Yolanda S. Castañeda

The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid

BACKGROUND The range of human milk docosahexaenoic acid (DHA) concentrations worldwide is much broader than the range explored in randomized clinical trials to date. OBJECTIVE The primary objective was to determine the effect of 4 amounts of DHA supplementation on the visual acuity of formula-fed infants at 12 mo of age. Secondary objectives were to evaluate visual acuity maturation, red blood cell fatty acids, tolerance, anthropometric measures, and adverse events. DESIGN This double-masked, randomized trial was conducted at 2 sites (Dallas and Kansas City). Three hundred forty-three healthy, term, formula-fed infants were enrolled at 1-9 d of age and were randomly assigned to be fed 1 of the following 4 infant formulas containing equivalent nutrient amounts, except for long-chain polyunsaturated fatty acids: control (0% DHA), 0.32% DHA, 0.64% DHA, or 0.96% DHA; DHA-supplemented formulas also provided 0.64% arachidonic acid. Visual acuity was measured by visual evoked potentials in 244 infants who completed the 12-mo primary outcome examination. RESULTS Infants fed control formula had significantly poorer visual evoked potential visual acuity at 12 mo of age than did infants who received any of the DHA-supplemented formulas (P < 0.001). There were no significant differences in visual evoked potential visual acuity between the 3 amounts of DHA supplementation for either site at any age tested. CONCLUSIONS DHA supplementation of infant formula at 0.32% of total fatty acids improves visual acuity. Higher amounts of DHA supplementation were not associated with additional improvement of visual acuity. This trial was registered at clinicaltrials.gov as NCT00753818.

Impact of early dietary intake and blood lipid composition of long-chain polyunsaturated fatty acids on later visual development.

Background In contrast to human milk, current infant formulas in the United States do not contain ω3 and ω6 long-chain polyunsaturated fatty acids. This may lead to suboptimal blood lipid fatty acid profiles and to a measurable diminution of visual function in developing term infants. The need for docosahexaenoic acid and arachidonic acid supplementation in the infant diet was evaluated in a double-blind, randomized clinical trial. Methods Healthy term infants were randomized to diets of (1) commercial formula, (2) docosahexaenoic acid–enriched formula (0.35% of total fatty acids), or (3) docosahexaenoic acid– (0.36%) and arachidonic acid– (0.72%) enriched formula. Eighty-seven infants completed the 17-week nutritional trial, and 58 were observed until 52 weeks of life. A reference group was exclusively breast fed for at least 17 weeks (n = 29). Outcome measures included electroretinographic responses, visual evoked potentials, and blood fatty acid analysis in infants at birth and at 6, 17, and 52 weeks of age. Results Commercial formula-fed infants had 30% to 50% lower content of docosahexaenoic acid in total red blood cell lipids during the 17-week feeding trial compared with breast-fed infants. Significant differences persisted at the 1-year follow-up. Arachidonic acid content was consistently reduced in the commercial formula group by 15% to 20%. Infants fed long-chain polyunsaturated fatty acid–enriched formulas had docosahexaenoic acid and arachidonic acid blood lipid profiles resembling those of human milk-fed infants. Infants receiving this enriched formula had more mature electroretinographic responses than commercial formula-fed infants at 6 weeks of age. Human milk-fed and docosahexaenoic acid-enriched formula-fed infants had better visual acuity than commercial formula-fed infants at both 17 and 52 weeks of age. Early (17-week) fatty acid profiles in blood lipids were correlated with later (52-week) visual function development in study infants. Conclusions Results from this clinical trial demonstrate that long-chain polyunsaturated fatty acid supplementation of formula in term infants produces blood lipid fatty acid profiles that are similar to those observed in breast-fed infants. This supplementation leads to better visual function later in life (i.e., 1 year of age) than that shown by infants fed commercial formula.

The impact of early nutrition on incidence of allergic manifestations and common respiratory illnesses in children.

OBJECTIVE To investigate the incidence of allergic and respiratory diseases through age 3 years in children fed docosahexaenoic acid (DHA)- and arachidonic acid (ARA)-supplemented formula during infancy. STUDY DESIGN Children who completed randomized, double-blind studies of DHA/ARA-supplemented (0.32%-0.36%/0.64%-0.72% of total fatty acids, respectively) versus nonsupplemented (control) formulas, fed during the first year of life, were eligible. Blinded study nurses reviewed medical charts for upper respiratory infection (URI), wheezing, asthma, bronchiolitis, bronchitis, allergic rhinitis, allergic conjunctivitis, otitis media, sinusitis, atopic dermatitis (AD), and urticaria. RESULTS From the 2 original cohorts, 89/179 children participated; 38/89 were fed DHA/ARA formula. The DHA/ARA group had significantly lower odds for developing URI (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.08-0.58), wheezing/asthma (OR, 0.32; 95% CI, 0.11-0.97), wheezing/asthma/AD (OR, 0.25; 95% CI, 0.09-0.67), or any allergy (OR, 0.28; 95% CI, 0.10-0.72). The control group had significantly shorter time to first diagnosis of URI (P = .006), wheezing/asthma (P = .03), or any allergy (P = .006). CONCLUSIONS DHA/ARA supplementation was associated with delayed onset and reduced incidence of URIs and common allergic diseases up to 3 years of age.

