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Visual impairment in children born prematurely from 1972 through 1989
Visual Impairment in Children Born Prematurely from 1972 through 1989 Sirkka-Liisa Rudanko, MD,1 Vineta Fellman, MD, PhD,2 Leila Laatikainen, MD, PhD3 Purpose: To investigate the incidence and causes of visual impairment in children born prematurely in Finland from 1972 through 1989, and to determine what conditions and factors were associated with its occurrence. Design: Retrospective, cross-sectional study. Subjects: All visually impaired individuals from 0 to 17 years of age who had been born at fewer than 37 gestational weeks in Finland from 1972 through 1989 for whom records were available in the Finnish Register of Visual Impairment were eligible for this study. Methods: Data in the Finnish Register of Visual Impairment relating to 556 children were supplemented with data from hospital records, and from the Register of Births, the Register of Congenital Malformations, the Finnish Care Register, and the Finnish Cancer Register. Data relating to causes associated with visual impairment in particular were collected. Data relating to the children born prematurely were compared with data relating to children born at full term. The chi-square test (Mantel-Haenszel), the Mann–Whitney U test, Fisher exact test, and stepwise logistic regression analysis were used in statistical analysis of the data. Main Outcome Measures: Visual acuity, ophthalmologic diagnoses, associated systemic disease, multiple handicap, gestational age, birth weight, 5-minute Apgar scores, and prenatal, perinatal, and infantile or juvenile disorders or disease and treatment. Results: One hundred twenty-five of the 556 visually impaired children (23%; 11/100,000 children less than 18 years of age) had been born preterm. Retinopathy of prematurity, optic atrophy, and cerebral amblyopia were the main diagnoses associated with visual impairment (in 46%, 28%, and 12% of cases, respectively). Sixty-six percent of those born prematurely with visual impairment were also affected by other handicaps (mental, motor, auditory), 54% by cerebral palsy and 36% by epilepsy. Eighty-eight of the 125 children (70%) born preterm with visual impairment were blind. Very low birth weight (⬍1500 g), young gestational age (fewer than 30 weeks), prenatal infection, hyperbilirubinemia, respiratory disorders, asphyxia, and lengthy mechanical ventilation were associated with an increased risk of visual impairment. Conclusions: Premature birth was a major risk factor of severe visual impairment and blindness in childhood. The visual impairment often was accompanied by cerebral palsy, epilepsy, and other motor and mental handicaps. Retinopathy of prematurity, optic atrophy, and cerebral amblyopia were the main diagnoses associated with visual impairment. During the 18 years covered by the study, the increasing incidence of survival of infants born weighing fewer than 1500 g was associated with increasing incidence of blindness. Ophthalmology 2003;110:1639 –1645 © 2003 by the American Academy of Ophthalmology.
Developments in obstetrics and neonatal care over the last three decades have improved markedly the outcome in cases of premature birth and have increased the incidence of survival of very immature infants. The incidence of premature birth declined in Finland from 9% in the 1960s to 5% by the end of the 1980s, despite higher survival rates of
Originally received: August 8, 2002. Accepted: December 24, 2002. Manuscript no. 220545. 1 The Finnish Register of Visual Impairment, Finnish National Agency for Welfare and Health, Helsinki, Finland. 2 Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland. 3 Department of Ophthalmology, University of Helsinki, Helsinki, Finland. The authors have no proprietary interest in any material used in this study. Reprint requests to Sirkka-Liisa Rudanko, MD, The Finnish Register of Visual Impairment, Ma¨kela¨nkatu 50, 00510, Helsinki, Finland. © 2003 by the American Academy of Ophthalmology Published by Elsevier Inc.
extremely immature infants.1 Changes relating to visual impairment in childhood therefore were to be expected. Establishment of the Finnish Register of Visual Impairment in 1983 allowed collection of data relating to visual impairment in Finnish children. The aim of this study was to investigate the incidence, characteristics, causes, and risk factors of visual impairment in Finnish children born prematurely and at full-term from 1972 through 1989 using data from the Finnish Register of Visual Impairment. These data were also compared with data relating to children born prematurely with visual impairment in the 1990s.
Patients and Methods The data for children with visual impairment was obtained from the Finnish Register of Visual Impairment, which collects reports from ophthalmologists beginning in 1983 and records persons with ISSN 0161-6420/03/$–see front matter doi:10.1016/S0161-6420(03)00498-6
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Ophthalmology Volume 110, Number 8, August 2003 visual impairment at any age when so discovered. Data for a total of 556 visually impaired children less than 18 years of age were filed in the Finnish Register of Visual Impairment at the end of 1989. Their age at registration varied from a few months to 17 years. The main parameters included in the register data were the cause of visual impairment, associated ophthalmic and systemic conditions, other handicaps (mental, motor, auditory), age at onset of visual impairment, visual acuity, and visual fields. The data were supplemented by data from hospital records relating to the visually impaired children and their mothers and by data from other national registers (Register of Births, Register of Congenital Malformations, Finnish Care Register, Finnish Cancer Register). The data covered the period from fetal life to childhood.
