PEDIATRICS Vol. 106 No. 5 November 2000, pp. 998-1005

Severity of Neonatal Retinopathy of Prematurity Is Predictive of Neurodevelopmental Functional Outcome at Age 5.5 Years

Michael E. Msall, MD^*, Dale L. Phelps, MD, Kathleen M. DiGaudio, PNP, DNS^§, Velma Dobson, PhD, Betty Tung, MA^¶, Richard E. McClead, MD^#, Graham E. Quinn, MD^**, James D. Reynolds, MD, Robert J. Hardy, PhD^¶, Earl A. Palmer, MD^§§, and on Behalf of the Cryotherapy for Retinopathy of Prematurity Cooperative Group^||

From the ^* Child Development Center, Hasbro Children's Hospital, Brown University School of Medicine, Providence, Rhode Island;  Children's Hospital at Strong, University of Rochester, Rochester, New York; ^§ Robert Warner Rehabilitation Center, Children's Hospital of Buffalo, State University of New York at Buffalo, Buffalo, New York;  University of Arizona, Tucson, Arizona; ^¶ University of Texas Health Science Center, Coordinating Center for Clinical Trials, Houston, Texas; ^# Children's Hospital, Ohio State University, Columbus, Ohio; ^** The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania;  Children's Hospital of Buffalo, State University of New York at Buffalo, Buffalo, New York; and ^§§ Casey Eye Institute, Oregon Health Sciences University, Portland, Oregon.

	ABSTRACT

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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.  Key words:  retinopathy of prematurity, very low birth weight, developmental outcomes, longitudinal studies, prematurity, blindness, vision disorders, developmental disabilities, functional independence.

Survival is now reported for over 70% of inborn infants with birth weights between 750 and 1000 g and for nearly 90% of inborn infants with weights between 1001 and 1250 g.^1,2 With these increased survival rates, there is a high level of concern about disproportionately high rates of neuromotor, sensory, developmental, and educational disabilities.^3-14 These infants are also at increased risk of developing severe retinopathy of prematurity (ROP).¹⁵ Ophthalmologists have raised concerns that children with the most severe ROP have disproportionately high rates of severe multiple developmental disabilities and severe functional limitations.¹⁶ Attempts to measure neurodevelopmental functional status in children have been hampered by a lack of simple, inexpensive, concise instruments applicable to large-scale follow-up efforts.¹⁷ The Functional Independence Measure for Children (WeeFIM) instrument has been developed to meet this need.^18-20 WeeFIM has been used in over 500 children without disabilities to develop standardized norms, and further utilized in over 700 children with motor, sensory, genetic, and developmental disabilities.^21-22

The Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Multicenter Study was designed to evaluate the risk and benefit of transscleral cryotherapy to treat threshold ROP, and to describe the incidence and natural history of ROP.^23-25 This large cohort offers an opportunity to examine the relationship between severity of ROP and neurodevelopmental functional outcomes among infants who were studied systematically during the neonatal period and were also comprehensively examined for both visual and functional outcomes through age 5.5 years. The purpose of this report is: 1) to examine the relationship between acute neonatal ROP and subsequent neurodevelopmental function at 5.5 years of age using the WeeFIM in that cohort of infants followed from birth, and 2) to examine the spectrum of neurodevelopmental functional outcomes in self-care, continency, mobility, communicative, and social cognitive skills among infants who developed threshold ROP.

	METHODS

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Two Patient Cohorts

The 1208 infants surviving to 1 year of age from the 5 Natural History Centers of the original 23-center CRYO-ROP study had their follow-up extended through age 5.5 years. The 1199 survivors (9 deaths) are referred to as the extended natural history cohort (Fig 1). The second cohort included all 260 infants surviving at 1 year of age who developed severe ROP (defined as threshold; Table 1) and who were enrolled in the 23-center randomized, controlled trial of cryotherapy for threshold ROP.²³ Of these children, 255 survived to age 5.5 years (includes an overlap of 69 infants with threshold ROP from the extended natural history cohort). Children in both cohorts were preterm infants who had birth weights <1251 g born between January 1, 1986 and November 30, 1987. Infants were enrolled in the natural history study based on survival to 28 days, their parents' provision of informed consent, absence of eye anomalies or major congenital malformations, and initial ophthalmologic examination by a certified study ophthalmologist before age 49 days.^23,26 Additional ophthalmological examinations at intervals of 2 weeks or less were recorded using the international classification of ROP and continued until final ROP outcomes were determined.^24,25,27,28 Infants with at least 1 eye that progressed to threshold ROP, and whose parents consented to randomized treatment of not more than 1 eye with cryotherapy, make up the threshold randomized cohort (ThRz) group.

