Maternal and Neonatal Polyunsaturated Fatty Acid Intake and Risk of Neurodevelopmental Impairment in Premature Infants

The N3 and N6 long chain polyunsaturated fatty acids (LCPUFA) docosahexaenoic acid (DHA) and arachidonic acid (AA) are essential for proper neurodevelopment in early life. These fatty acids are passed from mother to infant via the placenta, accreting into fetal tissues such as brain and adipose tissue. Placental transfer of LCPUFA is highest in the final trimester, but this transfer is abruptly severed with premature birth. As such, efforts have been made to supplement the post-natal feed of premature infants with LCPUFA to improve neurodevelopmental outcomes. This narrative review analyzes the current body of evidence pertinent to neurodevelopmental outcomes after LCPUFA supplementation in prematurely born infants, which was identified via the reference lists of systematic and narrative reviews and PubMed search engine results. This review finds that, while the evidence is weakened by heterogeneity, it may be seen that feed comprising 0.3% DHA and 0.6% AA is associated with more positive neurodevelopmental outcomes than LCPUFA-deplete feed. While no new RCTs have been performed since the most recent Cochrane meta-analysis in 2016, this narrative review provides a wider commentary; the wider effects of LCPUFA supplementation in prematurely born infants, the physiology of LCPUFA accretion into preterm tissues, and the physiological effects of LCPUFA that affect neurodevelopment. We also discuss the roles of maternal LCPUFA status as a modifiable factor affecting the risk of preterm birth and infant neurodevelopmental outcomes. To better understand the role of LCPUFAs in infant neurodevelopment, future study designs must consider absolute and relative availabilities of all LCPUFA species and incorporate the LCPUFA status of both mother and infant in pre- and postnatal periods.     

A multilevel,multicomponent childhood obesity prevention group-randomized controlled trial improves healthier food purchasing and reduces sweet-snack consumption among low-income African-American youth

Long chain polyunsaturated fatty acids (LCPUFA) especially docosahexaenoic acid (DHA) and arachidonic acid (AA) are crucial for normal brain development in utero and in early infancy. Data on fatty acid status and cognitive development in infants and children from low-income countries are scarce. We examined the association between the DHA and AA status in infancy (n = 320) and developmental status and cognitive functioning five years later. At five years of age, we measured development by the Ages and Stages Questionnaire 3rd. ed. (ASQ-3) and cognitive functioning by subtests from the neuropsychological test battery NEPSY II. In addition, infant fatty acid composition in red blood cells (RBC) was analyzed. In multiple linear and logistic regression models, we estimated the associations between DHA and AA status in infancy and scores on the ASQ-3 and the NEPSY II subtests. There were no notable associations between infant AA and DHA status, and the scores on the ASQ-3 and the NEPSY II subtests five years later. It should be noted that we found better than expected concentrations of erythrocyte DHA and AA among the infants, and the ASQ scores were left-skewed, which limited the ability to identify associations. DHA and AA status in infancy is seemingly not related to neurodevelopment measured 5 years later in this peri-urban population from Nepal.     

Maternal fish oil supplementation in lactation: Effect on visual acuity and n−3 fatty acid content of infant erythrocytes

Studies on formula-fed infants indicate a beneficial effect of dietary DHA on visual acuity. Cross-sectional studies have shown an association between breast-milk DHA levels and visual acuity in breast-fed infants. The objective in this study was to evaluate the biochemical and functional effects of fish oil (FO) supplements in lactating mothers. In this double-blinded randomized trial, Danish mothers with habitual fish intake below the 50th percentile of the Danish National Birth Cohort were randomized to microencapsulated FO [1.3 g/d long-chain n−3 FA (n−3 LCPUFA)] or olive oil (OO). The intervention started within a week after delivery and lasted 4 mon. Mothers with habitual high fish intake and their infants were included as a reference group. Ninety-seven infants completed the trial (44 OO-group, 53 FO-group) and 47 reference infants were followed up. The primary outcome measures were: DHA content of milk samples (0, 2, and 4 mon postnatal) and of infant red blood cell (RBC) membranes (4 mon postnatal), and infant visual acuity (measured by swept visual evoked potential at 2 and 4 mon of age). FO supplementation gave rise to a threefold increase in the DHA content of the 4-mon milk samples (P<0.001). DHA in infant RBC reflected milk contents (r=0.564, P<0.001) and was increased by almost 50% (P<0.001). Infant visual acuity was not significantly different in the randomized groups but was positively associated at 4 mon with infant RBC-DHA (P=0.004, multiple regression). We concluded that maternal FO supplementation during lactation did not enhance visual acuity of the infants who completed the intervention. However, the results showed that infants with higher RBC levels of n−3 LCPUFA had a better visual acuity at 4 mon of age, suggesting that n−3 LCPUFA may influence visual maturation.     