Prenatal Period Data relating to maternal age; medical examinations undergone (e.g., ultrasonography, radiographs, magnetic resonance imaging, amnioscopy, fetoscopy, amniocentesis, amniotic fluid analysis); maternal disease; medication; operations; trauma; use of alcohol, tobacco, and drugs; pregnancy disorders and complications; multifetal pregnancies; and unusual status of fetal presentation or of birth canal were recorded. All prenatal diagnoses recorded by the physicians responsible for medical treatment of the pregnant women were noted.
Perinatal Period Data relating to method of delivery, gestational age (defined on the basis of the last menstrual period and confirmed by clinical evaluation of early uterine size), birth weight, perinatal complications, neonatal disease, congenital malformations, and major treatments and procedures were recorded. The traditional criterion for prematurity, gestational age less than 37 weeks, was used. Asphyxia was defined as a 5-minute Apgar score of 0 to 6. All perinatal diagnoses recorded by the physicians responsible for obstetric and neonatal treatment were noted.
Children’s Health after the Perinatal Period Data relating to other impairments; ophthalmic operations for cataract, glaucoma, retinal detachment, or other conditions; and retinal cryotherapy were recorded. Diagnoses of retinopathy of prematurity (ROP), optic atrophy, and other ophthalmic disorders were obtained from hospital records. Cause of visual impairment, diagnoses, and multiple handicaps were coded according to the system devised by the Nordsyn Study Group.2 Cerebral amblyopia was the diagnosis in cases in which cerebral lesions affected posterior visual pathways, cortical areas, or both and the ocular pathologic features did not explain the visual impairment.3 Visual impairment was classified according to the categories of the World Health Organization International Classification of Diseases (1980). Children with unspecified degree of remaining vision were placed in World Health Organization category 9 and classified as blind. Corresponding data in the Finnish Register of Visual Impairment relating to all 431 visually impaired children born at full-term from 1972 through 1989 had been collected by the first author for another paper (Rudanko et al, 2002, in preparation) and was used for comparative statistical analysis.
Analysis and Statistical Methods SAS for Windows version 6.12 (SAS Institute Inc., Finland) was used for data analysis. Significant bivariate variables for risk factor
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determinations of visual impairment were determined using the chi-square test (Mantel-Haenszel), the Mann–Whitney U test, and Fisher’s exact test. Variables independently associated with visual impairment were analyzed further by stepwise logistic regression analysis.
Results Demographic Data Relating to Children Born Prematurely Of the 556 visually impaired children, 125 (23%) were born preterm. Seventy-three of the latter (58%) were male; 52 (42%) were female. The male-to-female ratio (1.44) was higher than that for the Finnish newborn population in general (1.05; P ⬍ 0.001) but does not differ significantly from that for the children born at full-term with visual impairment (1.68). Gestational age ranged from 23 to 36 weeks (median, 29 weeks), and birth weight ranged from 570 to 3820 g (median, 1360 g). Almost half (59/125) of the infants born preterm (47%) were of gestational age of less than 30 weeks. Sixty-eight of the 125 (55%) weighed less than 1500 g at birth (very low birth weight), and 31 (25%) weighed less than 1000 g at birth (extremely low birth weight). Fifteen of the 125 (12%) weighed 2500 g or more at birth. Eight were large for their gestational age.
Maternal Factors Related to Prematurity The percentages for young (less than 20 years; n ⫽ 27 [22%]) and older (more than 35 years; n ⫽ 42 [34%]) mothers of children born preterm differed considerably from the corresponding percentages for all women who gave birth in Finland (young mothers, 3%; older mothers, 13%). Only a few of the mothers had systemic disease during pregnancy. Three had diabetes mellitus, one had alcoholism, and one had a benign ovarian tumor. Thirty-six of the mothers had an infection during pregnancy. Medications (mainly antibiotics) during pregnancy were used by 15 of the mothers. The information on smoking (n ⫽ 5) and use of alcohol (n ⫽ 2) during pregnancy was self-reported, and it was assumed that more mothers fell into each of the two categories. All of the children of the mothers who had smoked had a handicap additional to visual impairment and were affected by at least one malformation.
Prenatal Period Prenatal disorders occurred in 89 cases (71%) of the infants born preterm, being more common in premature children than in children born at full term (P ⫽ 0.001; Table 1). Occurrence of a prenatal disorder did not correlate with the severity of visual impairment or the incidence of additional handicap.
