Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial

Abstract

Background & aimsNutritional supplementation with polyunsaturated fatty acids is important in preterm infants neurodevelopment, but it is not known if the omega-6/omega-3 ratio affects this process. This study was designed to determine the effects of a balanced contribution of arachidonic acid in very preterm newborns fed with formula milk.MethodsThis was a randomized trial, in which newborns <1500 g and/or <32 weeks gestational age were assigned to one of two groups, based on the milk formula they would receive during the first year of life. Initially, 60 newborns entered the study, but ultimately, group A was composed of 24 newborns, who were given formula milk with an ω-6/ω-3 ratio of 2/1, and Group B was composed of 21 newborns, given formula milk with an ω-6/ω-3 ratio of 1/1. The infants were followed up for two years: growth, visual-evoked potentials, brainstem auditory-evoked potentials, and plasma fatty acids were periodically measured, and psychomotor development was assessed using the Brunet Lézine scale at 24 months corrected age. A control group, for comparison of Brunet Lézine score, was made up of 25 newborns from the SEN1500 project, who were fed exclusively with breast milk.ResultsAt 12 months, arachidonic acid values were significantly higher in group A than in group B (6.95 ± 1.55 % vs. 4.55 ± 0.78 %), as were polyunsaturated fatty acids (41.02 ± 2.09 % vs. 38.08 ± 2.32 %) achieved a higher average. Group A achieved a higher average Brunet Lézine score at 24 months than group B (99.9 ± 9 vs. 90.8 ± 11, p =0.028). The Brunet Lézine results from group A were compared with the control group results, with very similar scores registered between the two groups (99.9 ± 9 vs. 100.5 ± 7). There were no significant differences in growth or evoked potentials between the two formula groups.ConclusionsVery preterm infants who received formula with an ω-6/ω-3 ratio of 2/1 had higher blood levels of essential fatty acids during the first year of life, and better psychomotor development, compared with very preterm newborns who consumed formula with an ω-6/ω-3 of 1/1. Therefore, formula milk with an arachidonic acid quantity double that of docosahexaenoic acid should be considered for feeding very preterm infants.Trial registrationClinicalTrials.gov Identifier NCT02503020.

Plasma Oxidative Status in Preterm Infants Receiving LCPUFA Supplementation: A Pilot Study

“…Secondly, it is closer to human milk content, which is higher in ARA [31]. Thirdly, we have previous evidence, from a randomized clinical trial in very preterm neonates, that infants who received formula with an ARA:DHA ratio of 2:1 had higher blood levels of essential fatty acids during the first year of life, and better psychomotor development, compared to those who received 1:1 ratio [32].…”

Arachidonic Acid in Human Milk

“…Alshweki et al reported that preterm infants receiving a combined ARA and DHA-supplemented preterm infant formula at a 2:1 ratio scored 9 points higher in the Brunet Lezine test for psychomotor development at 24 months of age as compared to preterm infants receiving a similar formula but only supplemented at a 1:1 ratio [71]. At 12 months of age, the infant plasma fatty acyl distribution demonstrated significantly higher ARA levels.…”

A More Comprehensive Approach to the Neuroprotective Potential of Long-Chain Polyunsaturated Fatty Acids in Preterm Infants Is Needed—Should We Consider Maternal Diet and the n-6:n-3 Fatty Acid Ratio?

“…In our review, results from 13 randomized controlled trials (RCTs) of LCPUFA intervention for preterm infants that have reported neurodevelopmental outcomes are presented ( Table 1). We discuss the trials included in the Cochrane review (52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62), as well as two trials that compared formulas with different ratios of LCPUFA (43)(44)(45)(46), one trial of an LCPUFA supplement added in human milk (47)(48)(49)(50)(51), and two trials with subgroups of preterm infants at higher risk of neurodevelopmental impairment (63,64).…”

“…of exclusively breastfed infants (43). Conversely, the DINO trial randomized infants born <33 weeks' gestation to formula with a high DHA content (1%) to normal DHA content (0.3%), with a fixed content of AA (0.4%).…”