Visual acuity and erythrocyte docosahexaenoic acid status in breast-fed and formula-fed term infants during the first four months of life

It has been recognized that preterm infants have a more rapid development of visual acuity if fed human milk or a formula enriched with the long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) compared to a standard formula devoid of LCPUFA. Few studies have addressed whether the same is also true in term infants. The aim of the present study was to follow visual acuity and fatty acid composition in red blood cells (RBC) for the first 4 mon of life in 17 breast-fed and 16 formula-fed term infants. The formula used did not contain LCPUFA, but contained 1.7 wt% α-linolenic acid, and the linoleic/α-linolenic acid ratio was 8.5. The increase in visual acuity measured by Teller acuity cards developed more rapidly in breast-fed infants compared to formula-fed infants (P<0.001). This was parallelled by a decrease in DHA of RBC in formulafed infants, and with a significantly lower level at two and four months as compared to breast-fed infants. The content of DHA in milk from the breast-feeding mothers was high compared to other Western countries. The difference in visual acuity between the two feeding groups could be due to differences in DHA status as reflected by the RBC levels, but other explanations are possible. Intervention studies are required to verify if development of visual acuity in term formula-fed infants is dependent on the DHA level of formula. Based on a presentation at the AOCS Annual Meeting & Expo in San Antonio, Texas, May 7–11, 1995.     

The effect of α-linolenic acid and linoleic acid on the growth and development of formula-fed infants: A systematic review and meta-analysis of randomized controlled trials

This systematic review and meta-analysis aimed to evaluate the effect of modifying 18-carbon PUFA [18-C PUFA: α-linolenic acid (ALA, 18∶3n−3) and linoleic acid (LA, 18∶2n−6)] in the diets of term and preterm infants on DHA (22∶6n−3) status, growth, and developmental outcomes. Only randomized controlled trials (RCT) involving formula-fed term and preterm infants, in which the 18-C PUFA composition of the formula was changed and growth or developmental outcomes were measured, were included. Differences were presented as control (standard formula) and treatment (18-C PUFA-supplemented formula). Primary analyses for term infants were 4 and 12 mon and for preterm infants 37–42 and 57 wk postmenstrual age. Five RCT involving term infants and three RCT involving preterm infants were included in the systematic review. Infants fed ALA-supplemented formula had significantly higher plasma and erythrocyte phospholipid DHA levels than control infants. There was no effect of ALA supplementation on the growth of preterm infants. In term infants, ALA supplementation was associated with increased weight and length at 12 mon, which was at least 4 mon after the end of dietary intervention. Developmental indices of term infants did not differ between groups. There was a transient improvement in the retinal function of preterm infants fed ALA-supplemented diets compared with controls. The findings suggest that ALA-supplemented diets improve the DHA status of infants. Further studies are needed to provide convincing evidence regarding the effects of ALA supplementation of formula on infant growth and development.     

Effect of dietary docosahexaenoic acid on brain composition and neural function in term infants

There is a need to determine whether there is a dietary requirement for docosahexaenoic acid (DHA, 22:6n-3) by term infants to achieve their full developmental potential. Studies of brain fatty acid composition demonstrated that infants who were breast fed had greater levels of cerebral cortex DHA than did infants who were formula fed, suggesting that DHA in the cerebrum is dependent on a supply in the diet. Some physiological studies reported that electrophysiological and behavioral assessments of visual function were improved in breast-fed infants relative to those fed formula and that this was related to the length of breast feeding. While some randomized studies of DHA supplementation of infant formula to term infants demonstrated that the visual function of formula-fed infants could be improved to breast-fed levels by adding DHA to formula, others failed to demonstrate an effect. Variations in dietary treatments and methods of assessment make comparison of the studies difficult. Further work is necessary to rigorously establish if there are long-term benefits of dietary DHA to the term infant.     