View larger version (26K): [in this window] [in a new window]   Fig. 1.   Cohorts in the CRYO-ROP 5.5-year follow-up study. One thousand two hundred eight children from the extended natural history cohort and 260 in the randomized cohort were initially eligible for follow-up. Deaths occurred before 5.5 years of age in 9 from the extended natural history cohort and in 5 from the randomized cohort.

ROP Categories

Each child's ROP was categorized according to the most severe stage of active ROP reached in either eye during the neonatal period. The ROP classification categories are defined in Table 1.^23,27

Assessments at Follow-Up

Complete eye examinations, including funduscopic evaluations as well as cycloplegic retinoscopy, were performed by study-certified ophthalmologists, and visual function was measured by study-certified visual acuity testers, as previously described.^29,30 For this report, Teller acuity cards^31,32 were used to assess visual acuity because of the number of subjects unable to complete letter recognition testing at this age. Children were exempt from formal acuity testing if the ophthalmologist and parents agreed that the child had no light perception in either eye, or if 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 (>1 octave below the normal range) was defined as unfavorable. Favorable vision was defined as a measurable acuity better than the unfavorable category. Ophthalmic outcomes have been reported elsewhere.³³ In this report, children are classified by the vision in their better eye at age 5.5 years.

The WeeFIM instrument was administered to assess the consistent and regular performance of the child in essential tasks of self-care, continency, mobility, locomotion, communication, and social cognition.³⁴ The WeeFIM involves 18 items that describe 7 levels of independence.³⁵ Self-care items include eating, grooming, bathing, dressing of upper and lower body, and toileting hygiene. Sphincter control (continency) items include bladder and bowel management. Mobility and locomotion items include changing positions from chairs and toilet seats, walking indoors and outdoors, self-mobility (crawl or wheelchair), and negotiating stairs and community distances. Communication items included receptive and expressive use of language, whether aural or visual. Social cognitive items include social interaction, problem solving, and memory. Each item is scored on a 7-level ordinal scale (see Table 2 

). Table 2 is a sample score sheet with accompanying polar graphic for a 5.5-year-old boy with threshold ROP, favorable visual function, and diplegic cerebral palsy. Levels 6 and 7 reflect independence, and no personal assistance by an adult is required for the child to successfully complete all components of the task on a daily basis. Levels 3, 4, and 5 reflect modified dependence; either supervision or a degree of personal assistance is required to complete the task but the child performs at least one half of the activity. Levels 1 and 2 indicate dependence, with an adult performing the majority of the tasks. Total possible WeeFIM scores range from 18 to 126. The mean score for normal 5.5-year-olds is 114.8, with a standard deviation (SD) of 9.4.²¹

All WeeFIM interviewers were certified to use the instrument after participating in a 3-hour training workshop and successful completion of model cases. Cronbach's  for the interviewers exceeded .90 with 100% of the interviewers passing 2 model cases within 4 total WeeFIM points. This is consistent with previous reliability studies.^36,37

The WeeFIM scores were used to classify each child's functional status as average if scores were within 1 SD of the mean for age (scores of >105), and as at-risk if scores were 1 to 2 SDs below the mean (scores: 96-105). The mild delays of children in the at-risk category are rarely perceived by parents and educational professionals as problematic and occur in 16% of normal children. Overall, children whose scores are within 2 SDs of the mean are globally normal (WeeFIM: >95). Some disability was the category for children with scores of 2 to 4 SDs below the mean. These scores corresponded to a WeeFIM of 77 to 95 and are termed mild/moderate disability because the child also has many developmental strengths. Children with severe disability have scores >4 SDs below the mean. These correspond to WeeFIM scores <77 and reflect a child's need for adult assistance in many skills. A WeeFIM score of 77 is equivalent to the performance of an average 2.5-year-old child.

