Challenges of infant nutrition research: a commentary.

Considerable advances have been made in the field of infant feeding research. The last few decades have witnessed the expansion in the number of studies on the composition and benefits of human milk. The practice of breastfeeding and use of human milk represent today's reference standards for infant feeding and nutrition. Additional research regarding the benefits of breastfeeding is needed to determine which factors in human milk and in the act of breastfeeding itself, singly or in combination, are most important for producing the beneficial effects on infant growth, body composition, and neurodevelopmental outcome. We examine evidence that breastfeeding confers health benefits and offer suggestions on how best to interpret the data and present it to the public. We also describe some examples of well-designed infant nutrition studies that provide useful and clinically meaningful data regarding infant feeding, growth, and development. Because not all mothers choose to breastfeed or can breastfeed, other appropriate feeding options should be subjected to critical review to help establish how infant formula and bottle feeding can confer benefits similar to those of human milk and the act of breastfeeding. We conclude with the overarching point that the goal of infant feeding research is to promote optimal infant growth and development. Since parents/families may take different paths to feeding their infants, it is fundamental that health professionals understand how best to interpret research studies and their findings to support optimal infant growth and development.

Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline.

BACKGROUND: Docosahexaenoic acid (DHA) plays an important role in neural function. Decreases in plasma DHA are associated with cognitive decline in healthy elderly adults and in patients with Alzheimer's disease. Higher DHA intake is inversely correlated with relative risk of Alzheimer's disease. The potential benefits of DHA supplementation in age-related cognitive decline (ARCD) have not been fully examined. OBJECTIVE: Determine effects of DHA administration on improving cognitive functions in healthy older adults with ARCD. METHODS: Randomized, double-blind, placebo-controlled, clinical study was conducted at 19 U.S. clinical sites. A total of 485 healthy subjects, aged ≥55 with Mini-Mental State Examination >26 and a Logical Memory (Wechsler Memory Scale III) baseline score ≥1 standard deviation below younger adults, were randomly assigned to 900 mg/d of DHA orally or matching placebo for 24 weeks. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. RESULTS: Intention-to-treat analysis demonstrated significantly fewer PAL six pattern errors with DHA versus placebo at 24 weeks (difference score, -1.63 ± 0.76 [-3.1, -0.14, 95% CI], P = .03). DHA supplementation was also associated with improved immediate and delayed Verbal Recognition Memory scores (P < .02), but not working memory or executive function tests. Plasma DHA levels doubled and correlated with improved PAL scores (P < .02) in the DHA group. DHA was well tolerated with no reported treatment-related serious adverse events. CONCLUSIONS: Twenty-four week supplementation with 900 mg/d DHA improved learning and memory function in ARCD and is a beneficial supplement that supports cognitive health with aging. TRIAL REGISTRATION: Clinicaltrials.gov, Identifier: NCT0027813.

A Prospective, Double-Blind, Randomized, Placebo-Controlled, Crossover Study Using an Orally Administered Oxalate Decarboxylase (OxDC).

Background: Hyperoxaluria is typically associated with excessive oxalate intake in the diet, decreased dietary calcium, hyperabsorption of oxalate, or increased endogenous production of oxalate. The disorder spectrum extends from recurrent kidney stones to ESKD. This clinical trial sought to evaluate the effectiveness of an acid stable oxalate decarboxylase (OxDC) to reduce urinary oxalate in healthy subjects on a high-oxalate diet. Methods: In this prospective, double-blind, randomized, placebo-controlled, crossover clinical trial, 33 healthy volunteers were randomized into two crossover sequences separated by a 2-day washout period. A controlled high-oxalate diet (750-800 mg oxalate, 500-550 mg calcium daily) was utilized, and six 24-hour urine collections were measured. Subjects were given approximately 1000 U (micromoles per minute per milligram) of OxDC or placebo with meals three times daily during the 4 days of treatment. Results: Urinary oxalate significantly decreased with OxDC treatment. The baseline corrected within-subject mean reduction in 24-hour urinary excretion (after OxDC dosing versus high-oxalate baseline preceding treatment) was 12.5 mg or 29% (P<0.001). OxDC treatment was effective (>5% reduction) in 31 of 33 subjects (94%). Compared with placebo, OxDC produced a 24% reduction (P<0.001) in 24-hour oxalate excretion. Other urinary parameters (creatinine, uric acid, citrate, magnesium, calcium) were not affected by OxDC. No serious adverse events and no product-related adverse events occurred. Conclusions: An orally administered OxDC is capable of significantly reducing urinary oxalate levels in healthy volunteers on a high-oxalate diet without affecting creatinine clearance, urine creatinine, or other solutes related to supersaturation of calcium oxalate. Clinical Trial registry name and registration number: Evaluation of Nephure, and the Reduction of Dietary Oxalate, in Healthy Volunteers, NCT03661216.

