Double-blind, randomized trial of long-chain polyunsaturated fatty acid supplementation in formula fed to preterm infants.
OBJECTIVE
We tested the hypothesis that balanced addition of long-chain polyunsaturated fatty acid (LCPUFA) to preterm formula during the first weeks of life would confer long-term neurodevelopmental advantage in a double-blind, randomized, controlled trial of preterm formula with and without preformed LCPUFA.


METHODS
The participants were 195 formula-fed preterm infants (birth weight <1750 g, gestation <37 weeks) from 2 UK neonatal units and 88 breast milk-fed infants. Main outcome measures were Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at 18 months and Knobloch, Passamanick and Sherrard's Developmental Screening Inventory at 9 months' corrected age. Safety outcome measures were anthropometry at 9 and 18 months, tolerance, infection, necrotizing enterocolitis, and death.


RESULTS
There were no significant differences in developmental scores between randomized groups, although infants who were fed LCPUFA-supplemented formula showed a nonsignificant 2.6-point (0.25 standard deviation) advantage in MDI and PDI at 18 months, with a greater (nonsignificant) advantage (MDI: 4.5 points; PDI: 5.8 points) in infants below 30 weeks' gestation. LCPUFA-supplemented infants were shorter than control infants at 18 months (difference in length standard deviation score: 0.44; 95% confidence interval: 0.08-0.8). No other significant short- or long-term differences in safety outcomes were observed. Breastfed infants had significantly higher developmental scores at 9 and 18 months than both formula groups and were significantly heavier and longer at 18 months than LCPUFA-supplemented but not control infants.


CONCLUSIONS
With the dose, duration, and preparation of LCPUFA used, efficacy was not demonstrated, although an advantage in later neurodevelopment cannot be excluded by global tests of development up to 18 months, particularly in infants below 30 weeks' gestation. The surprising effect of LCPUFA-supplemented formula on growth 18 months beyond the intervention period needs to be confirmed in other studies using similar supplementation strategies. Additional follow-up of this cohort is critical at an age when more specific tests of cognitive function are possible.
Fewtrell
Mary S
MS
MRC Childhood Nutrition Research Center, Institute of Child Health, London, United Kingdom. m.fewtrell@ich.ucl.ac.uk
Morley
Ruth
R
Abbott
Rebecca A
RA
Singhal
Atul
A
Isaacs
Elizabeth B
EB
Stephenson
Terence
T
MacFadyen
Una
U
Lucas
Alan
A
D000367:Age Factors; D001942:Breast Feeding; D002657:Child Development; D019587:Dietary Supplements; D004311:Double-Blind Method; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007225:Infant Food; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development*; D008297:Male; D016896:Treatment Outcome
D005231:Fatty Acids, Unsaturated