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M Makrides

Publications and source records attributed to M Makrides.

34 records · Page 2Linked to original sources

The role of long chain polyunsaturated fatty acids (LCPUFA) in neonatal nutrition.

Exciting new research has shown that both preterm and term infants can actively convert the essential fatty acids linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3) to long chain polyunsaturated fatty acids (LCPUFA). However, the amount of LCPUFA being produced, particularly of docosahexaenoic acid (DHA, 22:6n-3), may not be sufficient to meet the developmental requirement of the infant. Because DHA is a major component of retinal and brain tissues, a number of studies have been initiated to test the effect of dietary LCPUFA on neural outcomes in infants. These studies have largely involved a comparison of neural responses from infants fed standard infant formula (no LCPUFA) with infants receiving LCPUFA from either supplemented formula or breast milk. The results have been equivocal and may be due to the variety of LCPUFA supplements and formula fat blends used, differing testing techniques as well as variations in clinical trial conduct, but are clearer in preterm than term infants. Overall the results indicate a possible role for LCPUFA in neurodevelopment.

Breast Feeding↗

Effect of increasing breast milk docosahexaenoic acid on plasma and erythrocyte phospholipid fatty acids and neural indices of exclusively breast fed infants.

OBJECTIVES: To determine the effect of increasing docosahexaenoic acid (DHA, 22:6 n-3) in breast milk on infant fatty acid profiles. A secondary aim was to examine aspects of neural development. DESIGN AND SETTING: Double blind, placebo controlled study of infants recruited from postnatal wards at Flinders Medical Centre. SUBJECTS: Fifty-two healthy term infants who were breast fed for at least 12 weeks and were from middle class families. INTERVENTION: Breast milk with DHA concentrations that ranged from 0.1-1.7% of total fatty acids. This was achieved by supplementation of the maternal diet for the first 12 weeks post partum. RESULTS: Breast milk with DHA was related to infant plasma (r = 0.89, P < 0.001) and erythrocyte (r = 88, P < 0.001) phospholipids in a saturable curvilinear manner so that breast milk DHA above 0.8% of total fatty acids resulted in little further increase in infant plasma or erythrocyte DHA levels. The rise in plasma and erythrocyte DHA was approximated by a fall in total n-6 polyunsaturated fatty acids. We could detect no relationship between visual evoked potential acuity (measured at 12 and 16 weeks) of infants by either the dietary grouping or the DHA status of individuals. A stepwise multiple regression showed that infant erythrocyte DHA at 12 weeks and home stimulation were the only independent factors associated with Bayley's MDI at 1 y (adjusted model r2 = 0.18, P < 0.005); while at 2 y gender and social score of the spouse were the only significant predictors of Bayley's MDI (adjusted model r2 = 0.22, P < 0.005). CONCLUSIONS: Increasing breast milk DHA levels caused a dose dependent saturable increase in infant plasma and erythrocyte phospholipid DHA. There were no long-term effects of infant DHA status on indices of neurodevelopment.

Breast Feeding↗

Is dietary docosahexaenoic acid essential for term infants?

There is a need to determine whether there is a dietary requirement for docosahexaenoic acid (DHA, 22:6 omega 3) 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.

Brain↗

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.

Brain↗

Effect of maternal docosahexaenoic acid (DHA) supplementation on breast milk composition.

