7 ESSENTIAL FATTY ACID PROFILE IN THE EARLY CHOLESTASIS OF INFANCY

Abstract

Long-chain polyunsaturated fatty acids seem to be essential for early central nervous system development not only in premature but also in term infants. Since cholestatic infants suffer from fat malabsorption and disturbed lipid metabolism, they are prone to develop polyunsaturated fatty acid deficiency in early life. To test this hypothesis, thirty- four cholestatic infants (biliary atresia, 13; Alagille syndrome, 1; α1-ATD, 3; galactosemia, 1; CMV hepatitis, 2; intrahepatic cholestasis of unknown origin, 14) aged 1 to 7 months (median 2.3 m) were investigated. We took 24h dietary records, determined midarm, subscapular and supraspinal skin folds, bilirubin levels, activities of ALAT, AP and γ-GT, prothrombin time, serum concentrations of albumin, bile acids, total lipids, phospholipids, cholesterol and vitamins A and E, as well as the fatty acid composition of plasma phospholipids [%wt/wt] and plasma lipid peroxides expressed as TBARS (thiobarbiturate reactive substance, nmol/ml). Compared to 12 age-matched control infants, the patients studied had very low percentage values of phospholipid essential fatty acids, particularly linoleic acid (18:2ω-6, median 14.86 vs 20.76 in patients and controls, P<0.001) and arachidonic acid (20:4ω-6, 6.79 vs 7.87, P=0.004) of the ω-6 series. The poor essential fatty acid status of the patients was also indicated by increased levels of the non-essential fatty acids, Mead acid (20:3ω-9, 0.74 vs 0.21, P<0.001) and palmitoleic acid (16:1ω-7, 2.20 vs 0.43, P<0.001). There were no differences in polyunsaturated fatty acid profiles between groups of infants with biliary atresia and intrahepatic cholestasis as well as groups of infants with severe malnutrition (all skin folds below the 10th percentile) and mild malnutrition (at least one between the 10th and 25th percentile). Fatty acid values did not correlate with results of clinical chemistry, vit E/total lipid ratios and TBARS. TBARS were significantly increased in cholestatic patients compared to controls (2.74 vs 0.85, P<0.001) and correlated with direct bilirubin (R=0.41, P=0.02) and total bilirubin. Breast fed cholestatic infants (N=6) had higher ω-3 LCP docosapentaenoic (22:5ω-3, 0.47 vs 0.28, P=0.0006) and docosahexanoic acid (22:6ω-3, 2.39 vs 1.73, P=0.01) levels than formula fed infants, while parameters of clinical chemistry were similar. The daily linoleic acid intake per kg body weight correlated with the sum of all ω-6 fatty acids in plasma (R=0.42, P=0.02) and was inversely related to the sum of ω-3 fatty acids (R=-0.52, P=0.003). Conclusions: 1. Cholestatic infants have a high risk of essential fatty acid deficiency. 2. Lipid peroxidation is enhanced in these patients and related to bilirubin concentration. 3.Dietary factors have a significant influence on polyunsaturated fatty acid status in cholestatic infants.