Gerard Hornstra

Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status

Although essential fatty acids (EFA) and their longer chain, more unsaturated derivatives play a major role during pregnancy, hardly any information is available with respect to the course of the maternal EFA status during an uncomplicated pregnancy and its relationship to the neonatal EFA status. Therefore, a longitudinal study was started in which 110 pregnant women gave repeated blood samples from the 10th week of gestation until delivery. After birth a blood sample from the umbilical vein and a maternal venous blood sample were collected as well, and 6 months after delivery a final blood sample from the mother was taken. The absolute (mg/l) and relative (% total fatty acids) amounts of the fatty acids in plasma phospholipids were determined. The total amounts of fatty acids increased significantly during pregnancy. This pattern was similar for the individual fatty acids and fatty acid families. The relative amount of linoleic acid (18:2n-6) did not change during pregnancy, whereas the relative amount of arachidonic acid (20:4n-6) decreased. Despite maternal mobilization of docosahexaenoic acid (22:6n-3, DHA), suggested by a temporary increase in the DHA status until 18 weeks gestation, the DHA status steadily declined thereafter. This pattern was associated with a progressive increase in the DHA deficiency index in maternal blood throughout pregnancy and resulted in a sub-optimal neonatal DHA status. The overall maternal EFA status also declined steadily during pregnancy. Therefore, the question arises whether the mother, under the prevailing dietary conditions, is able to meet the high fetal requirement for EFA.

Long chain polyunsaturated fatty acids (LC-PUFA) and perinatal development

This paper reports on the conclusions of a workshop on the role of long chain polyunsaturated fatty acids (LC‐PUFA) in maternal and child health The attending investigators involved in the majority of randomized trials examining LC‐PUFA status and functional outcomes summarize the current knowledge in the field and make recommendations for dietary practice. Only studies published in full or in abstract form were used as our working knowledge base.

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.

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.

Essential fatty acid status in neonates after fish-oil supplementation during late pregnancy

Healthy pregnant women (n 23) were supplemented with fish-oil capsules (2.7 g n-3 polyunsaturated fatty acids/d) from the 30th week of gestation until delivery. Subjects in a control group were either supplemented with olive-oil capsules (4 g/d, n 6) or received no supplementation (n 10). Fatty acid compositions of the phospholipids isolated from umbilical plasma and umbilical arterial and venous vessel walls were determined. Fatty acid compositions of maternal venous plasma phospholipids were determined as well. Maternal plasma phospholipids of the fish-oil-supplemented group contained more n-3 fatty acids and less n-6 fatty acids. Moreover, the amounts of the essential fatty acid deficiency markers Mead acid (20:3n-9) and Osbond acid (22:5n-6) were significantly lower. The extra amount of n-3 fatty acids consumed by the mothers resulted in higher contents of n-3 fatty acids, and of docosahexaenoic acid (22:6n-3) in particular, in the phospholipids of umbilical plasma and vessel walls. It is, indeed, possible to interfere with the docosahexaenoic acid status at birth: children born to mothers supplemented with fish oil in the last trimester of pregnancy start with a better docosahexaenoic acid status at birth, which may be beneficial to neonatal neurodevelopment.

Essential fatty acids in pregnancy and early human development

Essential fatty acids (EFA) are vitally important structural elements of cell membranes and, therefore, instrumental in the formation of new tissues. The primary EFA cannot be synthesized by man and, consequently, humans depend on dietary sources for an adequate EFA supply. Fetal development is associated with a high EFA requirement, and for its EFA supply, the developing fetus depends on the availability of maternal EFA. At delivery, a strong correlation is observed between the relative amounts of the various EFA in maternal and umbilical plasma phospholipids (PL), which underlines this fetal dependence. In a longitudinal study, we observed that, in women, the EFA status progressively decreases during pregnancy. This particularly holds for cervonic acid (CA, 22:6n-3, also named Docosahexaenoic acid, DHA), the major structural and functional EFA in the CNS. In addition, evidence was obtained for CA mobilization from maternal stores during pregnancy. Furthermore, the maternal CA status appeared significantly higher in primigravida than in multigravida. This was associated with a tendency for the first child of a given woman to have a higher CA status than her following children. This suggests that maternal CA mobilization during pregnancy occurs from a pool that is not easily replenished after pregnancy. The fetal CA status of premature infants is positively related to head circumference, birth weight and birth length. This may imply that increasing the fetal CA status could promote fetal growth and, thereby, improve the general prognosis of prematures. In conclusion, our data suggest that increasing the maternal EFA intake during pregnancy may be beneficial to both mother and child.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary alpha-linolenic acid on the conversion and oxidation of 13C-alpha-linolenic acid.