In addition to total WeeFIM scores, self-care, continency, mobility-locomotion (motor), and communication-social cognitive domains were analyzed in children with ThRz ROP. Children with any 1-item score of <4 in self-care were considered to have some self-care disability. A score of 1, 2, or 3 on a WeeFIM item indicates that the child requires significant amounts of assistance by an adult in order for the child to complete the task. Similarly, children with any 1-item score of <4 in the other domains were considered to have some disability in that category.

Statistics

WeeFIM assessments were obtained on all children and compared with their worst-stage ROP in either eye during infancy. Descriptive statistics included frequency distributions, and measures of central tendency. Comparisons between groups were documented using appropriate statistics including ² and t tests.

Two separate univariate analyses were performed to obtain crude relative risks (RRs) and corresponding 95% confidence intervals (CIs) for a number of infant characteristics in relation to having: 1) severe disability (WeeFIM: <77) compared with absence of severe disability (WeeFIM: 77), and 2) any disability (WeeFIM: 95) compared with no disability (WeeFIM: >95).

Based on the univariate analyses and adjusting for multicollinearity among study variables, the 5-center extended natural history cohort data were used to examine the effects of the most significant variables identified in predicting WeeFIM outcome. This multiple regression model used total WeeFIM scores as a continuous dependent variable and both sociodemographic factors and biomedical factors as independent variables. The sociodemographic variables in these analyses included mother's race, gender, outborn status (ie, infant born in a hospital not providing neonatal intensive care), private health insurance (ie, any insurance other than Medicaid or self-pay), and highest educational level achieved by the head of household. In the regression, the dichotomy between high and low educational status was chosen as high school completion for the head of the household. The biomedical variables in these analyses included gestational age at birth, plurality (singleton vs multiple birth), small for gestational age (ie, birth weight less than the 10th percentile), having an abnormal 2-year neurological disability score (ie, recurrent seizures, microcephaly, or shunted hydrocephalus), and visual status defined as favorable if at least 1 eye had favorable Teller acuity at age 5.5 years.

	RESULTS

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There were 1199 survivors from the 5-Center Extended Natural History Cohort, and 1063 (88.7%) were assessed at age 5.5 years, including 66 ThRz. Among the 255 children surviving to 5.5 years who were ThRz for treatment of their ROP from all 23 centers, 223 (87.5%) completed 5.5-year follow-up examination (Fig 1).

Figure 2 demonstrates the relationship between ROP status and WeeFIM status in the 5-center extended natural history cohort. With more severe ROP, there is a lower percentage of children who are globally functionally normal (WeeFIM: >95), from 92% in no ROP to 76% in ThRz (P < .01). Similarly, with more severe ROP, severe disability (WeeFIM: <77) is more frequent and involves 3.7% of children with no ROP, but 19.7% of the children with ThRz ROP (P < .01).

View larger version (58K): [in this window] [in a new window]   Fig. 2.   ROP Status and WeeFIM status in the 5-center extended natural history cohort. See Table 1 for definitions of categories. N = number of infants evaluated in each category of neonatal ROP severity.

The first univariate analysis was performed to obtain crude relative risk (RR) for study variables and risk of severe disability (WeeFIM: <77) compared with freedom from severe disability (WeeFIM: 77) (Table 3). Risks for severe disability included abnormal neurological score, ThRz ROP, any ROP, gestational age <27 weeks, birth weight <750 g, and absence of private health insurance. Protective factors from risk of severe disability included favorable 5.5-year Teller visual acuity status and black race.

A second univariate analyses examined the study variables' effects on the risk of any disability (WeeFIM: 95) compared with no disability (WeeFIM: >95). Abnormal neurological score at 2 years (RR: 4.41; 95% CI: 3.15-6.16), ThRz ROP (RR: 2.07; 95% CI: 1.31-3.27), any ROP (RR: 1.76; 95% CI: 1.19-2.60), and more immaturity (gestational age <27 weeks; RR: 1.43; 95% CI: 1.03-1.98) were significantly predictive of some disability. Favorable 5.5-year Teller visual acuity status (RR: .12; 95% CI: .09-.15), black race (RR: .40; 95% CI: .25-.66), and inborn status (RR: .67; 95% CI: .46-.96) were apparently protective factors that predicted a lower probability of disability (WeeFIM: >95).

