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Original Research Communication |
-linolenic acid in the diet of term infants: effects on visual function and growth1,2,3
1 From the Department of Paediatrics & Child Health, Flinders University of South Australia and Flinders Medical Centre, Bedford Park (Adelaide), Australia, and Wyeth Nutritionals International, Radnor, PA.
See corresponding editorial on page 1
2 Supported by Wyeth Nutritionals International, USA; the Australian National Health & Medical Research Council; and the MS McLeod Research Trust.
3 Address reprint requests to RA Gibson, Child Nutrition Research Centre, Child Health Research Institute, 72 King William Road, North Adelaide, SA 5006, Australia. E-mail: rgibson{at}flinders.edu.au.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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-linolenic acid (LA:ALA) in formula for term infants be between 5:1 and 15:1. These recommendations were made in the absence of data on functional or clinical outcomes. Objective: We compared the fatty acid status, visual evoked potential (VEP) acuity, and growth of term infants fed formula containing an LA:ALA of 10:1 or 5:1 with those of a breast-fed reference cohort.
Design: Formula-fed infants were allocated randomly in a double-blind fashion to receive formula with an LA:ALA of either 10:1 (16.9:1.7; n = 36) or 5:1 (16.3:3.3; n = 37) from near birth to 34 wk of age. Increased ALA was attained by replacing soy oil with low–erucic acid canola oil. A parallel group of breast-fed infants was also recruited. Infant growth and fatty acid status were assessed at 6, 16, and 34 wk of age. VEP acuity was assessed at 16 and 34 wk.
Results: Infants fed the 5:1 formula had greater docosahexaenoic acid (DHA) concentrations in plasma and erythrocyte phospholipids than did infants fed the 10:1 formula, but DHA concentrations of infants fed the 5:1 formula remained less than those in breast-fed infants. The VEP acuity of all formula-fed and breast-fed infants was not significantly different at 16 and 34 wk of age. At birth, infants fed the 5:1 formula were heavier, were longer, and had a greater head circumference than infants assigned to the 10:1 formula group; this differential was maintained throughout the trial. The rate of gain in weight, length, and head circumference was not significantly different between the 2 formula-fed groups, although breast-fed infants had lower weight and length gains than did formula-fed infants between 16 and 34 wk of age.
Conclusion: Lowering the LA:ALA in formula from 10:1 to 5:1 by using low–erucic acid canola oil resulted in a modest increase in plasma DHA but had no effect on VEP acuity or growth rate.
Key Words: -Linolenic acid • ALA • linoleic acid • LA • docosahexaenoic acid • DHA • growth • visual evoked potential • VEP • infants • breast milk • infant formula
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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-linolenic acid (ALA; 18:3n-3) and linoleic acid (LA; 18:2n-6) has been the subject of some debate. Early work measuring 
6-desaturase activity in liver samples from a small group of infants suggested that infants might have negligible ability to synthesize LCPUFAs (1). These data were repudiated by the findings of Carnielli et al (2) and Sauerwald et al (3), however, who showed that both ALA and LA are converted to LCPUFAs in both preterm and term infants.
There is little doubt that concentrations of LCPUFAs attained in infants fed formulas containing only ALA and LA are lower than concentrations measured in age-matched breast-fed infants, who receive a supply of LCPUFAs in breast milk. Although concentrations of both docosahexaenoic acid (DHA; 22:6n-3) and arachidonic acid (AA; 20:4n-6) in breast milk are low (
0.2% and 0.4% of total fatty acids, respectively), the amount each breast-fed infant receives per day from the milk of Western women can be 
100 mg DHA and 200 mg AA (4). There also appear to be some differences in the ability of infants to synthesize DHA and AA from the precursors ALA and LA, respectively. This assumption is based on the fact that formula-fed infants can accumulate more AA than DHA even with sufficient substrate (5, 6). This accumulation is almost certainly because synthesis of the 20-carbon AA is not subject to the same regulatory steps as is the synthesis of DHA. Synthesis of DHA involves a second 6-desaturase step and ß-oxidation in the peroxisomes, which are potential sites of regulation (7–9).