Perinatal Period Thirty-seven of the 125 preterm births (30%) were by Cesarean section. This corresponds to the regular level in relation to premature births. The percentage in relation to all labors was 14%.4 Neonatal morbidity was high. Half of the infants had birth asphyxia according to low 5-minute Apgar scores (Table 1). Low 5-minute Apgar scores were most common in children with cerebral amblyopia (67%) and ROP (60%). Postnatal treatment of the preterm infants included mechanical ventilation (n ⫽ 61 [49%]), exchange blood transfusion (n ⫽ 17; [14%]), and surgery for patent ductus arteriosus (n ⫽ 6; [5%]), for hydrocephalus (n ⫽ 13; [10%]), and for other reasons (n ⫽ 5; [4%]).
Rudanko et al 䡠 Visual Impairment in Premature Children Table 1. Differences in the Incidences of Prenatal and Neonatal Disorders between Children Born Prematurely and Children Born at Full Term in Finland from 1972 through 1989
Prenatal and Neonatal Disorders
Premature (%)
Full term (%)
MantelHaenszel P Value
Pregnancies with prenatal disorders Multifetal pregnancy Infection Uterine hemorrhage Placental disorders Infants with neonatal disorders Birth asphyxia Respiratory disorders Hypoglycemia Infection Hyperbilirubinemia Cerebral hemorrhage
71 9 27 20 13 89 50 74 10 26 26 22
36 3 12 6 4 33 2 9 3 7 4 3
0.001 0.008 0.001 0.004 0.003 0.001 ⬍0.001 0.001 0.002 0.001 0.001 0.001
Table 2. Differences in the Conditions Present in Children Born Prematurely and at Full Term in Finland from 1972 through 1989 (Bivariate Analyses)
Parameters
Premature (%)
Full-term (%)
MantelHaenszel P Value
46 28 12 0 4 26 18 64 54 36 66
0 20 6 26 13 50 38 43 18 19 45
0.001 0.048 0.049 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001
70
40
0.001
Diagnoses associated with visual impairment ROP Optic atrophy Cerebral amblyopia Retinal dystrophy Congenital cataract Congenital malformations, all Ocular malformation Neurological sequelae Cerebral palsy Epilepsy Handicap other than visual impairment Blindness ROP ⫽ retinopathy of prematurity.
Ophthalmologic operations were carried out on 28 of the 125 children born prematurely (22%). Retinal cryotherapy was undertaken in 11 cases. The operation was for congenital cataract in six cases, congenital glaucoma in three cases, retinal detachment in seven cases, and ptotic eyelids in a single case. Cryotherapy was performed for ROP in nine cases and for complications of congenital cataract and persistent hyperplastic primary vitreous in a single case each. All cryotherapy occurred in the 1980s, in 8 of the 11 cases (73%) in the latter half of the 1980s.
Parameters Related to General Infant Health Ocular malformation was much rarer in the children born prematurely with visual impairment than in the full-term children with visual impairment. Neurologic sequelae and existence of other handicap were considerably more common in the children born prematurely (Table 2). Motor impairment developed in 69 (55%), mental impairment in 66 (53%), and both in 44 (35%) of the children born prematurely. Hearing was affected in nine children (6%).
Visual Impairment and Ophthalmologic Diagnoses Blindness was significantly more common in the children born prematurely (Table 2), and in male (50/125; 58%) than in female children (37/125; 42%). Blindness was most common in infants with extremely low birth weight (⬍1000 g; Table 3). Visual impairment developed before birth in 26 cases (21%) and was related to the prematurity itself in 99 cases (79%). Most of the ophthalmic disease in the children born prematurely was retinal and neuro-ophthalmologic (Table 4). The risk factors primarily associated with visual impairment in the children born prematurely were very low birth weight (⬍1500 g; P ⫽ 0.001) and low gestational age (⬍30 weeks; P ⫽ 0.007). Other factors found by means of logistic regression analysis to be significantly associated with visual impairment in the prematurely born children were occurrence of respiratory disorders (odds ratio [OR], 8.96; 95% confidence interval [CI], 4.91–16.43; P ⬍ 0.001), hyperbilirubinemia (OR, 6.40; CI, 2.60 –15.73; P ⬍ 0.001), birth asphyxia (OR, 3.82; CI, 2.10 – 6.95; P ⬍ 0.001), prenatal infection (OR, 2.15; CI, 1.05– 4.40; P ⬍ 0.05), and duration of mechanical ventilation (P ⬍ 0.05). Retinopathy of prematurity was significantly more common when mechanical ventilation continued for more than 2 weeks (Mann–Whitney U test).