OBJECTIVE: To assess the effect of varying maternal intake of docosahexaenoic acid (DHA, 22 : 6n-3), in the absence of other dietary polyunsaturates, on breast milk fatty acids. DESIGN AND INTERVENTION: Lactating mothers were randomised on day 5 post-partum to groups consuming equal numbers of capsules but containing either placebo or an oil containing DHA (43%) as its only polyunsaturate to receive 0, 0.2, 0.4, 0.9, 1.3 g DHA/day. Breast milk fatty acids as well as maternal plasma and erythrocyte phospholipids were assessed at 12 weeks post partum by capillary gas chromatography. RESULTS: Breast milk DHA levels ranged from 0.2 to 1.7% of total fatty acids and increased in a dose dependent manner (r2 = 0.89, P < 0.01). Maternal plasma (r2 = 0.71, P < 0.01) and erythrocyte (r2 = 0.77, P < 0.01) phospholipid DHA levels increased and were also strongly associated with dietary dose of DHA. Increasing maternal dietary doses of DHA did not affect breast milk arachidonic acid (AA, 20 : 4n-6) levels or antioxidant status as measured by plasma vitamin A or E levels. CONCLUSIONS: Our results have demonstrated that DHA in the diet has a strong, specific and dose-dependent effect on breast milk DHA.

Antioxidants↗

Are long-chain polyunsaturated fatty acids essential nutrients in infancy?

We investigated whether the disparity in neural maturation between breastfed and formula-fed term infants could be corrected by the addition of fish oil, a source of docosahexaenoic acid (DHA, 22:6 omega 3), to infant formula. Healthy, term infants were randomised at birth to receive either a supplemented or placebo formula if their mothers had chosen to bottle feed. Breastfed term infants were enrolled as a reference group. Infant erythrocyte fatty acids and anthropometry were assessed on day 5 and at 6, 16, and 30 weeks of age. Visual evoked potential (VEP) acuity was determined at 16 and 30 weeks. VEP acuities of breastfed and supplemented-formula-fed infants were better than those of placebo-formula-fed infants at both 16 and 30 weeks of age (p < 0.001 and p < 0.01). Erythrocyte DHA in breastfed and supplemented-formula-fed infants was maintained near birth levels throughout the 30-week study period but fell in placebo-formula-fed infants (p < 0.001). Erythrocyte DHA was the only fatty acid that consistently correlated with VEP acuity in all infants at both ages tested. A continuous supply of DHA may be required to achieve optimum VEP acuity since infants breastfed for short periods (< 16 weeks) had slower development of VEP than infants receiving a continuous supply of DHA from either breastmilk or supplemented formula. Erythrocyte arachidonic acid (20:4 omega 6) in supplemented-formula-fed infants was reduced below that of infants fed breastmilk or placebo formula at 16 and 30 weeks (p < 0.001), although no adverse effects were noted, with growth of all infants being similar. DHA seems to be an essential nutrient for the optimum neural maturation of term infants as assessed by VEP acuity. Whether supplementation of formula-fed infants with DHA has long-term benefits remains to be elucidated.

Adult↗

Erythrocyte fatty acids of term infants fed either breast milk, standard formula, or formula supplemented with long-chain polyunsaturates.

The purpose of our study was to assess whether a supplement of fish oil (FO) and evening primrose oil (EPO) for formula-fed infants was capable of avoiding reductions in erythrocyte docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) associated with standard formula feeding. Healthy, term infants, whose mothers chose to formula feed, were randomized to either a placebo or supplemented formula for their first 30 wk of life. A reference group of beast-fed infants also was enrolled. Erythrocyte fatty acids were measured by capillary gas chromatography on day 5 and in weeks 6, 16, and 30. Supplementation of formula with 0.36% of total fatty acids as DHA resulted in erythrocyte DHA being maintained at or above breast-fed levels for the entire 30-wk study period, and breast feeding (0.21% DHA) resulted in a modest fall in erythrocyte DHA relative to baseline (day 5) values. The level of erythrocyte DHA in placebo formula-fed infants was halved by week 16. AA levels decreased in all infants in the first six weeks, but the levels in breast- and placebo formula-fed infants increased with age and returned to approximate baseline (day 5) values by 16 and 30 wk of age, respectively. Erythrocyte AA in FO+EPO-supplemented infants remained low and below breast- and placebo formula-fed levels. Our data suggest that dietary supplementation with DHA at 0.36% total fatty acids results in erythrocyte DHA levels above those found in breast-fed infants. EPO supplementation was not effective at maintaining erythrocyte AA when given with FO.

