Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study.

OBJECTIVE: To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids, arachidonic acid (AA), and docosahexaenoic acid (DHA) on multiple indices of infant growth and development. DESIGN: A double-masked, randomized, parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year (N = 239). Reference groups of breastfed infants (N = 165) weaned to formulas with and without AA+DHA were also studied. Infants in the formula groups were randomized at

Comparison of preschool vision screening methods in a population with a high prevalence of astigmatism.

PURPOSE: To compare the effectiveness of four methods of screening 3- to 5-year-old children for astigmatism high enough to require spectacle correction. METHODS: Lea Symbols Visual Acuity Screening (LSVAS), MTI Photoscreening (MTIPS), Nidek KM-500 Keratometry Screening (KERS), and Retinomax K-Plus Noncycloplegic Autorefraction Screening (NCARS) were attempted on 379 preschool children who are members of a Native American tribe having a high prevalence of astigmatism that is primarily corneal in origin. The need for spectacle correction was determined by cycloplegic refraction. Receiver Operating Characteristic (ROC) curves were fit, confidence intervals were determined, and area under the curves was compared. RESULTS: Astigmatism > or = 1.00 D was present in the right eye of 47.5% and in the left eye of 48.0% of children. Spectacles were prescribed for children < 48 months of age who had cylinder > or = 2.00 D and children > or = 48 months who had cylinder > or = 1.50 D, with the result that 33% of subjects required spectacles. Area under the ROC curve was 0.98 for NCARS, 0.92 for KERS, 0.78 for MTIPS, and 0.70 for LSVAS, and each of these values differed significantly from the other three (all P < 0.007). Testability was significantly higher for NCARS (99.5%) and KERS (99.7%) than for MTIPS (93.5%) and LSVAS (92.0%). CONCLUSIONS: In a population that included many children with astigmatism, objective, fully automated screening methods (NCARS and KERS) were superior to both visual acuity screening and photoscreening with subjective interpretation in identifying children who had astigmatism requiring spectacle correction.

Does cryotherapy affect refractive error? Results from treated versus control eyes in the cryotherapy for retinopathy of prematurity trial.

PURPOSE: To evaluate the effect of cryotherapy on refractive error status between ages 3 months and 10 years in children with birth weights of less than 1251 g in whom severe retinopathy of prematurity (ROP) developed in one or both eyes during the neonatal period. DESIGN: Randomized clinical trial. PARTICIPANTS: Two hundred ninety-one children in whom severe ROP developed during the neonatal period. INTERVENTION: Cryotherapy for ROP. MAIN OUTCOME MEASURES: Cycloplegic Refraction METHODS: The children underwent repeated follow-up eye examinations, including cycloplegic retinoscopy, between 3 months and 10 years after term due date. Refractive error data from all eyes that were randomized to cryotherapy were compared with data from all eyes that were randomized to serve as controls. Refractive error data were also compared for a subset of children who had both a treated and a control eye that could be refracted. RESULTS: At all ages, the proportion of treated eyes that were unable to be refracted because of retinal detachment, media opacity, or pupillary miosis was approximately half the proportion of the control eyes that were unable to be refracted. When data from all eyes that could be refracted were considered, the distribution of refractive errors between fewer than 8 diopters (D) of myopia and more than 8 D of hyperopia was similar for treated and control eyes at all ages. The proportion of eyes with 8 D or more of myopia was much higher in treated than in control eyes at all ages after 3 months. In the subset of children who had a treated eye and a control eye that could be refracted, distributions of refractive errors in treated versus control eyes were similar at most ages. CONCLUSIONS: In both treated and control eyes, there was an increase in the prevalence of high myopia between 3 and 12 months of age. Between 12 months and 10 years of age, there was little change in distribution of refractive error in treated or control eyes. The higher prevalence of myopia of 8 D or more in treated eyes, as compared with control eyes, may be the result of cryotherapy's preservation of retinal structure in eyes that, in the absence of cryotherapy, would have progressed to retinal detachment.

The effect of flicker rate on measured visual field extent in very young children.

