PEDIATRICS Vol. 122 No. 6 December 2008, pp. e1193-e1198 (doi:10.1542/peds.2008-1888)
ARTICLE |
Visual Function at 35 and 40 Weeks' Postmenstrual Age in Low-Risk Preterm Infants
a Pediatric Neurology Unit, Catholic University, Rome, Italy
b Department of Paediatrics and Imaging Sciences, Hammersmith Hospital, Imperial College, London, United Kingdom
c Division of Child Neurology and Psychiatry, Department of Pediatrics, University of Catania, Italy
d Neonatal Unit
f Ophthalmologic Unit, Catholic University, Rome, Italy
e Neonatal
g Ophthalmologic Units, Ospedale Maggiore Policlinico, Mangiagalli, Fondazione IRCCS, Milan, Italy
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVES. The objectives of this study were to (1) assess visual function in low-risk preterm infants at 35 and 40 weeks' postmenstrual age, (2) compare preterm visual abilities at term-equivalent age with term-born infants, and (3) evaluate effects of preterm extrauterine life on early visual function.
METHODS. Visual function was assessed by using a validated test battery at 35 and 40 weeks' postmenstrual age in 109 low-risk preterm infants who were born at <31 weeks' gestation. The preterm findings were compared with data from term-born infants collected by using the same test protocol.
RESULTS. All preterm infants completed both assessments. The 35-week responses were generally less mature than those at 40 weeks. Preterm infants at both ages were significantly more mature than term-born infants for ocular movements and vertical and arc tracking and at 40 weeks for stripe discrimination. In contrast, tracking a colored stimulus, attention at distance, and stripe discrimination were more mature at term age (in both term-born and preterm infants) than at 35 weeks.
CONCLUSIONS. Our findings provide data for visual function at 35 and 40 weeks' postmenstrual age in low-risk preterm infants. The results suggest that early extrauterine experience may accelerate the maturation of aspects of visual function related to ocular stability and tracking but does not seem to affect other aspects that may be more cortically mediated.
Key Words: brain maturation • neonatal preterm infants • vision screening
Abbreviations: GA—gestational age • ROP—retinopathy of prematurity
Very preterm infants are at higher risk for neurodevelopmental1,2 and visual impairment compared with term-born infants. Visual deficits may be attributable to retinopathy of prematurity or to brain lesions in the optic pathways and associated areas.3,4 Although a few studies have reported on ocular findings in the neonatal period in preterm infants, behavioral aspects of visual function have mainly been studied after the neonatal period, when more mature aspects of visual function can be assessed.3,5,6 The few studies that reported on visual function in preterm infants mainly assessed ability to fix and follow. In infants who were born between 28 and 35 weeks' gestation, maturation of visual function was inferred because infants were better able to fix and follow at term age as compared to 1 week from birth.7–9 Less is known about the early development of other aspects of visual function and their maturation.
We recently developed and reported a clinical assessment battery that is suitable for newborn infants for the evaluation of various aspects of visual function, including the ability to fix and follow a target, reaction to color contrast, discrimination of black and white stripes of increasing spatial frequency, and attention at distance.10 The final version of this assessment has been validated in a cohort of low-risk term-born infants as early as 48 hours from birth, providing normative data about the distribution of responses at this age.11 The visual test battery was used recently in a study correlating the visual findings with probabilistic diffusion tractography of the optic radiations, suggesting that, in preterm infants at term-equivalent age, aspects of visual function are directly related to the maturation of white matter in the optic radiations.12
The aim of this study was to assess visual function in a cohort of low-risk preterm newborns defining the distribution of responses at 35 and 40 weeks' (term equivalent) postmenstrual age. We also compared these results with those previously obtained for term-born infants to address the possible role of extrauterine life on the early development of visual function.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Infants were recruited from the NICU at Gemelli Hospital (Rome, Italy) from June 2004 to February 2007 and Mangiagalli Hospital (Milan, Italy) from September 2006 to June 2007.
Infants were consecutively enrolled when
- they were born between 25.0 and 30.9 weeks' gestational age (GA) as determined from first trimester ultrasound scans;
- their cranial ultrasound scans were normal or showed only transient flares or germinal layer hemorrhages during the first 2 postnatal weeks, showed no parenchymal abnormality at term-equivalent age and no evidence of atrophy (ie, no dilated ventricles [>14 mm ventricular index],13 irregular ventricular margins, widened interhemispheric fissure, or enlarged extracerebral space);
- their clinical condition was stable at 35 weeks.