Aging↗

Changes in the polyunsaturated fatty acids of breast milk from mothers of full-term infants over 30 wk of lactation.

The fatty acid composition of breast milk from 23 breast-feeding women was serially assessed by capillary gas chromatography from the 6th to the 30th wk of lactation. The proportions of total n-3 and n-6 fatty acids were unchanged with time, although some significant differences were noted for individual polyunsaturated fatty acids (PUFAs). Of the n-3 PUFAs, only docosahexaenoic acid (DHA, 22:6n-3) concentrations changed, decreasing between 6 and 16 wk from 0.26 +/- 0.13% to 0.21 +/- 0.13% of total fatty acids but remaining at this proportion until 30 wk. Of the n-6 PUFAs, 18:3, 20:3, 20:4, and 22:5 all showed reductions with time. Compared with concentrations observed in a 1981 study, linoleic acid was higher (14% compared with 11% of total fatty acids), whereas the concentration of DHA was lower (0.21% compared with 0.32% of total fatty acids), possibly reflecting a general change in the diets of Australian women.

Adult↗

Sudden infant death syndrome: effect of breast and formula feeding on frontal cortex and brainstem lipid composition.

METHODOLOGY: Docosahexaenoic acid levels were measured by gas chromatography in samples of frontal lobe and brainstem taken from 28 and 26 infants, respectively, who had died of sudden infant death syndrome (SIDS). RESULTS: Significantly higher levels of docosahexaenoic acid were present in the frontal lobe tissues derived from the 13 breast fed infants (age range = 3.3-36.3 weeks; mean 15.9 +/- 11.3 weeks) compared to the 15 formula fed infants (age range = 6.9-47.7 weeks; mean 19.3 +/- 10.6 weeks); mean (+/- s.d.) levels were 8.5 +/- 1.1% and 7.6 +/- 0.8% of total fatty acids (P = 0.019). There was, however, no significant difference in brainstem docosahexaenoic acid levels between breast and formula fed infants. CONCLUSIONS: Given these variable findings, further investigation of the relationship between dietary fatty acid intake and cerebral lipid levels may help to clarify whether different modes of feeding have a role in the pathogenesis of SIDS.

Autopsy↗

Ratios of linoleic acid to alpha-linolenic acid in formulas for term infants.

Commercial infant formulas with a ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) of 10:1 or higher are nutritionally inadequate; the tissue levels of docosahexaenoic acid (DHA) are lower and the visual function indices are reduced in infants who are fed these formulas. All the evidence points to using LA:ALA ratios of less than 8:1, but there has been only one study in infants that used formulas with reduced LA:ALA ratios, and only biochemical indices were monitored. There is a need for both short-term studies to establish the ratios of LA to ALA that will make possible the accumulation of DHA to levels close to those in breast-fed infants and long-term trials to determine the effects of such fat blends on growth and development.

Breast Feeding↗

Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants.

Breast-fed infants score better on visual and developmental tests than do formula-fed infants and this has been related to higher concentrations of erythrocyte docosahexaenoic acid (DHA, 22:6 omega 3). This prompted an investigation into the relationship between brain, retina, and erythrocyte fatty acids and diet in infancy. Total lipids of erythrocytes, retina, and brain cortex from 35 term infants were analyzed by capillary gas chromatography. Breast-fed infants had a greater proportion of DHA in their erythrocytes and brain cortex relative to those fed formula (P < 0.005) but differences were not observed in retina. Cortex DHA increased in breast-fed (but not formula-fed) infants with age (r2 = 0.72, P < 0.01, n = 15), largely an effect of length of feeding (r2 = 0.62, P < 0.01, n = 35). There was an association between age at death and erythrocyte DHA with cortex DHA (r2 = 0.50, P < 0.01). In contrast, accretion of cortex arachidonic acid was dependent on age but not diet. The higher concentration of DHA in brains of breast-fed infants may explain the improved neurodevelopment reported in breast-fed compared with formula-fed infants.

