Erythrocyte fatty acid composition in term infants fed human milk or a formula enriched with a low eicosapentanoic acid fish oil for 4 months

When term infants are fed standard formula that does not contain long-chain polyunsaturated fatty acids (LC-PUFA), they still show lower levels of docosahexaenoic acid (DHA) in red blood cell (RBC) phospholipids by several weeks or months postnatally. This study was designed in order to evaluate a potential alternative for supplementing term infant formulas with DHA by adding a high-DHA/low-eicosapentanoic acid fish oil to levels similar to that in human milk (0.3%). A total of 37 term infants were included in the study at 3 days of life. DHA concentrations remained stable between inclusion and 4 months of life at around 8% of the RBC phospholipids in the LC-PUFA enriched formula-fed group whereas it decreased significantly in the standard formula-fed group. In the human milk-fed group, RBC DHA concentrations at 4 months of age were significantly lower than that at birth and were significantly correlated with the duration of breast feeding (r = 0.85; P = 0.0002). A significant decrease of arachidonic acid between inclusion and 4 months of age was observed in the enriched formula-fed group and reached a mean value at 4 months, which was significantly lower than that observed in the human milk or standard formula-fed groups (P < 0.0001). Conclusion Supplementing term formulas with a high-docosahexaenoic acid/low-eicosapentanoic acid fish oil up to 4 months of age is efficient in improving docosahexaenoic acid status, however it increases the risk of impaired n-6 fatty acid status. Received: 25 September 1998 / Accepted: 14 June 1999     

The fatty acid composition of banked human milk and infant formulas: The choices of milk for feeding preterm infants

The fatty acid composition of 48 samples of banked human milk for preterm infants and four standard infants formulas available in Finland were analysed by capillary gas liquid chromatography. The banked milk was collected from mothers who had given birth 0–8 weeks previously. Saturated fatty acids accounted for approximately 50% of the fatty acids in both human milk and the formulas, while the relative content of monoenoic fatty acids tended to be higher in human milk than in the formulas. The relative content of 182n–6 was higher in the formulas (range 14.7%–23.2%) than in human milk (median 9.1%, range 6.3%–13.4%). Fat of banked human milk contained 0.9% and 0.7% polyunsaturated fatty acids with 20 and 22 carbon atoms (LCP), respectively, which is comparable to that of fresh mature human milk. In contrast, LCP could not be detected in any of the formulas. Conclusion: Banked human milk is a good source of LCP and offers a good alternative to LCP containing formulas.     

Effects of Pyrimethamine and Folic Acid on Plasma Level of 5-Methyltetrahydrofolic Acid in Rats

Abstract: The relationship between pyrimethamine (PYR) teratogenesis and the plasma level of 5-methyltetrahydrofolic acid (5MF), known as an active form of folate in plasma, was studied in rats using an HPLC-ECD method for 5MF determination. The rat received, for 5 days, in-feed PYR with or without folic acid (FA), which was previously reported as a potentiator of PYR teratogenesis. PYR alone caused a dose-dependent decrease in the plasma 5MF level after the 5 day dosings. A potentiated decrease in the 5MF level was observed after the concomitant dosing of PYR with FA. The concomitant dosing of PYR 1.6 mg/kgBW/day (subteratogenic dose of PYR alone) with FA 50 mg/kg/day, which was 100% teratogenic dose in our previous report, decreased the 5MF level more than that after the dosing of PYR 3.6 mg/kg/day alone (100% teratogenic dose of PYR alone).
The sequential changes of the plasma 5MF level after the single oral dosing of PYR 3.6 mg/kg with or without oral FA 50 mg/kg also revealed a strong potentiative effect of oral FA on the 5MF-level-lowering effect of PYR. These results indicate that a decrease in the plasma 5MF level may be related to PYR teratogenesis.     

