Essential Fatty Acid Supplementation and Early Inflammation in Preterm Infants: Secondary Analysis of a Randomized Clinical Trial

Abstract

<b><i>Introduction:</i></b> Postnatal inflammation is associated with increased mortality and adverse outcomes in preterm infants. The essential fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) are precursors of lipid mediators with a key role in resolving inflammation. Our aim was to investigate the effect of ARA and DHA supplementation on systemic inflammation in very preterm infants and to identify clinical factors associated with early inflammation. <b><i>Methods:</i></b> Secondary analysis of data from a randomized clinical trial (ImNuT study). Infants with gestational age (GA) less than 29 weeks were randomized to receive a daily enteral supplement with ARA 100 mg/kg and DHA 50 mg/kg (ARA:DHA group) or MCT oil (control group) from the second day of life to 36 weeks postmenstrual age. ARA, DHA, and four proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were analyzed in repeated dried blood samples from birth to day 28 and the area under the curve (AUC) for each variable was calculated. <b><i>Results:</i></b> The intention to treat population included 120 infants with mean (SD) GA 26.4 (1.7). The ARA:DHA group had significantly lower IL-6 levels from day 3 to day 28 compared to the control group, mean difference AUC log<sub>10</sub> (95% CI): 0.16 (0.03–0.30) pg/mL, <i>p</i> = 0.018. There was no correlation between ARA or DHA blood concentrations and cytokine levels. Having a low gestational age was independently associated with increased levels of all cytokines during the first 4 weeks of life. <b><i>Conclusions:</i></b> Enhanced supplementation with ARA and DHA may modulate inflammation in very preterm infants.

Lung function in preterm infants at 3 months corrected age after neonatal LC‐PUFA supplementation

“…In this study, enteral ARA and DHA supplementation during neonatal hospitalization in infants with GA < 29 weeks did not lead to improved lung function at 3 months CA. Despite the positive effect on early inflammation and short‐term lung function previously reported, 6,7 we did not find any differences in t PTEF / t E ratio or tidal volumes per kilo between the study groups. Twenty‐four percent of the study participants with an awake TFV assessment had a t PTEF / t E ratio ≤ 0.25, a cut‐off regarded to represent impaired lung function during infancy 13 .…”

“…Despite the anti‐inflammatory properties of DHA, there are concerns that DHA supplementation may increase the risk of BPD 5 . However, in a randomized controlled trial (ImNuT) we recently reported that infants with GA < 29 weeks had less systemic inflammation and fewer days with respiratory support after enteral ARA and DHA supplementation during neonatal hospitalization 6,7 . The effect of a balanced supply of both ARA and DHA on lung function development is not clear.…”

Evidence on docosahexaenoic acid and arachidonic acid supplementation for preterm infants

“…Despite modulating markers of inflammation (i.e. lowering interleukine-6), supplementation with ARA and DHA did not alter the risk of BPD or other major neonatal morbidities [48 ▪ ,49 ▪ ]. There was also no difference in lung function at 3 months corrected age [50].…”

Dietary intake of different ratios of ARA/DHA in early stages and its impact on infant development

“…7 A RCT has demonstrated that enhanced supplementation with ARA 100 mg per kg and DHA 50 mg per kg (ARA/DHA = 2 : 1) may modulate inflammation in very preterm infants. 96 So far, studies have concentrated on the beneficial effects of various ARA to DHA ratios on infant development, specifically focusing on cognitive and immune development (Table 4).…”