The amount of DHA that an infant can synthesize is limited to some extent by the ratio of LA to ALA (LA:ALA) in dietary fats. We showed in an earlier study that the amount of erythrocyte DHA in formula-fed infants was increased from 53% to 73% of the amount found in breast-fed infants by simply lowering the LA:ALA in formula from 19:1 to 3 or 4:1 (6). These and other data (10) have been the basis of committee recommendations to lower the LA:ALA in formula to between 15:1 and 5:1 (11). However, such recommendations were made in the absence of data relating to functional or clinical outcomes.
Although several trials showed that infants fed formula with only LA and ALA have lower visual performance than do infants fed formula supplemented with DHA and other LCPUFAs (12–14), until recently, no trials had tested the effect of lowering the dietary LA:ALA on the DHA status, growth, and visual function of formula-fed infants (15). A limited number of oils are available that are sufficiently rich in ALA to allow an oil blend with a 5:1 LA:ALA. An oil that may be useful is low–erucic acid (22:1n-9) canola oil, which does not have general approval for use in infant formula in the United States. Our aim was to assess the fatty acid profiles, growth, and visual evoked potential (VEP) acuity of formula-fed infants randomly allocated to receive infant formula with either a 10:1 or a 5:1 LA:ALA and of a breast-fed reference cohort.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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37 wk gestation) infants born at Flinders Medical Centre and the Women's & Children's Hospital between November 1994 and June 1995 were eligible for entry into the trial. Infants were excluded if they were small for gestational age, if there was evidence of a congenital disease, or if their mothers had diabetes requiring insulin or a history of drug or alcohol abuse. Infants were withdrawn from the VEP aspect of the study if an ophthalmic examination carried out at 10–12 wk revealed refraction outside the range of –3 to 5 diopters, severe astigmatism (1.75 diopters), or strabismus. The Committee on Clinical Investigations (Ethics) at Flinders Medical Centre and the Research and Ethics Committee of the Women's and Children's Hospital approved the trial protocol. To avoid any possibility of influencing the mothers' feeding choice, only mothers who had never attempted breast-feeding were approached to enter the randomized trial of formula feeding. Each mother and her family could discuss the study with a research nurse. Written, informed consent was obtained from each mother before she was discharged from the hospital. After consent was obtained, infant-mother pairs were randomly assigned to a formula group according to a randomization schedule prepared by Wyeth Nutritionals International. Formula assignment was according to sequentially numbered, opaque, and sealed envelopes. Investigators and families were blinded to the randomization. To further facilitate masking of the formula composition, each of the formulas was given 2 codes.
A reference group of breast-fed infants was also recruited for the trial. Written, informed consent was obtained in the same manner as for formula-fed infants. Full breast-feeding was defined as 200 mL formula/wk in the first 16 wk of life and 200 mL formula/d between the ages of 16 and 34 wk. Formulas were self-selected by mothers and none contained LCPUFAs. This definition of full breast-feeding is consistent with the definition of high partial breast-feeding (>80% of feedings are breast-feedings) of the Interagency Group for Action on Breast-feeding (16).
Study formulas
Wyeth Nutritionals International supplied the formulas in powder form in 450-g cans. Reconstitution instructions and packaging were identical. All formulas had similar nutrient compositions and the protein, fat, and carbohydrate contents were 15, 36, and 72 g/L, respectively. Formulas contained either an LA:ALA of 16.9:1.7 (10:1) or 16.6:3.3 (5:1) (Table 1
). The fats in each formula were derived from a combination of 4 vegetable oils, with the 5:1 formula having 29% of the fat contributed by canola oil. Erucic acid was not detectable in either test formula.
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Infants were assessed at 6, 16, and 34 wk of age at Flinders Medical Centre. At each of these assessment times, weight, length, and head circumference were measured and a blood sample was taken by heel-prick to quantify plasma and erythrocyte phospholipid fatty acid concentrations. Information on infant well-being, the frequency and volume of formula feedings, the frequency of breast-feeding, and the types and frequency of solid foods consumed were also assessed. Visual acuity was measured by VEP at 16 and 34 wk of age. Tolerance data were collected at 6 and 16 wk of age because these were the only assessment times at which formula was the predominant source of nutrition for formula-fed infants.
Fatty acid analyses
Plasma and erythrocytes were separated by centrifugation at 1500 x g for 10 min at room temperature and the erythrocytes were washed 3 times with isotonic saline. Plasma and erythrocyte lipids were extracted with chloroform:methanol (18) and chloroform:propanol (19), respectively. The phospholipid fractions of both plasma and erythrocyte lipid extracts were separated by thin-layer chromatography, methylated, and quantified by capillary gas chromatography (20).
