Red blood cell fatty acid composition in low-birth-weight infants fed either human milk or formula during the first months of life

The fatty acid composition of red blood cell (RBC) phospholipids in low-birth-weight infants was determined immediately after delivery and during the first 3 months of life. In the first study, infants were fed either human milk or two formulas with different fatty acid compositions but no long chain polyunsaturated fatty acids (LCPUFA). Both groups of formula-fed infants had significantly lower levels of docosahexaenoic acid (DHA) in RBC phospholipids compared with breast-fed infants. RBC phospholipid DHA was similar in the two formula groups at all ages. In the second study, infants received either a non-supplemented or a LCPUFA-supplemented formula. DHA remained stable in RBC phospholipids of infants supplemented with LCPUFA, whereas DHA decreased in RBC phospholipids of unsupplemented infants. These results confirm that adding DHA to formulas is more effective than increasing 18:3 n-3 content, in maintaining RBC phospholipid DHA levels.     

A new breast milk supplement for preterm infants

Objective : To assess the effect of a new formula (Prenan), which contains n-3 and n-6 long-chain polyunsaturated fatty acids (LC PUFA) on the fatty acid profile of preterm infants.
Methodology : Plasma fatty acids were measured in 61 preterm infants at term by gas liquid chromatography. In 20 of these infants, paired samples were collected and changes in fatty acids with time analysed.
Results : Plasma docosahexaenoic acid (DHA) levels were higher in those who had been fed expressed breast milk (EBM) ±/or Prenan compared with those fed standard formula ± EBM, P <0.05. The plasma arachidonic acid (AA) levels of infants fed Prenan were not different to those fed EBM, both groups achieving higher levels than infants fed standard formula, P <0.05. Further, paired analysis demonstrated that DHA levels increased in infants changed from standard formula to Prenan to levels equal or higher than those of fully breast-fed infants ( P <0.01), whereas DHA levels remained unchanged with time in all other groups.
Conclusions : The fatty acid composition of Prenan enables preterm infants fed formula to have plasma DHA and AA levels similar to those of infants fed breast milk and consequently different to those of infants fed standard formula. Prenan is an appropriate supplement to breast milk for preterm infants in that it provides LC PUFA as well as additional phosphorus and protein without exposing the infant to intact cows milk protein.     

The influence of prematurity and long chain polyunsaturate supplementation in 4-week adjusted age baboon neonate brain and related tissues

Clinical studies show that docosahexaenoic acid (DHA) and arachidonic acid (ARA) supplemented formula improve visual function in preterm infants, however improved fatty acid status is known only for plasma and red blood cells (RBC) since target organs cannot be sampled from humans. Baboons were randomized to one of four groups: Term breast-fed (B); Term formula-fed (T-); Preterm formula-fed (P-); and Preterm DHA/ARA-supplemented formula-fed (P+). The P+ contained 0.61 +/- 0.03% DHA and 1.21 +/- 0.09% ARA, and breast milk had 0.68 +/- 0.22% and 0.62 +/- 0.12% as DHA and ARA, respectively. The B and P+ groups had significantly higher DHA concentration in all tissues than T- and P-. The P- group showed dramatically lower DHA content of 35%, 27%, 66%, and 75% in the brain, retina, liver, and plasma, respectively, compared with B. Supplementation prevented declines in DHA levels in the retina, and liver, and attenuated the decline in brain, plasma and RBC of preterm animals. In contrast, ARA was not significantly lower compared with B in any group in any tissue but was significantly elevated in liver and brain. RBC and plasma DHA were correlated with DHA in tissues; RBC/plasma ARA were uncorrelated with tissue ARA. We conclude that 1) DHA drops precipitously in term and preterm primates consuming formula without long chain polyunsaturates, while 22:5n-6 concentration rises; 2) tissue ARA levels are insensitive to dietary LCP supplementation or prematurity, 3) plasma and RBC levels of ARA are uncorrelated with total ARA levels; 4) DHA levels are correlated with group effects and are uncorrelated within groups.     

Docosahexaenoic acid status of term infants fed breast milk or infant formula containing soy oil or corn oil.