Influence of long-chain polyunsaturated fatty acids on infant cognitive function

Long-chain polyunsaturated fatty acids (LCPUFA) are important for normal visual and cortical development. In a previous study of the effects of LCPUFA on cognitive function of term infants at the age of 3 mon, we indicated that infants with evidence of reduced growth parameters at birth and impaired attention control as manifested by a late peak fixation during infant habituation assessment may benefit from LCPUFA supplementation. The aim of this prospective study was to determine whether LCPUFA supplementation and late peak fixation are related to means-end problem-solving ability in these same infants at the age of 9 mon. Term infants (58) were randomized to one of two formulas containing either LCPUFA or no LCPUFA and completed 4 mon of feeding with their formula. Cognitive function was assessed at 3 mon of age by measures of infant habituation. Infants (20 LCPUFA and 20 no-LCPUFA) completed the problem-solving assessment at 9 mon. The no-LCPUFA group had lower scores on both measures of intention and number of solutions, but neither of these differences was significant. Analysis of covariance for the effects of group and peak fixation, covaried with gestation and birth weight, showed that the number of solutions was significantly reduced in the late peak-fixation infants receiving no LCPUFA (P<0.02). Intention scores tended to be reduced in this group (P<0.06). The late peak-fixation infants who received LCPUFA had solution and intention scores similar to early peak-fixation infants receiving LCPUFA or no LCPUFA. These findings suggest that in term infants who have reduced growth parameters at birth and who show evidence of impaired attention control, information processing and problem-solving ability in infancy may be enhanced by LCPUFA supplementation. Based on a presentation at the AOCS Meeting on PUFA in Infant Nutrition: Consensus and Controversies, Barcelona, November 7–9, 1996.     

Is dietary docosahexaenoic acid essential for term infants?

There is a need to determine whether there is a dietary requirement for docosahexaenoic acid (DHA, 22∶6ω3) by term infants to achieve their full developmental potential. Studies of brain fatty acid composition have demonstrated that infants who were breast fed have greater levels of cerebral cortex DHA than infants who were formula fed, suggesting that DHA in the cerebrum is dependent on a supply in the diet. Some physiological studies report that electrophysiological and behavioral assessments of visual function are improved in breast-fed infants relative to those fed formula, and that this is related to the level of DHA in their erythrocytes, whereas other studies demonstrate equivalent visual function between breast-and formula-fed infants. However, randomized studies of DHA supplementation of infant formula demonstrate that the visual function of formula-fed infants can be improved to breast-fed levels by adding DHA to formula. Further work is necessary to establish if there are long-term benefits of dietary DHA to the term infant. Based on a presentation at the AOCS Annual Meeting & Expo in San Antonio, Texas, May 7–11, 1995.     

Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants

Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother's milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective was to develop a DHA supplementation strategy to overcome these barriers. This double‐blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50 mg/day) in addition to standard nutrition for preterm infants (24–34 weeks gestational age) beginning in the first week of life. Blood FA levels were analyzed at baseline, full feedings and near discharge in DHA (n = 31) or placebo supplemented (n = 29) preterm infants. Term peers (n = 30) were analyzed for comparison. Preterm infants had lower baseline DHA levels (p < 0.0001). Those receiving DHA had a progressive increase in circulating DHA over time (from 3.33 to 4.09 wt% or 2.88 to 3.55 mol%, p < 0.0001) while placebo‐supplemented infants (receiving standard neonatal nutrition) had no increase over time (from 3.35 to 3.32 wt% or 2.91 to 2.87 mol%). Although levels increased with additional DHA supplementation, preterm infants still had lower blood DHA levels than term peers (4.97 wt% or 4.31 mol%) at discharge (p = 0.0002). No differences in adverse events were observed between the groups. Overall, daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants.     

Fish Oil Supplementation During Lactation: Effects on Cognition and Behavior at 7 Years of Age

Early accumulation of n-3 long-chain PUFA (LCPUFA) in the brain may contribute to differences in later cognitive abilities. In this study, our objective was to examine whether fish oil (FO) supplementation during lactation affects processing speed, working memory, inhibitory control, and socioemotional development at 7 years. Danish mothers (n = 122) were randomized to FO [1.5 g/d n-3 LCPUFA] or olive oil (OO) supplementation during the first 4 months of lactation. The trial also included a high-fish intake (HFI) reference group (n = 53). Ninety-eight children were followed-up with an assessment of processing speed, an age-appropriate Stroop task, and the Strength and Difficulties Questionnaire at 7 year. A group effect of the intervention (FO vs. OO) was found in prosocial behavior scores; this negative effect was carried by the boys. Exploratory analyses including all participants revealed the speed of processing scores were predicted by maternal n-3 LCPUFA intake during the intervention period (negative relation) and maternal education (positive relation). Stroop scores indicative of working memory and inhibitory control were predicted by infant erythrocyte DHA status at 4 months of age (negative relation). Early fish oil supplementation may have a negative effect on later cognitive abilities. Speed of processing and inhibitory control/working memory are differentially affected, with speed of processing showing effects of fish oil intake as a whole, whereas inhibitory control/working memory was related more specifically to DHA status.     

