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

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 cm 3 , 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 .