Michael B. Montalto

Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year

The CNS and the retina are enriched in long chain polyunsaturated (LCP) fatty acids, specifically docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are present in human milk but not in most infant formulas. In the present study of 134 formula-fed and 63 breast-fed infants, we prospectively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell (RBC) phospholipid levels of these fatty acids, enhance visual function, or affect growth during the first year. Healthy term infants <7 d old were randomized to be fed formulas containing linoleic acid (≈10% kcal) andα-linolenic acid (≈1% kcal) plus (1) no added LCP fatty acids (control formula), (2) DHA (0.12 wt% fatty acids) and AA (0.43 wt%) from egg yolk phospholipid (AA + DHA formula), or (3) DHA (0.2 wt%) from fish oil (DHA formula). A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo. Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2, 4, 6, 9, and 12 mo. Infants fed the control formula had 10-40% lower RBC levels of DHA and AA than infants in the breast-fed group. Infants fed the AA+ DHA formula had levels of both LCP within ≈10% of the values for infants in the breast-fed group, and infants fed the DHA formula had 25-55% higher DHA levels and 15-40% lower AA levels. There were no differences in growth or in visual function during this 12-mo feeding study.

Formula Supplementation With Long-chain Polyunsaturated Fatty Acids: Are There Developmental Benefits?

Objective. To evaluate the developmental outcomes of children who participated in an augmented randomized clinical trial of supplementing a standard infant formula with long-chain polyunsaturated fatty acids. Design. Randomized clinical trial, augmented with a nonrandomized human milk comparison group. There were three randomized formula groups: standard formula, standard formula containing docosahexaenoic acid (DHA), and standard formula containing DHA and arachidonic acid. Setting. Three clinical sites serving diverse populations: Kansas City, MO; Portland, OR; and Seattle, WA. Participants. A total of 274 healthy full-term infants were enrolled in the infant-feeding protocol; of these, 197 (72%) participated in assessments of developmental outcome. Formula Supplements. In the randomized trial, one group received a standard formula, another group received a formula that had been supplemented with DHA from fish oil, and a third group received a formula supplemented with both DHA and arachidonic acid from an egg phospholipid. Outcome Measures. Mental and Motor Scales of the Bayley Scales of Infant Development at 12 months of age; vocabulary and gesture communication scores from the MacArthur Communicative Development Inventories at 14 months of age. Results. There were no statistically significant differences for either the Bayley Mental Scale or the Bayley Motor Scale, neither when the analysis was restricted to the three randomized formula groups nor when the analysis included all four groups. However, the DHA formula group had significantly lower scores on two of the MacArthur scales: the DHA group scored lower than the nonrandomized human milk comparison group on the Vocabulary Comprehension Scale, and the DHA group scored lower than the randomized control formula group on the Vocabulary Production Scale. Moreover, additional analyses both in the formula groups and in the human milk comparison group found significant negative correlations between DHA levels and vocabulary outcomes. Conclusion. We believe that additional research should be undertaken before the introduction of these supplements into standard infant formulas.

Lower Incidence of Necrotizing Enterocolitis in Infants Fed a Preterm Formula with Egg Phospholipids

Necrotizing enterocolitis (NEC) causes approximately 4000 deaths/y and significant morbidity among U.S.-born preterm infants alone. Various combinations of inadequate tissue oxygenation, bacterial overgrowth, and enteral feeding with immaturity may cause the initial damage to intestinal mucosa that culminates in necrosis. Presently, there is not a way to predict the onset of the disease or to prevent its occurrence. As part of risk-benefit assessment, we compared disease in hospitalized preterm infants fed a commercial (control) preterm formula or an experimental formula with egg phospholipids for a randomized, double-masked, clinical study of diet and infant neurodevelopment. Infants fed the experimental formula developed significantly less stage II and III NEC compared with infants fed the control formula (2.9 versus 17.6%, p < 0.05), but had similar rates of bronchopulmonary dysplasia (23.4 versus 23.5%), septicemia (26 versus 31%), and retinopathy of prematurity (38 versus 40%). Compared with the control formula, the experimental formula provided 7-fold more esterified choline, arachidonic acid (AA, 0.4% of total fatty acids), and docosahexaenoic acid (0.13%). Phospholipids are constituents of mucosal membranes and intestinal surfactant, and their components, AA and choline, are substrates for intestinal vasodilatory and cytoprotective eicosanoids (AA) and the vasodilatory neurotransmitter, acetylcholine (choline), respectively. One or more of these components of egg phospholipids may have enhanced one or more immature intestinal functions to lower the incidence of NEC in this study. Regardless of the potential mechanism, a larger randomized trial designed to test the effect of this egg phospholipid-containing formula on NEC seems warranted.