Table 4 shows the predictors of WeeFIM scores as a continuous dependent variable in a multivariate regression model. Favorable 5.5-year Teller visual acuity had the greatest predictive effect on functional status as measured by higher WeeFIM scores (P < .001). With adjustment for favorable vision, the other significant predictors in order of their magnitude of the regression coefficients were absence of threshold ROP, normal 2-year neurological score, maternal black race, and higher income as reflected by private health insurance (P < .001).

Noting the frequency of functional limitation in the threshold infants, the distribution of WeeFIM scores in the larger group of all ThRz infants from the CRYO-ROP study was examined. Of the 216 ThRz children evaluated with both Teller acuity and WeeFIM assessments, 82 had unfavorable acuity and 134 had favorable acuity in their better eye. Among children with favorable acuity despite ThRz ROP, the overwhelming majority (91%) were globally functionally normal with WeeFIM scores >95. Of the children with unfavorable acuity status (ie, children effectively blind), 55% had severe disabilities (WeeFIM: <77), ie, children were blind and had self-care, continency, mobility-locomotion (motor), and/or communicative-social cognitive limitations. Despite unfavorable Teller acuity status, 34% of the ThRz from all centers had globally normal WeeFIM outcomes (WeeFIM: >95).

Figure 3 shows the relationship between favorable and unfavorable visual acuity in the ThRz group and having some disability in the WeeFIM domains of self-care, continency, mobility-locomotion (motor), and communicative-social cognition areas. Among the 134 children with ThRz ROP and favorable visual acuity status at age 5.5 years, 25.4% had self-care disability, 4.5% had continency disability, 5.2% had mobility-locomotion (motor) disability, and 22.4% had communicative-social cognitive disability. In contrast, among the 82 children with unfavorable visual acuity status, self-care disability occurred in 76.8%, continency disability occurred in 50.0%, motor disability occurred in 42.7%, and communicative-social cognitive disabilities occurred in 65.9%. For all the tasks, children with unfavorable visual acuity status had much higher disability rates (P < .001).

View larger version (36K): [in this window] [in a new window]   Fig. 3.   Threshold randomized ROP and 5.5-year visual acuity and disability status. Favorable and unfavorable acuity levels were based on the child's better eye. Subcategories on the WeeFIM assessment were considered a disability if any one of the self-care, continency, motor, or communication-social cognition items were scored <4. Data are expressed as percent of children in each category with disability on one or more items.

	DISCUSSION

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Our study demonstrates that there are high rates of disability in children of very low birth weight status who develop threshold ROP and subsequently have unfavorable visual outcomes. These children are multiply disabled and have functional limitations in self-care, continency, mobility-locomotion (motor), communicative, and social cognitive skills. Historic studies of very low birth weight preterm survivors performed before 1965 by Hess,³⁸ Knobloch et al,³⁹ Lubchenco et al,^40,41 Drillien,^42,43 Fledelius,⁴⁴ and McCormick and colleagues,⁴⁵ demonstrated rates of severe ROP causing blindness in 2% to 11% of survivors. Fifty percent of these blind children were multiply disabled, which is similar to our results.

Previous regional epidemiologic studies in Canada, New Zealand, The Netherlands, Denmark, Sweden, England, and Australia have involved fewer than 70 children with severe ROP.^46-55 Recent studies in Victoria, Australia; Perth, Australia; Alberta, Canada; and San Francisco, California have examined trends in rates of motor, cognitive, and sensory disabilities in children with birth weights of <1000 to 1251 g.^7,8,46,56 Rates of blindness ranged from 1% to 7%, while rates of cerebral palsy ranged from 6% to 17%, and rates of cognitive disability ranged from 7% to 25%. Because of various definitions of disability and nonuniformity in reporting combinations of disabilities, it is difficult to determine the impact of severe ROP on multiple disabilities in these studies. More recently, Jacobson et al⁵² used the Swedish registry for visual impairment for the years 1980 to 1990 to evaluate 29 children with stage 5 ROP and total blindness. Significant neurodevelopmental disabilities including cerebral palsy, mental retardation, and autism were present in 76% of children.¹⁶

The strengths of our study include the systematic adherence to the diagnosis, staging, and tracking of ROP, and high follow-up rates. We were not able to relate these findings to degrees of intraventricular hemorrhage or parenchymal brain injury because intracranial hemorrhage data were not available.⁵⁷ Data on periventricular leukomalacia are also known to be useful in predicting outcomes but were not available to this study.^57-61 The finding that black race was a protective factor for disability was unexpected and warrants further investigation. Because race effect was not an a priori hypothesis in this study, we consider the observation to be hypothesis-generating because it may be difficult to separate race effect from known reduction in rates of threshold ROP among black infants.⁶²

In our study, factors that lead to severe ROP seem to have an adverse impact on brain systems involved in self-care, continency, mobility-locomotion, and communicative-social cognition functional skills. This is also supported by our finding that children with abnormal neurological status at age 2 years have significantly lower WeeFIM scores at age 5.5 years.