The objective of this study was to compare circulating lipid docosahexaenoic acid [22:6(n-3), DHA] levels in term infants fed a powdered (CORN oil) or liquid (SOY oil) infant formula or human milk (HM). Infants whose mothers chose not to breast feed were randomly assigned to the CORN or SOY formula group. The formula fat differed in linolenic acid [18:3(n-3)] content: it was 0.8% for the CORN and 4.8% for the SOY. Linoleic acid [18:2(n-6)] was 31.5 and 34.2% fatty acids in the CORN and SOY formula, respectively. The formulas or HM were fed from birth through 8 wk of age, and growth and the plasma and red blood cell (RBC) phospholipid fatty acid composition was determined at 3 d, 4 wk, and 8 wk of age. Growth did not differ among groups. The plasma phospholipid and RBC phosphatidylethanolamine DHA was similar in the CORN and SOY formula groups at all ages. Plasma and RBC phosphatidylethanolamine levels of DHA were significantly lower in infants fed the CORN or SOY formula than in infants fed HM during wk 4 and 8. Plasma and RBC 22:5(n-6) was not increased in the formula groups at any age. The formula content of linolenic acid had no effect on the RBC or plasma DHA levels of the infants. The biologic or functional significance of the lower plasma and RBC DHA in infants fed formula rather than HM is unknown. The need for a dietary source of DHA and specificity of plasma or RBC phospholipid DHA as a measure of desaturation and elongation of linolenic acid in developing organs remains uncertain.     

Effect of fish oil supplementation on the n-3 fatty acid content of red blood cell membranes in preterm infants

Very low birth weight infants demonstrate significant reductions in red blood cell membrane docosahexaenoic acid (DHA, 22:6n-3) following delivery unless fed human milk. The purpose of the present study was to determine if a dietary source of DHA (MaxEPA, R. P. Scherer Corporation, Troy, MI) could prevent the decline in red blood cell phospholipid DHA in very low birth weight infants whose enteral feeding consisted of a preterm formula without DHA. Longitudinal data were obtained on membrane phospholipid DHA in both unsupplemented and MaxEPA-supplemented infants by a combination of thin-layer and gas chromatography. These infants (n = 39) ranged in age from 10 to 53 days at enrollment (0 time). At enrollment, phospholipid DHA and arachidonic acid (20:4n-6) were inversely correlated with age in days. During the study, mean red blood cell phospholipid DHA declined without supplementary DHA as determined by biweekly measurement, but infants supplemented with MaxEPA maintained the same weight percent of phospholipid (phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine) DHA as at enrollment. The pattern of red blood cell phospholipid fatty acids in supplemented infants was similar to that reported for preterm infants fed human milk.     

Assessment of feeding different amounts of arachidonic and docosahexaenoic acids in preterm infant formulas on the fatty acid content of lipoprotein lipids

This study evaluated preterm infants of less than 2.3 kg birth weight fed commercial formula (Preemie SMA^®) devoid of arachidonic acid (AA) and docosahexaenoic acid (DHA) and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32-1.1% AA and 0.24-0.75% DHA in the fat component of the formula. An analogous group of infants fed on their mothers' breast milk and a breast milk fortifier was also studied. Individual lipoprotein fractions were isolated from blood samples collected at 12 d of age and after a further 4 wk of feeding. The fatty acid content of individual lipid components, isolated from each lipoprotein fraction was quantitatively determined in order to identify change in marker pools of essential fatty acid. The high density lipoproteins (HDL) and low density lipoproteins (LDL) phospholipid and cholesterol ester fractions contain most of the AA and DHA found in the lipoprotein fractions (total of 0.49% and 0.35%, respectively). Infants fed a formula without AA and DHA showed a reduction in AA level in the phospholipid fraction of all lipoproteins and in the HDL and LDL cholesterol ester fraction. A reduced level of DHA was also observed primarily in the lipoprotein phospholipid fraction in comparison with infants fed breast milk or infant formula containing AA and DHA. Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the level of AA found in the HDL and LDL phospholipid fraction. From comparison of the fatty acid levels present in the lipoproteins it appears that a formula level of 0.49% AA and 0.35% DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid content to that of infants fed breast milk for the major lipoprotein fractions examined.     