Reduced bone mineralization in infants fed palm olein-containing formula: a randomized, double-blinded, prospective trial.

after diagnosis. Nonetheless, observation is simply an option in the new guideline, not a recommendation, which leaves substantial room for clinician and parent preference.3 There is nothing wrong with immediate antibiotic therapy for any case of properly diagnosed AOM if that is what the family prefers. Most symptom relief with AOM, however, results from natural history, not antibiotics, and the modest therapeutic benefits seen after 24 hours may be offset by undesirable side effects.OBJECTIVE Palm and palm olein (PO) oils are used in some infant formula fat blends to match the fatty acid profile of human milk, but their presence has been shown to lower calcium and fat absorption. We aimed to determine if the reported differences in calcium absorption could affect skeletal development by comparing bone mineral accretion in healthy term infants fed a milk-based formula with (PMF) or without PO. METHODS Whole body bone mineralization was evaluated in healthy term infants fed 1 of 2 coded, commercially available, ready-to-feed infant formulas in a randomized, double-blind, parallel study. Subjects were fed either 1). PMF formula (Enfamil with iron; Mead Johnson Division of Bristol Myers, Evansville, IN; N = 63) containing PO/coconut/soy/high-oleic sunflower oils (45/20/20/15% oil); or 2). milk-based formula without PO (Similac with iron; Ross Products Division Abbott Laboratories, Columbus, OH; N = 65), containing high-oleic safflower/coconut/soy oils (40/30/30% oil) from enrollment by 2 weeks after birth until 6 months. Anthropometrics and formula intake were determined monthly; total body bone mineral content (BMC) and bone mineral density (BMD) were measured at baseline, 3, and 6 months of age using dual energy x-ray absorptiometry. RESULTS Intent-to-treat analyses indicated no significant differences between feeding groups in weight, length, head circumference, or formula intake throughout the study. BMC and BMD were not different at baseline but repeated measures analyses show that infants fed PMF had significantly lower BMC and BMD at 3 and 6 months. CONCLUSIONS Healthy term infants fed a formula containing PO as the predominant oil in the fat blend had significantly lower BMC and BMD than those fed a formula without PO. The inclusion of PO in infant formula at levels needed to provide a fatty acid profile similar to that of human milk leads to lower bone mineralization.

Lactose-Free Milk Protein-Based Infant Formula: Impact on Growth and Gastrointestinal Tolerance in Infants

Lactose, the major carbohydrate in human milk and standard milk—based formulas, provides energy for growth in infants. The use of lactose-free milk protein—based infant formulas has increased in the United States. However, clinical studies of their impact on growth, safety, and gastrointestinal tolerance in infants are limited. Thus, a prospective, blinded, randomized clinical trial was conducted in healthy, normal-term infants fed an experimental lactose-free milk protein—based formula (NoLAC; n = 63) versus a standard commercial lactose-containing milk-based formula (LAC; n = 65) for 112 days. Growth (weight, length, and head circumference) was similar and normal in both groups (weight gain: NoLAC = 31.1 ± 0.9 g/day, LAC = 29.4 ± 0.9 g/day, mean ± SEM; P = .895). Serum biochemistries for both groups were within infants’ normal reference ranges. Both groups had comparable tolerance but the NoLAC group had softer stools and lower spit-ups. Thus, the study suggests that absence of lactose in milk-based formula does not adversely affect normal growth in term infants.

Cognitive and Language Assessment of 3.25 Yr Old Children Fed Formulas with or without Long-Chain Polyunsaturated Fatty Acids (LCP) in the First Yr.• 1428

