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* Pritzker School of Medicine, University of Chicago, Comer Children’s and La Rabida Children’s Hospitals, Chicago, Illinois
Golisano Children’s Hospital at Strong, University of Rochester, Rochester, New York
University of Texas Health Science Center, Coordinating Center for Clinical Trials, Houston, Texas
|| University of Arizona, Tucson, Arizona
¶ Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania
# University of Minnesota, Minneapolis, Minnesota
** Providence, Rhode Island
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONAPPENDIX A: 8-YEAR FOLLOW-UP...REFERENCES |
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Methods. A prospective study was conducted of a cohort of children who had birth weight of <1251 g and threshold ROP in the Cryotherapy for Retinopathy of Prematurity multicenter study. At age 5.5 years, visual status, functional skills, and social information were obtained. At 8 years, special education classes, developmental disabilities, rehabilitation therapies, and academic and social competencies were determined by questionnaire. Visual status was considered favorable/unfavorable on the basis of the better eye.
Results. Of 255 survivors, 216 (85%) were evaluated at both 5.5 and 8 years. Major impairments were significantly more prevalent in children with unfavorable versus favorable visual status: cerebral palsy (39% vs 16%), developmental disability (57% vs 22%), autism (9% vs 1%), and epilepsy (23% vs 3%). Special education services (63% vs 27%), below-grade-level academic performance (84% vs 48%), and school-based rehabilitation services were significantly less common in children with favorable visual status. Favorable visual status, favorable functional ratings at 5.5 years, markers of higher socioeconomic status, and nonblack race were associated with significantly lower rates of both special education placement and below-grade-level academic performance at age 8. On multivariate logistic regression, only favorable visual status and functional status remained significant predictors for decreasing special education placement.
Conclusion. Threshold ROP is associated with high rates of developmental, educational, and social challenges in middle childhood; preserved vision was associated with a clear advantage, with more than half of the children with favorable visual status performing at grade level.
Key Words: very low birth weight • developmental disabilities • retinopathy of prematurity • long-term follow-up • special education
Abbreviations: ELBW, extremely low birth weight • VLBW, very low birth weight • CRYO-ROP, Cryotherapy for Retinopathy of Prematurity • ROP, retinopathy of prematurity • WeeFIM, Functional Independence Measure for Children • SD, standard deviation • CI, confidence interval • RR, relative risk
Increased survival of micropremature infants (birth weights <750–800 g), extremely low birth weight (ELBW) infants (birth weights <1000 g), and very low birth weight (VLBW) infants (birth weights <1500 g) has occurred in the past decade.1–3 This raises major concerns for the impact of neurosensory disabilities in the long-term survivors who were born very premature and medically frail.3–16 Approximately 50% of VLBW survivors need special education supports in the areas of academics, attention, slow learning, and developmental disorders.17–32 In addition, severe neurosensory disorders (cerebral palsy, blindness, sensorineural hearing loss, and neurodevelopmental disabilities) occur in 10% to 30% of survivors of VLBW status.3–16 The Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) multicenter study has provided sequential surveillance of retinal, visual, developmental, and functional status through the first 5.5 years of life in a prospective cohort of survivors who had severe retinopathy of prematurity (ROP), defined as threshold ROP.33–37 No more than 1 eye of each infant who developed threshold ROP was treated with cryotherapy, with the other half randomized to serve as control. Most recently, the ophthalmic and visual outcomes in these children were reported at 10 years of age.38–40 We previously reported the strong association of severity of ROP, particularly threshold ROP, with functional limitations at 5.5 years of age.37 However, functional limitations in self-care, mobility, and communication at such a young age do not always reflect children’s academic or social deficiencies as they progress in school. The purpose of this report was to examine the 8-year educational and social outcomes of a high-risk cohort of children who had birth weights <1251 g and had threshold ROP. During the analyses, we paid particular attention to the relation between visual status and special education classification, academic performance, and social competencies.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIX A: 8-YEAR FOLLOW-UP...REFERENCES |
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Assessments at Age 5.5 Years
At 5.5 years, survivors were assessed for ophthalmic outcomes, including visual acuity, functional status, and social information.
