Effect of DHA-containing formula on growth of preterm infants to 59 weeks postmenstrual age

Abstract

Between May 1993, and September 1994, a randomized, blinded clinical trial was conducted to evaluate measures of growth and body composition in 63 (32 males; 31 females) healthy, low‐birth‐weight infants (940–2250 g) who were randomly assigned to an infant formula with docosahexaenoic acid (22:6n3, DHA, 0.2 wt%) from fish oil or to a control formula. A preterm formula with or without DHA was fed beginning at 7–10 days prior to hospital discharge through 43 weeks postmenstrual age (PMA). Then, from 43‐59 weeks PMA, infants were fed a term infant formula with or without a corresponding amount of DHA. Growth (weight, length, head circumference), regional body fatness (triceps, subscapular, suprailiac skinfold thicknesses), circumferences (arm, abdominal, chest), and estimates of body composition determined by total body electrical conductivity (TOBEC) (fat‐free mass [FFM]) were evaluated. Growth was slower in males fed the DHA formula. They had significantly (P < 0.05) smaller gains in weight, length, and head circumference between study enrollment to 59 weeks PMA than those fed the control formula. At 51 weeks PMA, males in the DHA group had significantly smaller head circumferences (P < 0.05) and lower FFM (P < 0.05). At 59 weeks PMA, males in the DHA group weighed less (P < 0.05), had shorter recumbent lengths (P < 0.01), smaller head circumferences (P < 0.05), and lower FFM (P < 0.01) than those fed the control formula. Energy intakes from formula (kcal/d), however, were lower at 51 weeks (P < 0.05) and 59 weeks (P < 0.05) PMA in males fed the DHA formula. Adjusted for body weight (kcal/kg/d), mean energy intakes from formula at 51 and 59 weeks PMA were not significantly different between feeding groups. The differences in recumbent length, head circumference, and FFM remained statistically significant after controlling for energy and protein intakes (P < 0.01). For all males, neither FFM nor total body fat (TBF), when expressed as a percentage of total body weight, differed significantly between feeding groups. Among females, there were no significant differences between the feeding groups in measures of growth, body composition, or energy intake. The results indicated that infant formula with fish oil containing DHA and EPA in a 5:1 ratio had a significant, negative effect on growth and body composition in males during the first 6 months of life. It is not clear why the growth deficits were limited to males and not females. The eicosanoids, bioactive metabolites of omega‐3 and omega‐6 fatty acids, may mediate several important growth hormones. The present results do not support the addition of DHA alone in infant formulas. Am. J. Hum. Biol. 11:457–467, 1999. © 1999 Wiley‐Liss, Inc.

N-3 Long-Chain Polyunsaturated Fatty Acids Prevent Excessive Fat Deposition in Adulthood in a Mouse Model of Postnatal Nutritional Programming

“…Dietary DHA and ARA differentially affect early growth. In human, preterm infants dietary DHA reduced growth (30,31), whereas addition of both DHA and ARA enhanced growth (31). Rat offspring fed with fish oil mainly consisting of n-3 LCP during both pregnancy and lactation had a reduced birth weight and decreased BW gain during lactation (32).…”

Body Composition in Preterm Infants Who Are Fed Long-Chain Polyunsaturated Fatty Acids: A Prospective, Randomized, Controlled Trial

“…When considering animal (12,(32)(33)(34)(35)(36)(37) and infant (20) studies that have examined body composition, the increase in lean body mass and corresponding reduced fat mass in the preterm Data are reported as the unadjusted mean Ϯ SEM (number of subjects). Differences among groups were determined using repeated measures ANCOVA controlling for visit, body weight at study visit, sex, race, breast milk intake, and feeding group-by-visit interactions.…”

“…These studies, however, did not examine diets rich in ARA to evaluate possible interactions between high dietary DHA and EPA and dietary ARA. In addition, Ͼ25-and 150-fold greater amounts of DHA and EPA, respectively, were fed in the rodent studies than in the present and other (20) infant formula studies that have examined body composition. In the study by Ryan et al (20), preterm infants were fed formulas with DHA and EPA at Ͻ0.3% of calories for~5 mo after hospital discharge.…”

“…The estimated sample size was targeted to detect a 0.5-SD difference in fat-free mass with 80% power using a two-sided 0.05 level test. Preterm infants who were fed formulas with and without supplemental DHA and who had their fat-free mass measured at 4 mo CA were used to estimate variability (20). Formula assignment was determined using a computer-generated randomization schedule based on a permuted blocks algorithm.…”

Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids

“…[46][47][48] Early clinical studies reported lower blood lipid ARA in preterm infants fed formulas containing fish oil (as a source of DHA) than in infants fed unsupplemented preterm formulas, lower growth, and an association between ARA status and growth. [49][50][51][52] Lower growth has not been reported in term infants fed formulas with DHA, although language development assessed with the MacArthur Communicative Developmental Inventory (CDI) at 14 months of age was lower in term infants fed formula with DHA and no ARA than in infants fed unsupplemented formula. 53 These clinical studies suggest that the balance of DHA or EPA+DHA to ARA may be important, but specific data to explain a mechanism of effect is lacking.…”