Four examiners (Drs Ricci and Cesarini in Rome and Drs Groppo and DeCarli in Milan) performed the assessments. All infants were evaluated by using the recently published version of the visual assessment battery.10 This includes 9 items that assess ocular movements (spontaneous behavior and in response to a target), the ability to fix and follow a black/white target (horizontally, vertically, and in an arc), the reaction to a colored target, the ability to discriminate black and white stripes of increasing spatial frequency, and the ability to keep attention on a target that is moved slowly away from the infant. Figure 1 shows the instructions and the specific target used for each item.
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The infants were propped up at 30° in a supine position7 in a quiet environment with low background lighting, which facilities eye-opening.7,14 All infants in our study were examined between feeds; they started the examination in a quiet, awake state, state 4 according to Brazelton,14 and they were able to complete the whole test battery in 1 session without any interruption in 5 minutes.
The examiners avoided talking to the infant while presenting the visual stimuli and kept their face out of the infant's line of vision. Each infant was assessed twice, at 35 (n = 109) and at 40 weeks' (n = 109; term-equivalent age) postmenstrual age. The examiners were not aware of the infant's gestational age or whether the infant had had ROP. All the infants included in this study had a similar level of care that did not include any specific stimulation of visual or other sensory pathways.
Interobserver and Intraobserver Reliability Assessment
In each center, 2 examiners performed the assessments. All of them had experience of observing visual responses in neonates and had been involved in the data collection using the same assessment in term infants. The senior examiner (Dr Ricci) held training sessions with the other 3 examiners (Drs Cesarini, Groppo, and DeCarli) to ensure that the assessment was performed similarly. The interobserver reliability of the examination among the 4 examiners has been previously reported (
= 0.97).10,11
Statistical Analysis
The comparison of the results of each item at 35 vs 40 weeks was assessed by using the Wilcoxon matched-pairs signed-ranks test. The results at both test ages in the preterm cohort were compared with data collected in parallel by the same examiners11 in a term-born infant population (n = 110) by using the Wilcoxon rank-sum test (Mann-Whitney U test; preterm at 35 weeks versus term-born, preterm at 40 weeks versus term-born). Because of the large number of comparisons, P < .01 was considered significant.
The association among gestational age, stage of ROP, and the results of each visual item was tested using the Kruskal-Wallis equality-of-populations rank test at both 35 and 40 weeks' postmenstrual age. A 2-tailed value of P < .01 was considered significant. Statistical analysis was performed by using the Stata 10 (Stata Corp, College Station, TX).
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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A total of 109 infants (60 female, 49 male) fulfilled the inclusion criteria and were assessed by using the visual test battery. The mean gestational age was 28.2 weeks (range: 25.0–30.9; SD: ±1.5), and birth weight was 1155 g (range: 520–1800; SD: ±262). All completed the examination at the first attempt at both 35 and 40 weeks. At 40 weeks, all of the infants were assessed as outpatients.
We subdivided the cohort in 5 GA subgroups: 25 to 26 weeks (n = 14), 27 weeks (n = 18), 28 weeks (n = 14), 29 weeks (n = 31), and 30 weeks (n = 32). The mean postnatal age at the first examination was 35.4 (range: 34.3–36.6) and 40.3 weeks (range: 37.2–41.7) at the second evaluation (term-equivalent age). At the 35-week assessment, 13 (12%) infants had stage 1 ROP and 17 (16%) had stage 2 ROP. At the 40-week assessment, 13 (12%) infants had stage 1 ROP and 22 (20%) had stage 2 ROP. None of these infants had zone 1 involvement.
Visual Assessment at 35 and 40 Weeks' GA
Each item from our assessment can be scored by circling the most appropriate column. The spread of each item response is reported as a stacked bar graph according to the postmenstrual age at assessment (Fig 2). The responses that were obtained at 35 weeks' postmenstrual age were overall less mature than those obtained at 40 weeks (Fig 2), but by using the Wilcoxon matched-pairs signed-ranks test (35 vs 40 weeks), the difference was significant at P < .01 for only 3 of the 9 items (Table 1).