Table 3. Visual Impairment (World Health Organization Categories) in Children Born Preterm in Finland from 1972 through 1989, by Birth Weight (International Classification of Diseases, World Health Organization, 1980) Birth Weight ⬍1000 g (n ⫽ 31; 25%)
1000–1499 g (n ⫽ 37; 30%)
Categories of Visual Impairment
n
%
n
%
n
%
n
%
WHO 1 (moderate; VA, ⬍6/18–6/60) WHO 2 (severe; VA, ⬍6/60–3/60) WHO 3 (profound; VA, ⬍3/60–1/60) WHO 4 (nearly blind; VA, ⬍1/60– LP) WHO 5 (blind; NLP) WHO 9 (blind; unknown degree) Low vision (WHO 1–2) Blind (WHO 3–5 and 9) All categories
3 0 0 13
10 0 0 42
7 3 3 12
19 8 8 32
22 3 8 8
39 5 14 14
32 6 11 33
26 5 9 26
12 3 3 28 31
38 10 10 90 100
8 4 10 27 37
22 11 27 73 100
4 12 25 32 57
7 21 44 56 100
24 19 38 87 125
19 15 30 70 100
1500 g or more (n ⫽ 57; 45%)
All Birthweights (n ⫽ 125; 100%)
LP ⫽ light perception; NLP ⫽ no light perception; VA ⫽ visual acuity; WHO ⫽ World Health Organization.
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Ophthalmology Volume 110, Number 8, August 2003 Table 4. Main Diagnosis, Handicaps Other than Visual Impairment and Blindness in Children Born Preterm in Finland from 1972 through 1989 in Relation to Birth Weight Birth Weight ⬍1000 g (n ⫽ 31; 25%)
1000–1499 g (n ⫽ 37; 30%)
1500 g or more (n ⫽ 57; 45%)
All Birthweights (n ⫽ 125; 100%)
Parameters
n
%
n
%
n
%
n
%
All ophthalmic diagnoses ROP Optic nerve atrophy Cerebral amblyopia Cataract, congenital Other ophthalmic diagnoses Cerebral palsy Epilepsy Multiple handicap Blindness
31 30 1 0 0 0 8 7 15 28
100 97 3 0 0 0 26 23 48 90
37 21 7 5 2 2 20 10 23 27
100 56 19 14 5 6 54 27 62 73
57 6 27 10 3 11 39 28 45 32
100 11 47 18 5 19 68 49 79 56
125 57 35 15 5 13 67 45 83 87
100 46 28 12 4 10 54 36 66 70
ROP ⫽ retinopathy of prematurity.
In all of the infants born at less than 26 gestational weeks (n ⫽ 9), ROP developed, but in none of the infants (n ⫽ 34) born after 32 gestational weeks did it develop (Fig 1). The correlation of gestational weeks categorized in this way was negative in relation to the other ophthalmic conditions, neurologic sequelae, and occurrence of handicap other than visual impairment in the children born prematurely. Cryotherapy was undertaken in 9 of 57 children with ROP (16%), and the remaining 48 of 57 children (84%) were left untreated. Of the 48 not treated, 40 (83%) were blind. Of the nine children with ROP who underwent cryotherapy, eight (89%) were blind and one was partially sighted.
Incidence and Nature of Visual Impairment in Infants Born Prematurely from 1972 through 1989 The prevalence of visually impaired children born prematurely in the Finnish population of the corresponding age (n ⫽ 1,138,326) was 11 in 100,000 children. The corresponding statistics for ROP, optic atrophy, and cerebral amblyopia were 5, 3, and 1, respectively. The mean annual incidence of preterm children with visual impairment did not change between the 1970s and 1980s, with the exception of a relative increase in prematurely born blind children. Preterm children with different diagnoses of visual impairment differed markedly in other respects, too (Table 5).
Discussion
Figure 1. Main ophthalmologic diagnoses in visually impaired preterm children by gestational age.
