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.

Pregnancy-induced hypertension: maternal and neonatal plasma lipid-soluble antioxidant levels and its relationship with fatty acid unsaturation.

OBJECTIVE: Our purpose was to investigate whether plasma lipid-soluble antioxidant levels during the third trimester of pregnancy and immediately after birth are altered in women with pregnancy-induced hypertension. DESIGN: Nested case-control study of women with pregnancy-induced hypertension. SUBJECTS: A group of 23 women with (mild) pregnancy-induced hypertension and their neonates, were compared with 23 matched controls with uncomplicated pregnancies. METHODS: Concentrations of vitamin E isomers, several carotenoids, and retinol were determined by HPLC in venous plasma which had been stored for 2-5 y. Antioxidant levels were adjusted for the degree of fatty acid unsaturation in plasma phospholipids as analysed 2-5 y before. RESULTS: In the third trimester of pregnancy, lipid-soluble antioxidant levels were similar in women with pregnancy-induced hypertension and controls. From the third trimester to postpartum, mean (+/- s.e.m.) beta + gamma-tocopherol levels decreased by 0.38 +/- 0.17 mumol/l or 5% (P = 0.038) in the control group. In the pregnancy-induced hypertension group, however, plasma levels of most antioxidants decreased from the third trimester to postpartum, but only the decreases in plasma levels of beta + gamma-tocopherol of 1.08 +/- 0.27 mumol/l or 26% (P = 0.042), of alpha-tocopherol of 2.51 +/- 1.58 mumol/l or 6% (P = 0.024), and of lutein of 0.13 +/- 0.04 mumol/l or 15% (P = 0.013) reached statistical significance as compared with the changes in the control group. At the same time, the polyunsaturated fatty acid unsaturation index of plasma phospholipids (UI) decreased in the pregnancy-induced hypertension group as well. Consequently, antioxidant levels, adjusted for UI, changed similarly in both groups. Umbilical vein plasma antioxidant levels were also similar after complicated and uncomplicated pregnancies. CONCLUSION: Plasma lipid-soluble antioxidant levels in mother and child are affected by mild pregnancy-induced hypertension, but this effect disappears after adjustment for fatty acid unsaturation.

Maternal and neonatal plasma antioxidant levels in normal pregnancy, and the relationship with fatty acid unsaturation.

During pregnancy, maternal plasma concentrations of the peroxidation-susceptible polyunsaturated fatty acids (polyenes) increase. In addition, the proportion of polyenes is higher in neonatal plasma than in maternal plasma. To study whether these increased amounts of polyenes affect antioxidant levels, we measured lipid-soluble antioxidants in maternal and neonatal plasmas obtained during thirty-five normal pregnancies. These values were then related to the degree of phospholipid-fatty acid unsaturation. Maternal plasma levels of tocopherols and lutein increased during pregnancy, as assessed at 14, 22, and 32 weeks of gestation. However beta-carotene levels decreased, and levels of other carotenoids remained unchanged. Retinol levels were only decreased at 32 weeks of gestation. The value for alpha-tocopherol: phospholipid-polyene unsaturation index (UI) also increased during pregnancy, despite the observed increase in UI. Corresponding ratios for several carotenoids and retinol, however, decreased during pregnancy. After delivery, maternal plasma levels of delta-tocopherol and beta + gamma-tocopherol, as well as beta + gamma-tocopherol: UI values, were lower than values at 32 weeks of gestation. Umbilical-cord plasma antioxidant levels and antioxidant: UI values, except retinol: UI, were significantly lower than maternal values. Significant and consistent cord v. maternal correlations were observed for plasma levels of beta + gamma-tocopherol, lutein and beta-carotene, but not for delta-tocopherol, alpha-tocopherol, lycopene, alpha-carotene, and retinol. In conclusion, although during pregnancy maternal plasma tocopherol levels increased concurrently with, or more than, fatty acid unsaturation in plasma phospholipids, the decrease in carotenoid: UI values during gestation, the decrease in maternal plasma levels of delta-tocopherol and beta + gamma-tocopherol after delivery, and the low neonatal antioxidant levels merit further investigation.