危重症患儿血清脂肪酸构成的临床研究

目的 探讨危重症患儿血清游离脂肪酸构成及含量的变化.方法 采用气相色谱法测定27例危重症患儿和34例健康儿的血清游离脂肪酸谱,比较健康儿、危重症患儿恢复前后的血清游离脂肪酸谱的改变.结果 危重症阶段,血清中棕榈酸、棕榈油酸、油酸、山嵛酸、花生四烯酸及二十碳五烯酸的含量较健康者明显增高(P＜0.05);危重症抢救成功者恢复两周后,血清中豆蔻酸、棕榈酸、棕榈油酸、油酸、花生酸的含量较健康者明显增高(P＜0.05).结论 危重症阶段及危重症抢救成功者恢复后,患儿血清游离脂肪酸谱有变化;危重症的严重应激状态影响血清游离脂肪酸的构成及含量.     

兴奋性氨基酸与儿童抽动障碍的关系

目的 探讨兴奋性氨基酸(EAAs)中谷氨酸(GLU)、天门冬氨酸(ASP)在儿童抽动障碍发病机制中的作用。方法 采用高效液相色谱法检测48例抽动障碍患儿血浆GLU、ASP水平,其中暂时性抽动13例,慢性多发性抽动20例,抽动-秽语综合征15例;单纯性抽动23例,抽动并多动障碍25例。结果1.抽动障碍患儿血浆GLU水平明显高于对照组(P<0.01)。2.慢性抽动组和抽动-秽语综合征组血浆GLU、ASP分别与对照组和暂时性抽动组比较,结果前两者血浆GLU水平明显高于对照组和暂时性抽动组(P<0.05,P<0.01)。各组血浆ASP水平比较,无显著性差异(P>0.05)。3.抽动并多动障碍组血浆GLU水平明显高于单纯性抽动组(P<0.01)。各组血浆ASP水平与对照组比较无显著性差异(P>0.05)。结论 儿童抽动障碍存在EAAs水平变化,GLU可能参与抽动障碍的病理生理过程。     

上海地区人乳中脂肪酸成分的研究

目的对上海地区人乳脂肪酸成分再次进行调查,以获得上海地区人乳脂肪酸成分的最新数据。方法选择健康产妇31例,平均年龄(27±4)岁,平均孕期(39±1)周,婴儿平均出生体质量为(3 405±375)g。采集每位产妇产后1～7 d的初乳、14 d和28 d的过渡乳以及42 d的成熟乳,采用气相色谱法对人乳中的脂肪酸成分进行测定。结果人乳中的总脂肪酸含量从初乳、过渡乳到成熟乳逐渐增加;饱和脂肪酸的含量在1～7 d的初乳中逐渐增加,至过渡乳和成熟乳逐渐下降;单不饱和脂肪酸含量在1～7 d的初乳中逐渐降低,到过渡乳和成熟乳又逐渐升高;长链多不饱和脂肪酸、花生四烯酸(AA)和二十二碳六烯酸(DHA)的含量在初乳中很高,到成熟乳后明显降低,而必需脂肪酸、亚油酸(LA)和α-亚麻酸(ALA)则随哺乳期的延长逐渐增加。与10年前的上海人乳资料相比较,DHA含量有所增加,而ALA含量却有下降。结论人乳中的脂肪酸含量随哺乳期的延长不断发生变化。中国上海地区人乳中必需脂肪酸、LA的含量显著高于国外报道。     

