The n-3 and n-6 essential fatty acids alpha linolenic acid (ALA) and linoleic acid (LA) are the precursors of the n-3 and n-6 longchain polyunsaturated fatty acids (LCPUFA). Controversy exists over whether LCPUFA are essential nutrients for preterm infants who may not be able to synthesise sufficient amounts of LCPUFA to satisfy the needs of the developing brain and retina.
The aim of this review is to assess whether supplementation of formula with LCPUFA is safe and of benefit to preterm infants.
Trials were identified by MEDLINE (October 2003), Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2003) and by checking reference lists of relevant articles and conference proceedings.
All randomised trials of formula supplemented with LCPUFA and with clinical endpoints were reviewed.
Eleven randomised trials assessing the clinical effects of feeding formula supplemented with LCPUFA were included in the review.
Of the eleven randomised trials included in the review, two of these were not classified as of high quality despite blinded assessment and complete follow-up, due to problems with assessment methodology. VISUAL ACUITY: Visual acuity over the first year was measured by Teller acuity cards in six studies, by VEP in four studies and by ERG in two studies. Most studies found no significant differences in any visual assessment between supplemented and control infants.
Most of the trials have used Bayley Scales of Infant Development (BSID) at 12 to 24 months postterm and shown no significant effect following supplementation. Meta-analysis of BSID of three studies (Fewtrell 2002, O'Connor 2001, van Wezel 2002) shows no significant effect of supplementation on development. Carlson 1993 and Carlson 1996 demonstrated lower novelty preferences (possibly predictive of lower intelligence) in the supplemented compared with the control group. The investigators however concluded that supplemented infants may have more rapid visual information processing given that they had more looks and each look was of shorter duration.
Most trials have reported no significant effect of LCPUFA supplementation on growth of preterm infants. Two trials (Carlson 1993, Carlson 1996) suggest that LCPUFA supplemented infants grow less well than controls, possibly due to a reduction in AA levels which occurs when n-3 supplements are used without n-6 supplements. Recent trials with addition of AA to the supplement have reported no significant effect on growth. Fewtrell 2002 reported mild reductions in length and weight z scores at 18 months. Contrary to these results, the meta-analysis of five studies (Uauy 1992, Carlson 1996, Hansen 1997, Vanderhoof 1999, Innis 2002) showed increased weight and length at two months post-term in supplemented infants.
Uauy 1992 reported no significant effect of LCPUFA supplementation on bleeding time and red cell membrane fragility.
Infants enrolled in the trials were relatively mature and healthy preterm infants. Assessment schedule and methodology, dose and source of supplementation and fatty acid composition of the control formula varied between trials. No long-term benefits were demonstrated for infants receiving formula supplemented with LCPUFA. There was no evidence that supplementation of formula with n-3 and n-6 LCPUFA impaired the growth of preterm infants.