Fetal growth is associated positively with maternal intake of riboflavin and negatively with maternal intake of linoleic acid.

OBJECTIVE: To examine whether dietary factors in pregnancy are related to fetal growth. DESIGN: Prospective longitudinal study during pregnancy; midway through gestation a dietary history was obtained. SUBJECTS/SETTING: Subjects (n = 372) were participants in a study on maternal essential fatty acid status during pregnancy who did not have hypertension or any metabolic, cardiovascular, neurological, or renal disorder. Only pregnant white women with the intention to give birth in one of the three hospitals involved in the study were included. All three hospitals were located in the southern part of the Netherlands. STATISTICAL ANALYSES PERFORMED: The relation between maternal nutrition and fetal growth was evaluated using multiple regression analyses. RESULTS: Maternal intake of n-3 fatty acids plus arachidonic acid and of riboflavin were associated positively with fetal growth. A negative relation was observed between linoleic acid intake and fetal growth. APPLICATIONS/CONCLUSIONS: Our data suggest that the maternal diet during pregnancy is associated with fetal growth. Although this relationship ought to be more closely investigated, our results imply that much more attention should be paid to an adequate maternal diet during pregnancy, especially with respect to riboflavin and fatty acid intake.

Relation between birth order and the maternal and neonatal docosahexaenoic acid status.

OBJECTIVE: To investigate whether succeeding pregnancies will affect the maternal and neonatal docosahexaenoic acid (DHA, 22:6n-3) status. DESIGN: Cross-sectional study. SUBJECTS: Women who were pregnant for the 1st to 7th time and took part in a longitudinal study to investigate the essential fatty acid status of pregnant women and their infants. The total study population comprised 98 primigravidae (PG) and 146 multigravidae (MG). MAIN OUTCOME MEASURES: Fatty acid profiles of phospholipids isolated from maternal plasma samples collected during pregnancy and after delivery, and of umbilical plasma, vein and artery, obtained immediately after birth. RESULTS: The absolute (mg/L) and relative (% of total fatty acids) amounts of DHA in maternal plasma phospholipids (PL) were significantly lower in MG than in PG. In addition, a significant negative correlation was observed between gravida number and the DHA content in maternal plasma samples. The DHA deficiency index (22:5n-6/22;4n-6) was significantly higher and the DHA sufficiency index (22:6n-3/22:5n-6) was significantly lower in umbilical plasma of infants born of MG than in that of infants born of PG. The relative DHA content of umbilical artery and vein vessel walls was significantly lower in MG- than in PG-neonates and significant negative associations were observed between birth order and the relative amounts of DHA in cord tissues. CONCLUSIONS: These results indicate that the maternal DHA status becomes reduced after each following pregnancy, which may result in a lower neonatal DHA status. Whether or not this has also functional consequences needs to be investigated further.

Essential fatty acid status measured in umbilical vessel walls of infants born after a multiple pregnancy.

The essential fatty acid (EFA) status of full-term infants born after an uneventful, singleton pregnancy has been reported to be marginal. If this low EFA status is caused by a limiting maternal EFA supply, the higher total fetal EFA demand associated with a multiple pregnancy would result in an even lower EFA status of the infants born after a multiple pregnancy. Therefore, we compared the EFA status at birth of 30 pairs of twins, seven sets of triplets, and one set of quintuplets with that of 94 infants (51 preterm, 43 full-term) born after a singleton pregnancy. Phospholipid-associated EFA profiles of the umbilical vessel walls, considered a longer-term reflection of the fetal EFA status, were studied. After correction for gestational age at birth, levels of n-6 and n-3 EFAs were generally lower, while levels of EFA-deficiency indicating n-9 polyunsaturated fatty acids were significantly higher both in the draining umbilical arteries and the supplying veins of infants born after a multiple pregnancy. EFA profiles of twins and triplets were similar, but the average EFA status of the set of quintuplets was lower than that of twins and triplets. In conclusion, the observation that the EFA status of infants born after a multiple pregnancy is lower than that of infants born after a singleton pregnancy supports the view that the maternal EFA supply to the fetus is limiting. Considering the importance of EFAs and their longer chain derivatives for proper growth and development, this finding warrants further studies of the adequacy of the maternal EFA intake during pregnancy.