Maternal and fetal circulation of unusual bile acids: A pilot study

Background: Large amounts of unusual bile acids are synthesized by the fetal liver in late gestation. These compounds are mostly transferred from fetus to mother, although some are excreted into the amniotic fluid. We investigated the role of placental transfer of bile acids in fetal bile acid metabolism, particularly with respect to the unusual bile acids (1β‐hydroxylated and ketonic bile acids). Methods: We measured concentrations of bile acids in umbilical cord blood and urine of newborn infants, and in perinatal maternal serum and urine, using gas chromatography‐mass spectrometry. Serum and urine specimens from healthy non‐pregnant women were used as controls. Results: In newborn infants at delivery, cord blood and urine contained mostly primary and 1β‐hydroxylated bile acids, respectively. We also detected large amounts of ketonic bile acids in their urine, and the urinary concentration of total bile acids was elevated. Main maternal bile acids at 30 and 35 weeks of gestation and at delivery were 1β‐hydroxylated bile acids. After delivery, main bile acids changed from 1β‐hydroxylated bile acids to primary bile acids (P < 0.03), which also predominated in healthy non‐pregnant women. Conclusion: Fetally synthesized unusual bile acids were transported from fetus to mother. Pregnant women appear to excrete these bile acids into the urine, lowering both fetal and maternal serum bile acid concentrations.     

Retinal neurodevelopmental assessment with electroretinogram in patients with biliary atresia

BACKGROUND: To evaluate the effect of n-3 polyunsaturated fatty acid (PUFA) deficiency on the development of retinal function in children with biliary atresia (BA), we examined serum fatty acid levels and performed electororetinogram (ERG) in patients with BA. METHODS: The study group was composed of one male and four female BA patients (8-14 years) with serum bilirubin levels ranging from 0.40 to 1.48 mg/dL. All of the subjects were born as full-term infants. The fatty acid composition of total lipids in serum was analyzed by gas chromatography before the Kasai operation, approximately 10 months after the Kasai operation, and at the time of the ERG study. The ERG was recorded using corneal contact lens electrodes. RESULTS: Two of the five patients showed decreased levels of arachidonic acid and docosahexaenoic acid (DHA) before and after the operation, but no abnormal findings on ERG were detected in these patients. The other three patients had decreased levels of alpha-linolenic acid or DHA after the operation, but again, no abnormalities were found on ERG. CONCLUSION: These results suggest that insufficiencies of DHA and other n-3 PUFA in full-term infants might not have an influence on later ERG results.     

Fatty acid composition in breast milk and serum phospholipids of healthy term Chinese infants during first 6 weeks of life

AIM: To compare the fatty acid (FA) pattern in early and mature breast milk with that in plasma phospholipids of cord blood and breast-fed infants. METHODS: Forty-five mother-infant pairs from western Shanghai were studied. All infants, born at term with normal weight and length, were examined at birth and days 5 and 42. FA was analyzed by capillary gas-liquid chromatography. RESULTS: Cord blood showed higher concentration of long-chain polyunsaturated FA (LCPUFA) but lower saturated (SFA) and monounsaturated (MUFA) FA than postnatal infants' plasma. SFA decreased with age in the infants, but MUFA and linoleic acid (LA, 18:2omega6) increased. LCPUFA were lower in the plasma of 5-day-old infants than in cord blood, but LA was 80%, alpha-linolenic acid (ALA, 18:3omega3) 33% and the ratio omega-6/omega-3 42% higher. At day 42, LA increased further, LCPUFA remained similar, and was in breast milk lower than at day 5, while ALA and gamma-linolenic acid (18:3omega6) were higher. The activity index of desaturases indicated high Delta9 activity in breast milk and high activity of Delta5 desaturase in the infants. CONCLUSION: Breast milk FA composition changed markedly from day 5 to 42 with increasing correlation to infants' plasma. Calculation of desaturase activities suggested high capacity of LCPUFA synthesis.     

DEOXYCHOLIC AND SULPHOLITHOCHOLIC ACID CONCENTRATIONS IN SERUM DURING INFANCY AND CHILDHOOD

ABSTRACT. The concentrations of the two secondary bile acids (deoxycholic (DCA) and sulpholithocholic (SLCA) acid) were determined by radioimmunoassays in the serum of infants and children at ages ranging from 1 hour to 15 years. The same bile acids were measured also in the umbilical cord serum. The concentrations of the secondary bile acids in the serum of 1-hour old infants corresponded to those in the umbilical cord serum. Secondary bile acid serum concentrations were after the age of 7 days and up to the age of 3 to 6 months significantly lower than those in the umbilical cord serum. After the age of 6 months a significant increase in DCA serum concentrations could be shown. During the first 6 months of life DCA concentrations were clearly lower than those of SLCA. Our observations suggest that in the perinatal period DCA is mainly of maternal origin and that an alternate hepatic pathway may exist for the synthesis of lithocholic acid in early infancy.     