PURPOSE: To investigate the effect of flicker rate on measured visual field extent in toddlers. METHODS: A total of 270 full-term children (90 each at 11-, 17-, and 30-months of age) and 36 adults were tested binocularly with an LED static perimetry procedure using a black double-arc perimeter. Each subject was tested with one of three flicker rates: 0, 3, or 10 Hz. The median farthest location seen and an interpolated estimate of the location at which 50% of the subjects detected the peripheral stimulus were calculated for each age group for each flicker rate. RESULTS: For 11-, 17-, and 30-month-old subjects, but not adults, flickering stimuli produced a larger measured visual field extent than nonflickering stimuli. For the 10-Hz stimuli, measured visual field extent in children did not differ from that of adults. CONCLUSIONS: In infants and young children, binocular measured visual field extent is enhanced by peripheral stimulus flicker. Maturity of the measured visual field depends on the stimulus parameters used during testing.

Absorption and DNA protective effects of flavonoid glycosides from an onion meal.

BACKGROUND: It is widely believed that antioxidant micronutrients obtained from fruit and vegetables afford significant protection against cancer and heart disease, as well as ageing. Flavonoids are potential antioxidants found in foods such as onions; information on their effectiveness in vivo is so far lacking. AIMS: To determine uptake as well as in vivo antioxidant effects of flavonoids from foods. METHODS: Six healthy non-obese normocholesterolaemic female volunteers in the age range 20-44 years participated in a randomised two-phase crossover supplementation trial to compare the antioxidant effects associated with (a) a meal of fried onions and (b) a meal of fried onions and fresh cherry tomatoes. Plasma flavonoids, lymphocyte DNA damage, plasma ascorbic acid, tocopherols and carotenoids, urinary malondialdehyde and 8-hydroxy-2'-deoxyguanosine were determined to assess flavonoid absorption and antioxidant efficacy. RESULTS: Flavonoid glucosides (quercetin-3-glucoside and isorhamnetin-4-glucoside) were significantly elevated in plasma following ingestion of the onion meal and the increases were associated with an increased resistance of lymphocyte DNA to DNA strand breakage. A significant decrease in the level of urinary 8-hydroxy-2'-deoxyguanosine was evident at 4 h following ingestion of the onion meal. After the combined tomato and onion meal, only quercetin was detected in plasma. Endogenous base oxidation was decreased but resistance to strand breakage was unchanged. There was no significant change in the excretion of urinary malondialdehyde following either meal. CONCLUSION: Both meals--onions, and onions together with tomatoes--led to transient decreases in biomarkers of oxidative stress, although the particular biomarkers affected differ. It is possible that the differences in patterns of response reflect the different uptakes of flavonoids but the underlying mechanism is not understood.

Severity of neonatal retinopathy of prematurity is predictive of neurodevelopmental functional outcome at age 5.5 years. Behalf of the Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: The purpose of this study was to assess the relation between neonatal retinopathy of prematurity (ROP) in very low birth weight infants and neurodevelopmental function at age 5.5 years. METHODS: Longitudinal follow-up of children occurred in 2 cohorts of the Multicenter Cryotherapy for Retinopathy of Prematurity Study. The extended natural history cohort followed 1199 survivors of <1251 g birth weight from 5 centers. The threshold randomized cohort (ThRz) followed 255 infants <1251 g from 23 centers who developed threshold ROP and who consented to cryotherapy to not more than 1 eye. At 5.5 years both cohorts had ophthalmic and acuity testing and neurodevelopmental functional status determined with the Functional Independence Measure for Children (WeeFIM). RESULTS: Evaluations were completed on 88.7% of the extended natural history cohort; 87% had globally normal functional skills (WeeFIM: >95). As ROP severity increased, rates of severe disability increased from 3.7% among those with no ROP, to 19.7% of those with threshold ROP. Multiple logistic regression analysis demonstrated that better functional status was associated with favorable visual acuity, favorable 2-year neurological score, absence of threshold ROP, having private health insurance, and black race. Evaluations were completed on 87.4% of the ThRz children. In each functional domain, the 134 children with favorable acuity in their better eye had fewer disabilities than did the 82 children with unfavorable acuity: self-care disability 25.4% versus 76.8%, continency disability 4.5% versus 50.0%, motor disability 5.2% versus 42.7%, and communicative-social cognitive disability 22.4% versus 65.9%, respectively. CONCLUSION: Severity of neonatal ROP seems to be a marker for functional disability at age 5. 5 years among very low birth weight survivors. High rates of functional limitations in multiple domains occur in children who had threshold ROP, particularly if they have unfavorable visual acuity.