Cognitive function in 18-month-old term infants of the DIAMOND study: A randomized, controlled clinical trial with multiple dietary levels of docosahexaenoic acid

BACKGROUND Studies investigating cognitive outcomes following docosahexaenoic acid (DHA) supplementation of infant formula yield conflicting results, perhaps due to inadequate dietary concentrations. AIM To determine the optimal DHA concentration in term formula to support cognitive maturation. DESIGN This was a double-masked, randomized, controlled, prospective trial. A total of 181 infants were enrolled at 1-9 days of age and assigned randomly to receive one of four term infant formulas with one of four levels of docosahexaenoic acid: Control (0% DHA), 0.32% DHA, 0.64% DHA, or 0.96% DHA. All DHA-supplemented formulas contained 0.64% arachidonic acid (ARA). Infants were fed the assigned formulas until 12 months of age. One hundred forty-one children completed the 12-month feeding trial and were eligible for this study. Cognitive function was assessed in 131 children at 18 months of age using the Bayley Scales of Infant Development II (BSID II). RESULTS There were no diet group differences on the Mental Development Index (MDI), the Psychomotor Development Index (PDI), or the Behavior Rating Scale (BRS) of the BSID II. However, when the scores of children who received any of the three DHA-supplemented formulas were combined and compared to control children, a significant difference emerged: the MDI scores of DHA-supplemented children were higher (104.1 v. 98.4; p=0.02). CONCLUSIONS These results suggest that dietary supplementation of DHA during the first year of life leads to enhanced cognitive development at 18 months of age. DHA concentration of 0.32% is adequate to improve cognitive function; higher concentrations did not confer additional benefit.

Three Randomized Controlled Trials of Early Long-Chain Polyunsaturated Fatty Acid Supplementation on Means-End Problem Solving in 9-Month-Olds

This study examines whether feeding infants formula supplemented with long-chain polyunsaturated fatty acids (LCPUFA) improves cognitive function of 9-month-olds. Participants included 229 infants from 3 randomized controlled trials. Children received either formula supplemented with docosahexaenoic acid and arachidonic acid, or a control formula beginning at 1-5 days (12-month feeding study), or following 6 weeks (6-week-weaning study) or 4-6 months of breastfeeding (4-to 6-month weaning study). Infants were assessed with a 2-step problem solving task. In the 12-month feeding and 6-week weaning studies, supplemented children had more intentional solutions (successful task completions) and higher intention scores (goal-directed behaviors) than controls. These results suggest that LCPUFA supplementation improves means-end problem solving.

A randomized trial of DHA intake during infancy: School readiness and receptive vocabulary at 2–3.5 years of age

BACKGROUND Studies investigating the effects of docosahexaenoic acid (DHA) in infant formula on language development yield conflicting results. No study to date has investigated the effects of DHA in infant formula on school readiness. AIM To determine the effects of different dietary concentrations of DHA provided during the first 12 months of life on language development and school readiness. DESIGN This was a double-masked, randomized, controlled, prospective trial. A total of 182 infants were enrolled at 1-9 days of age and assigned randomly to receive infant formula with one of four levels of DHA: control (0% DHA), 0.32% DHA, 0.64% DHA, or 0.96% DHA. All formulas with DHA also contained 0.64% arachidonic acid. One hundred forty-one children completed the 12-month feeding trial and were eligible for this study. Consent was obtained from 131 participants. School readiness was assessed at 2.5 years using the Bracken Basic Concept Scale-Revised (BBCS-R) and receptive vocabulary was assessed at 2 and 3.5 years using the Peabody Picture Vocabulary Test-Third Edition (PPVT-III). RESULTS There were no diet group differences on any of the BBCS-R subscales. On the PPVT-III, the control group had higher raw scores and standard scores than both the 0.32% and 0.96% groups at 2 years of age. These differences were not evident at 3.5 years. CONCLUSIONS Dietary DHA during the first year of life did not enhance school readiness or language development. Children who consumed infant formula with 0.32% and 0.96% DHA showed lower receptive vocabulary scores than controls at 2 but not 3.5 years of age.

Addendum to "Cognitive function in 18-month-old term infants of the DIAMOND study: a randomized, controlled clinical trial with multiple dietary levels of docosahexaenoic acid" [Early Hum. Dev. 87 (2011) 223-230].

The authors would like to publish an addendum to the article as below: This study (Phase II) was supported by Mead Johnson Nutrition (Evansville, IN). Mead Johnson Nutrition also funded Phase I of this study and provided the infant formulas for Phase I. Drs. Hoffman and Birch have received research funding from Mead Johnson Nutritionals and Martek Biosciences for subsequent nutrition studies not reported here. Dr. Hoffman has received consultant fees from Mead Johnson Nutritionals to provide educational seminars to pediatricians and pediatric nutritionists. Neither Drs. Birch and Hoffman nor their institution (Retina Foundation of the Southwest) have received any compensation related to US Patent #7141266, entitled “Baby-food compositions enhancing visual acuity and methods therefor” or US Patent 7413759, entitled “Method of enhancing cognitive ability in infant fed DHA containing baby-food compositions.” The authors formally waived any potential financial compensation associated with the patents to Beech-Nut Nutrition Corporation before they were filed and have no financial interest as patentees.