The composition of polyunsaturated fatty acids in erythrocytes of lactating mothers and their infants

Long-chain polyunsaturated fatty acids (LCPUFA) in breastmilk, specifically docosahexaenoic acid (DHA), are important for infant brain development. Accretion of DHA in the infant brain is dependent on DHA-status, intake and metabolism. The aim of this study was to describe changes in maternal and infant erythrocyte (RBC) DHA-status during the first four months of lactation. We examined 17 mothers and their term infants at 1, 2 and 4 months of age. Milk samples and RBC from the mothers and infants were obtained and analysed for fatty acid composition. Comparative analysis of the results showed that the content of DHA in maternal RBC-phosphatidylcholine (PE) decreased over the four month period and this was not accompanied by a decrease in DHA in infant RBC-PE (P = 0.005). The ratio of n-6 PUFA to n-3 PUFA increased over time in maternal RBC-PE, but not in infant RBC-PE (P < 0.001). The level of 22:5n-6 and the ratio of LCPUFA to precursor PUFAs in infant RBC was higher than in maternal RBC phospholipids. (P = and P < 0.001 respectively). We found a decrease in the level of LCPUFA in milk, specifically AA. However, we did not observe a significant decrease in milk DHA, which may have been due to two outliers. These results indicate better DHA-status and a higher n-3/n-6 PUFA in RBC of infants than in mothers. Whether these differences reflect preferential n-3 PUFA transfer via breastmilk or differences in PUFA-metabolism and utilization remains to be shown.     

The value of determination of homovanillic and vanillylmandelic acids in plasma for the diagnosis and follow-up of neuroblastoma in children

The plasma levels of homovanillic and vanillylmandelic acids were determined in 84 children with neuroblastoma prior to treatment to evaluate the usefulness of these parameters for the diagnosis of this disease. Elevated levels of one or both of these metabolites were observed in 50% of children with Stage I or II disease, in 88% of those with Stage III, in 93% of those with Stage IV and in 100% of children with Stage IV-S for a total of 88% of all patients. The clinical course of the disease can be followed readily by determination of these metabolites, successful therapy or surgery being accompanied by a corresponding decrease in the plasma levels and relapse by a corresponding increase. Determination of homovanillic and vanillylmandelic acids in plasma can obviate many of the problems associated with the collection of urine, especially in young children or ambulant patients, and thus facilitates a more frequent control with consequent advantages for the management of this disease.Abbreviations HVA Homovanillic acid - VMA Vanillylmandelic acid     

Comparison of the fatty acid composition of total lipids and phospholipids in breast milk from Japanese women

Fatty acid (FA) composition of total lipids (TL) and phospholipids (PL) in breast milk obtained from 20 normal delivery healthy women in Tokyo, Japan was analyzed. Total lipids were extracted from the samples and then PL, consisting of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (Sph) and phosphatidylinositol (PI), were separated by two-dimensional thin-layer chromatography. The FA composition of TL and PL was analyzed by gas liquid-chromatography. Compared with previous reports, the contents of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in TL from Japanese women were higher than those from Chinese and Canadian women, which may be caused by different dietary habits and food types consumed by those populations. The contents of arachidonic acid (AA; 20:4n-6), EPA and DHA in PE and PI were much higher than those in PC. In addition, no significant correlation of EPA or DHA content was found between TL and PL. The findings indicate that PL especially PE and PI in human milk may be a source of EPA and DHA for infants in the rapid developmental stage. These results should be considered in infant formula production.     

