Summary
Term Infants
Fourteen randomized controlled trials (RCTs) enrolling
1719 children fed with milk formula enriched with DHA plus AA or DHA alone
compared to standard milk formula were included for this review. The
sources of LCPUFA included fish oil, egg triglycerides, vegetable oils or
fungal oils. The duration of use of the study formula ranged from 2 months
to 1 year. The outcomes assessed included visual acuity (as measured by
using visual evoked potential or visual acuity cards), neurodevelopmental
outcome (as measured by development scales), and physical growth. Nine
studies evaluating effect of supplementation with LCPUFA on visual acuity
had inconsistent results with most reporting no benefit at various ages
throughout the first three years of life. Pooled meta-analysis of the data
from eight studies did not show any statistically significant benefit of
LCPUFA supplementation on either mental or psychomotor developmental index
of Bayley scale of infant development (BSID) at various ages throughout
first two years. Individual studies evaluating other developmental scores
had inconsistent results which could not be meta-analyzed because of
heterogeneity. Twelve studies evaluated effect on physical growth (weight,
length and head circumference) at various ages throughout first three
years; none found any benefit or harm of LCPUFA supplementation. The
authors concluded that routine supplementation of milk formulae with
LCPUFA to improve the physical, neuro-developmental or visual outcomes of
infants born at term can not be recommended based on the current evidence.
Preterm Infants
Fifteen RCTs evaluating the effect of LCPUFA
supplemented formulae in enterally-fed preterm (<37 weeks gestation)
infants, were included for this review. Meta-analysis of BSID of four
studies at 12 months (n = 364) and three studies at 18 months (n
= 494) post-term showed no significant effect of supplementation on
neurodevelopment. Meta-analysis of five studies showed increased weight
and length at two months post-term in supplemented infants. However,
meta-analysis of four studies at 12 months (n = 271) and two
studies at 18 months (n = 396) post-term showed no significant
effect of supplementation on weight, length or head circumference. The
authors concluded that there is no evidence of any benefit or harm of
supplementation of formula with n-3 and n-6 LCPUFA on visual development,
growth or neurodevelopment of preterm infants.
Commentary
Are the Results Valid and Clinically Important?
These reviews address some sensible and specific
questions. The literature search is comprehensive and most included
studies were sound in methods. Although, the functional importance of some
of the outcomes such as visual evoked potentials is questionable, more
important outcomes of growth and neurodevelopment have been dealt well in
these reviews. There was heterogeneity in terms of type and duration of
supplementation, the outcome measurement tools, and timing of assessment.
Despite this, the authors could formally meta-analyze the results for many
important outcomes because of the availability of large number of relevant
trials. In the review including term infants, the authors have separately
analyzed the results for supplementation with DHA alone or with DHA plus
AA. It would have been better if the combined results for any LCPUFA
supplementation were available for these infants as has been done for the
review paper on preterm infants.
Implications for Practice and Policy
These systematic reviews provide sound evidence that
there is no consistent benefit of supplementing formula with LCPUFA on
visual acuity, neurodevelopmental outcomes and physical growth in term or
preterm infants. LCPUFA are also considered to be important for
development of immune function in the infants(1). The present reviews do
not address this issue and it would be interesting to study the effect of
LCPUFA supplementation on neonatal/infant infectious morbidities and
mortality.
Despite the lack of evidence of benefit from randomized
controlled trials, manufacturers are likely to continue adding LCPUFA to
formula milks used for preterm and term infants. This is because of the
fact that LCPUFA are present in breastmilk and the formula milk companies
shall do every effort to match the components with the best in the market
i.e. breastmilk. The supplemented formulae fetch much more profit
for the manufacturers because of their high cost. Unfortunately, the
infant food manufacturers of the world are not always driven by evidence!