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Spontaneous Ocular Motility
Mainly conjugated ocular motility or occasional strabismus/nystagmus was found in 98% of the infants at 35 weeks and in 100% at 40 weeks.
Ocular Movements With Target
Conjugated ocular motility or occasional strabismus/nystagmus was found in 92% of the infants at 35 weeks and in 94% at 40 weeks.
Fixation
Stable fixation to a black-and-white target was found in 91% of the infants at 35 weeks and in 97% at 40 weeks.
Tracking
The ability to track horizontally was found in 97% of the infants at 35 weeks and in 100% at 40 weeks. The ability to track vertically was found in 86% of the infants at 35 weeks and in 95% at 40 weeks. The ability to track for an arc was found in 75% of the infants at 35 weeks and in 84% at 40 weeks.
Reaction to a Colored Contrast Target
The ability to track on a colored target was found in 66% of the infants at 35 weeks and in 94% at 40 weeks.
Ability to Discriminate Stripes
The ability to discriminate striped black/white targets for 
3 cards, with a spatial frequency of at least 0.64 cycle per degree, or 20/866 according to Snellen acuity equivalents, was found in 97% of infants at 35 weeks and 100% at 40 weeks. At 40 weeks, more (41%) infants were able to discriminate higher spatial frequencies (cards 7 and 8, respectively, 2.4 and 3.2 cycles per degree [up to 20/200 Snellen acuity equivalents]) than at 35 weeks [3%]). This represents an activity measure.
Attention at Distance
The ability to keep attention on the target up to a distance of at least 30 cm was found in all but 3 infants at 35 weeks (97%) and in all (100%) infants at 40 weeks, but the responses at 40 weeks were overall more mature than at 35 weeks.
Comparison Between Preterm Infants Examined at 40 Weeks' Postmenstrual Age and Term-Born Infants Examined at 48 Hours After Delivery
When we compared the assessments that were obtained from our preterm cohort at 40 weeks with previously published data that were obtained from term-born infants at 48 hours after birth by the same examiners11 (Fig 2, Table 1), we found that the results were not significantly different for 4 of the 9 items (fixation, horizontal tracking, response to a color contrast target, and attention at distance). For 5 items (spontaneous and targeted ocular movements, vertical and arc tracking, and the ability to discriminate stripes of different spatial frequencies), preterm infants at 40 weeks seemed more mature compared with the term-born infants.
Comparison Between Assessment at 40 Weeks and GA at Birth
When the cohort was subdivided into 5 groups according to their gestational age at birth (25–26, 27, 28, 29, and 30), there were no significant differences in visual abilities between the groups.
Comparison Between the Assessments in Infants With Stages 1 and 2 ROP and Without ROP
When the cohort was subdivided according to the presence/absence and stage 1 or 2 ROP, there was no significant difference in responses among the 3 groups at 35 and at 40 weeks.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Our findings suggest that our recently published battery of tests of visual function validated in a term-born population is suitable for use with preterm infants and can be easily and reliably used not only at term-equivalent age but also at 35 weeks' postmenstrual age. The age of 35 weeks was chosen because, in many centers, preterm infants are discharged from the hospital before term-equivalent age and it is therefore important to have some normative data around this age. All the infants were able to complete the whole test battery in 1 session without any interruption.
Our results confirm previous observations that preterm infants at 36 and 40 weeks are able to fix and track horizontally and vertically on a black and white circular target.7,8,15 By using our more structured assessment in a larger cohort, we were also able to demonstrate infants' ability to follow in a circle, to react to a target with color contrast, to follow a target at a distance, and to discriminate stripes of decreasing width. The magnitude of the responses did not seem to be related to gestational age at birth or to the presence of stage 1 or 2 ROP.
Preterm infants who were examined at 35 weeks' postmenstrual age were generally less mature in their visual responses than at term-equivalent age, but the difference was not significant for 6 of the 9 items; these were the items that assessed ocular motility, fixation, and tracking on a black-and-white target. Differences between the testing ages were significant, with the younger infants being less mature for tracking on a colored target, attention at distance, and stripe discrimination.