Increased docosahexaenoic acid levels in human newborn infants by administration of sardines and fish oil during pregnancy

In rhesus monkeys, maternal n-3 fatty acid deficiency during pregnancy produces infant monkeys deficient in n-3 fatty acids at birth. These results stimulated current experiments to find out if n-3 fatty acids from fish in the diets of pregnant women would influence the concentration of docosahexaenoic acid (DHA, 22:6 n-3) in the newborn human infant. Fifteen healthy pregnant women were enrolled to receive a 9-wk dietary supplementation of n-3 fatty acids from the 26th to the 35th wk of pregnancy. Sixteen pregnant women were not supplemented and served as controls. n-3 Fatty acid supplementation consisted of sardines and additional fish oil, which provided a total of 2.6 g of n-3 fatty acids per day (d) for the 9-wk period of supplementation. This included 1.01 g DHA. The end point of this study was the blood concentrations of DHA in the newborn infant. DHA in maternal red blood cells increased from 4.69% of total fatty acids to 7.15% at the end of the supplement period and at the time of delivery decreased (as expected) to 5.97% of total fatty acids. Maternal plasma showed a similar change from 2.12 to 3.51% of total fatty acids and then decreased to 2.35%. Levels of DHA in plasma and red blood cells of unsupplemented mothers did not change during the same time period. Levels of DHA in blood of newborn infants differed greatly in infants born from n-3-supplemented mothers compared with control infants. In red blood cells, DHA was 7.92% of total fatty acids compared with 5.86% (control infants). Plasma values showed a similar difference: 5.05% vs. 3.47% (controls). In n-3-supplemented infants, DHA concentrations were 35.2% higher than in control infants in red blood cells and 45.5% higher in plasma. These data indicate the importance of maternal dietary n-3 fatty acids and, in particular, maternal dietary DHA in promoting higher concentrations of DHA in the blood of the newborn infant.     

Dietary supplementation with arachidonic and docosahexaenoic acids has no effect on pulmonary surfactant in artificially reared infant rats

Despite the potential use of long-chain polyunsaturated fatty acid (LCPUFA) supplementation to promote growth and neural development of the infant, little is known about potential harmful effects of the supplementation. The present study determined whether supplementation with arachidonic acid (AA) and/or docosahexaenoic acid (DHA) in rat milk formula (RMF) affects saturation of pulmonary surfactant phospholipids (PL). Beginning at 7 d of age, infant rats were artificially fed for 10 d with RMF supplemented with AA at 0, 0.5, and 1.0% of total fatty acid, or supplemented with DHA at 0, 0.5, and 1.0%, or cosupplemented with AA and DHA at levels of 0∶0, 0.5∶0.3, and 1.0∶0.6% of the fat blend. Lung tissue PL contained 43 weight percent palmitate (16∶0) of total fatty acids in infant rats fed the unsupplemented RMF. The supplementation with AA at both 0.5 and 1.0% decreased the weight percentage of 16∶0 and stearate (18∶0), indicating a decrease in saturation of PL. The observed decreases were accompanied by increases in AA and linoleic acid (18∶2n−6). Surfactant phosphatidylcholine (PC) consisted of 71 weight percent 16∶0 in the unsupplemented group, and this highly saturated PC was not altered by the cosupplementation with AA and DHA although there was a slight increase in DHA. Similarly, the cosupplementation did not change fatty acid composition of surfactant PL when compared with the unsupplemented group. The cosupplementation slightly decreased the weight percentage of 16∶0 with a proportional increase in 18∶0 leading to an unchanged weight percentage of total saturated fatty acids. These results suggest that, unlike lung tissue PL, the composition of saturated fatty acids in surfactant PL, particularly PC, is resistant to change by dietary AA and DHA supplementation. This, together with the unchanged concentration of total fatty acids in surfactant PC, indicates that LCPUFA cosupplementation causes no effect on pulmonary surfactant.     

