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Polyunsaturated fatty acids in preterm infants: opportunity to revisit tenets of study design and reporting for nutrient intervention trials

Pediatric Research (2024)Cite this article

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With understanding that polyunsaturated fatty acids (PUFA) influence immune and inflammatory responses, efforts continue to define how much and in what conditions we should provide these nutrients to preterm infants. Preterm birth leaves infants at the starting line with a few disadvantages: they are born prior to the third trimester fetal accrual of arachidonic acid (n-6; ARA) and docosahexaenoic acid (n-3; DHA) and they are at risk of late onset sepsis. Sepsis in preterm infants has decreased significantly over the past decades, yet infants born at the earliest gestational ages remain the most susceptible.1 The seriousness of sepsis is revealed in the possibility of mortality in most severe cases or neurodevelopmental impairment in survivors. So, bridging these concepts and studying whether and how ARA and DHA can reduce sepsis risk, or mitigate catastrophic physiologic instability and end-organ consequences for those who cannot avoid sepsis, is worthwhile.

The current issue of Pediatric Research includes Witte Castro et al.’s meta-analysis of clinical trials that randomized preterm infants to receive or not receive these PUFA, including trials of parenteral and enteral formulations.2 The primary outcome was sepsis. The work is a thorough dive into primary literature. The methodology utilized is clear regarding search strategies, triaging of identified and then included studies, and the conditions tested in each combined statistic. Thirty five studies reported data for the outcome of sepsis. This included 17 studies of parenteral PUFA as contained in intravenous lipid emulsions. Eighteen studies of enteral PUFA tested discrete supplements separate from baseline feedings, manipulation of the feeding itself (i.e., study formulas with different PUFA composition) and even maternal supplementation of DHA thereby altering breast milk content. As a first pass “qualitative review,” the authors documented other conditions relevant to studying sepsis, such as duration of mechanical ventilation and “antibiotic exposure,” although not defined. Only four trials specified antibiotic exposure. Central venous catheter exposures are lacking.

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References

  1. Bell, E. F. et al. Mortality, in-hospital morbidity, care practices, and 2-year outcomes for extremely preterm infants in the US, 2013–2018. JAMA 327, 248–263 (2022).

    Article  PubMed  Google Scholar 

  2. Witte Castro, A. et al. Long-chain polyunsaturated fatty acids supplementation and sepsis: a systematic review and meta-analysis. Pediatr. Res. https://doi.org/10.1038/s41390-024-03579-5 (2024).

  3. Lichtenstein, A. H. et al. Perspective: Design and conduct of human nutrition randomized controlled trials. Adv. Nutr. 12, 4–20 (2021).

    Article  PubMed  Google Scholar 

  4. Heaney, R. P. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr. Rev. 72, 48–54 (2014).

    Article  PubMed  Google Scholar 

  5. Brenna, J. T., Plourde, M., Stark, K. D., Jones, P. J. & Lin, Y. H. Best practices for the design, laboratory analysis, and reporting of trials involving fatty acids. Am. J. Clin. Nutr. 108, 211–227 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  6. McGovern, M. et al. Challenges in developing a consensus definition of neonatal sepsis. Pediatr. Res 88, 14–26 (2020).

    Article  PubMed  Google Scholar 

  7. Dong, Y. & Speer, C. P. Late-onset neonatal sepsis: Recent developments. Arch. Dis. Child Fetal Neonatal Ed. 100, F257–F263 (2015).

    Article  PubMed  Google Scholar 

  8. Follett, M. et al. Commentary on guidelines for parenteral nutrition in preterm infants: limitations reveal opportunities. JPEN J. Parenter. Enter. Nutr. 48, 524–526 (2024).

    Article  Google Scholar 

  9. Alshaikh, B. N. et al. Enteral long-chain polyunsaturated fatty acids and necrotizing enterocolitis: A systematic review and meta-analysis. Am. J. Clin. Nutr. 117, 918–929 (2023).

    Article  CAS  PubMed  Google Scholar 

  10. Riley, R. D., Lambert, P. C. & Abo-Zaid, G. Meta-analysis of individual participant data: Rationale, conduct, and reporting. BMJ 340, c221 (2010).

    Article  PubMed  Google Scholar 

  11. Marc, I. et al. Enteral supplementation with high-dose docosahexaenoic acid on the risk of bronchopulmonary dysplasia in very preterm infants: A collaborative study protocol for an individual participant data meta-analysis. BMJ Open 13, e076223 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Department of Pediatrics, Northwestern University Feinberg School of Medicine; Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Daniel T. Robinson

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  1. Daniel T. Robinson
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D.T.R. was responsible for the development and final version of this commentary.

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Correspondence to Daniel T. Robinson.

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D.T.R. previously received compensation as a consultant and speaker for Baxter, Inc. This relationship has ended.

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Robinson, D.T. Polyunsaturated fatty acids in preterm infants: opportunity to revisit tenets of study design and reporting for nutrient intervention trials. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03702-6

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