We have demonstrated that ROP is a marker for being at risk for severe functional disability, and poor vision after threshold ROP increases the risk for severe disability. It is tempting to conclude that the use of cryotherapy to preserve vision may reduce severe disability rates. However, ROP nonresponsive to cryotherapy may indicate children with brain injury. Additionally, children with visual impairment are not all severely functionally limited on the WeeFIM. In our study 34% of children with unfavorable visual acuity had globally normal WeeFIM scores (WeeFIM: >95). Unquestionably, those children who retained vision in at least 1 eye functioned much more independently. Our data do not allow us to categorically state that rescuing vision in children with severe ROP guarantees better functional status. There are many confounding variables that impact on functional competencies at kindergarten entry, including the degree of initial brain injury, chronic childhood illness, family resources, and quality early childhood experiences (eg, early intervention, Head Start, preschool). In contrast, retaining vision in at least 1 eye is strongly associated with better functional status and efforts to increase visual status should be pursued. In addition, comprehensive developmental interventions are required to optimize long-term outcomes and support families in the care of children who are born very prematurely.^6,63-66

	ACKNOWLEDGMENTS

This research was supported by Cooperative Agreement EYO5874 from the US Public Health Service, National Institutes of Health, National Eye Institute.

All of the marks associated with WeeFIM belong to the Uniform Data System for Medical Rehabilitation, a division of UB Foundation Activities.

The Center for Functional Assessment Research of UDSMR-SUNY at Buffalo provided manuals and training tapes.

Maryann Kihl, Judy daSilva, J. DeRobbio, H. Ripstein, and Michelle Tremont assisted in manuscript preparation. Germaine Buck, PhD; Lewis Rubin, MD; Betty Vohr, MD; and Dennis Hogan, PhD, provided critical feedback.

We gratefully acknowledge the efforts of the many site coordinators and investigators and participating families and children.

This manuscript is dedicated to Dr Robert E. Cooke for his lifelong dedication to the prevention of developmental disabilities and advocacy for children and families with multiple disabilities.

	FOOTNOTES

^|| A complete list of the members of the Cryotherapy for Retinopathy of Prematurity Cooperative Group appears on pages 420-421 of reference 33.

Dr Msall is Medical Director and Scientific Advisory Chair of the WeeFIM-UDS, a not-for-profit organization within the Center for Functional Assessment Research, State University of New York at Buffalo. He has no financial interest in the WeeFIM assessment tool.

Dr Dobson receives royalties from the sale of the Teller acuity cards.

Received for publication Sept 21, 1999; accepted Mar 17, 2000.

Reprint requests to (E.A.P.) CRYO-ROP Study Headquarters, Oregon Health Sciences University, Casey Eye Institute, 3375 SW Terwilliger Blvd, Portland, OR 92701-4197. E-mail: palmere{at}ohsu.edu

	ABBREVIATIONS

ROP, retinopathy of prematurity; WeeFIM, Functional Independence Measure for Children; CRYO-ROP, cryotherapy for retinopathy of prematurity; ThRz, threshold randomized cohort; SD, standard deviation; RR, relative risk; CI, confidence interval.

