Visual attention and dietary supplementation in children with perinatal brain injury.

AIM: To investigate whether children with perinatal brain injury have impairments in specific components of visual attention, and whether early dietary supplementation can reduce any deficits. METHOD: Children participating in the Dolphin neonatal trial of dietary supplementation were tested at age 6 months with the Infant Fixation Shift Attention Test, and at 4 to 5 years with four subtests of the Early Childhood Attention Battery (ECAB) assessing different components of attention (selective, sustained, and executive function), and the Fluid Crystallized Intelligence Index of the Kaufman Assessment Battery for Children, Second Edition (KABC-II). From 59 children originally assigned to trial groups, 33 were available for testing at 4 to 5 years (18 treatment group of whom seven, six, and five showed mild, moderate, or severe neonatal brain injury; 15 controls with one, seven, and seven in the neonatal brain injury categories respectively). Given the imbalance in numbers with mild brain injury, analysis of trial group differences is restricted to moderate and severe brain injury severities (n=25). RESULTS: Children with perinatal brain injury showed poorer attention across all components relative to age norms (mean standard scores 75-87; p<0.001 for three of the four subtests), with the greatest impairment in sustained attention. These impairments remained when compared with cognitive age assessed using the Fluid Crystallized Intelligence Index. Impairment was reduced in the treatment compared to the control group (p=0.04 for flanker test, p=0.002 for counterpointing, and p=0.027 for the overall ECAB score). INTERPRETATION: Perinatal brain injury is associated with later impaired attention, beyond that predicted from any general cognitive disability. Impairment varies across attention components, being most severe for sustained attention. The effects on flanker and counterpointing suggest that dietary supplementation from 0 to 2 years of age may reduce attention problems. Measuring the different components of attention is important when considering assessment and interventions for children with perinatal brain injury.

Neurodevelopmental outcome of nutritional intervention in newborn infants at risk of neurodevelopmental impairment: the Dolphin neonatal double-blind randomized controlled trial.

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.

Nutritional intervention and neurodevelopmental outcome in infants with suspected cerebral palsy: the Dolphin infant double-blind randomized controlled trial.

AIM: To investigate whether docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) supplementation improves neurodevelopmental outcome in infants with suspected cerebral palsy (CP) versus a comparison group of children. METHOD: Infants aged 1 to 18 months with suspected CP were recruited from UK child development centres. Participants received daily treatment or control supplementation for 2 years (double-blind randomized control design). Stratification was by age, sex, predominant pattern of motor involvement (four limbs or other), and visual impairment (or not). The primary outcome was the cognitive composite score of the Bayley Scales of Infant and Toddler Development, Third Edition (CCS-Bayley-III). Secondary outcomes included language composite and motor composite scores of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). RESULTS: Forty infants were recruited; 35 began supplementation, 29 completed 1 to 2 years' supplementation. The treatment group CCS-Bayley-III was non-significantly higher than the comparison group (mean 77.7 [SD 19.2] and 72.2 [SD 19.8] respectively, mean modelled difference 4.4 [-2.8, 11.6]). The treatment group language scores, but not motor scores, were non-significantly higher than for the comparison group. INTERPRETATION: Most families found supplementation feasible. No statistically significant differences in neurodevelopmental outcome between the treatment and comparison groups were identified. Further investigation of neurodevelopmental outcome after supplementation with DHA, choline, and UMP of infants with suspected CP is warranted. WHAT THIS PAPER ADDS: This was the first trial of phosphatidylcholine precursor supplementation in infants with suspected cerebral palsy (CP). Families of infants with suspected CP found 2-year nutritional supplementation feasible. There was no statistically significant neurodevelopmental advantage for the treatment group versus the comparison group. However, treatment group cognitive and language advantage were of clinically meaningful magnitude.

Optimising nutrition to improve growth and reduce neurodisabilities in neonates at risk of neurological impairment, and children with suspected or confirmed cerebral palsy.

BACKGROUND: Neurological impairment is a common sequelae of perinatal brain injury. Plasticity of the developing brain is due to a rich substrate of developing neurones, synaptic elements and extracellular matrix. Interventions supporting this inherent capacity for plasticity may improve the developmental outcome of infants following brain injury. Nutritional supplementation with combination docosahexaenoic acid, uridine and choline has been shown to increase synaptic elements, dendritic density and neurotransmitter release in rodents, improving performance on cognitive tests. It remains elusive whether such specific 'neurotrophic' supplementation enhances brain plasticity and repair after perinatal brain injury. METHODS/DESIGN: This is a two year double-blind, randomised placebo controlled study with two cohorts to investigate whether nutritional intervention with a neurotrophic dietary supplement improves growth and neurodevelopmental outcomes in neonates at significant risk of neurological impairment (the D1 cohort), and infants with suspected or confirmed cerebral palsy (the D2 cohort). 120 children will be randomised to receive dietetic and nutritional intervention, and either active supplement or placebo. Eligible D1 neonates are those born <30(+6) weeks gestation with weight <9(th) centile, ≤ 30(+6) weeks gestation and Grade II, III or IV Intra-Ventricular Haemorrhage or periventricular white matter injury, or those born at 31-40(+28) weeks gestation, with Sarnat grade I or II or III Hypoxic Ischaemic Encephalopathy or neuroimaging changes compatible with perinatal brain injury. Eligible D2 infants are those aged 1-18 months with a suspected or confirmed clinical diagnosis of cerebral palsy. The primary outcome measure is composite cognitive score on the Bayley Scales of Infant and Toddler Development III at 24 months. Secondary outcomes include visuobehavioural and visual neurophysiological assessments, and growth parameters including weight, height, and head circumference. DISCUSSION: This is the first study to supplement neonates and infants with perinatal brain injury with the combination of factors required for healthy brain development, throughout the period of maximal brain growth. A further study strength is the comprehensive range of outcome measures employed. If beneficial, supplementation with brain phosphatide precursors could improve the quality of life of thousands of children with perinatal brain injury. TRIAL REGISTRATION: Current Controlled trials: ISRCTN39264076 (registration assigned 09/11/2012), ISRCTN15239951 (registration assigned 23/04/2010).

Feeding difficulties in children with cerebral palsy.

Feeding difficulties are common in children with cerebral palsy and have an effect on growth, nutritional state, general health, social interaction and behaviour and developmental outcomes. Many factors have an effect on feeding ability. Identification of these factors and amelioration of their impact on feeding difficulties is essential to promote adequate growth and nutrition. Appropriate assessment and management is best achieved by a multiprofessional team skilled in the care of children with cerebral palsy and feeding impairments. Feeding difficulties must be considered within the wider context of family and social circumstance.

Growth in cerebral palsy.

Cerebral palsy is often accompanied by abnormalities of growth and nutrition; children with severe motor impairments are most at risk. Nutrition, neurological, and endocrine factors all contribute to suboptimal growth. Poor growth and nutrition are associated with poor general health outcomes and reduced levels of participation, and therefore warrant careful evaluation and appropriate intervention. The lack of normative data combined with the complex interaction of nutrition and nonnutrition factors contributing to growth in this population present real difficulties in management. Particular care is needed to avoid overfeeding and the resultant increase in fat mass and associated morbidity.