Peter B. Sullivan

There is no universally agreed definition of environmental enteric dysfunction (EED) but is it generally regarded to be an acquired subclinical disorder of the small intestine, characterized by villous atrophy, crypt hyperplasia, and lymphocytic infiltration of the lamina propria [ 1]. This state of chronic intestinal inflammation is associated with reduced absorptive capacity, and reduced barrier function in the small intestine, and low-grade systemic inflammation. EED has been proposed to underlie stunted growth among children in lower- and middle-income countries and is currently the subject of intense research interest.

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.

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 suspectedCPwere recruited fromUKchild 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 groupCCS‐Bayley‐IIIwas non‐significantly higher than the comparison group (mean 77.7 [SD 19.2] and 72.2 [SD19.8] 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 withDHA, choline, andUMPof infants with suspectedCPis 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.