Clinical overview of algal-docosahexaenoic acid: effects on triglyceride levels and other cardiovascular risk factors.

The cardiovascular benefits of fish-derived long-chain polyunsaturated fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid are well established. Less studied are specific effects of individual long-chain polyunsaturated fatty acids. Based on data from 16 published clinical trials, this review examines effects of DHA triglyceride (TG) oil derived from algae (algal-DHA) on serum TG levels and related parameters. Study populations included subjects with both normal and elevated TG levels including those with persistent hypertriglyceridemia treated with concomitant 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. At doses of 1-2 g/d, algal-DHA significantly lowered plasma TG levels (up to 26%) either administered alone or in combination with statins. The reduction in TG levels was markedly greater in hypertriglyceridemic than in normal subjects. Algal-DHA modestly increased plasma levels of both high-density lipoprotein and low-density lipoprotein cholesterol. The increased plasma level of low-density lipoprotein cholesterol was associated with a shift of lipoprotein particle size toward larger, less atherogenic subfractions. In some subjects, blood pressure and heart rate were significantly reduced. Algal-DHA was safe and well tolerated. Unlike fish oil, algal-DHA seldom caused gastrointestinal complaints such as fishy taste and eructation, attributes of importance for patient compliance in high-dose therapy. Regression analysis that showed a linear relationship between baseline TG and magnitude of TG reduction suggests that a study of patients with very high TG levels (>500 mg/dL) is warranted. Future pharmacologic therapies for treating hypertriglyceridemia may include algal-DHA.

Validation of a rapid measure of blood PUFA levels in humans.

An assay involving a finger stick and filter paper blood spotting was developed to determine polyunsaturated fatty acid (PUFA) levels in blood. Capillary whole blood from a finger stick was blotted on antioxidant impregnated filter paper, air dried, saponified and methylated using sodium hydroxide and boron trifluoride in methanol. The method differed from those described previously because separation of plasma and red blood cells (RBCs) was not needed, thin-layer chromatography (TLC) was not required to separate phospholipids, initial extraction of lipids before transesterification was not necessary, and the fatty acid methyl ester (FAME) method was able to methylate steryl esters, free fatty acids, and sphingomyelins. Twenty-six subjects provided blood samples by finger stick and venipuncture. Levels of long-chain polyunsaturated fatty acids (LC-PUFA) from capillary whole blood were correlated with those from RBCs and PLs in venous blood (P < 0.001, R(2) ranged from 0.64 to 0.86). Although highly significant (P < 0.002), the R(2) values for the correlation between arachidonic acid (ARA) levels in capillary whole blood with ARA levels in RBCs and plasma phospholipids (PLs) were relatively lower (R(2) = 0.31-0.41, respectively). Results indicate that the described finger stick assay represents a fast, reliable method to measure specific LC-PUFA levels.

Assessing the effect of docosahexaenoic acid on cognitive functions in healthy, preschool children: a randomized, placebo-controlled, double-blind study.

The utility of multicenter cognitive test methodology and resultant outcomes of supplementation with docosahexaenoic acid in healthy 4-year-old children was evaluated in a randomized, placebo-controlled, double-blind study. Subjects received 400-mg/d docosahexaenoic acid (n = 85) or matching placebo (n = 90) in capsules for 4 months. Cognitive tests included the Leiter-R Test of Sustained Attention, Peabody Picture Vocabulary Test, Day-Night Stroop Test, and Conners' Kiddie Continuous Performance Test. The relationship of docosahexaenoic acid levels in capillary whole blood from a subsample (n = 93) with scores on cognitive tests was evaluated. For each test, results indicated that changes from baseline to end of treatment were not statistically significantly different between the docosahexaenoic acid group and the placebo group. Regression analysis, however, yielded a statistically significant positive (P = .018) association between the blood level of docosahexaenoic acid and higher scores on the Peabody Picture Vocabulary Test, a test of listening comprehension and vocabulary acquisition.

Breastfeeding and the risk of childhood obesity.