Bioavailability and efficiency of rutin as an antioxidant: a human supplementation study.

OBJECTIVE: To determine the potential antioxidant effect of rutin (quercetin-3-O-beta-rutinoside) supplementation. DESIGN: A 6-week randomized single-blind placebo controlled trial was conducted; 500 mg rutin supplement was compared to an equivalent amount of glucose placebo. In addition, a pharmacokinetic study was carried out. SETTING: The Rowett Research Institute, Aberdeen, UK. SUBJECTS: Eighteen healthy non-obese normocholesterolaemic female volunteers in the age range 18-48 y. MAIN OUTCOME MEASURES: Plasma flavonoids, ascorbic acid, tocopherols and carotenoids, plasma antioxidant capacity, lymphocyte DNA damage, blood chemistry and haematology, liver function tests, urinary malondialdehyde, 8-hydroxy-2-deoxyguanosine and 8-iso-prostaglandin F2alpha. RESULTS: Eighteen volunteers completed the trial. Rutin supplementation did not induce any adverse changes in blood chemistry or indices of liver function. Plasma flavonoids were significantly elevated in the rutin-supplemented group. Endogenous oxidation of pyrimidines was significantly decreased in both rutin- and placebo-treated volunteers. There was no significant change in the level of urinary 8-hydroxy-2'-deoxyguanosine or urinary malondialdehyde in either group. A linear correlation was observed between urinary malondialdehyde and urinary 8-iso-prostaglandin F2alpha (R = 0.54, P<0.01). CONCLUSION: Six weeks' rutin supplementation significantly elevated the levels of three plasma flavonoids (quercetin. kaempferol and isorhamnetin) but there was no significant change in plasma antioxidant status. The decrease in the level of endogenous base oxidation in lymphocyte DNA seen in both the placebo- and rutin-supplemented subjects may reflect seasonal changes in other dietary antioxidants.

Inter-rater and intra-rater reliability in the interpretation of MTI Photoscreener photographs of Native American preschool children.

PURPOSE: To evaluate inter- and intra-rater reliability for the interpretation of MTI Photoscreener photographs taken in a population of Native American preschool children with a high prevalence of astigmatism. METHODS: Photographs of 369 children were rated by 11 nonexpert and 3 expert raters. Photographs for each child were scored as pass, refer, or retake. Nonexpert raters scored photos on two separate occasions, permitting analysis of intra-rater reliability. RESULTS: Analyses of pass/refer responses only: inter-rater reliability was moderate to substantial among nonexpert raters and substantial among expert raters. Intra-rater reliability among nonexperts was substantial. Analyses of all responses (pass, refer, and retake): inter-rater reliability for pass and refer scores was moderate among nonexperts and substantial among experts; for retake scores inter-rater reliability was slight for nonexperts and moderate for experts. Intra-rater reliability among nonexperts was substantial for pass and refer scores and moderate for retake scores. CONCLUSIONS: In this population with a high prevalence of astigmatism, whether MTI photoscreening results are interpretable is much more variable among and within raters than whether an interpretable photograph should be scored as pass or refer. The level of agreement among raters in the current study was influenced by the experience of the raters. In addition, nonexpert raters were more likely to deem a photograph uninterpretable than expert raters.

Astigmatism and Amblyopia among Native American Children (AANAC): design and methods.