Essential fatty acid status of fetal plasma phospholipids: similar to postnatal values obtained at comparable gestational ages.

Hardly any direct information is available on the essential fatty acid (EFA) status of the fetus during intrauterine development. Therefore, we studied 86 umbilical plasma samples obtained by trans-abdominal puncture during ongoing pregnancies (18.3-39.0 weeks of gestational age). These were compared with 51 samples of umbilical cord blood, collected immediately after birth (gestational ages, 28.5-39 weeks). The total amounts of fatty acids in fetal plasma phospholipids (mg/l) did not change during gestation. The relative amounts of linoleic acid (% of total fatty acids) showed a slight increase (P = 0.03) during fetal maturation. Arachidonic acid (20:4n-6) decreased (both absolute (mg/l) and relative (% wt/wt) P < or = 0.0001), while docosahexaenoic acid (22:6n-3) increased (absolute P < 0.003, relative P < 0.0001) when pregnancy progressed. The EFA profiles of fetal samples were in general comparable with postnatal results of infants born at similar gestational ages. However, the fetal linoleic acid status was lower than the linoleic acid status of the neonates. The same was true for the overall EFA status. The results of this study indicate that the low EFA status observed in preterm infants at birth, is a developmentally related phenomenon.

Fat intake of women during normal pregnancy: relationship with maternal and neonatal essential fatty acid status.

OBJECTIVE: To study the relationships between the essential fatty acid (EFA) composition of maternal diet, maternal EFA status and the EFA status of healthy newborn infants. METHODS: A prospective longitudinal study was performed in which 176 pregnant women completed a food frequency questionnaire (FFQ) before 13, at 22, and at 32 weeks of gestation, so that changes in nutrient intake throughout pregnancy could be recorded. Around 22 weeks, a dietary history was performed and a maternal blood sample was collected. Immediately after delivery, a blood sample from the umbilical vein and a piece of the umbilical cord were collected. Fatty acid compositions were determined for phospholipids (PLs) isolated from maternal and umbilical plasma and from umbilical vein and artery vessel walls. RESULTS: No significant differences in the mean daily intake of total fat, saturated fat, mono-unsaturated fat, polyunsaturated fat and linoleic acid (18:2(n-6), LA) were observed between the three trimesters. Maternal LA intake was positively associated with LA levels in maternal and umbilical plasma and negatively associated with 20:3(n-9), 18:3(n-3), 20:4(n-3) and 22:5(n-3) levels in maternal plasma, with 20:5(n-3) levels in umbilical plasma and with 22:6(n-3) levels in umbilical vein vessel walls. Significant positive correlations for almost all (n-6) and (n-3) fatty acids were observed between maternal and umbilical plasma levels. CONCLUSIONS: The maternal dietary fat composition appears to be consistent during pregnancy. A high maternal LA intake may have a lowering effect on the maternal as well as on the neonatal (n-3) fatty acid status. Finally, neonatal EFA status is strongly related to maternal EFA status.

Some aspects of neonatal essential fatty acid status are altered by linoleic acid supplementation of women during pregnancy.

To study the effect of maternal linoleic acid [18:2(n-6), LA] supplementation during pregnancy on neonatal essential fatty acid status, pregnant women with relatively low plasma linoleic acid concentrations before 16 wk of gestation (n = 21) were supplied with foods rich in linoleic acid, resulting in an additional intake of 10 g/d of linoleic acid from the 20th week of gestation until delivery. One of the two control groups consisted of pregnant women with comparably low plasma linoleic acid concentrations at the start of the study (LL-control group, n = 22); the other consisted of women with habitually high plasma linoleic acid concentrations (HL-control group, n = 21). The neonatal essential fatty acid status was assessed by determining the fatty acid composition of phospholipids (PL) isolated from umbilical plasma and umbilical vessel walls. The maternal linoleic acid status in the LA-supplemented group increased to a level comparable to that of the HL-control group, but the neonatal linoleic acid status did not differ from that of either control group. Linoleic acid supplementation did result in slightly, but significantly, higher total amounts of (n-6) long-chain polyenes in umbilical plasma and vein vessel wall phospholipids compared with the LL-control group. This increase was associated with significantly lower total amounts of (n-3) long-chain polyenes. In the HL-control group, the concentration of (n-3) long-chain polyenes in umbilical plasma and vessel walls was significantly lower than in the LA-supplemented and the LL-control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison between the essential fatty acid status of preterm and full-term infants, measured in umbilical vessel walls.

