Effect of arachidonic and docosahexaenoic acid supplementation on respiratory outcomes and neonatal morbidities in preterm infants

Wendel, Kristina; Fossan, Marlen; Gunnarsdottir, Gunnthorunn; Rossholt, Madelaine Eloranta; Bratlie, Marianne; Nordvik, Tone; Landsend, Erlend Christoffer Sommer; Fugelseth, Drude; Domellöf, Magnus; Pripp, Are Hugo; Stiris, Tom; Moltu, Sissel J.

doi:10.1016/j.clnu.2022.11.012

Cited by 19 publications

(14 citation statements)

References 43 publications

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“…This study did not allow the comparison of the association of DHA alone with the association of DHA in combination with AA. The trial by Hellström et al was the only one that evaluated the effect of combined DHA and AA supplementation on BPD and showed there was no association with BPD; this finding was similar to that of a recent secondary analysis of another RCT published after the completion of the present study. By contrast, data suggested a benefit of DHA alone for inflammation in preterm infants and for lung architecture in animals, with observational studies also supporting a reduced risk of chronic lung disease with higher postnatal levels of DHA in very preterm infants .…”

Section: Discussionsupporting

confidence: 90%

Association Between Enteral Supplementation With High-Dose Docosahexaenoic Acid and Risk of Bronchopulmonary Dysplasia in Preterm Infants

et al. 2023

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ImportanceHigh-dose docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid, may affect the risk of bronchopulmonary dysplasia (BPD). However, high-level summative evidence supporting such clinical association in very preterm infants is lacking.ObjectiveTo examine the association between enteral supplementation with high-dose DHA during the neonatal period and the risk of BPD in preterm infants born at less than 29 weeks’ gestation.Data SourcesPubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, medRxiv, and ClinicalTrials.gov were searched from inception to August 1, 2022, for eligible articles with no language restrictions.Study SelectionRandomized clinical trials (RCTs) were eligible for inclusion (1) if their interventions involved direct administration of a minimum DHA supplementation of 40 mg/kg/d or breast milk or formula feeding of at least 0.4% of total fatty acids, and (2) if they reported data on either BPD, death, BPD severity, or a combined outcome of BPD and death.Data Extraction and SynthesisTwo investigators completed independent review of titles and abstracts, full text screening, data extraction, and quality assessment using the Cochrane Risk of Bias 2.0. Risk ratios (RRs) with 95% CIs were pooled using random-effect meta-analyses.Main Outcomes and MeasuresPrimary outcome was BPD using trial-specific definitions, which was further stratified for RCTs that used a more stringent BPD definition based on systematic pulse oximetry assessment at 36 weeks’ postmenstrual age. Other outcomes were BPD, death, BPD severity, or combined BPD and death.ResultsAmong the 2760 studies screened, 4 RCTs were included, which involved 2304 infants (1223 boys [53.1%]; mean [SD] gestational age, 26.5 [1.6] weeks). Enteral supplementation with high-dose DHA was associated with neither BPD (4 studies [n = 2186 infants]; RR, 1.07 [95% CI, 0.86-1.34]; P = .53; I2 = 72%) nor BPD or death (4 studies [n = 2299 infants]; RR, 1.04 [95% CI, 0.91-1.18]; P = .59; I2 = 61%). However, an inverse association with BPD was found in RCTs that used a more stringent BPD definition (2 studies [n = 1686 infants]; RR, 1.20 [95% CI, 1.01-1.42]; P = .04; I2 = 48%). Additionally, DHA was inversely associated with moderate-to-severe BPD (3 studies [n = 1892 infants]; RR, 1.16 [95% CI, 1.04-1.29]; P = .008; I2 = 0%).Conclusions and RelevanceResults of this study showed that enteral supplementation with high-dose DHA in the neonatal period was not associated overall with BPD, but an inverse association was found in the included RCTs that used a more stringent BPD definition. These findings suggest that high-dose DHA supplementation should not be recommended to prevent BPD in very preterm infants.