Dietary nucleotides do not alter erythrocyte long-chain polyunsaturated fatty acids in formula-fed term infants

There have been conflicting reports regarding the effectiveness of dietary nucleotides (NT) to regulate tissue desaturases and hence stimulate accumulation of both n−6 and n−3 long-chain polyunsaturated fatty acids (LCPUFA). The aim of this study was to examine the effect of NT-supplemented cow's milk-based formula on erythrocyte phospholipid FA status in a large randomized controlled trial involving a well-nourished infant population born at term. Formula-fed infants were allocated to control formula with an innate level of NT at 10 mg/L (n=102), or formula fortified with NT at 34 mg/L (n=98). A parallel group of breastfed infants was included as a reference. Peripheral blood samples were collected by venipuncture at 7 mon of age and erythrocyte phospholipid FA determined by capillary GC. Erythrocyte LCPUFA levels did not differe between the NT-supplemented and control formula groups and were reduced in both groups compared with breastfed infants. We conclude that there is no induction of LCPUFa accumulation in erythrocyte phospholipids of term, formula-fed infants following 7 mon of NT supplementation.     

A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until nine months

This randomized, double-blind trial tested the hypothesis that the addition of 0.2% docosahexaenoic acid (DHA, 22∶6n−3) from marine oil to commercially-available preterm and term formulas with ≥3% linolenic acid (18∶3n−3) would enhance novelty preference and visual attention of preterm infants. Among preterm infants cared for in our center, study infants were a select group considered to be at lower risk for developmental delay. Study infants received their assigned diet (control, DHA-supplemented) from a mean postnatal age of 25 d until 9 mon past term. At 6.5, 9, and 12 mon past term, they were tested for visual recognition memory (novelty preference) and attention with the Fagan Test of Infant Intelligence. The effects of DHA supplementation were analyzed by repeated measures analysis of variance. In paired comparisons of novel and familiar stimuli, DHA-supplemented and control infants had the same novelty preference, but supplemented infants had more discrete looks to both novel (P<0.03) and familiar (P<0.02) stimuli and a shorter overall look duration (P<0.03). These data are analogous to those from n−3-deficient and n−3-fed monkeys in that the group with better DHA status had shorter overall look duration. Because shorter look duration has been associated with more rapid information processing, preterm infants fed formulas with only linolenic acid may have had slower information processing than those fed DHA. Based on a presentation at the AOCS Annual Meeting & Expo in San Antonio, Texas, May 7–11, 1995.     

High-DHA eggs: Feasibility as a means to enhance circulating DHA in mother and infant

Dietary DHA enhances infant attention and visual development. Because the DHA content of red blood cells and plasma lipids varies approximately threefold in pregnancy, maternal DHA status may influence subsequent infant function. It would be feasible to study the effects of higher maternal DHA intake on infant development if dietary intake of DHA could be increased by a reliable means. This study was designed to determine whether women provided with one dozen high-DHA hen eggs (135 mg DHA/egg) would consume the eggs and have higher blood DHA levels than women consuming ordinary eggs (18 mg DHA/egg). The study was a randomized, double-masked comparison of the effect of eggs with different concentrations of DHA on intake and blood lipid DHA content of women and their infants. A third nonrandomized group ate few eggs. In this study, DHA intake reported from eggs was eightfold higher in the high-DHA egg group compared to the ordinary egg group. Including all groups, DHA intake ranged from 0 to 284 mg/d. In this intake range, maternal blood lipid DHA content at enrollment best predicted DHA content at delivery, accounting for 36.5 and 51.7% of the variance in ordinary and high-DHA egg intake groups, respectively. The high-DHA vs. ordinary egg groups had similar maternal and cord blood lipid DHA, but there was a positive relationship between maternal plasma phospholipid DHA and daily DHA intake from eggs controlled for study duration (r=0.278, P=0.048). DHA intake and birth weight were also correlated (r=0.299, P=0.041). High-DHA eggs were well accepted and increased DHA intake. Other benefits of DHA intake during pregnancy were also suggested.     

Influence of formulas with borage oil or borage oil plus fish oil on the arachidonic acid status in premature infants