Fatty acid composition of the milk lipids of Fulani women and the serum phospholipids of their exclusively breast-fed infants

We previously reported that, relative to milk of women elsewhere in the world, the lipid fraction of milk of Fulani women in northern Nigeria contained relatively low proportions of alpha-linolenic acid and docosahexaenoic acid (DHA). This led us to question the essential fatty acid status of Fulani infants and the relation between the proportion of critical n-3 and n-6 fatty acids in the serum phospholipids of the mothers, their milk, and the serum phospholipids of their exclusively breast-fed infants. We were also interested in the effect de novo intermediate chain length-fatty acids (C10-C14) had on the proportions of critical and non-essential fatty acids in milk. Capillary gas-liquid chromatography was used to analyze the fatty acid content of the total milk lipids of 34 Fulani women, as well as the fatty acid content of serum phospholipids of the women and their breast-fed infants during the first 6 months of life. The proportions of critical n-3 and n-6 fatty acids in the milk of the Fulani women were adequate, but the proportions of these same fatty acids were low in their exclusively breast-fed infants. The serum phospholipids of the infants contained 18.8% linoleic acid, 0.13% alpha-linolenic acid, 12.8% arachidonic acid, and 3.40% DHA, whereas, the mean percentages of linoleic, alpha-linolenic, arachidonic and DHA in the serum phospholipids of the Fulani mothers' were 21.4, 0.20, 9.79, and 1.97, respectively. There was a strong positive correlation between fatty acid content of serum phospholipids of Fulani women and the fatty acid content of their milk lipids. As the proportion of C10-C14 fatty acids in the milk lipids increased, the proportions of critical n-3 and n-6 fatty acids in milk remained relatively constant; however, proportions of three non-essential fatty acids decreased dramatically. C10-C14 fatty acids do not appear to displace critical n-3 and n-6 fatty acids in milk.     

Fatty acid formula supplementation and neuromotor development in rhesus monkey neonates

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is highly concentrated in CNS tissues. Although breast milk contains the fatty acids DHA and arachidonic acid, infant formulas marketed in North America do not contain these nutrients. The potential deleterious effects of rearing infants with formulas devoid of these nutrients was assessed by comparing nursery-reared rhesus macaque infants (Macaca mulatta) fed standard formula with infants fed standard formula supplemented with physiologically relevant concentrations of DHA (1.0%) and arachidonic acid (1.0%). Neurobehavioral assessments were conducted on d 7, 14, 21, and 30 of life using blinded raters. The 30-min assessment consisted of 45 test items measuring orienting, temperament, reflex capabilities, and motor skills. Plasma concentrations of DHA in standard formula-fed infants were significantly lower than those fed supplemented formula or mother-raised (breast-fed) infants; however, infants fed the supplemented formula exhibited higher arachidonic acid levels than either mother-reared infants or infants fed standard formula. Infant monkeys fed the supplemented formula exhibited stronger orienting and motor skills than infants fed the standard formula, with the differences most pronounced during d 7 and 14. This pattern suggests an earlier maturation of specific visual and motor abilities in the supplemented infants. Supplementation did not affect measures of activity or state control, indicating no effect on temperament. These data support the assertion that preformed DHA and arachidonic acid in infant formulas are required for optimal development.     

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     

Docosahexaenoic acid in red blood cells of term infants receiving two levels of long-chain polyunsaturated fatty acids

OBJECTIVES: A randomized, double-blind, prospective trial assessed effects of different formula levels of polyunsaturated fatty acids on blood phospholipid docosahexaenoic (DHA; 22:6omega3) and arachidonic acids (ARA; 20:4omega6) in term infants at 120 days of age. METHODS: Healthy, formula-fed term infants (n = 78) were randomized to 1) routine milk-based formula with 8 mg DHA, 21 mg ARA, 110 mg alpha-linolenic (ALA; 18:3omega3), and 1,000 mg linoleic acids (LA; 18:2omega6) per 100 kcal (Lower-long-chain polyunsaturated fatty acids [LCPUFA]; n = 39) or 2) routine milk-based formula with 17 mg DHA, 34 mg ARA, 85 mg ALA, and 860 mg LA per 100 kcal (Higher-LCPUFA; n = 39). Fatty acid methyl esters from red blood cell (RBC) and plasma phospholipid fractions were assessed using capillary column gas chromatography. RESULTS: Compared with infants fed Lower-LCPUFA formula, the Higher-LCPUFA group had significantly greater percentages of fatty acids as DHA in RBC phosphatidylethanolamine (PE), RBC phosphatidylcholine (PC), total RBC, and plasma phospholipids (P < 0.001). Infants fed Lower-LCPUFA formula had higher percentages of precursor omega6 fatty acids in the desaturation/elongation pathway but lower percentages of ARA (RBC PE, RBC PC, and plasma phospholipid, P < 0.001; total RBC, P = 0.017) compared with the Higher-LCPUFA group. CONCLUSIONS: Greater amounts of dietary ALA do not produce as great an increase in DHA in blood lipids as preformed dietary DHA. Infants fed DHA at levels similar to human milk had significantly greater percentage of DHAat 120 days of age compared with the Lower-LCPUFA group despite higher precursor levels of ALA.     