Arachidonic Acid↗

Infant weaning practices in Adelaide: the results of a shopping complex survey.

The results are presented of a survey of infant weaning practices carried out in shopping complexes in the Adelaide metropolitan area. The types of foods and fluids currently being consumed by the sample of 258 healthy infants was documented, and a comparison made between the feeding practices of breast and artificially fed infants and with respect to socio-economic status. While the majority of weaning diets were compatible with the South Australian guidelines, 40% of infants under 4 months of age were having solid foods and a greater percentage of these infants were artificially fed. Iron intake may not be optimal after six months of age with the increasing use of cow's milk and non-fortified adult cereals. There is an increasing awareness of the inappropriateness of adding sugar and salt to infant foods; however, foods high in sugar and salt are still being used. The results suggest that parents may not always be aware of or understand the rationale behind recommendations for weaning and that dietary guidelines for adults and children may not always be appropriate for infants. Consistent guidelines for infants, modified to consider current food trends, would be useful for parents.

Age Factors↗

Erythrocyte docosahexaenoic acid correlates with the visual response of healthy, term infants.

Recent studies have reported that formula-fed preterm infants score lower on visual and developmental tests relative to breast-fed preterm infants. This phenomenon has been associated with the presence of docosahexaenoic acid (DHA), an omega-3 fatty acid, in breast milk and its absence from infant formula. To investigate the possibility that DHA status of healthy, term infants is also related to neuronal function of the visual pathway, we studied the erythrocyte fatty acid profiles of 16 infants at 22.3 +/- 3.9 wk of age and related these to maturity of the visual pathway as assessed by visual-evoked potentials. Healthy, term infants fed breast milk had better visual-evoked potential acuity (p < 0.05) and higher DHA levels (p < 0.001) than infants who received infant formula as their major energy source. There was a positive correlation between erythrocyte DHA and visual-evoked potential acuity (p < 0.01). The data are preliminary and the long-term effects as yet unknown. However, our results suggest that there is an urgent need to evaluate the dietary fatty acid supply of formula-fed term infants.

Breast Feeding↗

Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas.

The fatty acid composition of erythrocyte total lipids taken from a group of term infants 10 weeks after being fed a commercial infant formula with a high ratio of linoleic acid (18:2n-6) (LA) to alpha-linolenic acid (18:3n-3) (ALA) (19:1; LA, 14%; ALA, 0.7%; group A, n = 10) was compared with the fatty acid composition of erythrocytes from infants fed formulas that contained LA/ALA ratios reduced by either increasing ALA (4:1; LA, 13%; ALA, 3.3%; group B, n = 11) or decreasing LA (3:1; LA, 3.5%; ALA, 1.1%; group C, n = 8). Results were compared with those in an age-controlled group (n = 9) of breast-fed infants. Decreasing the LA/ALA ratio increased n-3 C20 and C22 fatty acid incorporation (formula B = 8.98% +/- 0.65%; formula C = 9.30% +/- 0.95%) relative to formula A (5.97% +/- 0.76%; p less than 0.05). Although docosahexaenoic acid (22:6n-3) (DHA) incorporation was highest in infants fed formulas B and C (4.78% +/- 0.45% and 4.48% +/- 0.49%, respectively) relative to formula A (3.47% +/- 0.46%; p less than 0.05), it did not reach levels found in breast-fed infants (6.55% +/- 1.23%; p less than 0.05). In addition, levels of arachidonic acid (20:4n-6) (AA) were lower in all formula-fed groups (p less than 0.05) relative to those in breast-fed infants. Based on some equations, it is predicted that AA levels in tissues of infants fed lower LA/ALA ratios would be reduced even further. Because both AA and DHA are probably essential for normal neural development of the infant, formulas with LA/ALA ratios below 4:1 are likely to result in fatty acid profiles notably different from those of breast-fed infants.

Arachidonic Acid↗