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Nutritional intervention and neurodevelopmental outcome in newborn infants at risk of neurodevelopmental impairment: The Dolphin neonatal double-blind randomized controlled trial

Lookup NU author(s): Professor Jeremy Parr



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Wiley-Blackwell Publishing Ltd., 2018.

For re-use rights please refer to the publisher's terms and conditions.


© 2018 Mac Keith Press. Aim: To investigate whether neonates at risk for neurodevelopmental impairment have improved neurodevelopment after docosahexaenoic acid, choline, and uridine-5-monophosphate supplementation versus controls. Method: Recruitment was from UK neonatal units. Eligible for inclusion were infants born at less than 31 weeks' gestation with a weight less than the ninth centile; infants born at less than 31 weeks' gestation with a grade II or higher intraventricular haemorrhage/preterm white matter injury; infants born between 31 weeks' and 40 weeks' gestation plus 28 days with a grade II or higher intraventricular haemorrhage/preterm white matter injury, moderate or severe hypoxic-ischaemic encephalopathy, or defined neuroimaging abnormalities. Treatment/control supplementation was for 2 years (double-blind, randomized, controlled design). Infants were stratified according to sex, gestation, and brain injury severity. Primary outcome was cognitive composite score (CCS) of the Bayley Scales of Infant Development, Third Edition (Bayley-III at 24mo). Secondary outcomes were language composite score (LCS) of the Bayley-III, motor composite score (MCS) of the Bayley-III, and Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) score. Results: Sixty-two neonates were recruited, 59 were randomized (34 males, 25 females). Fifty-three started supplementation. Most families found supplementation acceptable. The treatment group CCS-Bayley-III scores were non-significantly higher than controls (mean score difference at 24mo: 9.0; 95% confidence interval -0.2 to 18.2). Language and VABS-II scores, but not motor score, were non-significantly higher in the treatment group. Interpretation: Most families found supplementation feasible. Improved neurodevelopmental outcomes in the treatment group were not statistically significant. A larger multicentre trial exploration is warranted. What this paper adds: Dietary supplementation of neonates at risk of neurodevelopmental impairment is feasible. No statistically significant neurodevelopmental advantages were identified for the treatment group compared to controls. Treatment group cognitive and language advantage are of a clinically meaningful magnitude.

Publication metadata

Author(s): Andrew MJ, Parr JR, Montague-Johnson C, Laler K, Holmes J, Baker B, Sullivan PB

Publication type: Article

Publication status: Published

Journal: Developmental Medicine and Child Neurology

Year: 2018

Volume: 60

Issue: 9

Pages: 897-905

Print publication date: 01/09/2018

Online publication date: 27/05/2018

Acceptance date: 27/03/2018

Date deposited: 12/06/2018

ISSN (print): 0012-1622

ISSN (electronic): 1469-8749

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/dmcn.13914


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