When we compared preterm infants who were examined at term-equivalent age with term-born infants who were examined at 48 hours after delivery by using the same assessment, visual responses were similar on 4 items and preterm infants seemed to have more mature responses on the remaining 5 items. The results could be easily compared because the data in term-born infants had been collected in parallel by the same examiners by using the same battery of tests.7 It was surprising that for 4 of the 5 items, term-born infants had less mature visual responses even when compared with the preterm assessments performed at 35 weeks.
The overall comparison of the data that were collected for preterm infants at 35 weeks and term-equivalent age with term-born infants at 48 hours after delivery led us to identify broadly 2 groups of items. The difference between the 2 groups is likely to reflect different mechanisms underlying the early development of the specific aspects of visual function.
The responses for the first group of items, comprising ocular movements (spontaneous or following a target) and tracking on a black/white target vertically and in a arc, were more mature in preterm infants at both 35 and 40 weeks than in term-born infants; the abilities to fixate centrally and track horizontally were not different among the 3 groups. After the observation of normal ocular movements and ability to fix and follow in the first postnatal weeks in preterm newborns with severe occipital lesions, it has been suggested that these early aspects of visual function may be mediated by subcortical rather than by cortical systems.16 Our findings that full responses can already be elicited at 35 weeks and seem more mature even at that age for some items than in newborn term infants suggest that the maturation of these "subcortical" aspects of visual function is accelerated by preterm extrauterine exposure and early extra visual and visuomotor experiences, in agreement with recent animal studies that demonstrated the effect of enriched environment on the maturation of the central nervous system.17,18
Other responses, in contrast, were less mature in preterm infants at 35 weeks compared with both preterm infants at term-equivalent age and term-born infants. These were responses to color contrast, attention at distance, and discrimination of stripes, all aspects of visual function that are likely to require some cortical input and more mature subcortical/cortical connectivity. These findings are in agreement with previous studies that used structured orientation reversal visual evoked potentials, also considered to be early indicators of cortical functioning.5,19–21 The lack of significant differences in orientation-selective visual evoked responses between healthy preterm infants who were assessed at term age and term-born infants in the previous studies support our observation that more cortically mediated aspects of early visual development are likely to be more dependent on postmenstrual age than on the length of extrauterine life.12
The lack of effect of GA at birth on the findings is perhaps surprising, especially for responses to items that we found more mature in preterm than in the term-born infants, and we think is related to aspects of visual function that may be accelerated by early extra visual and visuomotor experiences.17,18 This may be attributable to relatively small numbers at the lower GA; however, it is more likely attributable to our population's being very preterm, and although none had abnormality detected on cranial ultrasound scan, it is likely that the younger infants in the cohort would have more immature white matter known that is not readily detected on ultrasound.22 This may account for their not being more mature in these aspects of visual function than the older preterm infant.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Our results provide additional data on the visual abilities of "well" preterm infants at 35 weeks and at term-equivalent age. They suggest that various aspects of early visual function mature at different times and that these are probably related to different underlying subcortical and cortical mechanisms. Additional studies of a larger cohort will help to define better the possible role of care or other variables such as gestational age or ROP that did not seem to have an obvious effect on maturation in our relatively small cohort. Additional studies are also needed to explore the possibility that the variability in maturation observed in our cohort may be partly attributable to the presence of punctate white matter lesions or other minimal changes on brain MRI scans that cannot easily be detected by neonatal cranial ultrasound.
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ACKNOWLEDGMENTS |
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This study is supported by the Mariani Foundation.
We thank Lilly Dubowitz for useful support and stimulating suggestions.
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FOOTNOTES |
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Accepted Aug 13, 2008.
Address correspondence to Eugenio Mercuri, MD, Catholic University, Pediatric Neurology, Largo Gemelli 8, 00168 Rome, Italy. E-mail: mercuri{at}rm.unicatt.it
The authors have indicated they have no financial relationships relevant to this article to disclose.
| What's Known on This Subject To our knowledge, no systematic study has been performed to evaluate different aspects of visual function as early as 35 and 40 weeks' postmenstrual age.
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| What This Study Adds Our results provide interesting clues for the interpretation of maturation of visual function in preterm infants and suggest a clinical use for our battery, which can be easily performed as part of the neonatal assessment.
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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
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