	REFERENCES

Top Abstract Methods Results Discussion References

1. Hack M, Wright LL, Shankaran S, , for the NICHHD Neonatal Research Network. Very-low-birth-weight outcomes of the National Institute of Child Health and Human Development Neonatal Network, November 1989 to October 1990. Am J Obstet Gynecol 1995; 172:457-464 [CrossRef][Medline]
2. Vohr B, Msall ME Neuropsychological and functional outcomes of very low birth weight infants. Semin Perinatol 1997; 21:202-220 [CrossRef][Medline]
3. Hack M, Fanaroff AA How small is too small? Considerations in evaluating the outcome of the tiny infants. Clin Perinatol 1988; 15:773-788 [Medline]
4. Allen MC The high-risk infant. Pediatr Clin North Am 1993; 40:479-490 [Medline]
5. Lorenz JM, Wooliever DE, Jetton JR, A quantitative review of mortality and developmental disability in extremely premature newborns. Arch Pediatr Adolesc Med 1998; 152:425-435 [Abstract/Free Full Text]
6. Msall ME, Bier JB, LaGasse L, Tremont M, Lester B The vulnerable preschool child: the impact of biomedical and social risks on neurodevelopmental function. Semin Pediatr Neurol 1998; 5:52-61 [CrossRef][Medline]
7. Piecuch RE, Leonard CH, Cooper BA, Sehring SA Outcome of extremely low birth weight infants (500-999 grams) over a 12-year period. Pediatrics 1997; 100:633-639 [Abstract/Free Full Text]
8. Victorian Infant Collaborative Study Improved outcome into the 1990's for infants weighing 500-999 grams at birth. Arch Dis Child 1997; 77:F91-F94
9. Victorian Infant Collaborative Study Group Neurosensory outcome at 5 years and extremely low birth weight. Arch Dis Child 1995; 73:F143-F146
10. Herrgard E, Karjalainen S, Martikainen A, Heinonen K Hearing loss at the age of 5 years of children born preterma matter of definition. Acta Paediatr 1995; 84:1160-1164 [Medline]
11. Msall ME, Buck GM, Rogers BT, Catanzaro NL Kindergarten readiness after extreme prematurity. Am J Dis Child 1992; 146:1371-1375 [Abstract]
12. Hack M, Taylor TG, Klein M, Eiben R, Schneider C, Mercunminich N School-age outcomes in children with birth weight <750 grams. N Engl J Med 1994; 331:753-759 [Abstract/Free Full Text]
13. Saigal S, Szatmari P, Rosenbaum P, Cognitive abilities and school performance of extremely low birth weight children and matched term control children at 8 years: a regional study. J Pediatr 1991; 118:751-760 [CrossRef][Medline]
14. Hack M, Klein NK, Taylor HG Long-term developmental outcomes of low birth weight infants. Future Child 1995; 5:176-196 [CrossRef][Medline]
15. Flynn JT Retinopathy of prematurity: perspective for the nineties. Acta Opthalmol Scand 1995; 73:12-14 [Medline]
16. Ek U, Fernell E, Jacobson L, Relation between blindness due to retinopathy of prematurity and autistic spectrum disorders: a population-based study. Dev Med Child Neurol 1998; 40:297-301 [Medline]
17. McCormick MC Long-term follow-up of infants discharged from neonatal intensive care units. JAMA 1989; 261:1767-1772 [Abstract]
18. Msall ME, DiGaudio KM, Duffy LC Use of functional assessment in children with developmental disabilities. Phys Med Rehabil Clin North Am 1993; 4:517-527
19. Msall ME, Rogers BT, Buck GM, Mallen S, Catanzaro NL, Duffy LC Functional status of extremely preterm infants at kindergarten entry. Dev Med Child Neurol 1993; 35:312-320 [Medline]
20. Rogers BT, Msall ME, Buck GM, Neurodevelopmental outcome of infants with hypoplastic left heart syndrome. J Pediatr 1995; 126:496-498 [CrossRef][Medline]
21. Msall ME, DiGaudio K, Duffy LC, LaForest S, Braun S, Granger CV WeeFIM: normative sample of an instrument for tracking functional independence in children. Clin Pediatr 1994; 33:431-438
22. Msall ME, DiGaudio K, Rogers BT, The Functional Independence Measure for Children (WeeFIM): conceptual basis and pilot use in children with developmental disabilities. Clin Pediatr 1994; 33:421-430
