James R. Drover

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.

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.

Prevalence of amblyopia and other vision disorders in young Newfoundland and Labrador children

BACKGROUND Currently, there is a lack of adequate data on pediatric eye and vision disorders in Canada, particularly in the province of Newfoundland and Labrador. In the present study, we estimate the prevalence of eye and vision disorders among young children who participated in a vision screening program in the St. Johns, Newfoundland, metropolitan region. METHODS In daycare settings, 946 children (mean age 4.2 years) were screened with the latest tests of optics and functional vision. Those with suspected vision disorders were referred to an optometrist for a complete eye examination. From the results of these examinations, prevalence rates were estimated for several categories of vision disorders. RESULTS Overall, we estimate that 14.0% of the children possessed significant vision disorders, the most prevalent of which were hyperopia, amblyopia, and strabismus (4.8%, 4.7%, and 4.3%, respectively). Myopia and anisometropia, on the other hand, were relatively rare (1.1% and 1.4%, respectively). In general, prevalence estimates are within the range of existing estimates from other developed nations. INTERPRETATION Although the prevalence rates reported here must be interpreted cautiously because of methodological limitations, it appears that children in the present study do not possess an abnormally high prevalence of visual dysfunction. Nevertheless, because an estimated 14.0% of children tested had treatable vision disorders, early screening is clearly warranted in Newfoundland and Labrador.

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.

Final Version of the Distance Randot Stereotest: Normative data, reliability, and validity

PURPOSE Measurement of distance stereoacuity may be useful in assessing strabismic patients, especially those with intermittent exotropia. We developed the Distance Randot Stereotest as an easily administered quantitative test for distance stereoacuity in children. By using a prototype, we reported testability, validity, and normative data. Here we report normative and validity data for the final, commercially available version of the test. METHOD We administered both the Prototype and the Final Version Distance Randot Stereotest to 156 normal volunteers (2-40 years of age) and 77 strabismic patients (4-62 years of age). Test-retest data were collected for the Final Version. RESULTS Normative Final Version scores were similar to those obtained with the Prototype; 96% were < or = 100 arcsec. Test-retests were identical in 82% and within one disparity level in 100%. Final Version scores were correlated with Prototype scores (rs = 0.64, p < 0.001). Among strabismic patients, 62.3% had abnormal stereoacuity; those with normal scores had incomitant or intermittent deviations. Nil stereoacuity was found in 27 patients, confirmed in 90.9% of retests; 17 had measurable stereoacuity, confirmed in 96.3% of retests. Patients with constant strabismus were more likely to have nil stereoacuity than patients who had intermittent strabismus (95% vs 12.2%). CONCLUSIONS Distance Randot scores from normal subjects have low variability within each age group and high test-retest reliability. There is little overlap between Distance Randot scores from normal control and strabismic patients. The Distance Randot Stereotest is a sensitive measurement of binocular sensory status that may be useful in monitoring progression of strabismus and/or recovery after strabismus surgery.

The teller acuity cards are effective in detecting amblyopia.

Purpose. Detection of amblyopia in infants and toddlers is difficult because the current clinical standard for this age group, fixation preference, is inaccurate. Although grating acuity represents an alternative, studies of preschoolers and schoolchildren report that it is not equivalent to the gold standard optotype acuity. Here, we examine whether the Teller Acuity Cards (TAC) can detect amblyopia effectively by testing children old enough (7.8 ± 3.6 years) to complete optotype acuity testing. Methods. Grating acuity was assessed monocularly in 45 patients with unilateral amblyopia, 44 patients at risk for amblyopia, and 37 children with no known vision disorders. Each child’s grating acuity was classified as normal/abnormal based on age-appropriate norms. These classifications were compared with formal amblyopia diagnoses. Results. Grating acuity was finer than optotype acuity among amblyopic eyes (medians: 0.28 vs. 0.40 logMAR, respectively, p < 0.0001) but not among fellow eyes (medians: 0.03 vs. 0.10 logMAR, respectively, p = 0.36). The optotype acuity-grating acuity discrepancy among amblyopic eyes was larger for cases of severe amblyopia than for moderate amblyopia (means: 0.64 vs. 0.18 logMAR, respectively, p = 0.0001). Nevertheless, most cases of amblyopia were detected successfully by the TAC, yielding a sensitivity of 80%. Furthermore, grating acuity was relatively sensitive to all amblyopia subtypes (69 to 89%) and levels of severity (79 to 83%). Conclusions. Although grating acuity is finer than optotype acuity in amblyopic eyes, most children with amblyopia were identified correctly suggesting that grating acuity is an effective clinical alternative for detecting amblyopia.

Improving the effectiveness of the infant contrast sensitivity card procedure

Based on results from an earlier prototype, custom software and printing techniques were developed to construct a new card-based test of contrast sensitivity (CS) for nonverbal subjects. Compared with the prototype, the new CS card test contains three improvements: (1) larger, more salient test gratings; (2) higher contrast warm-up cards for each spatial frequency set; and (3) smaller contrast step size between adjacent cards. The success of the new cards was evaluated by testing 3.5- and 12-month-old human infants. Results indicated that the new version of the test required little time to complete (mean, 6.5 min) and provided accurate estimates of visual acuity. Also, group contrast sensitivity functions (CSFs) showed substantial development from 3.5 to 12 months of age. Surprisingly, however, group CSFs obtained with the new cards were lower than those obtained with the prototype, a discrepancy that may be due to differences in space average luminance between the two sets of cards. In all, the new CS card procedure possesses several merits that give it potential as an option for assessing spatial vision in infants, toddlers, and subjects with multiple impairments.

Retest variability of human infant contrast sensitivity: how many tests are sufficient?

Retest variability of a new infant contrast sensitivity (CS) card procedure was assessed by binocular measurement of a group of 20 6-month-olds twice within a 1-week period. Coefficient of reliability analyses showed that within-subject variability between tests was only slightly less than variation across subjects, which suggests that results from a single test are a poor predictor of an infant’s “true” visual functioning. To determine how many tests are needed to estimate when infant CS stabilizes to within an acceptable (0.15 log unit) criterion, a second experiment was conducted in which a small group of subjects was tested repeatedly over a 2-week period. The results showed that averaging performance on 2 to 3 tests was required before an accurate estimate of the subject’s performance could be obtained. Our results suggest that caution should be taken in the interpretation of a single measurement of infant visual functioning.

Accuracy of the contrast sensitivity card test for infants: retest variability and prediction of spatial resolution.

Purpose. We assessed the retest variability of a new contrast sensitivity (CS) card procedure and its ability to predict spatial resolution. Methods. Twenty-four 3-month-olds were tested twice with the CS cards and once with the Teller acuity cards (TAC) within a single session. Results. Coefficient of repeatability (COR) analysis revealed that retest variability of the new cards is superior to that of an earlier prototype at low to mid spatial frequencies. Furthermore, retest variability is comparable to that of infant visual evoked potential studies and the Vistech 6500, a chart commonly used to measure CS in adults. Finally, estimates of visual acuity based on the CS cards were consistent with those provided by the TAC (although CS-based estimates were generally lower overall). Conclusions. Given its reliability and accuracy, the new CS card procedure has good potential as a clinical tool for assessing spatial vision in infants and toddlers.