Diets deficient in the w-6 fatty acid linoleic acid reduce arachidonic acid (Ach) concentrations and retard growth of developing animals and humans. Nevertheless, plasma phosphatidylcholine Ach concentrations declined from 84 ± 23 mg/liter at birth to a nadir of 38 ± 11 mg/liter at 4 mo of age in preterm infants fed commercial formulas with linoleic acid, and weight normalized to that of term infants fell progressively beginning at 2 mo of age. The nadir of plasma phosphatidylcholine Ach (31 ± 7 mg/liter) and growth were further reduced by formula containing marine oil compared with the commercial formulas. Ach status (defined as the mean plasma phosphatidylcholne Ach concentration at 2, 4, and 6.5 mo) correlated with one or more measures of normalized growth through 12 mo. Ach status and maternal height accounted for as much as 59% of the weight variance and 68% of the length variance in infants fed standard formulas. Better Ach status was not from higher energy intakes. A conditional Ach deficiency in preterm infants may contribute to growth over the first year of life. On the strength of the relationship between Ach status and growth, we hypothesize that dietary Ach could improve first year growth of preterm infants.Despite recent advances in neonatal intensive care, preterm infants do not achieve first year growth equivalent to that of infants born at term (1-5). Moreover, preterm infants remain smaller than term infants after the first year of life (6, 7), and poorer individual growth is associated with poorer mental and motor performance (8)(9)(10)(11). That infants with chronic lung disease have poorer growth after discharge is well known (12-14); however, preterm infants free of chronic illness and fed standard formulas had progressive declines in normalized weight, weight-to-length ratio, and head circumference beginning 2 mo after expected delivery (15), as has been reported (1,3).Erythrocyte phospholipid arachidonic acid (Ach) in these infants also fell progressively, reaching a nadir 4 mo after expected term delivery (16) below that seen in formula-fed term infants of equivalent age (17). The nadir in plasma phospholipid Ach concentration coincided with the onset of the decline in normalized weight. The mean concentration of Ach in plasma phosphatidylcholine (PtdCho) of preterm infants at birth is 84 ± 23 mg/liter (mean ± SD, range 43-152, n = 86, unpublished data). When these infants were 3 weeks old, this value was 67 mg/liter (range 41-136 mg/liter, n = 59), and by 4 mo after term this value was 38 ± 11 mg/liter (n = 29). Direct evidence that normalized growth might relate to Ach status came from the observation that marine oilsupplemented formula further decreased the concentrations of plasma PtdCho Ach (31 ± 7 mg/liter) (16) and normalized weights (15) compared with standard formula. Plasma PtdCho linoleic acid (Lin) concentration remained high and was unaffected by marine oil supplementation.Diets deficient in the essential w6 fatty acid, Lin, cause declines in phospholipid Ach (18) and...
Docosahexaenoic acid (DHA; 22:6n-3) is important for normal visual development. We hypothesized that preterm infants fed formulas with marine oil as a source of DHA would have better visual acuity than infants fed formulas without marine oil, as measured by the Teller Acuity Card procedure. Marine oil (P < 0.001) and age (P < 0.0001) influenced visual acuity, by repeated-measures analysis of variance (ANOVA) corrected for the effect of subject. Marine-oil-supplemented infants had better visual acuity than those fed standard formulas at 2 and 4 mo of age, by Fishers' least-squares difference (LSD). Acuity of both dietary groups improved through 6.5 mo of age, then plateaued. Through 4 mo of age, acuity was inversely related to oxygen supplementation (log10 h) and positively related to DHA status, by general-linear-models (GLM) analysis. After 4 mo of age, birth weight and gestational age were the only variables consistently related to visual acuity by GLM. We conclude that marine-oil-supplemented formula improved visual acuity of preterm infants through 4 mo of age by improving DHA status.
Very low birth weight (VLBW) infants (748-1390 g, n = 65) were randomly assigned to receive control or marine oil-supplemented formula when they achieved intakes > 454 kJ (110 kcal)/kg/d of a formula designed for VLBW infants. Study formulas with or without marine oil were provided until 79 wk of postconceptional age (PCA), first in a formula designed for preterm infants followed by a formula designed for term infants. Infants were studied at regular intervals through 92 wk PCA. Weight, length, and head circumference were determined by standardized procedures and normalized to the National Center for Health Statistics figures for growth of infants born at term of the same age and gender. Mean normalized weight, weight-to-length, and head circumference were greatest at 48 wk and decreased thereafter. The decline in normalized weight was greater in infants fed the marine oil-supplemented formula. Beginning at 40 wk, marine oil-supplemented infants compared to controls had significantly poorer Z-scores for weight, length and head circumference. In addition, birth order (negatively) and maternal height (positively) influenced weight and length achievement in infancy as shown previously in infants born at term.
Healthy preterm infants fed formula with long-chain n-3 fatty acids (n-3 LCFAs) from marine oil have better early visual acuity but lower plasma phosphatidylcholine (PC) arachidonic acid (AA) and growth than infants fed formula containing linolenic acid (LLA) as the sole n-3 fatty acid. This randomized, double-blind trial was designed to study the effects of a different source of n-3 LCFAs and a shorter feeding interval on visual acuity (by Teller Acuity Card) and growth of preterm infants (n = 59; 747-1275 g birth wt), some of whom required long periods of supplemental oxygen and developed bronchopulmonary dysplasia (BPD). Infants were studied at 0, 2, 4, 6, 9, and 12 mo past term. Plasma PC AA, and normalized weight, length, and head circumference were not influenced by BPD or n-3 LCFAs except that n-3 LCFA-supplemented infants weighed less at 6 (P<0.05) and 9 (P<0.01) mo and had smaller head circumferences at 9 mo (P<0.05). Compared with control infants, however, those fed n-3 LCFAs had lower weight-for-length at 2, 6, 9, and 12 mo (P<0.0003, P<0.0114, P<0.0008, and P<0.006, respectively). n-3 LCFAs improved early (2-mo) but not later acuity among infants without BPD (P<0.02). Regardless of diet, infants with BPD had poorer grating acuity at 2 (P<0.0002) and 4 (P<0.04) mo but not thereafter.
Preterm infants fed formulas with docosahexaenoic acid (DHA, 22:6n-3) during the interval equivalent to the last intrauterine trimester and beyond have higher circulating DHA and transiently higher visual acuity compared with infants fed formulas containing linolenic acid. In term infants several nonrandomized studies of infants receiving DHA from human milk suggest a relationship between DHA status and acuity, but the evidence for a cause-and-effect relationship is mixed. In the present study, term infants were randomly assigned to a standard term formula (n = 20) or the same formula with egg yolk lecithin to provide DHA (0.1%) and arachidonic acid (AA, 20:4n-6, 0.43%) (n = 19) at levels reported in milk of American women. A third group of infants was breast fed for > or = 3 mo (n = 19). Grating visual acuity (Teller Acuity Card procedure) and plasma and red blood cell (RBC) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) DHA and AA were determined at corrected ages of 2, 4, 6, 9 (acuity only), and 12 mo past term = 40 wk postmenstrual age (PMA). At 2 mo breast-fed infants and infants fed the supplemented formula had higher grating acuity than term infants fed standard formula. As in preterm infants, the increase was transient. Plasma PC DHA and AA and RBC PE AA increased by 2 mo in supplemented infants, but RBC PE DHA in supplemented infants was not higher than in controls until 4 mo and beyond. Despite normal intrauterine accumulation of DHA and AA, infants fed formula with 2% linolenic acid and 0.1% DHA had better 2-mo visual acuity than infants fed formula with 2% linolenic acid.
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