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Section: Discussionsupporting

confidence: 90%

Association Between Enteral Supplementation With High-Dose Docosahexaenoic Acid and Risk of Bronchopulmonary Dysplasia in Preterm Infants

et al. 2023

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“…Taken together, these studies suggest that LCPUFA supplementation has the potential to reduce inflammation in preterm infants. In a recent publication from the ImNuT trial, we showed that the ARA:DHA group had a shorter duration of respiratory support and a lower mean oxygen demand during hospitalization, compared to the control group [11]. Since systemic inflammation is associated with respiratory morbidity, we speculate that the potential benefits of ARA and DHA supplementation on respiratory outcomes might be explained by the reduced IL-6 levels in the intervention group during the first 4 weeks of life.…”

Section: Discussionmentioning

confidence: 86%

“…However, studies of LCPUFA supplementation to premature infants have shown divergent results. Postnatal enteral DHA supplementation to infants with gestational age (GA) < 29 weeks may increase the risk of bronchopulmonary dysplasia [10], but in a recent randomized trial of supplementation with ARA and DHA in a 2:1 ratio, we showed improved short-term respiratory outcomes in a similar study population [11]. A balanced intake of ARA and DHA in extremely preterm infants also reduced the incidence of severe ROP in a randomized controlled trial by Hellstrom et al [12].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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Introduction: 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. Methods: 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. Results: 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 log10 (95% CI): 0.16 (0.03–0.30) pg/mL, p = 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. Conclusions: Enhanced supplementation with ARA and DHA may modulate inflammation in very preterm infants.

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“…PUFAs are necessary as nutrients for human and animal health, growth, and development [ 11 , 12 ]. Two families represent these PUFAs: n-6 (u ω-6) and n-3 (u ω-3), which are biosynthesized from linoleic acid and linolenic acid, respectively; humans cannot synthesize the latter; therefore, they must be incorporated through diet [ 11 , 12 , 13 , 14 ]. Among the ω-6 series, ARA stands out as one of the cell membrane phospholipids, esterified in the Sn-2 position.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, ARA regulates electrical activity in the brain, muscles, and heart by acting on voltage-gated ion channels [ 11 , 14 ]. The FAO recommends an additional intake of ARA and DHA in premature infants, without breastfeeding, to improve the growth and development of the central nervous system and retina [ 11 , 12 ]. Poor intake of ARA can cause hair loss, fatty liver, anemia, and reduced fertility in adults [ 11 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Screening and Identification of Coastal Chilean Thraustochytrids for Arachidonic Acid Production: Biotechnological Potential of Ulkenia visurgensis Lng2-Strain

et al. 2023

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Thraustochytrids are unicellular heterotrophic marine protists that have been described as producing a high content of polyunsaturated fatty acids (PUFAs). Among them, arachidonic acid (ARA) stands out as a precursor of several mediators of pivotal importance for the immune system. However, the biotechnological potential of thraustochytrids for ARA production has not been developed. The objective of this study is to isolate and identify native strains from different Chilean coastal environments and evaluate in vitro the effect of culture parameters such as C/N ratio (19 and 33) and temperature (15 °C and 23 °C) on biomass production and arachidonic acid content. A total of nine strains were identified and classified into four genera of the Thraustochitridae family. The Lng2 strain with 99% identity belongs to the species Ulkenia visurgenis and was the most prominent one for ARA production. Temperature had an effect on the PUFA profile but not on the ARA content nor on the biomass yield. Additionally, the C/N ratio has been identified as a key parameter. The ARA productivity increased by 92% (from 0.6 to 8.3 ARA mg/g-DW) and its total biomass by 62.7% (from 1.9 to 5.1 g/L) at a high C/N ratio (33) as compared to the control.

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Effect of arachidonic and docosahexaenoic acid supplementation on respiratory outcomes and neonatal morbidities in preterm infants

Cited by 19 publications

References 43 publications

Association Between Enteral Supplementation With High-Dose Docosahexaenoic Acid and Risk of Bronchopulmonary Dysplasia in Preterm Infants

Association Between Enteral Supplementation With High-Dose Docosahexaenoic Acid and Risk of Bronchopulmonary Dysplasia in Preterm Infants

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

Screening and Identification of Coastal Chilean Thraustochytrids for Arachidonic Acid Production: Biotechnological Potential of Ulkenia visurgensis Lng2-Strain

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