Infant cerebellar gray and white matter fatty acids in relation to age and diet

Abstract

There is little evidence as to the fatty acid composition of the cerebellum in infancy and it remains uncertain whether milk diet can influence its composition. We therefore examined cerebellar gray and white matter of infants less than 6 month old who had died unexpectedly. The fatty acid content of 33 gray and 21 white matter specimens from infants born at term and 6 gray and 5 white matter specimens from preterm infants was assessed by gas chromatographic/mass spectrometric analysis. Infants were grouped according to whether they had received human or manufactured formula milk. Whereas cerebellar cortex docosahexaenoic acid (DHA, 22:6n-3) concentrations were significantly lower (P<0.01) in the formula-fed than breast-fed infants, no differences existed between the term (n = 10) and preterm (n = 5) Synthetic Milk Adapted [corrected] (SMA) formula-fed infants. Cerebellar white matter DHA concentrations were similarly lower (P<0.01) in the SMA formula-fed infants (n = 8) than in an age-matched breast-fed group. Low concentrations of cerebellar white matter lignoceric (24:0) and nervonic acid (24:1n-9) in two 7-wk-old preterm infants appeared to correlate with postgestational rather than chronological age. Dietary long-chain polyunsaturated fatty acids, particularly DHA, are probably essential for normal development of the infant cerebellum.

Mildly abnormal general movement quality in infants is associated with higher Mead acid and lower arachidonic acid and shows a U-shaped relation with the DHA/AA ratio

“…1, panels A and C) proved different from the relation with AA. Generally, brain DHA is more sensitive to dietary DHA than brain AA is to dietary AA, which has been shown in baboons [35] and may also be derived from autopsy studies in breast and formula fed infants [36][37][38]. The descending part of the U-shaped relation between GM quality and the iRBC DHA/AA ratio (Fig.…”

Mechanisms of action of docosahexaenoic acid in the nervous system

“…However, animal studies have shown that when n-3 fat sources are inadequate during early neural development, then the levels of brain and retinal DHA decline (4,(20)(21)(22)(23)(24). This has also been confirmed in autopsy studies of human infants that were fed a vegetable oil-based formula with low n-3 fat sources vs. breast-feeding in which preformed DHA was present (25)(26)(27). This has naturally led to an interrogation of the functional consequences of neural DHA loss.…”

“…As mentioned above, formula-feeding of infants has been associated with a loss in brain DHA with respect to the level in those breast-fed (25)(26)(27). The pre-existing animal literature would predict that formula-fed infants would have a functional deficit if the neural DHA loss were of a sufficient magnitude.…”

Effect of placental function on fatty acid requirements during pregnancy

“…AA and DHA as a proportion of total fatty acids are shown for the diet of pregnant mothers (Lakin et al, 1998), 1 the adipose tissue (Leaf et al, 1995), 2 maternal and cord blood plasma phospholipids (Otto et al, 1997), 3 triglyceride (Berghaus et al, 2000), 4 cholesterol ester (Hoving et al, 1994), 5 and NEFA (Benassayag et al, 1999), 6 the placental microvillous and basal membranes (Powell et al, 1999), 7 and adipose tissue and brain at birth (Clandinin et al, 1981 Figure 3 The theoretical rate of oxidation was calculated from the rate of maternal energy expenditure (9453 MJ/day), the proportion of that energy derived from fat (30%), the energy content of fat (39 kJ/g) (Butte, 2000) and the proportion of DHA in the oxidised fat (0.1% DHA; Figure 2). The DHA content of fetal tissues was calculated from the lean mass (calculated as body weight minus the weight of fat, skeleton and skin (Widdowson, 1974)), the fat mass (Widdowson, 1974) and the weight of the placenta (Hytten, 1974) and brain (Clandinin et al, 1980) and the fat and DHA concentration of the brain (Clandinin et al, 1980;Jamieson et al, 1999), placenta (Widdowson & Spray, 1951;Lakin et al, 1998) and adipose tissue (Clandinin et al, 1981). For the purposes of the calculation the DHA content of the fetal lean tissue, blood vessels, etc, was assumed to be the same as the placenta.…”

“…It has also been deduced from these tracer studies that the rate of AA synthesis is significantly greater than that for DHA. Additional circumstantial evidence that the human infant is better able to synthesise AA than DHA comes from the observation that the concentration of DHA in the neonatal brain is dependent on the intake of preformed DHA, while there is little effect of AA intake on the brain concentration (Farquharson et al, 1993;Makrides et al, 1994;Jamieson et al, 1999). This difference in synthesis is consistent with the biochemical pathways involved as the final step in the synthesis of DHA is considerably more complex than that for AA (Figure 1) in that it requires the participation of enzymes in both peroxisomes and the endoplasmic reticulum as well as the controlled movement of fatty acids between these two cellular compartments (Sprecher & Chen, 1999).…”