The essential fatty acid (EFA) composition of umbilical vessel walls is increasingly being studied as a longer-term reflection of the fetal EFA status. We evaluated the EFA content of umbilical artery and vein vessel walls in 43 preterm infants and compared it with that of 43 full-term cord vessels. In addition, relations among cord vessel wall fatty acid composition, gestational age (GA) at birth, and anthropometric parameters at birth (weight, head circumference, and length) were explored in the preterm infants. Generally, n-6 and n-3 EFA levels were lower, while levels of EFA deficiency markers were higher in preterm than in term cords, both in the walls of the draining arteries and the supplying vein. In preterm cords, significant correlations were observed between GA at birth and levels of n-6 and n-3 EFAs (positive) and EFA deficiency markers (negative). Birth weight showed significant (P < or = 0.01), positive correlations with n-6 and n-3 EFA levels in the cord artery walls of preterm infants, all after correction for GA at birth. In conclusion, substantial differences between the EFA profiles of preterm and full-term cord vessel walls indicate a lower biochemical EFA status of the preterm than of the term fetus. This lower preterm EFA status might be a reflection of a physiologically lower EFA demand for growth and development of the preterm fetus than of the term fetus.

The composition of individual molecular species of plasma phosphatidylcholine in human pregnancy.

The molecular species composition of plasma phosphatidylcholine (PC) was measured in sequential blood samples from 13 pregnant women from 16 weeks of gestation to delivery at term. The increased total plasma PC concentration at term was due solely to increased concentrations of individual species containing palmitate (16:0) rather than stearate (18:0) at the sn-1 position. The specific increase of PC16:0/22:6 concentration in mid-gestation suggests that adaptations to maternal hepatic PC metabolism may provide a mechanism to ensure adequate supply of 22:6(n-3) to the fetus. While cord plasma PC was comparable to liver PC composition from three stillborn term infants, the compositions of these tissues differed from maternal plasma PC, which contained significantly more PC16:0/18:2 and PC18:0/18:2. These results suggest that, although fetal acquisition of polyunsaturated fatty acids (PUFA) is dependent on the maternal lipid supply, the detailed composition of fetal plasma PC may be regulated largely by intrinsic fetal mechanisms such as placental and liver PC metabolism. Similarly, the specific alterations to maternal plasma PC composition in pregnancy, which we postulate are associated with the supply of PUFA to the fetus, were substantially independent of variations in maternal dietary lipid nutrition.

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)

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.

The essential fatty acid status of mother and child in pregnancy-induced hypertension: a prospective longitudinal study.

OBJECTIVE: Our purpose was to investigate, in a prospective way, whether the altered essential fatty acid status observed in pregnancy-induced hypertension is a consequence of the disease or may contribute to its cause. STUDY DESIGN: Pregnant women healthy at the start of the study were asked to give a blood sample before 16 weeks, at 22 weeks, and at 32 weeks of gestation. After delivery a blood sample from the umbilical vein, a piece of the umbilical cord, and a maternal blood sample were collected. Fatty acid compositions were determined of the phospholipids isolated from plasma and umbilical arterial and venous vessel walls. The nutrient intake of the pregnant women was assessed by use of the dietary history method and food frequency questionnaires. The results of each woman with pregnancy-induced hypertension were compared with the results of three matched healthy controls. RESULTS: During pregnancy (16 to 32 weeks) no significant differences were observed in nutrient intake and maternal plasma fatty acid composition between the group with pregnancy-induced hypertension (n = 52) and the control group (n = 156). After delivery the relative amounts of 18:2(n-6) and 18:3(n-3) in maternal plasma were significantly lower in pregnancy-induced hypertension than in normal pregnancy. This was associated with significantly higher levels of (n-6) long-chain polyenes and cervonic acid (22:6[n-3]). In comparison with the situation at 32 weeks, the postpartum cervonic acid status increased in pregnancy-induced hypertension, whereas it decreased in normal pregnancy. The cervonic acid levels in umbilical plasma phospholipids were significantly higher after pregnancy-induced hypertension than after normal pregnancy. No significant differences were observed for the fatty acid content in umbilical vessel walls. CONCLUSION: The results indicate that the altered essential fatty acid status in pregnancy-induced hypertension is a late phenomenon and is therefore unlikely to have contributed to the pathogenesis of pregnancy-induced hypertension. Moreover, the neonatal essential fatty acid status is not negatively affected by pregnancy-induced hypertension.

