Archives of disease in childhood. Fetal and neonatal edition · 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.
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Hellström William, Lundgren Pia, Nilsson Anders K, Nilsson Staffan, Hård Anna-Lena, Sjöbom Ulrika, Löfqvist Chatarina, Björkman-Burtscher Isabella M, Wackernagel Dirk, Hansen-Pupp Ingrid, Smith Lois Eh, Hallberg Boubou, Sävman Karin, Ley David, Hellström Ann, Heckemann Rolf A
Аннотация
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.
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.