Several studies have reported that feeding γ-linolenic acid (GLA) has resulted in no increase in arachidonic acid (AA) in newborns. This result was ascribed to the eicosapentaenoic acid (EPA)-rich fish oil used in these formulas. Docosahexaenoic acid (DHA) sources with only minor amounts of EPA are now available, thus the addition of GLA to infant formulas might be considered an alternative to AA supplementation. Sixty-six premature infants were randomized to feeding one of four formulas [ST: no GLA, no long-chain polyunsaturated fatty acids; BO: 0.6% GLA (borage oil); BO + FOLOW: 0.6% GLA, 0.3% DHA, 0.06% EPA; BO + FOHIGH: 0.6% GLA, 0.3% DHA, 0.2% EPA] or human milk (HM, nonrandomized) for 4 wk. Anthropometric measures and blood samples were obtained at study entry and after 14 and 28 d. There were no significant differences between groups in anthropometric measures, tocopherol, and retinol status at any of the studied time points. The AA content of plasma phospholipids was similar between groups at study start and decreased significantly until day 28 in all formulafed groups, but not in the breast-fed infants [ST: 6.6±0.2%, BO: 6.9±0.3%, BO + FOLOW: 6.9±0.4%, BO + FOHIGH: 6.7±0.2%, HM: 8.6±0.5%, where values are reported as mean ±standard error; all formulas significantly different (P≤0.05) from HM]. There was no significant influence of GLA or fish oil addition to the diet. GLA had only a very limited effect on AA status which was too small to obtain satisfactory concentrations (concentrations similar to breast-fed babies) under the circumstances tested. The effect of GLA on AA is independent of the EPA and DHA content in the diet within the dose ranges studied.     

Modification of milk formula to enhance accretion of long-chain n−6 and n−3 polyunsaturated fatty acids in artificially reared infant rats

Artificially reared infant rats were used to determine the effects of long-chain polyunsaturated fatty acid (LCP-UFA) supplementation on blood and tissue concentrations of arachidonic acid (AA) and docosahexaenoic acid (DHA). Beginning at 7 d of age, infant rats were fed for 10 d with rat milk formulas supplemented with AA at 0,0.5 and 1.0%, or supplemented with DHA at 0,0.5 and 1.0% of total fatty acid. The supplementation of AA increased accretion of the fatty acid in tissue and blood phospholipids with a maximum increase of 9% in brain, 15% in liver, 25% in erythrocytes, and 43% in plasma above the values of unsupplemented infant rats. Rat milk formula containing 1.0% of AA had no added benefits over that containing 0.5% of AA. The supplementation of DHA increased phospholipid DHA by a maximum of 24% in brain, 87% in liver, 54% in erythrocytes, and 360% in plasma above the unsupplemented control. The increase in tissue and blood DHA was concentration-dependent on formula fatty acid. Brain phosphatidylcholine and phosphatidylethanolamine were similarly enriched with AA and DHA by supplementation of the corresponding fatty acids. In general the observed increase of AA was accompanied by a decrease in 16:0, 18:1n−9, and/or 18:2n−6, whereas the increased DHA was associated with a reduction of 18:1n−9, 18:2n−6, and/or 20:4n−6. Clearly, infant rats were more responsive to DHA than AA supplementation, suggesting a great potential of dietary manipulation to alter tissue DHA concentrations. However, the supplementation of DHA significantly decreased tissue and blood AA/DHA ratios (wt%/wt%), whereas there was little or no change in the ratio by AA supplementation. Although the physiological implications of the levels of AA and DHA, and AA/DHA ratios achieved under the present experimental conditions are not readily known, the findings suggest that artificial rearing could provide a suitable model to investigate LCPUFA requirements using various sources of AA and DHA in rats.     

Polyunsaturated fatty acids and T-cell function: Implications for the neonate

Infant survival depends on the ability to respond effectively and appropriately to environmental challenges. Infants are born with a degree of immunological immaturity that renders them susceptible to infection and abnormal dietary responses (allergies). T-lymphocyte function is poorly developed at birth. The reduced ability of infants to respond to mitogens may be the result, of the low number of CD45RO+ (memory/antigen-primed). T cells in the infant or the limited ability to produce cytokines [particularly interferon-γ, interleukin (IL)-4, and IL-10]. There have been many important changes in optimizing breast milk substitutes for infants; however, few have been directed at replacing factors in breast milk that convey immune benefits. Recent research has been directed at the neurological, retinal, and membrane benefits of adding 20∶4n−6 (arachidonic acid; AA) and 22∶6n−3 (docosahexaenoic acid; DHA) to infant formula. In addults and animals, feeding DHA affects T-cell function. However, the effect of these lipids on the development and function of the infant's immune system is not known. We recently reported the effect of adding DHA+AA to a standard infant formula on several functional indices of immune development. Compared with standard formula, feeding a formula containing DHA+AA increased the proporition of antigen mature (CD45RO+) CD4⁺ cells, improved IL-10 production, and reduced IL-2 production to levels not different from those of human milk-fed infants. This review will briefly describe T-cell development and the potential immune effect of feeding long-chain polyunsaturated fatty acids to the neonate.