VEP acuity determination
VEPs were recorded under transient conditions by using the Enfant 4010 system (Neuroscientific Corp, Farmingdale, NY). Infants were seated with a parent in front of an 48-cm (19-inch) monitor (Neuroscientific Corp) on which high-contrast, black and white, checkerboard pattern reversal (2 Hz) stimuli were presented. The luminance of the stimulus display was 50 cd/m2. The active electrode was placed 3 cm above the inion (Oz), the reference electrode was at Fz, and the inactive electrode was on the forehead. Different checkerboard patterns were tested at each age (7, 10, 14, 20, 28, 42, and 55 min arc at 16 wk and 4, 7, 9, 11, 14, and 20 min arc at 34 wk). The viewing distance for all patterns at 16 wk was 100 cm, whereas at 34 wk the 2 smallest patterns were viewed at both 100 and 150 cm to extend the range of small stimuli. Two recordings were performed for each checkerboard pattern and these were subsequently averaged. Four operators conducted the VEPs at 16 wk, whereas 3 operators conducted the VEPs at 34 wk.
The peak-to-peak amplitude of the VEP (N1–P100) response was measured and plotted against the log of the angle subtended by each check size. The linear portion of the plot was extrapolated to 0 µV to give the theoretical value that would just elicit a response (log of the minimum angle of resolution). Hence, lower values for the log of the minimum angle of resolution represent better visual acuity because they indicate detectable responses to smaller checkerboard patterns. Points were excluded from the regression if they were not on the linear portion of the stimulus-response function or if they represented amplitudes 2µV (21, 22). VEP acuity extrapolations were accepted as valid only if there were 3 points and the regression line was significant (P < 0.05). The process of conducting the VEP test was similar to that followed in our earlier study (12), although the hardware and software were updated to allow a greater range of checkerboard patterns to be presented to the infant. Thus, more points were available for a more reliable extrapolation (23).
Growth
Infants were weighed without clothes on a calibrated Seca Baby Balance (model 727; Seca, Hamburg, Germany). Length was measured in the supine position to the nearest 0.5 cm by 2 individuals using an infant measuring mat. Head circumference was measured at the largest occipitofrontal circumference to the nearest 0.1 cm with a nonstretchable tape. Weight-for-age and length-for-age z scores were calculated by using the National Center for Health Statistics reference data (24).
Sample size and statistics
We estimated that a sample size of 20 infants per feeding group would be sufficient for detecting a mean difference of 0.2 log units in VEP acuity at both 16 and 34 wk of age with a 0.05 level of significance and 90% power. To allow for the exclusion of VEP acuity extrapolations that did not meet our criteria for validity, we aimed for complete data for 30 infants per feeding group. Thirty complete infants per feeding group was also sufficient for detecting a mean difference in weight of 600 g at 34 wk of age with a 0.05 level of significance and 90% power. We hypothesized that such a difference in growth would be clinically relevant because it is similar in magnitude to the weight differences often observed between breast-fed and formula-fed infants.
One-way analysis of variance was used to examine differences in fatty acid status between infants who were fully breast-fed and infants who were fed 1 of the 2 test formulas at each assessment time. Post hoc analysis was by the Neuman-Keuls test with a Bonferroni adjustment. Comparisons of VEP acuity and growth indexes between the formula-fed groups were made by analysis of covariance. Environmental factors and infant characteristics that were significantly associated with the dependent variable were adjusted for in these analyses.
Multiple linear regression models were constructed to further investigate the effect of environmental and nutritional variables on VEP acuity at 16 and 34 wk. All measured environmental and nutritional variables that may have had an effect on development were considered as possible independent variables for these regression models. These variables included sex; gestational age; birth size; birth order; parental smoking status, education, and social scores; number of siblings; infant plasma and erythrocyte DHA, eicosapentaenoic acid (EPA; 20:5n-3), and AA concentrations; age at each test; size at each test; and the assessor. Models were constructed by using the independent variables that were associated (P < 0.2) with the dependent variable. Independent variables were removed from a given model if the independent variable's presence or absence did not influence the model. No independent variables in the final regression models were found to be colinear. All analyses were performed with SPSS for WINDOWS (version 6.0; SPSS Inc, Chicago).
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). However, proportionately more infants with parents who smoked were withdrawn from the trial.