23. Cryotherapy for Retinopathy of Prematurity Cooperative Group Multicenter trial of cryotherapy for retinopathy of prematurity: one year outcomestructure and function. Arch Ophthalmol 1990; 108:1408-1416 [Abstract]
24. The International Committee for the Classification of Retinopathy of Prematurity An international classification of retinopathy of prematurity. Pediatrics 1984; 74:127-133 [Abstract/Free Full Text]
25. International Committee for the Classification of the Late Stages of Retinopathy of Prematurity An international classification of retinopathy of prematurity, II: the classification of retinal detachment. Pediatrics 1988; 82:37-43 [Abstract/Free Full Text]
26. Phelps DL, Brown DR, Tung B, 28-day survival rates of 6676 neonates with birth weights of 1250 grams or less. Pediatrics 1991; 87:7-17 [Abstract/Free Full Text]
27. Palmer EA, Flynn JT, Hardy RJ, Incidence and early course of ROP. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1991; 98:1628-1640 [Medline]
28. Cryotherapy for ROP Cooperative Group The natural ocular outcome of premature birth and retinopathy: status at one year. Arch Ophthalmol 1994; 112:996
29. Cryotherapy for ROP Cooperative Group Multi center trial of cryotherapy for retinopathy of prematurity: 31/2-year outcomestructure and function. Arch Ophthalmol 1993; 111:339-344 [Abstract]
30. Dobson V, Quinn GE, Summers CG, Effect of acute-phase retinopathy of prematurity on grating acuity development in the very low birth weight infant. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Invest Ophthalmol Vis Sci 1994; 35:4236-4244 [Abstract/Free Full Text]
31. Dobson V, Quinn GE, Biglan AW, Tung B, Flynn JT, Palmer EA Acuity card assessment of visual functional in the cryotherapy for retinopathy of prematurity trial. Ophthalmol Vis Sci 1990; 31:1702-1708 [Abstract/Free Full Text]
32. Teller DY, McDonald M, Preston K, Assessment of visual acuity in infants and children: the acuity card procedure. Dev Med Child Neurol 1986; 28:779-789 [Medline]
33. Cryotherapy for Retinopathy of Prematurity Cooperative Group Multicenter trial of cryotherapy for retinopathy of prematurity: Snellen visual acuity and structural outcome at 51/2 years after randomization. Arch Ophthalmol 1996; 114:417-424 [Abstract]
34. Data Management Service of the Uniform Data System for Medical Rehabilitation, the Center for Functional Assessment Research. Guide for Use of the Uniform Data System for Medical Rehabilitation, Including the Functional Independence Measure for Children (WeeFIM), Version 1.5. Buffalo, NY: State University of New York at Buffalo; 1991
35. Msall ME, Braun S, Granger CV Use of the Functional Independence Measure for Children (WeeFIM): an interdisciplinary training tape. Dev Med Child Neurol 1990; 62:46
36. Ottenbacher KJ, Taylor ET, Msall ME, The stability and equivalence reliability of the Functional Independence Measure for Children (WeeFIM). Dev Med Child Neurol 1996; 38:907-916 [Medline]
37. Ottenbacher KJ, Msall ME, Lyon NR, Duffy LC, Granger CV, Braun S Interrater agreement and stability of the Functional Independence Measure for Children (WeeFIM®): use in children with development disabilities. Arch Phys Med Rehabil 1997; 78:1309-1315 [CrossRef][Medline]
38. Hess JH Experiences gained in a thirty-year study of prematurely born infants. Pediatrics 1953; 11:425-434 [Abstract/Free Full Text]
39. Knobloch H, Rider R, Harper P, Neuropsychiatric sequelae of prematurity. JAMA 1956; 161:581-585
40. Lubchenco LO, Horner FA, Reed LH, Sequelae of premature birth. Am J Dis Child 1963; 101:115
41. Lubchenco LO, Delivoria-Papadopoulos M, Butterfield LJ, Long term follow-up studies of prematurely born infants: relationship of handicaps to nursery routines. J Pediatr 1972; 80:501-508 [CrossRef][Medline]
42. Drillien CM The incidence of mental and physical handicaps in school age children of very low birth weight. Pediatrics 1967; 39:238-247 [Abstract/Free Full Text]
43. Drillien CM School disposal and performance for children of different birth weight born 1953-60. Arch Dis Child 1969; 44:562-570