Docosahexaenoic acid and arachidonic acid enhance growth with no adverse effects in preterm infants fed formula

OBJECTIVE: To determine if docosahexaenoic acid (DHA) and arachidonic acid (ARA) supplementation influences growth or visual acuity of formula-fed premature infants. STUDY DESIGN: Double-blind, multi-center study of 194 premature infants given preterm formula with no DHA or ARA (control), 0.15% energy DHA, or 0.14% DHA + 0.27% ARA from single-cell triglycerides for at least 28 days and then fed term formula (no DHA or ARA) to 57 weeks postmenstrual age (PMA), with 90 breast-fed term infants as reference. RESULTS: Infants fed DHA+ARA formula gained weight significantly faster (post-hoc analysis) during preterm formula feeding than control infants (34.7 vs. 30.7 g/d) and had weights and weight:length ratios not different from term breast-fed infants at 48 and 57 weeks PMA. Infants fed control or DHA formula had lower body weights than term infants. Red blood cell phosphatidylethanolamine ARA was significantly correlated to weight gain during preterm formula feeding and to weight and length at 40, 48, and 57 weeks PMA (r = 0.19 to 0.24, P =.004-.02). Providing DHA or DHA+ARA during the preterm period had no effect on subsequent visual acuity or incidence of adverse events. CONCLUSIONS: Feeding DHA+ARA from single-cell triglycerides enhances weight gain in formula-fed premature infants with no evidence of adverse effects.     

Increase in plasma phospholipid docosahexaenoic and eicosapentaenoic acids as a reflection of their intake and mode of administration

The fatty acid, docosahexaenoic acid (DHA, 22:6n-3), is a major constituent of red blood cell phosphatidylethanolamine and phosphatidylserine at birth but declines in all phospholipid classes following preterm delivery unless the diet contains DHA. A bolus of fish oil prevented declines in DHA of red cell phospholipids (phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine) during 4 to 6 wk of feeding, with red blood cell DHA indistinguishable from that of infants fed human milk. The amount of DHA fed was almost an order of magnitude greater than usually provided by human milk, however, suggesting poor absorption of fish oil by preterm infants. The purpose of these studies was to determine if uptake of fish oil DHA could be improved by dispersion in preterm formula. Since plasma phospholipids rapidly reflect changes in dietary fatty acid composition, DHA uptake was assessed by fatty acid analysis of plasma phosphatidylethanolamine and phosphatidylcholine. All groups receiving fish oil (both bolus and dispersed) demonstrated a rise in plasma phospholipid phosphatidylethanolamine DHA. Infants receiving 11 mg/kg/day DHA from dispersed fish oil, however, appeared to absorb as much or more as those receiving 71 mg/kg/day DHA in a bolus. The lower intake of DHA provided only 0.2% of total dietary fatty acids (human milk typically provides 0.1 to 0.3%). This study, in conjunction with an earlier report, demonstrates the feasibility of 1) long-term maintenance of red cell membrane DHA by its inclusion in infant formula and 2) DHA maintenance by "physiological" intakes of DHA; i.e. the amount provided by human milk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of liver transplantation on long-chain polyunsaturated fatty acid status in infants with biliary atresia