The overall goal of the AANAC study is to improve detection of astigmatism and prevention of amblyopia in populations with a high prevalence of astigmatism. To meet this goal, the study will evaluate four methods of screening for astigmatism in preschool children and will assess both the short-term and long-term benefits of early correction of astigmatism in improving acuity and preventing amblyopia. This paper presents an overview of the design and methodology of the AANAC study. Subjects are members of the Tohono O'Odham Nation, a Native American tribe with a high prevalence of astigmatism. Preschool-age children who attend Head Start are screened with four tools: the Marco Nidek KM-500 autokeratometer, the MTI photoscreener, the Nikon Retinomax K-Plus autorefractor, and the Lea Symbols acuity chart. Sensitivity and specificity for detection of significant astigmatism, as measured by a technique that uses both cycloplegic retinoscopy and cycloplegic autorefraction, is determined for each of the four screening tools. Presence of amblyopia is evaluated by measurement of best-corrected recognition acuity and acuity for orthogonal gratings. Spectacles are provided to all 3-year-old children with > or =2.00 diopters (D) of astigmatism and all 4- and 5-year-old children with > or =1.50 D of astigmatism. Persistence of amblyopia after glasses wearing is evaluated by follow-up measurement of best-corrected recognition acuity and acuity for orthogonal gratings, conducted 2-5 months after glasses are prescribed. Long-term effectiveness of early screening and glasses prescription is evaluated through measurement of recognition acuity in two groups of first-grade children: one group who participated in the Head Start program before the intensive vision screening program was initiated, and a second group who participated in the study's Head Start vision screening program.

Measurement of refractive error in Native American preschoolers: validity and reproducibility of autorefraction.

PURPOSE: To examine (1) reproducibility of cycloplegic retinoscopy (C-RNS), cycloplegic autorefraction (C-Autoref), and noncycloplegic autorefraction (NC-Autoref), and (2) validity of C-Autoref and NC-Autoref compared with C-RNS in preschoolers with astigmatism. METHODS: Subjects were 36 Native American preschoolers. Three measurements of right eye refractive error were obtained with each of three methods: C-RNS (by three different retinoscopists), C-Autoref, and NC-Autoref (Nikon Retinomax K+). Vector methods (vector dioptric distance, VDD) were used in the analyses. RESULTS: Mean reproducibility was 0.41 D (SD = 0.18) for C-RNS, 0.25 D (SD = 0.17) for C-Autoref, and 0.37 D (SD = 0.21) for NC-Autoref. Mean agreement between C-Autoref and C-RNS ranged from 0.51 to 0.61 VDD (SD = 0.24 to 0.35), and ranged from 1.66 to 1.74 VDD (SD = 1.11 to 1.25) for agreement between NC-Autoref and C-RNS. Mean bias was -0.07 +0.21 x 149 and -1.33 +0.34 x 178 for C-Autoref and NC-Autoref, respectively. CONCLUSIONS: C-Autoref provided reliable and valid measurements of refractive error in young children. NC-Autoref measurements were reliable within subjects, but there was large variability in validity among subjects.

Stimulus motion increases measured visual field extent in children 3.5 to 30 months of age.

PURPOSE: To examine the influence of stimulus motion on measured visual field extent of 3.5- to 30-month-old children and adults. METHODS: Each subject was tested with LED-hybrid and LED-kinetic perimetry procedures, using a black double-arc perimeter. Targets in both procedures were identical in size, color, luminance, contrast, and flicker rate. However, in the LED-hybrid procedure, peripheral targets were sequentially illuminated from more peripheral to more central locations, whereas in the LED-kinetic procedure, a peripheral target on a black wand was manually moved centrally along the perimeter arm. A subset of subjects was also tested with white sphere kinetic perimetry (WSKP). RESULTS: The LED-kinetic procedure produced larger measured visual field extent than the LED-hybrid procedure in 3.5-, 11-, 17-, and 30-month-olds, but not in 7-month-olds or adults. Data from subjects tested with WSKP indicated that both stimulus motion and discrepancies in scoring methods contributed to the difference reported previously between visual field measurements obtained with WSKP vs. LED-hybrid perimetry. CONCLUSION: In infants and toddlers, measured visual field extent is larger for moving than for nonmoving targets. Further research is needed to determine whether the effect of motion is related to the visual system or to attentional factors.