Twenty-three percent of visually impaired children in the population studied were born prematurely. The incidence of visual impairment among prematurely born children was at the same level as in other Nordic countries except Denmark, where a higher incidence has been recorded.5 The incidence of visual impairment was higher in male infants, as previously reported.6
Table 5. Characteristic Findings and Conditions Discovered in Preterm Children with Visual Impairment Born in Finland from 1972 through 1989 Diagnoses
Parameters
Retinopathy of Prematurity (n ⫽ 57)
Optic Atrophy (n ⫽ 35)
Cerebral Amblyopia (n ⫽ 15)
All diagnoses (n ⫽ 125)
Prevalence of visual impairment for 100,000 children Blindness (%) Male-to-female ratio Median gestational age (wks) Median birthweight (g) Low 5-minute Apgar score 0–6 (%) Mechanical ventilation (%) Cerebral palsy (%) Epilepsy (%) Multiple handicap (%)
5 83 1.11 27 930 60 70 26 12 46
3 66 2.18 32 1850 34 37 94 69 97
1 80 1.14 33 1850 67 47 100 73 100
11 70 1.44 30 1360 50 49 54 36 66
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Rudanko et al 䡠 Visual Impairment in Premature Children Prenatal and perinatal disorders were common in the children born prematurely. Prenatal maternal infection, for example, bacterial vaginosis or urinary infection, may have triggered some of the preterm births and consequently created a risk of visual impairment and other disability. Neonatal morbidity was substantial, and most of the infants born prematurely had risk factors (i.e., respiratory disorders, birth asphyxia, and hyperbilirubinemia) for brain damage and retinopathy. Retinopathy of prematurity, optic atrophy, and cerebral amblyopia were the main diagnoses associated with visual impairment in the children born prematurely. Retinopathy of prematurity was the most common diagnosis in relation to the smallest and most immature newborn children. Apart from ROP, the proportion of neuro-ophthalmologic disease (40%) with high occurrence of blindness, cerebral palsy, epilepsy, and multiple handicap was noteworthy. The relationship between optic atrophy and cerebral amblyopia may not reflect reality, because cerebral amblyopia was not a diagnostic term in general use at the time, and some cases that now would be so categorized might have been classed as instances of optic atrophy. What causes ROP is not yet fully understood. Apart from immaturity, several factors have been found to be associated with ROP. These factors mainly are involved in a chain reaction of hypoxia, reperfusion, hyperoxia, and ischemia.7–9 In this study, mechanical ventilation was found to be associated with ROP, although treatment for two weeks was found to be relatively safe. Ja¨ rvenpa¨ a¨ et al10 (1991) in Finland and Friedman et al11 (2000) in the United States have reported that oxygen therapy for more than 30 days was associated with ROP. Teoh et al12 (1995) in Malaysia calculated that every day in a ventilator increases risk of ROP by 1.156 times, and that oxygen therapy for more than 30 days results in a more than 90% chance of ROP. However, modern neonatal intensive care, including surfactant treatment, has altered considerably the need for mechanical ventilation. Results from the presurfactant era therefore may have little relevance to current circumstances. In the 1970s and 1980s, the incidence of ROP stage 3 to 5 varied between 2.5% to 20%, and the rate of severe visual impairment or blindness ranged between 2.5% to 10% in the Nordic preterm population with very low birthweight (⬍1500 g).13–15 Threshold ROP was rare in those born weighing ⬎1500 g, as we also found. Retinopathy of prematurity was diagnosed in this study only in 0.01% of children born prematurely weighing ⬎1500 g. For those born weighing ⬍1500 g, the corresponding percentage was 8%, and for those born weighing less than 1000 g, it was 11%. These percentages are lower than those reported in several other studies; for example, 30% in relation to children born at the end of the 1970s in the United States weighing ⬍1000 g, 26% in relation to children born between 1977 and 1984 in Australia weighing ⬍1000 g, and 18% in relation to children born between 1985 and 1992 in Australia weighing ⬍1000 g.16,17 In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity carried out in the United States from 1986 to 1987, threshold ROP affected 9% of infants born weighing ⬍1000 g.18 The introduction of ocular cryotherapy in 1972 and,