Trans fatty acids may impair biosynthesis of long-chain polyunsaturates and growth in man

Human diet contains large amounts of trans fatty acids originating primarily from hydrogenated fats. Consumption of trans fatty acids is considered safe for man, but side effects, including impaired biosynthesis of long-chain polyunsaturated fatty acids with 20 and 22 carbon atoms and reduced growth have been observed in animals. We studied whether or not there are indications of untoward effects of trans fatty acids in 29 premature infants (birth weight 1700 +/- 127 g, gestational age 33.6 +/- 1.4 weeks, mean +/- SD). Plasma samples obtained on day 4 of life were analysed for fatty acid composition. Trans octadecenoic acid and total trans fatty acids in plasma lipid fractions (% wt/wt) were not related to the precursor essential fatty acids linoleic and alpha-linolenic acids but correlated inversely to n - 3 and n - 6 long-chain polyunsaturated fatty acids and to the product/substrate ratios of long-chain polyunsaturate biosynthesis. Trans fatty acids were also inversely correlated to birth weight but not to gestational age. These data indicate a potential impairment of essential fatty acid metabolism and early growth by trans isomers in man, and question the safety of high dietary trans isomer intakes during pregnancy and the perinatal period.     

LOW MOLECULAR WEIGHT ORGANIC ACIDS IN THE URINE OF THE NEWBORN

Abstract The urinary excretion of seven selected low molecular weight organic acids in normal neonates was measured by gas chromatography. First and third to fourth day of life excretion of the following compounds was significantly unchanged: 3-OH-butyric acid (<13 μmol/mmol creatinine), succinic acid (approx. 43 μmol/mmol creatinine), adipic acid (approx. 12 μmol/mmol creatinine), 2-OH-glutaric acid (approx. 23 μmol/mmol creatinine), 3-OH-3-Me-glutaric acid (approx. 25 μmol/mmol creatinine) and citric acid (approx. 115 μmol/mmol creatinine). The excretion of 4-OH-phenyl-acetic acid increased during the first four days of life (from <8 μmol/mmol creatinine to approx. 20 μmol/mmol creatinine). It is postulated that urinary organic acid excretion in the neonate, which is clearly different from the adult urinary pattern, is a reflection of the specific neonatal metabolic situation, including a high fatty acid utilisation and a low protein catabolism.     

Polyunsaturated fatty acids in plasma lipids of diabetic children during and after diabetic ketoacidosis

BACKGROUND AND AIM: Previously we reported significantly higher plasma values of the essential fatty acids but significantly lower values of their longer-chain metabolites in diabetic children than in healthy controls. Here, we report data on the acute effect of diabetic ketoacidosis (DKA) on the fatty acid composition of plasma lipids. METHODS: Diabetic children (n=9; age: 16.1 [3.3] y; duration of diabetes: 5.0 [5.3.] y; daily insulin dose: 0.87 [0.66] unit/kg body weight/d; glycated haemoglobin: 13.4 [2.8] %; median [IQR]) were investigated at admission for DKA (during DKA) and at the end of the treatment of DKA (after DKA). Fatty acid composition of plasma lipid classes was determined by high-resolution capillary gas-liquid chromatography. RESULTS: Blood glucose (27.0 [8.5] vs 6.5 [1.6] mmol/l), pH (7.28 [0.35] vs 7.36 [0.06]) and base excess (-8.9 [15.1] vs -2.2 [6.3] mmol/l) were grossly abnormal during but not after DKA. Values of linoleic acid were significantly lower after than during DKA (non-esterifed fatty acids (NEFA): 15.55 [1.47] vs 12.27 [5.74] % wt/wt; triacylglycerols (TG): 20.84 [9.23] vs 17.40 [5.78]; p<0.05). In contrast, values of gamma-linolenic acid (NEFA: 0.87 [0.54] vs 2.34 [1.85]; p<0.05) and arachidonic acid (TG: 1.37 [0.71] vs 1.74 [0.57]; p<0.05) were significantly lower during than after DKA. The product/substrate ratios for delta-6 desaturation were significantly lower during than after DKA. CONCLUSION: Successful treatment of diabetic ketoacidosis is associated with a significant increase of long-chain polyunsaturated fatty acid values in blood plasma in diabetic children. This observation suggests that disturbances of essential fatty acid metabolism in diabetic children are related not only to diet but to hypoinsulinaemia as well.     