Corneal and refractive astigmatism in a sample of 3- to 5-year-old children with a high prevalence of astigmatism.

PURPOSE: To examine the relation between corneal and refractive astigmatism in a sample of pre-school-age Native American children with a high prevalence of astigmatism. METHODS: Subjects were 250 Tohono O'Odham children, 3 to 5 years of age. Each child had corneal astigmatism measured with the Marco Nidek KM-500 portable autokeratometer without pupil dilation, and with the Nikon Retinomax K-Plus portable autorefractor/autokeratometer without and with pupil dilation. Refractive astigmatism was measured using the Retinomax K-Plus, with cycloplegia, confirmed by retinoscopy. RESULTS: Corneal astigmatism exceeded refractive astigmatism, with a median vector dioptric difference of 0.88 D for the KM-500, 0.76 D for the Retinomax K-Plus without dilation, and 0.75 for the Retinomax K-Plus with dilation. The relation between corneal and refractive astigmatism was adequately described by the modification by Grosvenor et al. of Javal's rule, but not by laval's rule. CONCLUSIONS: The results are in agreement with data reported previously for older Native American and non-Native American populations. The modified laval's rule adequately describes the relation between corneal and refractive astigmatism in a population; however, this rule does not provide accurate prediction of refractive astigmatism in individual children or adults.

Visual acuity screening versus noncycloplegic autorefraction screening for astigmatism in Native American preschool children.

INTRODUCTION: Visual acuity screening (VAS) is less reliable in preschoolers than in school-aged children as a means of detecting significant refractive error. We wished to compare the effectiveness of VAS with the effectiveness of an objective method, noncycloplegic autorefraction screening (NCARS), in detecting the presence of significant astigmatism warranting spectacle correction. METHODS: We examined 245 Native American Head Start registrants aged 3 to 5 years. We attempted to obtain uncorrected visual acuity using Lea Symbols logMAR Chart (Precision Vision Inc, Villa Park, Ill), noncycloplegic autorefraction using the Nikon Retinomax K-plus (Nikon Corp, Melville, NY), and cycloplegic refraction (CR) on each eye. The VAS failure criterion was either a 2-line acuity difference between eyes or acuity worse than 20/40 in either eye. The NCARS and CR failure criterion was the spectacle correction threshold exceeding the 50th percentile on the basis of a survey of AAPOS members. RESULTS: We completed VAS in 96% of children and NCARS and CR in 100% of children. There was high prevalence (31%) of significant astigmatic refractive error in this sample. Ten subjects who did not permit bilateral visual acuity measurements were scored as having a positive test result. The sensitivity and specificity of VAS were 90% and 44%, respectively. NCARS had sensitivity and specificity of 91% and 86%, respectively. NCARS becomes cost-effective after 1044 children are screened, assuming that the cost of the autorefractor is 300 times the cost of the referral examination. CONCLUSION: VAS offers high sensitivity but suffers from poor specificity. NCARS greatly reduces the number of unnecessary referrals. In this population, NCARS becomes cost-effective after approximately 1000 children are screened.

Interobserver agreement for grating acuity and letter acuity assessment in 1- to 5.5-year-olds with severe retinopathy of prematurity.

PURPOSE: To evaluate interobserver test-retest reliability of the Teller Acuity Card procedure for assessment of grating acuity at ages 1, 2, 3.5, 4.5, and 5.5 years, for HOTV letter acuity at 3.5 and 4.5 years, and for Early-Treatment Diabetic Retinopathy Study (ETDRS) letter acuity at 5.5 years in the multicenter study of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP). METHODS: Subjects were the 73 participants in the CRYO-ROP study who had acuity assessed at one or more ages by two of the seven study visual acuity testers as part of a quality control procedure. All subjects had birth weights of less than 1251 g, and all had severe (threshold) ROP in one or both eyes. RESULTS: For sighted eyes, interobserver agreement for grating acuity (across all five test ages) was 0.5 octave or better in 57% of eyes and 1.0 octave or better in 85% of eyes. Interobserver agreement for letter acuity (3.5-, 4.5-, and 5.5-year test ages) was 0.5 octave or better in 71% of eyes and 1.0 octave or better in 93% of eyes. For all eyes (sighted and blind), Kendall rank correlation coefficients (Tau) were 0.86, 0.83, and 0.94 for grating, HOTV, and ETDRS acuity, respectively. Kappa statistics on data from all eyes indicated excellent interobserver agreement for grating, HOTV, and ETDRS acuity (0.73, 0.80, and 0.84, respectively). Interobserver agreement was not related to age or to severity of retinal residua of ROP. CONCLUSIONS: Excellent interobserver agreement for grating acuity measurements and for letter acuity measurements was obtained. Results suggest that with careful training and implementation of quality control procedures, high reliability of visual acuity results is possible in clinical populations of young children.

