New research on DHA and ARA: a novel strategy supporting eye health in extremely preterm infants

By:  Talking Nutrition Editors

DHA and ARA are reported to reduce the risk of severe retinopathy of prematurity in  extremely premature infants

  • As neonatal care has advanced in recent years, smaller and more premature infants are surviving.1 With this good news comes the challenge of managing medical complications associated with premature birth. Nutrition plays a key role in the health and development of these infants.  
  • Retinopathy of prematurity (ROP) is one of the most common causes of vision loss in childhood.3  A new publication by Hellstrom and colleagues outlines a novel strategy for decreasing the risk of severe ROP in extremely preterm infants through supplementation with arachidonic acid (ARA) in combination with docosahexaenoic acid (DHA).2 
  • These findings underpin present evidence and the agreement of renown pediatric nutrition experts on the need to provide infants with a balanced supply of both DHA and ARA in order to optimally support healthy growth and development.10,22

Retinopathy of Prematurity: A complication of preterm birth

Advances in medical care have improved survival rates and outcomes of infants born prematurely,1,4 however, complications from being born too early are still common.5 One such complication, retinopathy of prematurity (ROP), is an eye disease caused by abnormal development of blood vessels in the retina which can lead to vision loss and blindness in the most severe cases.6 While severe ROP occurs in a small percentage of all infants who develop ROP, it can have devastating and life-long effects.3,6 ROP has been associated with reduced brain volumes and poor developmental outcomes, suggesting there may be shared pathways that can impact brain and eye development.7

ARA and DHA are key fatty acids in eye and brain development 

The body of scientific evidence has continued to grow regarding the critical role of the long-chain polyunsaturated fatty acids (LC-PUFAs) omega-3 DHA and omega-6 ARA in brain and eye development, as well as immune function during early life.8-10 During the third trimester of pregnancy, DHA and ARA are selectively transferred from mother to the unborn baby. Thus, compared to term infants, infants born prematurely have lower levels of DHA and ARA, fatty acids which are key for the healthy development and function of the retina and brain.10-12 Indeed, low blood levels of DHA and ARA have been associated with an increased risk of certain neonatal morbities such as chronic lung disease, late onset sepsis13 and ROP.15

Scientists propose that deficits of these fatty acids may increase the risk of cell membrane damage and interfere with normal blood vessel functioning;14 indeed, these scenarios appear to play a role in the development of ROP.2,15

A novel approach to reduce ROP

While studies have been conducted to evaluate the impact of LC-PUFAs on ROP, few have assessed both DHA and ARA together. In order to do so, Hellstrom and colleagues evaluated the impact of supplemental DHA and ARA on the frequency of severe ROP in premature infants less than 28 weeks gestation. The researchers found that treatment with a combination of ARA and DHA in a 2:1 ratio reduced the risk of severe ROP by 50%, compared with the standard of care.  Additionally, blood levels of DHA and ARA were significantly higher in the infants who received the supplement. Importantly, there were no significant adverse effects.2  

This study clearly demonstrates the benefit of supplementing ARA and DHA together – and importantly, in a 2:1 ratio – in significantly reducing the risk of ROP for extremely preterm infants. It adds to the existing data that describes the importance of not only the amount, but also the balance of DHA and ARA in infant feeding.2,8

Earlier studies have documented a link between low DHA and ARA status and ROP risk. In one study, low blood levels of ARA in premature infants were strongly associated with later development of ROP15 and in others, the risk of severe ROP or ROP that required treatment was significantly decreased in premature infants who received either an oral or intravenous (IV) source of DHA.16-17 

In contrast, other studies looking at different outcomes have indicated the importance of adding both DHA and ARA in balanced amounts during early life. Clinical studies of term and preterm infants reported that when DHA was given in amounts either equal to or greater than ARA, ARA levels decline and the functional benefits associated with supplementation are reduced or not consistently observed.19-21  

A brief overview of other data reinforces the importance of the findings from the Hellstrom study: the positive outcomes observed are the result of an intervention that utilized ARA and DHA together and in an ideal ratio.2

DHA and ARA together: Key to beneficial outcomes

Always present in breast milk together, ARA and DHA are associated with positive functional outcomes. Pediatric nutrition experts recommend the addition of both ARA and DHA to infant formula in efficacious amounts. Indeed, both the levels and ratio of ARA and DHA have been found to be key factors in supporting beneficial outcomes.10,22 

Medical experts caring for premature infants should be encouraged by the findings from the study done by Hellstrom et al, which reports a novel strategy to reduce the risk of a potentially devastating eye disease in extremely premature infants: supplementation with both ARA and DHA in a 2:1 ratio to effectively reduce the risk of severe ROP by 50% while also increasing blood levels of both LC-PUFAs. 