44. Fledelius H. Prematurity and the eye. Acta Ophthalmol Scand Suppl. 1976;128
45. McCormick AQ, Tredger EM, Dunn HG, Grunau RVE. Ophthalmic disorders. In: Dunn HG, ed. Sequelae of Low Birthweight: The Vancouver Study. Philadelphia, PA: MacKeith Press; 1986:127-146
46. Robertson C, Sauve RS, Christianson HE Province-based study of neurologic disability among survivors weighing 500 through 1248 grams at birth. Pediatrics 1994; 93:636-640 [Abstract/Free Full Text]
47. Darlow BA, Horwood LJ, Clemett RS Retinopathy of prematurity: risk factors in a prospective population-based study. Paediatr Perinat Epidemiol 1992; 6:62-80 [Medline]
48. Fetter WPF, van Hof-vanDuin J, Baerts W, Heersema DJ, Wildervanck de Blecourt-Devilee M Visual acuity and visual field development after cryocoagulation in infants with retinopathy of prematurity. Acta Paediatr 1992; 81:25-28 [Medline]
49. Arroe M, Peitersen B Retinopathy of prematurity in a Danish neonatal intensive care unit, 1985-1991. Acta Ophthalmol Scand 1993; 210:37-40
50. Fledelius H. Prematurity and the Eye: Ophthalmic 10-Year Follow-Up of Children of Low and Normal Birth Weight. Copenhagan, Denmark: Scriptor; 1976
51. Fledelius HC Central nervous system damage and retinopathy of prematurity-an ophthalmic follow-up of prematures born in 1982-84. Acta Paediatr 1996; 85:1186-1191 [Medline]
52. Jacobson L, Fernell E, Broberger U, Ek U, Gillberg C Children with retinopathy of prematurity: a population-based study, perinatal data, neurological and ophthalmological outcome. Dev Med Child Neurol 1998; 40:155-159 [Medline]
53. Ng YK, Fielder AR, Shaw DE, Levene MI Epidemiology of retinopathy of prematurity. Lancet 1988; 2:1235-1238 [Medline]
54. Keith CG, Doyle LW Retinopathy of prematurity in low birth weight infants. Pediatrics 1995; 95:42-45 [Abstract/Free Full Text]
55. Yu VYH, Lim CT, Downe LM A 12-year experience of retinopathy of prematurity in infants 28 weeks gestation or  1000 g birth weight. J Pediatr Child Health 1990; 26:205-208
56. French NP, Parry TS, Evans S Improving outcome for Western Australian infants with birthweights 500-999 g. Med J Aust 1995; 162:295-299 [Medline]
57. Phillips J, Christiansen SP, Ware G, Landers S, Kirby RS Ocular morbidity in very low birth-weight infants with intraventricular hemorrhage. Am J Ophthalmol 1997; 123:218-223 [Medline]
58. Ng YK, Fielder AR, Levene MI, Trounce JQ, McLellan N Are severe acute retinopathy of prematurity and severe periventricular leukomalacia both ischemic insults. Br J Ophthalmol 1989; 73:111-114 [Abstract/Free Full Text]
59. Procianoy RS, Gacia-Prats JA, Hittnertt M, Adams JM, Rudolph AJ An association between retinopathy of prematurity and intraventricular hemorrhage in very low birth weight infants. Acta Paeditr 1981; 70:473-477
60. Msall ME, Buck GM, Rogers BT, Duffy LC, Mallen SR, Catanzaro NL Predictors of mortality, morbidity, and disability in a cohort of infants <28 weeks gestation. Clin Pediatr 1993; 32:521-527
61. Rogers B, Msall M, Owens T, Cystic periventricular leukomalacia and type of cerebral palsy in preterm infants. J Pediatr 1994; 125:S1-S8 [CrossRef][Medline]
62. Saunders RA, Donahue ML, Christmann LM, Racial variation in retinopathy of prematurity. Arch Ophthalmol 1997; 115:604-608 [Abstract]
63. Aylward GP The relationship between environmental risk and developmental outcome. J Dev Behav Pediatr 1992; 13:222-229 [Medline]
64. McCarton CM, Wallace IF, Bennett FC Preventive interventions with low birth weight premature infants: an evaluation of their success. Semin Perinatol 1995; 19:330-340 [CrossRef][Medline]
65. Bennett FC, Guralnick MJ Effectiveness of developmental intervention in the first five years of life. Pediatr Clin North Am 1991; 38:1513-1528 [Medline]
66. Hogan DP, Msall ME, Rogers ML, Avery RC Improved disability population estimates of functional limitation among American children aged 5-17. Matern Child Health J 1997; 1:203-216 [CrossRef][Medline]