BACKGROUND: The long-chain polyunsaturated fatty acid (LC-PUFA) status of infants with untreated biliary atresia (BA) is known to be poor and is correlated to the severity of the liver disease. Liver transplantation (LT) markedly increases survival of patients with BA but the extent to which this reverses poor LC-PUFA status is not known. METHODS: To explore this question, the erythrocyte (red blood cell, RBC) phospholipid content of eight infants with BA who underwent LT was determined 2 months after an initial portoenterostomy, immediately before LT, and 6 and 12 months after LT. Before LT, all infants were fed a protein hydrolysate formula containing medium-chain triglycerides and essential fatty acids. Afterward, they were fed a normal diet for age. The RBC phospholipid content at each time point was compared with that of 28 age-matched control infants. RESULTS: Just before LT, median RBC phospholipid content of C20:4n-6, C20:5n-3, and C22:6n-3 was 25%, 48%, and 30% lower, respectively, than that observed in age-matched control infants. After LT, the RBC phospholipid content of most fatty acids reached normal values by 6 months. However, that of C20:4n-6 and C22:6n-3 contents remained 5% and 15% lower, respectively, than in normal control infants. Twelve months after LT, C20:4n-6 content remained lower than in normal children, but that of C22:6n-3 did not differ. The ratio of C20:3n-6/C20:4n-6, a reflection of delta-5 desaturase activity, was abnormal compared with normal children before LT (0.17 vs. 0.10, P < 0.009) but normalized by 6 months after LT (0.11 vs. 0.10, not significant). CONCLUSIONS: These data show that the abnormal LC-PUFA status of children with BA improves after LT but is not entirely reversed within a year after surgery. They suggest that the abnormal status before LT may be secondary, in part, to low delta-5 desaturase activity. The extent to which a different pre- and/or post-LT diet can prevent PUFA deficiency and/or hasten recovery of PUFA status remains to be determined.     

Docosahexaenoic and arachidonic acid content of serum and red blood cell membrane phospholipids of preterm infants fed breast milk,standard formula or formula supplemented with n-3 and n-6 long-chain polyunsaturated fatty acids

The contents of docosahexaenoic (DHA) and arachidonic acid (AA) of plasma and red blood cell membrane phospholipids were studied in 41 very low birth weight infants fed either breast milk (n=18), a standard formula without long-chain polyunsaturated fatty acids with 20 or 22 carbon atoms (LCP) but with -linolenic acid and linoleic acid (n=11) or a formula additionally supplemented with n-3 and n-6 LCP in relations typical for human milk (n=12) after 2, 6, and 10 weeks of feeding. The content of DHA and AA in plasma phospholipids declined in the infants fed the LCP-free formula but remained more or less constant during the whole feeding period in those infants fed breast milk as well as in those fed the LCP-supplemented formula. The differences between the group fed the LCP-free standard formula and the two groups fed LCP-containing diets became significant during the first 2 weeks of feeding. In contrast, there were no differences between the group fed breast milk and the group fed the supplemented formula during the study period. Similar effects could be observed regarding the composition of red blood cell membrane phospholipids, but the differences between the infants fed the LCP-free standard formula and the two other groups with LCP-containing diets were significant only for AA. The data indicate that very low birth weight infants are unable to synthesize LCP from -linolenic acid and linoleic acid in sufficient amounts to prevent a decline of LCP in plasma and red blood cell phospholipids. Additionally, the data show, that supplementation of formulas with n-3 and n-6 LCP in amounts typical for human milk fat results in similar fatty acid profiles of plasma and red blood cell membrane phospholipids as found during breast milk feeding.Conclusion Supplementation of formula with long-chain polyunsaturated fatty acids improves the LCP status of very low birth weight infants.     

Long-chain polyunsaturated fatty acid status and early growth of low birth weight infants

We correlated arachidonic acid (AA) and docosahexaenoic acid (DHA) status with anthropometric measures and growth rates in a group of low birth weight infants (≤2500 g; gestational ages 30–41 weeks; n = 143). AA and DHA status were measured in erythrocytes (RBC) and plasma cholesterol esters (CE) during days 10 to 42. Infants received preterm formula without long-chain polyunsaturated fatty acids (LCP; n = 81), with LCP (n = 29) or maternal milk (n = 33). RBC AA contents on day 10 were correlated (P < 0.05) with birth weight in breast-fed infants and all formula-fed infants, with on day 10 a standard deviation score (SDS) for weight, length and occipito-frontal circumference in all formula-fed infants, and with on day 10 an SDS for length in breast-fed infants. Brain weight was related to RBC DHA and CE DHA contents on both day 10 and day 42 in formula-fed infants. Of the variances of brain growth parameters on day 42, 21–34% were explained by DHA status on day 42 and protein intake from days 10–42. Conclusion We conclude that parameters of early neonatal AA status are related to intra-uterine rather than to post-natal growth. Parameters of post-natal brain growth are related to RBC DHA and CE DHA contents on day 42, and to dietary protein intake. These results point to the importance of dietary DHA for brain growth in the first 6 post-natal weeks. Received: 23 July 1996 / Received in revised form and accepted: 18 June 1997     

Long-term feeding of formulas high in linolenic acid and marine oil to very low birth weight infants: phospholipid fatty acids.