The brain is rich in two LCP, docosahexaenoic acid (DHA) and arachidonic acid (AA). Small amounts of LCP are present in human milk, but not in most formulas. Studies of the effects of infant feeding regimens on visual and cognitive development in term infants have provided inconsistent results and few extend beyond 1 yr. Objective: This study evaluated development of children at age 3.25 yrs fed infant formulas with or without LCP through the first yr. Design: Infants 2 days of age were randomized to a control (no LCP), an AA+DHA (0.43 wt% AA and 0.12% DHA both from egg yolk phospholipid) or a DHA (0.20% DHA from a low-EPA fish oil) formula; breast fed infants served as a reference group. No differences in growth or development were found in the first yr and the DHA group at 14 mos had lower vocabulary scores (Pediatr Res 1997;41:1-10 & 1995;37:310A). Preplanned regression analyses controlled for birthweight, gender, ethnicity, maternal education, maternal age, childs exact age at testing, and site. Results: 157 of 196 (80%) eligible subjects were tested. There were no effects of LCP supplementation on test results in the 107 formula fed children. Stanford Binet IQ scores for the control, AA+DHA and DHA groups were(mean±SD) 103±15, 101±12, and 100±12, respectively. Scores for the Peabody Picture Vocabulary Test-Revised were 97±14, 97±16 and 96±13; mean length of utterance(morphemes) was 3.6±0.9, 3.7±0.9, 3.9±0.8. The breast fed group had higher scores in some comparisons. Conclusion: We found no evidence of effects of LCP supplementation in the first yr on cognitive function and language development at 3.25 yrs. We speculate that positive effects of supplementation reported in previous studies relate to the composition of the control formula (e.g., marginal levels of the DHA precursor, linolenic acid).Funded by Ross Products Division.

Visual Acuity Development of Preterm (PT) Infants Fed Docosahexaenoic Acid (DHA) and Arachidonic Acid (ARA): Effect of Age at Supplementation

Visual Acuity Development of Preterm (PT) Infants Fed Docosahexaenoic Acid (DHA) and Arachidonic Acid (ARA): Effect of Age at Supplementation

Lower Necrotizing Enterocolitis (NEC) in Preterm (PT) Infants Fed Formula With Egg Phospholipid (EPL) Arachidonate (ARA) and Docosahexaenoate (DHA)|[bull]| 567

Background. Damage to the intestine culminating in NEC may occur by reduced mesenteric blood flow, bacterial overgrowth, enteral feeding or a combination of these factors. Antenatal steroids, human milk, lower pH formula, enteral IgA and antibiotics have each been reported to lower the incidence of NEC. In this study, the inclusion of EPL in a PT formula led to an apparent reduction in the incidence of NEC but not other diseases in hospitalized PT infants. Methods. In a randomized, double-masked trial, PT infants (725-1375 g birth weight, n=119) were fed either a control formula (CF) or an egg phospholipid-supplemented formula (EPLF) made by replacing some coconut oil in CF with EPL (75% phosphatidylcholine, 20% phosphatidylethanolamine, 5% other PL). PT and T versions of CF and EPLF were fed from -3 mo to 2 mo and 2 mo to 12 mo, respectively (40 wks gestation = 0 mo). EPLF, but not CF, contained ARA (0.4%) and DHA (0.13%, total fatty acids). Infants were assigned to one of three treatments that were balanced for gender in three stratified weight ranges (725-925 g; 926-1150 g; 1151-1375 g): Control (CF from -3 mo to 12 mo, n=41); Late Supplementation (CF from -3 mo to -1 mo; EPLF from -1 mo to 12 mo, n=44); and Early Supplementation (EPLF from -3 mo to 12 mo, n=34). Subjects lost before 4 mo corrected age were replaced to ensure study of at least 30 infants/group through that age. Infants fed CF and EPLF had similar neonatal, perinatal and demographic characteristics. Results. Fifteen of 85 infants (17.6%) fed CF in hospital (Control and Late Supplementation) and 1 of 34 (2.9%) fed EPLF (Early Supplementation) developed NEC stage II or III (p<0.05). Diet had no apparent effect on other diseases including sepsis (CF, 28.2%; EPLF, 26.5%), BPD (CF,23.4%; EPLF, 23.5%), and ROP (CF,40.0; EPLF,38.2%). The incidence of NEC was higher among male than female infants (11/60 vs 5/59, p,<0.05). All 11 males who developed NEC were fed CF (11/43, 25.6%) (p<0.01 vs males fed EPLF). Summary. EPLF appeared to decrease the incidence of NEC but not other common diseases of PT infants. Conclusion. We speculate that EPL or some component of EPL (e.g., ARA, DHA or choline) protected the immature intestine by one of several plausible mechanisms. A prospective randomized trial to test the effect of EPLF on NEC seems warranted, because NEC remains a major cause of morbidity and mortality among PT infants.