipoproteins in a cohort of 7-year-old children.

BACKGROUND AND AIM: Common variations in genes, such as apolipoprotein E (apo E) and cholesteryl ester transfer protein (CETP), are major determinants of plasma lipid and lipoprotein levels. As both apo E and CETP contribute to the reverse transport of cholesterol to the liver, the effects of variations at the CETP locus may very well interact with the apo E genotype. METHODS AND RESULTS: As part of an ongoing study, the combined effects of the apo E genotype and heterogeneity at the CETP gene locus on plasma lipids and lipoproteins were studied in a birth cohort sample of 257 Dutch prepubescent boys and girls (aged 6.7-8.1 years). The children with an apo E2E3 genotype (carrying the epsilon 2 allele; arg158-->cys) had lower concentrations of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) than those with an apo E4E3 (carrying the epsilon 4 allele; cys112-->arg) or apo E3E3 genotype (homozygous for the parent epsilon 3 allele). These associations were statistically significant in children who were homozygous (p = 0.004 for LDL; p = 0.002 for apo B) or heterozygous (p < 0.0001 for LDL and apo B) for the absence of the Taq-IB polymorphism at the CETP gene locus (B2 allele), but not in those homozygous for the presence of this variant (B1B1). The highest plasma high-density lipoprotein cholesterol (HDL-C) concentrations were observed in children with the CETP B2B2 genotype. The difference in HDL-C levels between the CETP genotype groups was statistically significant only in E2E3 carriers (p = 0.01). The LDL/HDL ratio was significantly lower in E2E3 carriers, but not when combined with a CETP B1B1 genotype. CONCLUSION: These findings indicate that the apo E genotype and heterogeneity at the CETP gene locus have an additive and interactive influence on plasma lipid and lipoprotein levels in children.

Influence of dietary fat type on arterial thrombosis tendency.

Cardiovascular disease has a multifactorial aetiology, as is illustrated by the existence of numerous risk indicators, many of which can be influenced by the dietary fat type. It should be recalled, however, that only after a cause-and-effect relationship has been established between the disease and a given risk indicator (called a risk factor in that case), modifying this factor can be expected to affect disease morbidity and mortality. In this review, effects of dietary lipids on cardiovascular risk are considered, with special emphasis on modification of arterial thrombosis and platelet thrombotic processes, coagulation and fibrinolysis. Although epidemiological studies do not give entirely consistent results, replacement of dietary saturated by unsaturated fatty acids generally lowers cardiovascular morbidity and mortality. The few (secondary) prevention studies reported so far confirmed this for fish oil or fish oil concentrates, as well as for vegetable oils rich in oleic-, linoleic- or a-linolenic acids. Animal thrombosis models demonstrated that dietary unsaturated fatty acids reduce arterial thrombosis tendency as compared to saturated fatty acids. Using restenosis after percutaneous transluminal coronary angioplasty (PTCA) and occlusion of coronary artery bypass grafts (CABG) as human models of arterial thrombosis, fish oil treatment has been shown to have an anti-thrombotic effect, but results are inconsistent (PTCA) or need confirmation (CABG). Major thrombotic and anti-thrombotic conditions and processes include endothelial integrity, thrombotic functions of blood platelet, coagulation, and fibrinolysis. The dietary fat type can affect endothelial integrity, but results are inconsistent and often difficult to interpret in terms of arterial thrombosis tendency. The same can be concluded for platelet aggregation, especially because results of dietary interventions often depend on the aggregation measuring technique. Novel well-validated methods are required to solve this problem. Dietary fats can affect certain factors involved in blood coagulation and fibrinolysis. Thus, Factor VII activity is increased by the fat content of the diet. However, the dietary fat type seems of less importance. Studies addressing the effect of specific fatty acids on extrinsic clotting and thrombin formation in vivo did not produce consistent results. The same holds for the dietary fatty acid effects on promoters and inhibitors of the plasma fibrinolytic potential. Although trans unsaturated fatty acids may increase cardiovascular risk, this is probably not mediated by effects on arterial thrombosis.

Dietary vegetable oil and wood derived plant stanol esters reduce atherosclerotic lesion size and severity in apoE*3-Leiden transgenic mice.

The hypolipidemic and anti-atherosclerotic effects of vegetable oil- and wood-based dietary plant stanol esters were compared in female apoE*3-Leiden transgenic mice at relevant plasma cholesterol levels. The plant stanol esters derived from vegetable oil (sitostanol 65.7%, campestanol 30.1%) had different contents of sitostanol and campestanol than the plant stanol esters derived from wood (sitostanol 87.6%, campestanol 9.5%) or from a mixture of vegetable oil and wood (sitostanol 73.0%, campestanol 24.7%). The mice (10 per group) received for 38 weeks a control diet or diets containing 1.0% (w/w) plant stanol esters derived from either vegetable oil, wood or a mixture of both. Vegetable oil (-46%), wood (-42%) and vegetable oil/wood (-51%) plant stanol esters decreased the plasma cholesterol levels (P<0.0001) by reducing the cholesterol content in plasma very low density-, intermediate density- and to a lesser extent in low density-lipoprotein. Plant stanol ester feeding did not change plasma triglyceride levels. Dietary plant stanol esters reduced the atherosclerotic lesion area by 91+/-13% (vegetable oil), 97+/-4% (wood) and 78+/-34% (vegetable oil/wood) (P<0.0001) and the severity from regular intimal fatty streaks/mild plaques (on average type 2--3 lesions) in controls to individual intimal foam cells (