subsequently, retinal laser therapy have improved markedly the prognosis in cases of ROP in general. The improvement has been most marked from the 1980s onward.19 –23 A screening program for ROP (A Joint Statement of the American Academy of Pediatrics, the American Association for Pediatric Ophthalmology and Strabismus, and the American Academy of Ophthalmology) was adopted in Finland in the mid-1980s for children born weighing ⬍1500 g and children born at gestational age less than 30 to 34 weeks. The recommendations were also modified further. For example, threshold ROP had to be treated within 72 hours of diagnosis. A reduction in unfavorable outcome in cases of ROP of some 50% was seen. By the end of the 1980s, it was possible theoretically, by means of cryotherapy and laser therapy, to prevent progression of threshold ROP to stages 4 to 5 in more than 75% of cases. During the 1990s, further improvement of cryotherapy and laser therapy has led to success rates exceeding 90%, even in cases of severe posterior ROP. Results of vitreoretinal surgery for stages 4 to 5 have, however, remained poor.24,25 However, this study covered the most severe recorded cases of visual impairment. Only 9 of 57 children (16%) with ROP had been treated with cryotherapy, and one of them was saved from blindness. Cortical cells and other central visual pathways are especially vulnerable to acidosis and hypoxia during their intensive development between the sixth and eighth months of gestation, and in the perinatal period in cases of preterm birth. Cerebral injuries leading to hydrocephalus, periventricular leukomalacia, cerebral palsy, epilepsy, and other neurologic sequelae correlate with the degree of infant immaturity and metabolic activity at birth.3,26 Those injuries are more common causes of severe visual impairment accompanied by cognitive and motor disabilities than generally assumed. In a Swedish study, brain malformations and hypoxic–ischemic encephalopathy were the main causes of visual deficits in children born prematurely and screened for ROP.27 In Finland, periventricular leukomalacia was found in 32% of infants of birth weight ⬍1750 g.28 In this study, the incidence of neuro-ophthalmologic visual impairment was notably high (40%). During the 1990s, according to the Register of Visual Impairment, it was even higher (56%).29 There was no decrease in the incidence of visual impairment associated with prematurity in Finland from the 1970s through the 1980s. Retinopathy of prematurity was by far the most common diagnosis in cases of visual impairment and blindness associated with premature birth. Its incidence increased as the consequence of higher survival of infants of extremely low birth weight. The pattern has been similar in other countries.30 No reduction in incidences of ROP and severity of forms of visual impairment was reported in relation to Finland until the 1990s. Records relating to children with extremely low birth weight born between 1996 and 1997 were studied by Tommiska et al (2001).31 Retinopathy of prematurity was found only in infants born at gestational age less than 28 weeks. Retinopathy of prematurity of stages 3 to 5 was recorded in 19 of 211 children (9%). Two children with extremely low birth weight born in Finland during this period (gestational age, 25 weeks; birth weight, 880 g; and gestational age, 24 weeks; birth weight,
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Ophthalmology Volume 110, Number 8, August 2003 710 g) are recorded in the Finnish Register of Visual Impairment. This corresponds to an incidence of visual impairment associated with a diagnosis of ROP of 4% to 9% in 536 children with extremely low birth weight born in Finland (Finnish Perinatal Statistics), lower than the 11% for the 1970s and 1980s. The data from the 1990s in the Finnish Register of Visual impairment reveals a marked change in the incidence and characteristics of visual impairment in children born prematurely.29 The percentage of children born prematurely with visual impairment increased in the 1990s, but the percentage of children born prematurely who were blind remained at the level it was in the 1980s. Retinopathy of prematurity became a less common diagnosis in relation to visual impairment or blindness (35% of cases). The severity of ROPrelated visual impairment also decreased. Neuro-ophthalmologic disease became the most common disorder in relation to children born prematurely and visually impaired (56% of cases). The causes of prematurity and factors associated with it are not thoroughly understood, and the prevention of preterm birth itself has been difficult. However, rapid improvement in perinatal care has resulted in a higher survival of children with extremely low birth weight. Concern has been expressed about whether this is resulting in increases in incidences of disability.32 This study provides baseline information about visual impairment in children born prematurely before the surfactant period, when laser therapy of ROP was also uncommon. Compared with the results from 1996 and 1997 and with several other reports from industrialized countries, the risk of ROP appears to have decreased since the 1980s, despite the increase in survival rates of premature infants.33–36 However, the results of this study indicate that higher survival rates in relation to preterm children are associated with higher incidences of children with optic nerve atrophy, cerebral visual impairment, severe neurologic sequelae, and multiple handicap. More epidemiologic studies are needed to determine the success of attempts to prevent retinopathy and lesions in central visual pathways. Data in national registers of visual impairment are therefore very valuable and need to be assessed in combination with data from other registers. Reliable national registers are crucial in this connection.