Visual Status
At 5.5 years, visual acuity was measured by study-certified visual acuity testers using both letter recognition and Teller acuity card procedures as previously described.36,41 In the present report, data from the Teller acuity card assessment of grating visual acuity were used to assign visual status because nearly all children completed this testing, compared with the smaller number who could be tested with letter recognition (Early Treatment Diabetic Retinopathy Study) testing.36 Children were exempt from formal acuity testing and coded as having unfavorable visual status when the ophthalmologist and parents agreed that the child had no light perception in either eye or the ophthalmologist and parents agreed that visual acuity was, at best, light perception and both eyes had total retinal detachment. Grating acuity below 6.4 cycles per degree (greater than 1 octave below the normal range) was also defined as unfavorable visual status. Favorable visual status was defined as a measurable grating acuity better than the defined unfavorable category. Children were classified by the visual acuity in their better eye at 5.5 years, because standardized masked visual acuity testing was not repeated at 8 years.
Functional Status
At age 5.5 years, the Functional Independence Measure for Children (WeeFIM) instrument was used to measure the consistent and regular performance of the child in essential tasks of self-care, continence, mobility, locomotion, communication, and social cognition42–45 (results previously reported for the larger natural history cohort from the CRYO-ROP multicenter study37). Children were classified as globally normal when their scores were within 2 standard deviations (SDs) of the mean for nondisabled children of similar age (WeeFIM total score >95).
Social Information
At age 5.5 years social information was obtained during an in-person or telephone interview and included health insurance, child’s supplemental social security income because of disability and poverty, family resources (telephone in household, access to car), and the head-of-household’s educational status.36,37 Interviewees were encouraged to answer all questions, but social information was not mandatory.
Assessments at Age 8 Years
At 8 years of age, the child’s academic and social competencies were assessed by a structured questionnaire for parents/caregivers administered at the time of follow-up examination or during a telephone interview (see Appendix A). The questions used were selected from the Child Behavior Check List (Parents Report form,46 and Teacher’s Report form47) and the Functional Academic Resource Scale to represent key indicator categories. (The questions are unpublished but available from author M.M. Results from using this scale are published.32) The questions were asked by the study coordinators, who also assisted the families in answering the questions when they had any confusion. To simplify the administration of the questionnaire and on the basis of feedback from the study coordinators, we reduced response categories from 4 to 3. The study coordinators participated in a training session at the start of the study, going over each question with 1 of the authors (M.M.) to resolve potential concerns. Formal validity and reliability testing on the instrument was not done. Information in the questionnaire also included parental report of developmental diagnoses and class size; frequency and need for school-based rehabilitation therapies (physical, occupational, and speech-language), visual services (low-vision aides, Braille, and talking books), hearing services (wearing hearing aids); and use of behavioral counseling, tutoring, and academic special educational services. Academic achievement was rated by the parent/caregiver as 1) "at or above grade level," 2) "possibly below grade level," or 3) "definitely below grade level" for the areas of math, reading, handwriting, and sports/gym. Children who were rated as performing at or above grade level in each area were considered academically competent in that area. Social performance competency ratings included participating in unsupervised play, interaction with other children, making practical judgments, and following directions. Children who performed those skills "about the same or ahead of peers" were considered socially competent in each area, as contrasted with the other 2 available responses of "possibly lagging" and "definitely lagging behind children of similar age." Although it would have been useful to have independent evaluations from teachers, funding and logistic restrictions did not allow this to take place.
Statistics
Descriptive statistics included frequency distributions and measures of central tendency. Children with favorable and unfavorable visual status were compared with respect to developmental diagnoses, special education placement, rehabilitation therapies at school, visual services, academic performance, and social skills using relative risk with 95% confidence intervals (CIs) and multiple logistic regression.
