Long-chain polyunsaturated fatty acid supplementation in infants born at term

The n-3 and n-6 fatty acids linolenic acid and linoleic acid are precursors of the n-3 and n-6 longchain fatty acids (LCPUFA). Infant formula has historically only contained the precursor fatty acids. Controversy exists over whether LCPUFA are also essential nutrients in infancy. Over the last few years some manufacturers have added LCPUFA to formulae and marketed them as providing an advantage for the development of term infants.

The aim of this review is to assess whether supplementation of formula with LCPUFA is safe and of benefit to term infants.

Trials were identified by MEDLINE, checking reference lists of articles and conference proceedings, and by personal communication.

All randomised trials of formula supplemented with LCPUFA and with clinical endpoints were reviewed.

Ten randomised studies were identified. One of these studies was excluded due to supplementation commencing after three weeks of age. Eight of the nine included trials were assessed to be of good quality. There was insufficient information available to assess the quality of the other included trial.

Visual acuity was assessed by visual evoked potentials (VEP) at 4 and 7-8 months in the studies of Makrides et al (1995 & 1996). The supplemented infants had an improved rate of visual maturation at both time points in the first study, but no difference was found between the groups at the same time points in the second study. VEP acuity was also assessed in the study of Austed et al (1997) and no effect of supplementation was found at any time point over the first year. This contrasts with the study of Birch et al (1998) where VEP acuity was better in the supplemented group compared with the control group at 6 weeks, 4 and 12 months but not at 6 months. Visual acuity was assessed by Teller acuity cards in the study of Carlson et al (1996), Clausen et al (1996), Austed et al (1997) and Birch et al (1998). Supplementation had no effect on visual acuity over the first year of life except at one of five time points in the study of Carlson et al (1996). Intellectual development was measured in seven studies. The two largest studies showed no effect of supplementation on development, either at 18 months (Lucas et al 1999) or at one and three years (Janowsky et al 1995, Scott et al 1997). The next largest study reported better developmental scores at 18 months in the supplemented group (Birch et al 2000) but when combined with data of Lucas et al, no significant benefit is shown. Makrides et al (1995 & 1996) also showed no benefit to development with supplementation over the first two years of life. Agostini et al 1995 reported a benefit in development at 4 months of age with supplementation but when the infants were followed up with the same test at 1 and 2 years, no difference between groups was found (Agostini et al 1997). The Portland study showed no effect of supplementation on language development at one and three years (Janowsky et al 1995, Scott et al 1997). Clausen et al (1996) reported better novelty preference measured by Fagan Infant test at nine months in supplemented infants compared with controls. Willatts et al (1998) reported better problem solving at 10 months with supplementation. Growth was measured in the studies of Makrides et al (1995 & 1996), Austed et al (1997), Willatts et al 1998, Lucas et al 1999 and Birch et al 2000. LCPUFA supplementation did not influence growth in any of these studies.

At present there is little evidence from randomised trials of LCPUFA supplementation to support the hypothesis that LCPUFA supplementation confers a benefit for visual or general development of term infants. Minor effects on VEP acuity have been suggested but appear unlikely when all studies are reviewed. A beneficial effect on information processing is possible but larger studies over longer periods are required to conclude that LCPUFA supplementation provides a benefit when compared with standard formula. Data from randomised trials do not suggest that LCPUFA supplements influence the growth of term infants.