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5. Rosenberg T, Flage T, Hansen E, et al. Visual impairment in Nordic children. II. Aetiological factors. Acta Ophthalmol (Copenh) 1992;70:155– 64. 6. Riise R, Flage T, Hansen E, et al. Visual impairment in Nordic children. IV. Sex distribution. Acta Ophthalmol (Copenh) 1992;70:605–9. 7. Prendiville A, Schulenburg WE. Clinical factors associated with retinopathy of prematurity. Arch Dis Child 1988;63: 522–7. 8. Flynn JT, Bancalari E, Snyder ES, et al. A cohort study of transcutaneous oxygen tension and the incidence and severity of retinopathy of prematurity. New Engl J Med 1992;16: 1050 – 4. 9. Gallo JE, Jacobson L, Broberger U. Perinatal factors associated with retinopathy of prematurity. Acta Paediatr 1993;82: 829 –34. 10. Ja¨ rvenpa¨ a¨ AL, Virtanen M, Pohjavuori M. The outcome of extremely low birthweight infants. Ann Med 1991;23:699 – 704. 11. Friedman CA, McVey J, Borne MJ, et al. Relationship between serum inositol concentration and development of retinopathy of prematurity: a prospective study. J Pediatr Ophthalmol Strabismus 2000;37:79 – 86. 12. Teoh SL, Boo NY, Ong LC, et al. Duration of oxygen therapy and exchange transfusion as risk factors associated with retinopathy of prematurity in very low birthweight infants. Eye 1995;9:733–7. 13. Gallo JE, Holmstro¨ m G, Kugelberg U, et al. Regressed retinopathy of prematurity in children aged 5–10 years. Acta Ophthalmol Suppl 1993;210:41–3. 14. Barnekow BB, Stigmar G. Retinopathy of prematurity in the southern part of Sweden. Acta Ophthalmol Suppl 1993;210: 48 –51. 15. Holmstro¨ m G, el Azazi M, Jacobson L, Lennerstrand G. A population based, prospective study of the development of ROP in prematurely born children in the Stockholm area of Sweden. Br J Ophthalmol 1993;77:417–23. 16. Phelps DL. Vision loss due to retinopathy of prematurity [letter]. Lancet 1981;1:606. 17. Keith CG, Doyle LW. Retinopathy of prematurity in extremely low birth weight infants. Pediatrics 1995;1:42–5. 18. Palmer EA, Flynn JT, Hardy RJ, et al. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Incidence and early course of retinopathy of prematurity. Ophthalmology 1991;98:1628 – 40. 19. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. Ophthalmological outcomes at 10 years. Arch Ophthalmol 2001;119:1110 – 8. 20. Laatikainen L, Mattila J, Ka¨ rna¨ J. Combined use of argon laser photocoagulation and cryotherapy in the treatment of retinopathy of prematurity. Acta Ophthalmol Scand 1995;73:333–5. 21. The Laser ROP Study Group. Laser therapy for retinopathy of prematurity [letter]. Arch Ophthalmol 1994;112:154 – 6. 22. Noonan CP, Clark DI. Trends in the management of stage 3 retinopathy of prematurity. Br J Ophthalmol 1996;80:278 – 81. 23. Foroozan R, Connolly BP, Tasman WS. Outcomes after laser therapy for threshold retinopathy of prematurity. Ophthalmology 2001;108:1644 – 6. 24. Seaber JH, Machemer R, Eliott D, et al. Long-term visual results of children after initially successful vitrectomy for stage V retinopathy of prematurity. Ophthalmology 1995;102: 199 –204. 25. Knight-Nanan DM, Algawi K, Bowell R, O’Keefe M. Advanced cicatricial retinopathy of prematurity— outcome and complications. Br J Ophthalmol 1996;80:343–5.
Rudanko et al 䡠 Visual Impairment in Premature Children 26. Brodsky MC, Fray KJ, Glasier CM. Perinatal cortical and subcortical visual loss. Mechanisms of injury and associated ophthalmologic signs. Ophthalmology 2002;109:85–94. 27. Jacobson L, Lundin S, Flodmark O, Ellstro¨ m KG. Periventricular leukomalacia causes visual impairment in preterm children. A study on the aetiologies of visual impairment in a population-based group of preterm children born 1989 –95 in the county of Va¨ rmland, Sweden. Acta Ophthalmol Scand 1998;76:593– 8. 28. Olsen P, Pa¨ a¨ kko¨ E, Vainionpa¨ a¨ L, et al. Magnetic resonance imaging of periventricular leukomalacia and its clinical correlation in children. Ann Neurol 1997;41:754 – 61. 29. Ojamo M. The Finnish Register of Visual Impairment. Annual Statistics 2000. Helsinki: National Research and Development Centre for Welfare and Health in Finland (Stakes), 2001. 30. Valentine PH, Jackson JC, Kalina RE, Woodrum DE. Increased survival of low birth weight infants: impact on the incidence of retinopathy of prematurity. Pediatrics 1989;84:442–5.
31. Tommiska V, Heinonen K, Ikonen S, et al. A national shortterm follow-up study of extremely low birth weight infants born in Finland in 1996 –1997. Pediatrics 2001;107:1–9. 32. Gilbert C. Retinopathy of prematurity—the “second lull” [letter]? Br J Ophthalmol 2001;85:1017–9. 33. Fledelius HC. Retinopathy of prematurity in a Danish county. Trends over the 12-year period 1982–93. Acta Ophthalmol Scand 1996;74:285–7. 34. O’Shea TM, Klinepeter KL, Goldstein DJ, et al. Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994. Pediatrics 1997; 100:982– 6. 35. Hussain N, Clive J, Bhandari V. Current incidence of retinopathy of prematurity, 1989 –1997. Pediatrics [serial online] 1999;104:e26. Available at http://www.pediatrics.org/cgi/content/ full/104/3/e26. Accessed July 17, 2002. 36. Rowlands E, Ionides ACW, Chinn S, et al. Reduced incidence of retinopathy of prematurity. Br J Ophthalmol 2001;85:933–5.