Univariate analyses were performed using the STATA software to obtain crude relative risks (RRs) and corresponding 95% CIs for a number of sociodemographic, neonatal, early childhood, and 5.5-year assessment characteristics in relation to 2 outcomes at 8 years: receiving special education services and having below-grade-level academic performance. These variables included mother’s ethnic group, gender of child, outborn status (eg, infant born in a hospital outside the study center), 5.5-year social information including private health insurance (ie, any insurance other than Medicaid or self-pay), highest educational level achieved by the head of household, supplementary security income for child disability, presence of telephone in household, and access to a car. In the univariate analysis, the dichotomy between high and low educational status was chosen as high school completion for the head of household. The neonatal biomedical variables in these analyses included gestational age at birth, singleton versus multiple birth, and small for gestational age (birth weight <10th percentile). The early childhood variable included an abnormal neurologic disability score (recurrent seizures, microcephaly, or shunted hydrocephalus at age 2 years or optic atrophy at age 5.5 years). The 5.5-year developmental variables included favorable Teller acuity status in at least 1 eye and favorable WeeFIM functional status (>95) at 5.5 years. CIs that were significantly different at least at the P < .05 level are shown in bold in the tables.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIX A: 8-YEAR FOLLOW-UP...REFERENCES |
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Table 1 shows the abnormal neurodevelopmental, learning, and behavioral status among this group of children with threshold ROP, as determined from the questionnaire (Appendix A). Significantly higher rates of developmental delays/disabilities, cerebral palsy, autism, and seizure disorders occurred in children with unfavorable visual status compared with favorable visual status. Children with favorable visual status had higher rates of hearing impairment and behavioral/attention-deficit disorders, compared with children with unfavorable visual status, but this was not statistically significant. Overall, 56% of those with favorable visual status and 70% of those with unfavorable visual status had neurodevelopmental, behavioral, or learning disorders at 8 years of age (RR: 0.80; 95% CI: 0.65–0.99; P < .05).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIX A: 8-YEAR FOLLOW-UP...REFERENCES |
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Several studies of regional cohorts of children with VLBW status have examined developmental and educational outcomes during middle childhood.18–32 These studies have largely included regional samples from Melbourne, Canada, Scotland, New Zealand, the United Kingdom, and the Netherlands, but each have had relatively few (<10) children with visual impairment. The present study was restricted to infants who had threshold ROP and therefore was weighted toward infants with visual disabilities. The regional reports found major disabilities in 10% to 30%, and more than half received special education supports for learning, attention, and behavioral disorders. Similarly, in the present study, 33% of our cohort of children who had threshold ROP had major disabilities and similarly high rates of academic and social challenges; however, the distribution was greater among those with unfavorable visual status.
Hack et al23 examined social disadvantage and educational achievements at 8 years in 68 children who weighed <750 g at birth, compared with 65 children who weighed 750 to 1499 g and 61 children who were term and weighed >2500 g. The rates of limited academic achievement were 27% for children <750 g, 9% for children 750 to 1499 g, and 2% for term children. Social disadvantage was significantly correlated with poorer academic achievement scores. This relation was confirmed in the present cohort, in which not having access to a car and poverty as measured by not having private insurance were associated with risks for poor academic achievement.
To use these data to help predict the need for special education resource use, it is important to consider the regional differences for which a child receives special education services and the school’s policy for grade repetitions. In terms of special education across urban school districts in the United States, high rates of children are repeating grades in kindergarten and early elementary school years rather than receiving special education services,8 and availability of special educational services differ. Resnick et al20 in Florida examined special education placements of >2000 VLBW survivors who were born between 1980 and 1987 and were in kindergarten through third grade in public schools. Special education placement for sensory impairment (vision or hearing) occurred in 7.5% of those with birth weights 500 to 749 g, 3.6% of those with birth weights 750 to 999 g, and 0.8% of those with birth weights 1000 to 1499 g. Overall, special education placement occurred in 50% of 500- to 749-g survivors, 52% of 750- to 999-g survivors, and 45% of 1000- to 1499-g survivors compared with 14.4% of peers.
In the present cohort of infants with threshold ROP, 63% of children with unfavorable visual outcomes required special education services defined in their own locale. More recently, Saigal et al33 reported outcomes from 4 international population-based cohorts of ELBW survivors (500–1000 g birth weight). Data on special education services and grade repetition were similar in New Jersey (63%), Ontario (57%), Bavaria (68%), and Holland (51%). Despite the potential differences between the follow-up studies, these reports each bring to attention the high rates of resource utilization that micropremies require as they mature, and our study shows that although visual impairment from ROP results in somewhat higher rates, the increase is not as striking as might be suspected.
There are a number of noteworthy limitations to consider in interpreting and using the present study’s findings. Our population was composed exclusively of surviving preterm infants in whom 1 or both eyes reached threshold ROP. Because no more than 1 eye was treated with cryotherapy in this cohort, rates of bilateral vision impairment are likely higher in this group than would be found today when treatment with cryotherapy or laser surgery is usually offered to all eyes that develop threshold ROP.