Does rate of stimulus presentation affect measured visual field extent in infants and toddlers?

PURPOSE: To evaluate the effect of stimulus presentation rate on the measurement of visual field extent in infants and toddlers. METHODS: Visual field extent was measured for 300 children (N = 60 at 3.5, 7, 11, 17, and 30 months) and 24 adults using hybrid static-kinetic perimetry. Flickering light-emitting diode (LED) stimuli were illuminated sequentially, peripherally to centrally at 10.2 degrees intervals, along 4 diagonal meridia at 2 stimulus presentation rates: 2 s/stimulus (equivalent to 5 degrees/s) and 3 s/stimulus (equivalent to 3 degrees/s). Rate of presentation was a between-subjects variable. RESULTS: No effect of stimulus presentation rate was found for adults. The faster rate of stimulus presentation yielded smaller measured visual field extent for children between the ages of 7 and 30 months. The apparent difference seen with 3.5-month-olds did not reach significance. CONCLUSIONS: Faster rates of stimulus presentation may result in underestimation of visual field extent in children between the ages of 7 and 30 months.

Dietary flavonoids protect human colonocyte DNA from oxidative attack in vitro.

BACKGROUND & AIMS: Epidemiological studies suggest that antioxidant polyphenols in the human diet may protect against diseases such as cancer. In this study we investigated the cytoprotective potential of the flavonoids, quercetin, myricetin, kaempferol and rutin against oxidative DNA damage in human colonocytes in vitro. METHODS: Caco-2 cells, which display specialised enterocyte/colonocyte cell functions, were used as an in vitro model for human colonocytes. Hydrogen peroxide was employed as the oxidant. DNA damage (strand breakage, oxidised purines and oxidised pyrimidines) was determined using the alkaline single cell gel electrophoresis or comet assay. Cell growth and viability were measured. RESULTS: Hydrogen peroxide caused a dose-dependent increase in DNA strand breakage in human colonocytes, presumably via oxygen free radical generation. Quercetin and myricetin protected Caco-2 cells against oxidative attack. In addition, quercetin decreased hydrogen peroxide-mediated inhibition of growth. Neither rutin nor kaempferol was effective. However, quercetin, while inhibiting DNA strand breakage, did not alter the levels of oxidised bases following peroxide treatment. The antifungal agent ketoconazole, prevented quercetin cytoprotection in Caco-2 cells, indicating that P450-mediated metabolism may alter the efficacy of the flavonoids against oxidative DNA damage. CONCLUSION: Flavonoids, particularly quercetin, the most abundant flavonoid in the human diet, are likely to be important in defending human colonocytes from oxidative attack.

A survey of vision screening policy of preschool children in the United States.

A state-by-state survey regarding preschool vision screening guidelines, policies, and procedures was conducted. Currently 34 states provide vision screening guidelines and 15 states require vision screening of at least some of their preschool-aged children. The Department of Public Health administers the programs in 26 states, the Department of Education in 13. A wide range of professional and lay personnel conduct preschool vision screenings, and nurses participate in the screening process in 22 states. Visual acuity is assessed in 30 states, eye alignment in 24 states, refractive error in eight states, and color vision in 10 states. A combination of screening tests is recommended in 24 states. Currently, 45 states do not require screening of all preschool children. Thus, although laws, guidelines, and recommendations exist in most states, many preschool-age children do not have access to vision screening programs.