Breastfeeding is suggested to be a potential obesity prevention strategy, but the evidence that breast-fed infants have a lower risk of later obesity is equivocal. Fourteen studies published between 2003 and 2006 that considered the relationship between breastfeeding and risk of childhood overweight and obesity were reviewed. Three studies reported a protective effect in children (i.e., increased duration of breastfeeding was associated with a lower risk of childhood overweight/obesity), 4 reported a partial protective effect (i.e., only evident in a subgroup), 6 reported no protective effect, and 1 reported a protective effect in children but not in adults. While there is some evidence that breastfeeding may help to prevent childhood obesity, it should not be viewed as the only preventative nutrition measure. In the U.S., rates of breastfeeding have risen while rates for childhood obesity have increased dramatically. This finding reinforces the view that many factors are involved in maintaining a healthy body weight.

The effect of employment status on breastfeeding in the United States.

BACKGROUND: In the United States, more new mothers are part of the work force than ever before. This trend has implications for many child-rearing practices, including breastfeeding. METHODS: Based on a national sample of new mothers (n = 228,000), this study considered the prevalence of the initiation and duration of breastfeeding to 6 months after delivery in 2003 among women who were employed full time, who worked part time, or who were not employed outside the home. Breastfeeding trends since 1984 were also considered. RESULTS: In 2003, at the national level, the prevalence of the initiation of breastfeeding and breastfeeding to 6 months after delivery were 66.0% and 32.8%, respectively. In the hospital, mothers who worked part time had a significantly (p <0.05) higher rate of breastfeeding (68.8%) than those who were employed full time (65.5%), or who were not employed (64.8%). Working full time had a (p <0.05) negative effect on breastfeeding duration. By 6 months after delivery, 26.1% of mothers employed full time, 36.6% of mothers working part time, and 35.0% of nonworking mothers breastfed their infant. Mothers who were not employed were more than twice as likely to breastfeed at 6 months than mothers who worked full time. Breastfeeding trends since 1984 indicated a large increase in the rate of breastfeeding at 6 months after delivery among full-time working mothers (204.5%). However, rates for these women have not yet reached those of mothers who worked part time or were not employed. CONCLUSIONS: To ensure that the Healthy People 2010 goals for breastfeeding are achieved (75% in the hospital and 50% at 6 months), programs designed to support working mothers who choose to breastfeed must be continued and strengthened.

The Essentiality of Arachidonic Acid in Infant Development.

Arachidonic acid (ARA, 20:4n-6) is an n-6 polyunsaturated 20-carbon fatty acid formed by the biosynthesis from linoleic acid (LA, 18:2n-6). This review considers the essential role that ARA plays in infant development. ARA is always present in human milk at a relatively fixed level and is accumulated in tissues throughout the body where it serves several important functions. Without the provision of preformed ARA in human milk or infant formula the growing infant cannot maintain ARA levels from synthetic pathways alone that are sufficient to meet metabolic demand. During late infancy and early childhood the amount of dietary ARA provided by solid foods is low. ARA serves as a precursor to leukotrienes, prostaglandins, and thromboxanes, collectively known as eicosanoids which are important for immunity and immune response. There is strong evidence based on animal and human studies that ARA is critical for infant growth, brain development, and health. These studies also demonstrate the importance of balancing the amounts of ARA and DHA as too much DHA may suppress the benefits provided by ARA. Both ARA and DHA have been added to infant formulas and follow-on formulas for more than two decades. The amounts and ratios of ARA and DHA needed in infant formula are discussed based on an in depth review of the available scientific evidence.

Reference data for arm muscle and arm adipose tissue areas in Mexican Americans from the Hispanic Health and Nutrition Examination survey (HHANES 1982-1984): Comparisons with whites and blacks from NHANES II (1976-1980).

Data for arm muscle area (AMA) and arm adipose tissue area (AATA) from 3695 Mexican American children 6 months to 18 years of age included in HHANES (1982-1984) were used to obtain age-and gender-specific means and selected percentiles. These statistics were compared with those for non-Hispanic white and non-Hispanic black children from NHANES II (1976-1980). In comparison with non-Hispanic white and non-Hispanic black children, the Mexican American children tended to have smaller means and percentile values for AMA but larger values for AATA. There was considerable sexual dimorphism in AMA and AATA. Within each population, boys tended to have larger means and percentile values for AMA than girls, and girls tended to have larger values for AATA than boys. Within each population of boys, there was a prepubescent gain in AATA, followed by a midpubescent loss, and then an increase near the middle of the second decade. This "fat wave" pattern was not noticeable in girls. Population differences in age- and gender-specific mean values for AMA and AATA were small. Few statistically significant differences were observed; these were no more common than would occur by chance. Therefore, population-specific reference data for AMA and AATA may not be needed for the clinical evaluation of Mexican Americans, non-Hispanic blacks, and non-Hispanic whites. © 1996 Wiley-Liss, Inc.