Essential fatty acid status of neonates born to Inuit mothers: comparison with Caucasian neonates and effect of diet.

Fatty acid compositions were determined of phospholipids isolated from venous cord plasma and from the walls of umbilical arteries and veins, collected from healthy, a terme, Inuit and Caucasian (Dutch) neonates. The Inuit fatty acid profiles were characterized by a lower essential fatty acid (EFA) status, with higher levels of monounsaturated fatty acids, of Mead acid [20:3(n-9)] and its direct elongation product, and with lower amounts of the longer chain (greater than or equal to 20 carbon atoms), highly unsaturated (greater than or equal to 4 double bonds) fatty acids of both the (n-3) and (n-6) families. Levels of linoleic- and dihomo-gamma-linolenic acids were higher in Inuit as compared to Caucasian neonates, which suggests a low activity of the delta-5-desaturase in the Inuit. Within the Inuit group, a higher intake of marine food was associated with a better neonatal (n-3) status. Although the differences between Inuit and Caucasian neonates may be of genetic rather than of dietary origin, the results imply that dietary long-chain (n-3) or (n-6) fatty acids may be particularly important during pregnancy in Inuit mothers. Further studies are indicated with respect to the EFA content of the habitual Inuit diet and levels of delta-5-desaturase activity in the Inuit.

Fatty acid composition of serum lipids of mothers and their babies after normal and hypertensive pregnancies.

The biochemical essential fatty acid (EFA) status of neonates born after normal and hypertensive pregnancies (PIH) and that of their mothers was assessed by measuring the fatty acid composition of phospholipids (PL), triglycerides (TG) and cholesterol esters (CE) of umbilical cord serum and maternal serum, respectively. Relative contents of linoleic acid of serum PL and CE were significantly lower in mothers with PIH compared to normal pregnancies. Most other (n-6) polyenes in PL tended to be higher under hypertensive conditions. Total maternal (n-3) polyenes of serum PL were significantly higher in PIH, mainly due to clupanodonic acid, 22:5 (n-3), and cervonic acid, 22:6 (n-3). Total maternal (n-7) and (n-9) fatty acids were also significantly higher in PIH (PL and CE). The results indicate that PIH is associated with a relative increased unsaturation of maternal serum PL, which might facilitate the placental transfer of long-chain, polyunsaturated fatty acids. As a result, the neonatal EFA status after PIH only slightly differs from normal.

Biochemical EFA status of mothers and their neonates after normal pregnancy.

The essential fatty acid (EFA) status of neonates was compared with that of their mothers by determining the fatty acid compositions of phospholipids (PL), isolated from umbilical arterial and venous tissue, blood cells (BC) and plasma, from maternal venous plasma and BC, and from non-infarcted placental tissue. The PL of umbilical arterial tissue (efferent fetal vessels) contained fewer fatty acids of the (n-6) family and more of the (n-9) family than umbilical venous tissue (afferent fetal vessel). The relative amounts of (n-6) and (n-3) fatty acids were less in arterial than in venous plasma. Mead acid, 20:3(n-9), the presence of which indicates a poor EFA status, was 5 times higher in the efferent than in afferent cord vessels. In neonatal plasma and BC it was twice as high as compared with maternal levels. In general, the fatty acid composition of the placenta PL showed a comparable pattern as neonatal venous plasma PL. These findings demonstrate that the biochemical EFA status of neonates after a normal pregnancy is not optimal. The significant correlations between neonatal and maternal EFAs indicate that the neonatal EFA status depends on the EFA content of the maternal diet.