Red blood cell (RBC) phospholipids of infants fed human milk compared with formula have more arachidonic acid (AA) and docosahexanoic acid (DHA). The addition of low levels of marine oil to infant formula with 0.6 to 2.0% alpha-linolenic acid (LLA, 18:3n-3) prevented declines in DHA in formula-fed infants; however, the feeding trials were short (4 to 6 wk), LLA concentrations were low compared with current formulas (3.0 to 5.0% LLA), and the formulas were unstable. Trials with stable formulas were necessary to determine if dietary DHA could maintain phospholipid DHA after discharge from the hospital and, in fact, if it was necessary with higher intakes of LLA. The results of acute (4 wk) and extended (to 79 wk postconception) feeding of such formulas on RBC and plasma phospholipid AA and DHA are reported here. Control formulas were identical to commercially available formulas. Experimental formulas differed only in the addition of small amounts of marine oil. DHA in RBC and plasma phosphatidylethanolamine (PE) declined during four weeks of feeding but not if marine oil provided DHA (0.2% or 0.4%) and plasma phospholipid AA (g/100 g) decreased with time and marine oil feeding. Extended feeding with marine oil accounted for half the DHA in RBC and plasma phosphatidylethanolamine at equilibrium; however, RBC (g/100 g) and plasma AA (g/100 g; mg/L plasma) decreased progressively until late infancy and were depressed further by marine oil.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of different levels of intravenous alpha-linolenic acid and supplemental breast milk on red blood cell docosahexaenoic acid in very low birth-weight infants.

Preterm infants weighing less than 1,500 g were started on total parenteral nutrition (TPN) if unable to tolerate full enteral feedings. They were randomly assigned to receive intravenous lipids containing either 4.2 or 9.0% alpha-linolenic acid to assess the effect on red blood cell (RBC) phospholipid polyenoic fatty acid composition, particularly docosahexaenoic acid (22:6n3) (DHA). DHA ultimately comes from alpha-linolenic acid (18:3n3), although there is evidence in human preterm infants that they require preformed DHA. After 1 week of TPN, infants were started on gradually increasing amounts of enteral feeding, breast milk, if elected by mothers, or premature milk formula (Preemie Enfamil). RBC phospholipid fatty acids were measured weekly. Results were evaluated comparing samples from week 1 and week 6. Supplying 9% alpha-linolenic acid in intravenous lipids did not prevent a fall in DHA by 6 weeks; however, infants receiving breast-milk feeding did not have a significant decrease in DHA. Studies are needed to evaluate supplying DHA in intravenous lipids.     

Maternal and cord blood long-chain polyunsaturated fatty acids are predictive of bone mass at birth in healthy term-born infants

Long-chain polyunsaturated fatty acids (LC PUFA) are associated with bone mass in animals and human adults, yet no data exist for human infants. Thus, the objective of this study was to establish that LC PUFA status is associated with bone mass in healthy infants. Thirty mother-infant pairs were studied for LC PUFA status by measuring maternal and cord blood red blood cells (RBC) for arachidonic acid (AA), eicosapentaenoic acid (EPA), and DHA. Infant anthropometry and lumbar spine 1-4, femur and whole-body bone mineral content (BMC) were measured within 15 d of delivery. Maternal and infant LC PUFA were tested for their relationship to BMC using Pearson correlation and backward step-wise regression analyses. At birth, the average gestational age was 39.3+/-1.1 wk and body weight was 3433+/-430 g. Cord RBC AA was positively correlated with whole-body BMC, AA:EPA positively correlated with lumbar spine 1-4 BMC and femur BMC. Maternal RBC AA was positively correlated with whole-body BMC. After accounting for infant weight using regression, whole-body BMC was positively predicted by cord RBC AA but none of the maternal LC PUFA; lumbar spine 1-4 BMC was positively predicted by cord RBCAA:EPA ratio but negatively by maternal DHA; and femur BMC was not predicted by cord LC PUFA but was negatively predicted by maternal DHA. Imbalances among the n-6 and n-3 LC PUFA by term gestation are associated with lower bone mass, suggesting that the maternal diet should be balanced in n-6 and n-3 LC PUFA.     