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). Eighteen infants were withdrawn for the following reasons: 3 mothers changed their mind about participating in the trial, 2 families relocated to another state, 2 families did not wish their infants to have blood tests, 4 infants had recurrent illnesses not associated with the trial, 3 infants were lost to follow-up, and 3 mothers were too busy to accommodate the trial. One infant was withdrawn for an unknown reason. The gestational age at birth and social characteristics of breast-fed infants entering and completing the trial were not significantly different (Table 2). However, the fully breast-fed infants who completed the trial were exposed to less tobacco smoke than were other breast-fed infants.
Infant fatty acid profiles
Plasma and erythrocyte phospholipid DHA concentrations were significantly higher in infants fed the 5:1 formula than in those fed the 10:1 formula. However, the plasma and erythrocyte phospholipid DHA concentrations of infants fed the 5:1 formula were 55% and 62%, respectively, of concentrations in breast-fed infants at 16 wk of age (Table 3). Concentrations of plasma and erythrocyte phospholipid 22:5n-3 were also higher in infants fed the 5:1 formula than in those fed the 10:1 formula. Additionally, plasma and erythrocyte phospholipid EPA concentrations in infants fed the 5:1 formula were approximately double the concentrations in infants fed the 10:1 formula. In contrast with other n-3 LCPUFAs, plasma phospholipid EPA concentrations in infants fed the 5:1 formula increased significantly with age and surpassed the concentrations measured in fully breast-fed infants (Figure 1). Plasma concentrations of n-3 and n-6 LCPUFAs in breast-fed infants differed from those in formula-fed infants as early as the time of enrollment (days 4–6 of life).
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). Plasma and erythrocyte phospholipid AA concentrations in fully breast-fed infants were greater than those in all formula-fed infants at all ages (Table 3, Figure 1). Plasma and erythrocyte concentrations of both 22-carbon n-6 fatty acids (22:4n-6 and 22:5n-6) were significantly lower in infants fed the 5:1 formula than in infants fed the 10:1 formula (Table 3).
VEP acuity
Of 145 VEPs conducted at 16 wk of age, 109 (75%) resulted in a successful acuity extrapolation and 36 (25%) resulted in no acuity extrapolation (Table 4). There was no significant difference in the proportion of successful VEP extrapolations between the dietary groups. Similarly, there were no significant differences in sex or social and demographic characteristics of infants with successful and unsuccessful VEP extrapolations and no significant difference in VEP acuity between the 2 formula-fed groups, even after adjustment for significant covariates (maternal smoking, head circumference at birth, and postconceptional age) at 16 wk (Table 4). Additionally, there was no significant difference in VEP acuity between both the fully and the partially breast-fed infants and the formula-fed infants.
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). There was no significant difference in the rate of unsuccessful VEP extrapolations between breast-fed and formula-fed infants. However, infants with unsuccessful VEP extrapolations had male caregivers with a more prestigious social score (3.9 ± 1.4 compared with 4.4 ± 1.0, P < 0.02), a higher level of education (3.3 ± 1.4 compared with 2.8 ± 1.0, P < 0.02), and a lower likelihood of smoking (26% compared with 45%, P < 0.02) than did male caregivers of infants with successful VEP acuity extrapolations. Among the infants with successful VEP extrapolations, there was no significant difference in VEP acuity between the 2 groups of formula-fed infants before and after adjustment for the significant covariates of partner social score and level of education at 34 wk (Table 4). The acuity of breast-fed and formula-fed infants was also not significantly different.
Regardless of feeding group, the VEP acuity of all infants improved between 16 and 34 wk of age (Table 4). There was no significant effect of operator on VEP acuity scores at either 16 or 34 wk of age.
To determine whether any dietary or environmental factors independently influenced VEP acuity, separate regression models were constructed at 16 and 34 wk of age. Lower rates of partner smoking, greater head circumference at birth, lower weight at 16 wk, and greater postconceptional age at assessment were associated with better VEP acuity at 16 wk of age (Table 5). Only the partner's social score significantly predicted VEP acuity at 34 wk of age.