Because threshold ROP occurred in just 6% of survivors with birth weights <1251 g in the CRYO-ROP multicenter study, the present study represents a small subset of VLBW infants who are likely to be the most immature and medically unstable of their birth weight cohort. These multiple medical risks increase the chance of educational underachievement; need for special education services; and risks for motor, learning, behavioral, and developmental disabilities.
Informant bias is a second area for critical assessment, as we relied on parent/caregiver report and not on school reports. However, it seems unlikely that parents will overreport their child as having cerebral palsy, developmental disability, or autism. Although our data relied on an interview format, this was built on previously validated measures for education (the teacher report form of the Child Behavior Checklist46,47 and the Functional Academic Resource Scale32). Similarly, the reliance on parent/caregiver ratings of current social skills in unsupervised play, interaction with other children, practical judgment, and following directions was a strategy that has been accepted as a meaningful method to rate social skills in other studies. Klebanov et al26 effectively used this method in a large population of school-aged low birth weight children, as did Saigal et al in their most recent international report.33 Unfortunately, the limited funding available for conducting this assessment during the ophthalmologic follow-up visits did not permit independent validity and reliability testing of the tool used (see Appendix A); therefore, the data cannot be given the same weight as though the full, validated versions of the Child Behavior Check List had been used. Social data also were accepted as reported by the parents/caregivers and were not independently validated, and we did not compare results of an in-person versus telephone questionnaire response.
Last, a shortcoming of this study is that the reported vision was assessed 2.5 years before the primary outcomes reported. However, the recent report of 10-year ophthalmic outcomes in these same children provides reassurance that the 5.5-year visual assessment is a satisfactory predictor of the vision at 10 years and therefore is reasonable to use for an analysis at 8 years.36,38 The similarities between the 5.5-year visual status determined with grating acuity, and the Snellen recognition acuity in the 10-year report suggested that the visual assessment at 5.5 years was an effective measure to divide patients into favorable or unfavorable acuity status groups.
An apparent reverse in the direction of an ethnicity effect on functional outcomes appeared in these data between the 5.5-year and 8-year assessments. At 5.5 years in both univariate and multivariate analysis, we found that black ethnicity, favorable visual status, favorable neurologic status, absence of threshold ROP, and private health insurance were associated with lower risks for functional disability using the WeeFIM measure.37 However, the population at 5.5 years included children who had birth weights <1251 g and had threshold ROP and also many children who did not have threshold ROP. In contrast, the current cohort was limited just to children who had threshold ROP. At 8 years of age, with univariate analysis, black ethnicity was associated with an increased risk of special education placement, but when multiple regression was used to adjust for rates of less than high school education in head of household and lack of private health insurance, as well as several medical demographics, the effect of black ethnicity was no longer a significant predictor. Therefore, this would seem to be an effect of social disadvantage.
In examining predictors of special education placement, Resnick et al20 demonstrated that neonatal biomedical variables were most strongly predictive for receiving particularly intensive special education services for cerebral palsy, sensory disabilities, and severe developmental disabilities (IQ <40). However, they found that special education services for speech-language disorders and behavioral disorders (eg, attention-deficit/hyperactivity disorder) were strongly associated with social demographic variables, including poverty, minority status, male gender, and maternal education less than high school. Our results are consistent with this dual jeopardy of biomedical and social risk for special education services among VLBW survivors with threshold ROP.
In conclusion, we report high rates of developmental, educational, and social challenges among children who had threshold ROP, especially when there was an unfavorable visual outcome. Children who had threshold ROP but retained a favorable visual status had higher rates of academic and social competencies at 8 years of age, improved functional capabilities at 5.5 years of age, and lower rates of other developmental disorders compared with those with poor visual status. However, even among the children with favorable visual status after threshold ROP, the rates of 27% special education services and 48% below-grade-level academic performance were substantial. Our data indicate that threshold ROP is a marker for infants who are at high risk for long-term developmental and educational disorders and should prompt serious consideration of referral for comprehensive early intervention services.
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APPENDIX A: 8-YEAR FOLLOW-UP QUESTIONNAIRE |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIX A: 8-YEAR FOLLOW-UP...REFERENCES |
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16 students or more per teacher
10–15 students per teacher
4–9 students per teacher
1–3 students per teacher
attends no classes
2. Does your child currently receive any of the following special assistance, services, or therapies? (Mark all that apply.)