Weight, stature, and body mass index data for Mexican Americans from the third national health and nutrition examination survey (NHANES III, 1988-1994).

Selected age- and sex-specific percentiles are presented for 4,054 Mexican American children ages 1-18 years who were included in the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). These percentile values are compared with corresponding percentiles for Mexican Americans from the Hispanic Health and Nutrition Examination Survey (HHANES, 1982-1984). In each sex, the weight and weight/stature(2) percentiles from NHANES III were significantly larger than those from HHANES. For weight, the NHANES III values tended to be clearly larger after 11 years in males and females, and they were larger for weight/stature(2) at the 50th and 90th percentiles in each sex after 6 years. For stature, the NHANES III values were significantly larger at the 90th percentile among females, but the differences were not significant for any other percentiles among females or males. In comparison with non-Hispanic White children, Mexican American children tend to be shorter and heavier, especially after the preschool period. The similarity of the findings for stature from NHANES III and HHANES indicates that the shorter statures of Mexican Americans are not cohort-specific. The tendency to larger values for weight/stature(2) in Mexican Americans has important public heath implications since this ratio tends to track after early childhood, and high ratios in adulthood constitute an important risk factor for common diseases such as diabetes mellitus and coronary heart disease. Am. J. Hum. Biol. 11:673-686, 1999. Copyright 1999 Wiley-Liss, Inc.

Head circumference for Mexican American infants and young children from the Hispanic health and nutrition examination survey (HHANES 1982-1984): Comparisons with Whites and Blacks from NHANES II (1976-1980).

This study presents descriptive statistics for head circumference in Mexican American children 6 months to 7 years of age using data from the Hispanic Health and Nutrition Examination Survey (HHANES, 1982-1984) and compares these statistics with national estimates of head circumference for non-Hispanic White children and non-Hispanic Black children from the Second National Health and Nutrition Examination Survey (NHANES II, 1976-1980). Head circumference was measured in the same standardized fashion in the two surveys. The patterns of change with age in means and in empirical percentiles were similar for both genders and for all three ethnic groups. Values for head circumference increased with age, but the rate of increase became less as age advanced. Analyses indicated that at 1, 2, and 4 years of age, mean values for head circumferences for non-Hispanic White boys were significantly larger than those for Mexican American boys. The differences in mean values for head circumferences ranged from 0.7 to 1.1 cm. Because ethnic differences in head circumferences are small in magnitude, ethnic-specific sets of reference data for head circumference are not needed for clinical evaluation of Mexican Americans, non-Hispanic Whites, and non-Hispanic Blacks. Further analyses may be necessary when additional information from NHANES III allows the calculation of the 5th and 95th percentiles for Black and Mexican American children with small confidence limits. © 1995 Wiley-Liss, Inc.

Dietary patterns of older adults in the United States, NHANES II 1976-1980.

The second National Health and Nutrition Examination Survey (NHANES II) 1976-1980 provided detailed information concerning the dietary patterns of older Americans. By using 24-hour dietary recall and food frequency questionnaires, the dietary patterns of 2,615 adults aged 65-74 years were evaluated by types of living arrangements (living alone, with a spouse, or with someone other than a spouse) and income level (below poverty, at or above poverty). Analyzed indicators of dietary quality were caloric and nutrient intake, food group intake and frequency, and number of meals skipped. The most favorable dietary patterns of elderly persons were associated with living with a spouse, especially for men. Low-income men not living with a spouse were at highest risk of dietary inadequacy. For women, income was more strongly associated with dietary patterns than type of living arrangement. Results from NHANES II compare favorably to those of the first National Health and Nutrition Examination Survey (NHANES I) 1971-1974.

Effect of DHA-containing formula on growth of preterm infants to 59 weeks postmenstrual age.