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. At all time points, all infants were within normal ranges for weight, length, and head circumference. However, infants allocated to the 10:1 formula group were lighter (95% CI: -27, -444 g; n = 58), were shorter (95% CI: -0.09, -1.65 cm; n = 58), and tended to have a smaller head circumference (95% CI: -1.29, 0.12 cm; n = 58) at birth than infants in the 5:1 formula group. This size difference was maintained throughout the trial; infants in the 5:1 formula group were consistently heavier [95% CI: 48, 419 g at 6 wk (n = 58); -79, 620 g at 16 wk (n = 57); -2, 895 g at 34 wk (n = 58)] and longer [95% CI: -0.1, 1 cm at 6 wk (n = 58); 0.1, 1.9 cm at 16 wk (n = 57); -0.2, 2 cm at 34 wk (n = 58)] than infants in the 10:1 formula group, even after adjustment for significant covariates such as sex and birth variables. Indeed, weight-for-age and length-for-age z scores showed that median weight and length values for infants allocated to the 5:1 formula group were consistently above the 50th percentile (0 z score), whereas weight and length z scores for infants in the 10:1 formula group approximated the 50th percentile (Figure 2). Median weight and length z scores for breast-fed infants were above the 50th percentile at birth but decreased progressively with age (Figure 2). These data highlight that breast-fed infants had lower weight gains (P = 0.05) and lower length gains (P < 0.05) than did formula-fed infants at both 16 and 34 wk of age. There were no significant differences in weight, length, or head circumference gain between infants in the 2 formula-fed groups.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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We previously plotted (6) the predicted effect of lowering the LA:ALA in term infants by using a modification of the equations proposed by Lands et al (25). Although the equations could not accurately predict DHA concentrations, these curves suggested that little change would be seen in the balance of n-3 and n-6 LCPUFAs as a result of reducing the dietary LA:ALA from very high values (>10:1) until the ratio fell below 6:1 (6). Our general prediction has proven to be largely correct. For example, past studies showed that lowering the ratio from 39:1 to 7:1 (10) or from 12:1 to 9:1 (26) had no effect on DHA status. In the more complete study of Jensen et al (15), lowering the ratio from 44:1 to 9.7:1 had no effect on DHA status, whereas dropping the ratio further to 4.8:1 resulted in a significant increase in DHA in term infants. The combined results of our earlier study (6), the study of Jensen et al (15), and the present study make it clear that the LA:ALA needs to be lowered to <6:1 to improve the DHA status of formula-fed infants.
The proportionate increase in EPA was higher than that for DHA as a result of lowering the LA:ALA from 10:1 to 5:1. Despite the increase in plasma EPA, there was no detectable reduction in plasma AA and only a small reduction in erythrocyte AA. Our results are similar in this regard to the EPA and AA concentrations reported by Jensen et al (27) after the feeding of formulas with almost identical ratios.
Interestingly, the data presented in our study contrast with results observed in adults. Mantzioris et al (28) showed that reducing the LA:ALA to as low as 0.4:1 had little or no effect on the DHA status of healthy adults, but was effective at increasing the concentration of EPA. Note that the adult trial was conducted with background diets containing some preformed LCPUFAs and thus may not be directly comparable with a trial in which the formula-fed infants received only ALA and LA. Nevertheless, the combined data from infant and adult trials may indicate that tissues of infants have a higher rate of synthesis of n-3 LCPUFAs than do tissues of adults and an enhanced ability to incorporate these fatty acids. Such a hypothesis could be assessed with stable-isotope studies.
Growth is a sensitive indicator of nutritional adequacy in infants and should be monitored at regular intervals over an extended time period. In our trial, all infants regardless of diet were appropriate for all growth measures at all ages. However, although we used a rigorous randomization and allocation procedure, infants randomly assigned to the 10:1 formula group were proportionately smaller than infants in the 5:1 formula group. This highlights that properly performed randomization does not necessarily ensure similarity of groups in trials with relatively modest numbers (29). In a trial of this size for which we expect treatment effects to be of the order of 0.75–1 SD, a large difference in one or more prognostic factors can occur purely by chance (29). After we adjusted for the size differences at birth, there was no effect of dietary fat blend on growth of formula-fed infants. These findings contrast with the results of Jensen et al (15), who observed lower weights and lower weights-for-age at 4 mo in the group of infants fed formula with an LA:ALA of 15.6:3.2 (4.8:1) than in the group fed formula with an LA:ALA of 17.6:0.4 (44:1). However, in the trial by Jensen et al, the 4.8:1 formula group had the greatest dropout rate and only 13 infants were assessed at the single time point at which lower weight gain was observed, raising questions about statistical power in relation to growth in that study.