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The latest nutrition research shines a spotlight on DHA and ARA for healthy growth and development

Published on

31 March 2021

Tags

  • New Science
  • Health & Nutrition
  • Article
  • R&D
  • Early Life
  • Nutritional Lipids

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References

  1. Stoll BJ, Hansen NI, Bell EF, et al. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. Jama. 2015;314(10):1039-1051.
  2. Hellström A, Nilsson AK, Wackernagel D, et al. Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial. JAMA Pediatr. 2021.
  3. National Eye Institute. Retinopathy of Prematurity. National Institutes of Health.  Published 2019. Accessed 8 March 2021. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/retinopathy-prematurity.
  4. Kaempf J, Morris M, Steffen E, Wang L, Dunn M. Continued improvement in morbidity reduction in extremely premature infants. Arch Dis Child Fetal Neonatal Ed. 2020.
  5. Luu TM, Rehman Mian MO, Nuyt AM. Long-Term Impact of Preterm Birth: Neurodevelopmental and Physical Health Outcomes. Clin Perinatol. 2017;44(2):305-314.
  6. American Assoication for Pediatric Opthamology and Strabismus. Retinopathy of Prematurity.  Published 2020. Accessed 8 March 2021. https://aapos.org/glossary/retinopathy-of-prematurity.
  7. Sveinsdóttir K, Ley D, Hövel H, et al. Relation of Retinopathy of Prematurity to Brain Volumes at Term Equivalent Age and Developmental Outcome at 2 Years of Corrected Age in Very Preterm Infants. Neonatology. 2018;114(1):46-52.
  8. Lepping RJ, Honea RA, Martin LE, et al. Long-chain polyunsaturated fatty acid supplementation in the first year of life affects brain function, structure, and metabolism at age nine years. Dev Psychobiol. 2019;61(1):5-16.
  9. Beluska-Turkan K, Korczak R, Hartell B, et al. Nutritional Gaps and Supplementation in the First 1000 Days. Nutrients. 2019;11(12).
  10. Koletzko B, Bergmann K, Brenna JT, et al. Should formula for infants provide arachidonic acid along with DHA? A position paper of the European Academy of Paediatrics and the Child Health Foundation. Am J Clin Nutr. 2020;111(1):10-16.
  11. Martinez M. Tissue levels of polyunsaturated fatty acids during early human development. The Journal of Pediatrics. 1992;120(4):PS129-S138.
  12. Baack ML, Puumala SE, Messier SE, Pritchett DK, Harris WS. What is the relationship between gestational age and docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels? Prostaglandins Leukot Essent  Fatty Acids. 2015 Sep;100:5-11.
  13. Martin CR, Dasilva DA, Cluette-Brown JE, Dimonda C, Hamill A, Bhutta AQ, Coronel E, Wilschanski M,       Stephens AJ, Driscoll DF, Bistrian BR, Ware JH, Zaman MM, Freedman SD. Decreased postnatal docosahexaenoic and arachidonic acid blood levels in premature infants are associated with neonatal morbidities. J Pediatr. 2011 Nov;159(5):743-749.e1-2. 
  14. Crawford MA, Golfetto I, Ghebremeskel K, et al. The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants. Lipids. 2003;38(4):303-315.
  15. Löfqvist CA, Najm S, Hellgren G, et al. Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2018;136(3):271-277.
  16. Pawlik D, Lauterbach R, Walczak M, Hurkała J, Sherman MP. Fish-oil fat emulsion supplementation reduces the risk of retinopathy in very low birth weight infants: a prospective, randomized study. JPEN J Parenter Enteral Nutr. 2014;38(6):711-716.
  17. Bernabe-García M, Villegas-Silva R, Villavicencio-Torres A, et al. Enteral Docosahexaenoic Acid and Retinopathy of Prematurity: A Randomized Clinical Trial. JPEN J Parenter Enteral Nutr. 2019;43(7):874-882.
  18. Collins CT, Makrides M, McPhee AJ, et al. Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants. N Engl J Med. 2017;376(13):1245-1255.
  19. Columbo J, Carlson SE, Cheatham CL, et al. Long-term effects of LCPUFA supplementation on childhood cognitive outcomes. Am J Clin Nutr. 2013;98(2):403-412.
  20. Columbo J, Jill Shaddy D, Kerling EH, Gustafson KM, Carlson SE. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) balance in developmental oucomes. Prostiglandins Leukot Essential Fatty Acids. 2017;121:52-56. 
  21. Alshweki A, Munuzuri AP, Bana AM, et al. Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial. Nutr J. 2015;14:101.
  22. Tounian P, Bellaïche M, Legrand P. ARA or no ARA in infant formulae, that is the question. Arch Pediatr. 2021;28(1):69-74.

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