Noninvasive assessment of essential fatty acid status in preterm infants by buccal mucosal cell phospholipid analysis.

BACKGROUND: The dietary supply of long-chain polyunsaturated fatty acids is receiving increased attention since a linkage to infant growth and development has been reported. To avoid repeated blood collections for determination of long-chain polyunsaturated fatty acid status, the authors developed and evaluated a noninvasive method for analysis of buccal mucosal cell phospholipids. METHODS: Oral mucosal cells were gently collected with a soft cotton swab, buccal cell lipids separated by thin-layer chromatography, and fatty acid methyl esters of the phospholipid fraction prepared. Subsequently, the fatty acid methyl esters were analyzed by high-resolution gas chromatography. RESULTS: The method allowed reliable analysis from very small amounts of oral mucosal cells, and results were well reproducible. The intraindividual coefficients of variation in four samples of three subjects were less than 5% for both arachidonic and docosahexaenoic acid. Fatty acid composition was not altered by consumption of milk formula before and after sample collection. The method was applied in a clinical trial with preterm infants fed human breast milk or assigned by double-blind randomization to preterm formula with or without arachidonic and docosahexaenoic acid. Buccal mucosal cells were collected in infants less than 14 days of age and at the postconceptional ages of 52 weeks and 64 weeks. Dietary long-chain polyunsaturated fatty acids showed a lasting influence on buccal cell phospholipid composition. In the course of the study, arachidonic and docosahexaenoic acid decreased significantly in the nonenriched formula group, whereas stable or rising values were observed in the groups receiving breast milk or enriched formula. CONCLUSIONS: Buccal mucosal cell phospholipids are feasible for use as a noninvasive marker for long-chain polyunsaturated fatty acid status in preterm infants and yield reliable results. Dietary long-chain polyunsaturated fatty acids have a lasting influence on fatty acid composition of buccal cells in preterm babies.     

Impact of early dietary intake and blood lipid composition of long-chain polyunsaturated fatty acids on later visual development

BACKGROUND: In contrast to human milk, current infant formulas in the United States do not contain omega3 and omega6 long-chain polyunsaturated fatty acids. This may lead to suboptimal blood lipid fatty acid profiles and to a measurable diminution of visual function in developing term infants. The need for docosahexaenoic acid and arachidonic acid supplementation in the infant diet was evaluated in a double-blind, randomized clinical trial. METHODS: Healthy term infants were randomized to diets of (1) commercial formula, (2) docosahexaenoic acid-enriched formula (0.35% of total fatty acids), or (3) docosahexaenoic acid- (0.36%) and arachidonic acid- (0.72%) enriched formula. Eighty-seven infants completed the 17-week nutritional trial, and 58 were observed until 52 weeks of life. A reference group was exclusively breast fed for at least 17 weeks (n = 29). Outcome measures included electroretinographic responses, visual evoked potentials, and blood fatty acid analysis in infants at birth and at 6, 17, and 52 weeks of age. RESULTS: Commercial formula-fed infants had 30% to 50% lower content of docosahexaenoic acid in total red blood cell lipids during the 17-week feeding trial compared with breastfed infants. Significant differences persisted at the 1-year follow-up. Arachidonic acid content was consistently reduced in the commercial formula group by 15% to 20%. Infants fed long-chain polyunsaturated fatty acid-enriched formulas had docosahexaenoic acid and arachidonic acid blood lipid profiles resembling those of human milk-fed infants. Infants receiving this enriched formula had more mature electroretinographic responses than commercial formula-fed infants at 6 weeks of age. Human milk-fed and docosahexaenoic acid-enriched formula-fed infants had better visual acuity than commercial formula-fed infants at both 17 and 52 weeks of age. Early (17-week) fatty acid profiles in blood lipids were correlated with later (52-week) visual function development in study infants. CONCLUSIONS: Results from this clinical trial demonstrate that long-chain polyunsaturated fatty acid supplementation of formula in term infants produces blood lipid fatty acid profiles that are similar to those observed in breast-fed infants. This supplementation leads to better visual function later in life (i.e., 1 year of age) than that shown by infants fed commercial formula.