The effects of a diet rich in α-linolenic acid vs. one rich in oleic acid on the oxidation of uniformly labeled13C-α-linolenic acid and its conversion into longer-chain polyunsaturates (LCP) were investigatedin vivo in healthy human subjects. Volunteers received a diet rich in oleic acid (n=5) or a diet rich in α-linolenic acid (n=7; 8.3 g/d) for 6 wk before and during the study. After 6 wk, subjects were given 45 mg of13C-α-linolenic acid dissolved in olive oil. Blood samples were collected att=0, 5, 11, 24, 96, and 336 h. Breath was sampled and CO2 production was measured each hour for the first 12 h. The mean (±SEM) maximal absolute amount of13C-eicosapentaenoic acid (EPA) in plasma total lipids was 0.04 ±0.01 mg in the α-linolenic acid group, which was significantly lower (P=0.01) than the amount of 0.12±0.03 mg13C-EPA in the oleic acid group. Amounts of13C-docosapentaenoic acid (DPA) and13C-docosahexaenoic acid (DHA) tended to be lower as well. The mean proportion of labeled α-linolenic acid (ALA) recovered as13CO2 in breath after 12 h was 20.4% in the ALA and 15.7% in the oleic acid group, which was not significantly different (P=0.12). The cumulative recovery of13C from13C-ALA in breath during the first 12 h was negatively correlated with the maximal amounts of plasma13C-EPA (r=−0.58,P=0.047) and13C-DPA (r=−0.63,P=0.027), but not of13C-DHA (r=−0.49,P=0.108). In conclusion, conversion of13C-ALA into its LCP may be decreased on diets rich in ALA, while oxidation of13C-ALA is negatively correlated with its conversion into LCP. In a few pilot samples, low13C enrichments of n−3 LCP were observed in a diet rich in EPA/DHA as compared to oleic acid.

Hemostatic factors and platelet aggregation after a fish-enriched diet or fish oil or docosahexaenoic acid supplementation

The effects of a fish-enriched diet or dietary supplements consisting of either fish oil or a docosahexaenoic acid-rich oil (DHA-oil) on platelet aggregation and hemostatic factors were studied in healthy male students. After an experimental period of 15 weeks, the levels of tissue factor pathway inhibitor, prothrombin fragment 1+2 and fibrinogen as well as factor VII activity were not changed. Factor X activity was slightly decreased by the fish diet (P < 0.05). Collagen but not ADP-induced maximum platelet aggregation decreased in the fish diet and the fish oil groups (P < 0.05 in both). In the DHA-oil group there was a slight, statistically insignificant, increase of platelet aggregation which correlated significantly with the decrease of plasma triglycerides. Platelet aggregation measured 4 h after a standardized fat meal was lower than in the fasting state and this decrease correlated with the increase of plasma triglycerides. These results show that a fish diet and fish oil, but not DHA-oil, inhibit in vitro platelet aggregation and that hemostatic factors are not affected by moderate n-3 fatty acid supplementation.

Long-chain polyunsaturated fatty acids in preterm infants: Status at birth and its influence on postnatal levels

To determine the influence of the prenatal long-chain polyunsaturated fatty acid (LCP) supply on prenatal growth and on postnatal LCP levels, we studied 52 preterm infants and assessed the relations between the LCP status at birth (reflecting the prenatal LCP supply), gestational age and prenatal growth, and the relation between the LCP status at birth and at 37 to 42 weeks of gestational age. After a correction for gestational age at birth, significant relations (p < or = 0.05) were observed between anthropometric measurements at birth (weight, head circumference, and length) and LCP levels in the umbilical artery wall, the LCP content of which reflects the long-term fetal LCP status. Independent of the neonatal diet (human milk or formula), LCP levels in erythrocyte phospholipids at term were positively related to levels in the umbilical artery wall (docosahexaenoic acid (22:6n-3): p < or = 0.0003; arachidonic acid (20:4n-6): p = 0.02). Postnatal diet significantly influenced LCP levels in plasma phospholipids at term (docosahexaenoic acid: p < or = 0.004; arachidonic acid: p = 0.02); formula-fed infants had lower values. We conclude that the LCP status of preterm infants at birth is related to prenatal growth. Moreover, next to the postnatal enteral diet, the LCP status at birth significantly affects LCP levels at term postconceptional age. This finding may warrant further studies of the effects of essential fatty acid-enriched maternal diets during pregnancy on the neonatal LCP status at birth.

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.