Between May 1993, and September 1994, a randomized, blinded clinical trial was conducted to evaluate measures of growth and body composition in 63 (32 males; 31 females) healthy, low-birth-weight infants (940-2250 g) who were randomly assigned to an infant formula with docosahexaenoic acid (22:6n3, DHA, 0.2 wt%) from fish oil or to a control formula. A preterm formula with or without DHA was fed beginning at 7-10 days prior to hospital discharge through 43 weeks postmenstrual age (PMA). Then, from 43-59 weeks PMA, infants were fed a term infant formula with or without a corresponding amount of DHA. Growth (weight, length, head circumference), regional body fatness (triceps, subscapular, suprailiac skinfold thicknesses), circumferences (arm, abdominal, chest), and estimates of body composition determined by total body electrical conductivity (TOBEC) (fat-free mass [FFM]) were evaluated. Growth was slower in males fed the DHA formula. They had significantly (P < 0.05) smaller gains in weight, length, and head circumference between study enrollment to 59 weeks PMA than those fed the control formula. At 51 weeks PMA, males in the DHA group had significantly smaller head circumferences (P < 0.05) and lower FFM (P < 0.05). At 59 weeks PMA, males in the DHA group weighed less (P < 0.05), had shorter recumbent lengths (P < 0.01), smaller head circumferences (P < 0.05), and lower FFM (P < 0.01) than those fed the control formula. Energy intakes from formula (kcal/d), however, were lower at 51 weeks (P < 0.05) and 59 weeks (P < 0.05) PMA in males fed the DHA formula. Adjusted for body weight (kcal/kg/d), mean energy intakes from formula at 51 and 59 weeks PMA were not significantly different between feeding groups. The differences in recumbent length, head circumference, and FFM remained statistically significant after controlling for energy and protein intakes (P < 0.01). For all males, neither FFM nor total body fat (TBF), when expressed as a percentage of total body weight, differed significantly between feeding groups. Among females, there were no significant differences between the feeding groups in measures of growth, body composition, or energy intake. The results indicated that infant formula with fish oil containing DHA and EPA in a 5:1 ratio had a significant, negative effect on growth and body composition in males during the first 6 months of life. It is not clear why the growth deficits were limited to males and not females. The eicosanoids, bioactive metabolites of omega-3 and omega-6 fatty acids, may mediate several important growth hormones. The present results do not support the addition of DHA alone in infant formulas. Am. J. Hum. Biol. 11:457-467, 1999. Copyright 1999 Wiley-Liss, Inc.

Regional and sociodemographic variation of breastfeeding in the United States, 2002.

With use of data from the Ross Mothers Survey (RMS), rates for breastfeeding in the hospital and at 6 months of age were evaluated within 4 geographical regions of the United States. Odds ratios for determinants of breastfeeding were also calculated. Regardless of sociodemographic characteristics, breastfeeding in the hospital and at 6 months of age was most common in the West and least common in the South. College education and not participating in the Women, Infants, and Children (WIC) program were the strongest predictors of breastfeeding in the hospital. Not working outside the home and not participating in WIC were the strongest predictors of continued breastfeeding to 6 months of age. Region of residence is important in considering how to develop programs targeted to populations with lower breastfeeding rates.

Effects of long-chain polyunsaturated fatty acid supplementation on neurodevelopment in childhood: a review of human studies.

Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFA) are critical for infant and childhood brain development, but levels of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are often low in the Western diet. Increasing evidence from both epidemiological and intervention studies, reviewed here, indicates that DHA supplementation, during pregnancy, lactation, or childhood plays an important role in childhood neurodevelopment. Arachidonic acid (ARA) is also important for infant growth and development. Several studies have demonstrated positive associations between blood DHA levels and improvements on tests of cognitive and visual function in healthy children. Controlled trials also have shown that supplementation with DHA and EPA may help in the management of childhood psychiatric disorders, and improve visual and motor functions in children with phenylketonuria. In all studies, DHA and EPA supplementation is typically well tolerated. Further research is needed to determine optimal doses for efficacy at different developmental ages. The potential long-term benefits of early LCPUFA supplementation also require consideration.

The hypolipidemic effect of an ethyl ester of algal-docosahexaenoic acid in rats fed a high-fructose diet.