Speech therapy
Physical therapy
Occupational therapy
Visual services
Counseling services
Tutoring Academic special education services
3. How many hours per week are these services or therapies received?
Less than 2 hours
At least 2 hours, less than 6
At least 6 hours, less than 15
At least 15 hours, less than 30
30 or more hours per week
4. Is your child currently classified in any of the following categories? (Mark all that apply, if any.)
Learning disabled or a slow learner
Developmentally delayed
Has cerebral palsy
Hearing impaired
Autistic
Has hyperactivity, emotional or behavioral problems, or attention-deficit disorder
Has seizure disorder or epilepsy
5.Describe your child’s performance in the following subjects (use: 1 = at or above grade level, 2 = possibly below grade level. 3 = definitely below grade level):
Math _____
Reading _____
Handwriting _____
Sports/gym _____
6. Describe your child’s ability to work independently: _____
1 = always or usually
2 = sometimes
3 = seldom (rarely) or never
7. Describe your child’s abilities in the following areas relative to those of other children of similar age (use: 1 = about the same or ahead, 2 = possibly lagging, 3 = definitely lagging):
Unsupervised play _____
Interaction with other children _____
Practical judgment _____
Following directions _____
8. Reliability of informant (choose one)
Above average
Average
Below average
Poor
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ACKNOWLEDGMENTS |
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We gratefully acknowledge the efforts of site coordinators, investigators, and participating children and families.
A listing of the members of the CRYO-ROP Cooperative Group for the phase III outcome study appears on page 1116 of the following publication: Multicenter Trial of cryotherapy for retinopathy of prematurity: ophthalmological outcomes at 10 years. Arch Ophthalmol. 2001;119:1110–1118.
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FOOTNOTES |
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Reprint requests to CRYO-ROP Study Headquarters, Oregon Health & Science University, Casey Eye Institute, 3375 SW Terwilliger Blvd, Portland, OR 97239
During the period of the CRYO-ROP study, 1987–2003, Velma Dobson received approximately $500/yr in royalties from Vistech Inc, the manufacturer of the Teller Acuity Cards, which were used to measure visual acuity in study participants.
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REFERENCES |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONAPPENDIX A: 8-YEAR FOLLOW-UP...REFERENCES |
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28 weeks gestation or 1000 g birthweight.
J Paediatr Child Health.1990; 26
:205
–208[ISI][Medline]800 g) schoolchildren: multiple areas of hidden disability.
Arch Dis Child Fetal Neonatal Ed.1997; 77
:F85
–F90This article has been cited by other articles:
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  A. Farooqi, B. Hagglof, G. Sedin, L. Gothefors, and F. Serenius Mental Health and Social Competencies of 10- to 12-Year-Old Children Born at 23 to 25 Weeks of Gestation in the 1990s: A Swedish National Prospective Follow-up Study Pediatrics, July 1, 2007; 120(1): 118 - 133. [Abstract] [Full Text] [PDF]
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P. H. Casey, L. Whiteside-Mansell, K. Barrett, R. H. Bradley, and R. Gargus Impact of Prenatal and/or Postnatal Growth Problems in Low Birth Weight Preterm Infants on School-Age Outcomes: An 8-Year Longitudinal Evaluation Pediatrics, September 1, 2006; 118(3): 1078 - 1086. [Abstract] [Full Text] [PDF]
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C. Lofqvist, E. Engstrom, J. Sigurdsson, A.-L. Hard, A. Niklasson, U. Ewald, G. Holmstrom, L. E. H. Smith, and A. Hellstrom Postnatal head growth deficit among premature infants parallels retinopathy of prematurity and insulin-like growth factor-1 deficit. Pediatrics, June 1, 2006; 117(6): 1930 - 1938. [Abstract] [Full Text] [PDF]
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 A. R. Fielder Premature for Life Arch Ophthalmol, March 1, 2005; 123(3): 392 - 394. [Full Text] [PDF]
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CRYO-ROP Cooperative Group Health-Related Quality of Life at Age 10 Years in Very Low-Birth-Weight Children With and Without Threshold Retinopathy of Prematurity Arch Ophthalmol, November 1, 2004; 122(11): 1659 - 1666. [Abstract] [Full Text] [PDF]
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 23 Apr 2004 to 23 Jul 2004 Evid. Based Nurs., October 1, 2004; 7(4): e4 - e4. [Full Text] [PDF]
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 Other articles noted Evid. Based Med., September 1, 2004; 9(5): e5 - e5. [Full Text] [PDF]
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