Fluctuation in the concentrations of vanillylmandelic acid and homovanillic acid in mass screening for neuroblastoma

Fluctuations in the amount of vanillylmandelic acid (VMA) and homovanillic acid (HVA) were studied in random urine samples from 13 infants with neuroblastoma. In patients with a small tumour, many samples contained amounts below the cut off values, suggesting that detection of a patient with neuroblastoma depended on mathematical probability. Using high performance liquid chromatography a patient with a tumour of about 10 g may well be overlooked, whereas a patient whose tumour weighs over 30 g would probably be detected. With qualitative screening, although more likely to miss a patient with low VMA excretion, a patient with a tumour weighing over 50 g would be detected. In a thorough hospital examination care should be exercised in interpreting borderline values of VMA and HVA; excretion information suggesting the existence of a tumour may aid localization by radiological imaging procedures.     

Expression pattern of fatty acid transport protein-1 (FATP-1), FATP-4 and heart-fatty acid binding protein (H-FABP) genes in human term placenta

Placental tissue from five women undergoing elective caesarean did not present differences in fatty acids or mRNA expression of FATP-1, FATP-4 and H-FABP in different placental locations. mRNA expression of FATP-1 and FATP-4 was significantly higher than H-FABP. The expression of L-FABP was too low in placenta for accurate quantification.     

Effect of different types of feeding on fatty acid composition of erythrocyte membrane lipids in full-term infants

Significantly higher levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) in plasma lipids have previously been reported in 2 to 8-wk-old as well as in 6 to 12-mo-old full-term infants fed exclusively human milk than in infants exclusively receiving formula without AA and DHA. However, in real life many infants receive both human milk and breast milk substitute formula. Healthy, full-term infants aged 2 to 12 mo and fed exclusively human milk (n = 29, age: 29.2 [14.6] wk, mean [SD], no human milk substitute formula), exclusively formula without AA and DHA (n = 30, age: 26.6 [15.2] wk, no human milk after the age of 1 mo) or combined diet (n = 38, age: 30.3 [12.8] wk, human milk for > 1 mo and breast milk substitute formula) were investigated in this cross-sectional study. Fatty acid composition of erythrocyte membrane phosphatidylethanolamine (PE), phosphatidylcholine and sphingomyeline lipids was determined by high-resolution capillary gas-liquid chromatography. The most pronounced diet-related differences were seen in PE lipids. Values of PE alpha-linolenic acid (0.07 [0.05] vs 0.26 [0.18] vs 0.19 [0.19], median [range from the 1st to the 3rd quartile], exclusively breastfed vs. exclusively formula fed vs combined diet), eicosapentaenoic acid (0.19 [0.13] vs 0.35 [0.23] vs 0.27 [0.31]) and dihomo-gamma-linolenic acid (1.34 [0.42] vs 1.86 [0.62] vs 1.58 [0.73]) were significantly lower in exclusively breastfed infants than in those fed formula, exclusively or partially. In contrast, PE AA (26.48 [2.50] vs 24.34 [4.74] vs 24.94 [3.64]) and DHA (4.93 [2.91] vs 3.51 [2.14] vs 3.58 [2.27]) values were significantly higher in exclusively breastfed infants than in the other two groups. Conclusion: In full-term infants aged 2 to 12 mo, erythrocyte membrane AA and DHA values are significantly higher with exclusive breastfeeding than with partial breastfeeding or exclusive feeding of formula without AA and DHA.