Effect of enteral arachidonic acid and docosahexaenoic acid supplementation on brain volumes at term in preterm infants: a secondary outcome analysis of a randomised controlled trial.

Hellström, W., Lundgren, P., Nilsson, A. K., Nilsson, S., Hård, A.-L., Sjöbom, U., Löfqvist, C., Björkman-Burtscher, I. M., Wackernagel, D., Hansen-Pupp, I., Smith, L. E., Hallberg, B., Sävman, K., Ley, D., Hellström, A., & Heckemann, R. A. (2026). Effect of enteral arachidonic acid and docosahexaenoic acid supplementation on brain volumes at term in preterm infants: a secondary outcome analysis of a randomised controlled trial.. Archives of Disease in Childhood. Fetal and Neonatal Edition.

Abstract

OBJECTIVE: Investigate whether enteral supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA), from birth to term-equivalent age (TEA), promotes brain maturation as a prespecified secondary outcome of a multicentre randomised controlled trial.

PARTICIPANTS: 206 infants born at 22-28 weeks gestational age (GA) were randomised into intervention or control groups from three university hospitals in Sweden.

INTERVENTION: The intervention group received an oil with AA (100 mg/kg/d) and DHA (50 mg/kg/d) starting at birth until 40 weeks postmenstrual age (PMA) in addition to standard nutrition. Standard-of-care infants received standard nutrition according to national guidelines.

MAIN OUTCOME AND MEASURES: MRI volumetrics were defined a priori as a secondary outcome of the trial and included total brain, white and cortical grey matter, central structures and cerebellum. Univariable and multivariable linear regression models were used for comparisons.

RESULTS: MRI data in 117 infants had sufficient quality for inclusion (n=58 intervention). Birth weight, GA at birth, sex distribution, and PMA at MRI were similar in the groups. Infants receiving intervention had significantly larger white-matter volume at TEA, as compared with standard of care, in models adjusted for GA at birth, sex, study centre and PMA at MRI (β=6.8 cm3, 95% CI 0.7 to 12.9, p=0.028). The contribution of the intervention to white-matter volume corresponded to 10 days of prolonged gestation.

CONCLUSION AND RELEVANCE: Our findings in this hypothesis-generating study suggest that AA+DHA promotes white matter growth, which may protect the developing brain in this vulnerable population.

TRIAL REGISTRATION NUMBER: NCT03201588.

Last updated on 04/01/2026
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