Preclinical and clinical studies demonstrate that the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as a triacylglycerol (TAG) or an ethyl ester are protective against cardiovascular disease. Both have significant TAG-lowering effects. We developed a concentrated ethyl ester of DHA (MATK-90, 900 mg/g) using microalgae as its source. This study evaluated the effects that different doses of MATK-90 had on lipid levels and clinical parameters in male Wistar rats fed a high-fructose diet used to induce hypertriglyceridemia (TAG > or = 300 mg/dL). Effects of MATK-90 were compared to those produced by a pharmaceutical product (Lovaza, formerly Omacor, P-OM3; 465 mg EPA + 375 mg DHA), a TAG oil used in food (DHASCO, algal-DHA, 40% DHA by weight), and a control (corn oil). Doses of MATK-90 (0.6, 1.3, 2.5, 5.0 g kg(-1) day(-1)), algal-DHA (2 g DHA kg(-1) day(-1)), and P-OM3 (5.0 g kg(-1) day(-1)) were administered by oral gavage for 28 days. A significant dose-related decrease was observed in TAG and cholesterol levels in all but the lowest dose of MATK-90 treatment group vs. control. The high-dose group of MATK-90 and the P-OM3 group produced similar reductions in TAG levels.

Lower breastfeeding rates persist among the Special Supplemental Nutrition Program for Women, Infants, and Children participants, 1978-2003.

OBJECTIVE: We set out to compare rates of breastfeeding between women who participated in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) with those of non-WIC mothers from 1978 to 2003. METHODS: The Ross Laboratories Mothers Survey is a national survey designed to determine patterns of milk feeding during infancy. Mothers were asked to recall the type of milk fed to their infant in the hospital and during each month of age. Rates of breastfeeding in the hospital and at 6 months of age were evaluated. Logistic regression analyses identified significant predictors of breastfeeding in 2003. RESULTS: From 1978 through 2003, rates for the initiation of breastfeeding among WIC participants lagged behind those of non-WIC mothers by an average of 23.6 +/- 4.4 percentage points. At 6 months of age, the gap between WIC participants and non-WIC mothers (mean: 16.3 +/- 3.1 percentage points) steadily increased from 1978 through 2003 and exceeded 20% by 1999. Demographic factors that were significant and positive predictors of breastfeeding initiation in 2003 included some college education, living in the western region of the United States, not participating in the WIC program, having an infant of normal birth weight, primipary, and not working outside the home. For mothers of infants 6 months of age, WIC status was the strongest determinant of breastfeeding: mothers who were not enrolled in the WIC program were more than twice as likely to breastfeed at 6 months of age than mothers who participated in the WIC program. CONCLUSIONS: Breastfeeding rates among WIC participants have lagged behind those of non-WIC mothers for the last 25 years. The Healthy People 2010 goals for breastfeeding will not be reached without intervention. Food package and programmatic changes are needed to make the incentives for breastfeeding greater for WIC participants.

Nutritional therapy improves growth and protein status of children with a urea cycle enzyme defect.

BACKGROUND: Poor growth has been described in patients with urea cycle enzyme defects treated with protein-restricted diets, while protein status is seldom reported. OBJECTIVE: To assess the effects of nutritional therapy with a medical food on growth and protein status of patients with a urea cycle enzyme defect. METHODS: A 6-mo multicenter outpatient study was conducted with infants and toddlers managed by nutrition therapy with Cyclinex-1 Amino Acid-Modified Medical Food with Iron (Ross Products Division, Abbott Laboratories, Columbus, OH). Main outcome variables were anthropometrics and plasma amino acids (selected), albumin, and transthyretin concentrations. RESULTS: Seventeen patients completed the study. Mean (+/-SE) baseline age was 11.30+/-3.20 months (median 4.40 months; range 0.22-38.84 months). Length and weight z-scores increased significantly during the 6-month study. Head circumference increased, but not significantly. Three patients were stunted and two were wasted (-2.0 z-score) at baseline while at study end, only one patient was both stunted and wasted. The majority of patients increased in length, head circumference, and weight z-scores during study. Mean (+/-SE) plasma albumin concentration increased from 34+/-2g/L at baseline to 38+/-1g/L at study end. Plasma transthyretin increased from a mean (+/-SE) of 177+/-13 mg/L at baseline to 231+/-15 mg/L at study end. No correlation was found between plasma NH(3) concentrations and medical food intake. Plasma NH(3) concentration was positively correlated with the percentage of Food and Agriculture Organization/World Health Organization/United Nations recommended protein ingested. CONCLUSIONS: Intakes of adequate protein and energy for age result in anabolism and linear growth without increasing plasma NH(3) concentrations. Medical food intakes did not correlate with plasma NH(3) concentrations.