The growth pattern observed for breast-fed and formula-fed infants in our study was quite different. Weight-for-age and length-for-age z scores decreased progressively in fully breast-fed infants, whereas the weight and length z scores of both groups of formula-fed infants remained fairly stable with age. These data indicate that the rate of weight and length gain in breast-fed infants was lower than that observed in formula-fed infants. This observation highlights the well-known differences in growth patterns between breast-fed and formula-fed infants (30, 31).
In our trial we found no effect of diet on transient VEP acuity development at 16 or 34 wk of age. However, at 34 wk of age a large number of infants had VEPs that resulted in no acuity extrapolations. We observed that infants with unsuccessful acuity extrapolations were from families with more social advantages than those of infants with successful VEP extrapolations. Regression analysis of infants with acuity extrapolations showed that improved VEP acuity was associated with a more prestigious partner social score. This may indicate that the visual stimuli presented at 34 wk did not cover a sufficient range of small patterns, resulting in a limitation in sensitivity of our VEP test at this age. On the contrary, there is no evidence of a similar problem in sensitivity at 16 wk.
In only one published study was the effect of the LA:ALA on VEP acuity measured in preterm infants (32). In this study, the authors detected no significant difference at 4 mo corrected age between infants fed a corn oil–based formula with an LA:ALA of 48:1 and infants fed a soy-based formula with an LA:ALA of 8:1. Jensen et al (15) measured the latency and amplitude of the VEP response to only one checkerboard pattern at 4 and 8 mo of age and found no significant effect of the dietary LA:ALA in term infants. That data, however, cannot be extrapolated to give an acuity value. Although these trials assessed only a limited range of visual functions, none showed a beneficial effect on visual outcomes of increasing dietary ALA or decreasing the LA:ALA.
Of perhaps greater interest was our observation of no significant difference in acuity values between breast-fed and formula-fed infants, even though breast-fed infants had higher plasma and erythrocyte DHA concentrations than did formula-fed infants. This finding contrasts with our earlier reports (12, 33). The current trial was designed to have power to detect a minimum difference of 0.2 log units between dietary groups to a level of 90%. We chose 0.2 log units as a clinically relevant cutoff; furthermore, differences of this order are similar to those reported previously (12). The actual VEP acuity values of breast-fed and formula-fed infants at 16 wk of age in the current trial were similar to values observed in the placebo formula–fed infants in our original study (12). More recent trials reported VEP acuity values in breast-fed and formula-fed infants similar to those in the current trial (34, 35). The VEP acuity values reported recently by Birch et al (14) for infants aged 17 wk are 1 SD lower than the values in the current trial and 2 recent studies (34, 35). However, all these trials reported acuity values within the expected normal range.
The differences in VEP acuity between breast-fed and formula-fed term infants reported by Birch et al (14) were small and did not exceed 0.1 log unit. If indeed actual differences in VEP acuity between breast-fed and formula-fed infants are small, it is also possible that such differences could be enhanced or masked by the influence of other environmental variables that are associated with VEP acuity development. For example, in the present study, smoking, postconceptional age, and head circumference at birth were all independent factors that significantly influenced VEP acuity at 16 wk, whereas the partner's social score independently influenced VEP acuity at 34 wk of age. These findings highlight the need to adjust for environmental influences on any developmental outcome.
In summary, we saw no decrease in weight gain among infants fed the formula containing 29% canola oil with no detectable erucic acid. In addition, VEP acuity was not significantly different between formula groups and neither formula group was significantly different from breast-fed infants. Our data provide evidence for the safe use of canola oil in infant formula.
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ACKNOWLEDGMENTS |
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M. Makrides, J. S Hawkes, M. A Neumann, and R. A Gibson Nutritional effect of including egg yolk in the weaning diet of breast-fed and formula-fed infants: a randomized controlled trial Am. J. Clinical Nutrition, June 1, 2002; 75(6): 1084 - 1092. [Abstract] [Full Text] [PDF]
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E. A Tolley and S. E Carlson Considerations of statistical power in infant studies of visual acuity development and docosahexaenoic acid status1 Am. J. Clinical Nutrition, January 1, 2000; 71(1): 1 - 2. [Full Text] [PDF]
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), infants fed formula containing an LA:ALA of 5:1 (
), and fully breast-fed infants (•). Different superscript letters indicate significant differences at each time point, P < 0.001.