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Developments in obstetrics and neonatal care over the last three decades have improved markedly the outcome in cases of premature birth and have increased the incidence of survival of very immature infants. The incidence of premature birth declined in Finland from 9% in the 1960s to 5% by the end of the 1980s, despite higher survival rates of
Originally received: August 8, 2002. Accepted: December 24, 2002. Manuscript no. 220545. 1 The Finnish Register of Visual Impairment, Finnish National Agency for Welfare and Health, Helsinki, Finland. 2 Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland. 3 Department of Ophthalmology, University of Helsinki, Helsinki, Finland. The authors have no proprietary interest in any material used in this study. Reprint requests to Sirkka-Liisa Rudanko, MD, The Finnish Register of Visual Impairment, Ma¨kela¨nkatu 50, 00510, Helsinki, Finland. © 2003 by the American Academy of Ophthalmology Published by Elsevier Inc.
extremely immature infants.1 Changes relating to visual impairment in childhood therefore were to be expected. Establishment of the Finnish Register of Visual Impairment in 1983 allowed collection of data relating to visual impairment in Finnish children. The aim of this study was to investigate the incidence, characteristics, causes, and risk factors of visual impairment in Finnish children born prematurely and at full-term from 1972 through 1989 using data from the Finnish Register of Visual Impairment. These data were also compared with data relating to children born prematurely with visual impairment in the 1990s.
Patients and Methods The data for children with visual impairment was obtained from the Finnish Register of Visual Impairment, which collects reports from ophthalmologists beginning in 1983 and records persons with ISSN 0161-6420/03/$–see front matter doi:10.1016/S0161-6420(03)00498-6
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Ophthalmology Volume 110, Number 8, August 2003 visual impairment at any age when so discovered. Data for a total of 556 visually impaired children less than 18 years of age were filed in the Finnish Register of Visual Impairment at the end of 1989. Their age at registration varied from a few months to 17 years. The main parameters included in the register data were the cause of visual impairment, associated ophthalmic and systemic conditions, other handicaps (mental, motor, auditory), age at onset of visual impairment, visual acuity, and visual fields. The data were supplemented by data from hospital records relating to the visually impaired children and their mothers and by data from other national registers (Register of Births, Register of Congenital Malformations, Finnish Care Register, Finnish Cancer Register). The data covered the period from fetal life to childhood.
Prenatal Period Data relating to maternal age; medical examinations undergone (e.g., ultrasonography, radiographs, magnetic resonance imaging, amnioscopy, fetoscopy, amniocentesis, amniotic fluid analysis); maternal disease; medication; operations; trauma; use of alcohol, tobacco, and drugs; pregnancy disorders and complications; multifetal pregnancies; and unusual status of fetal presentation or of birth canal were recorded. All prenatal diagnoses recorded by the physicians responsible for medical treatment of the pregnant women were noted.
Perinatal Period Data relating to method of delivery, gestational age (defined on the basis of the last menstrual period and confirmed by clinical evaluation of early uterine size), birth weight, perinatal complications, neonatal disease, congenital malformations, and major treatments and procedures were recorded. The traditional criterion for prematurity, gestational age less than 37 weeks, was used. Asphyxia was defined as a 5-minute Apgar score of 0 to 6. All perinatal diagnoses recorded by the physicians responsible for obstetric and neonatal treatment were noted.
Children’s Health after the Perinatal Period Data relating to other impairments; ophthalmic operations for cataract, glaucoma, retinal detachment, or other conditions; and retinal cryotherapy were recorded. Diagnoses of retinopathy of prematurity (ROP), optic atrophy, and other ophthalmic disorders were obtained from hospital records. Cause of visual impairment, diagnoses, and multiple handicaps were coded according to the system devised by the Nordsyn Study Group.2 Cerebral amblyopia was the diagnosis in cases in which cerebral lesions affected posterior visual pathways, cortical areas, or both and the ocular pathologic features did not explain the visual impairment.3 Visual impairment was classified according to the categories of the World Health Organization International Classification of Diseases (1980). Children with unspecified degree of remaining vision were placed in World Health Organization category 9 and classified as blind. Corresponding data in the Finnish Register of Visual Impairment relating to all 431 visually impaired children born at full-term from 1972 through 1989 had been collected by the first author for another paper (Rudanko et al, 2002, in preparation) and was used for comparative statistical analysis.
Analysis and Statistical Methods SAS for Windows version 6.12 (SAS Institute Inc., Finland) was used for data analysis. Significant bivariate variables for risk factor
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determinations of visual impairment were determined using the chi-square test (Mantel-Haenszel), the Mann–Whitney U test, and Fisher’s exact test. Variables independently associated with visual impairment were analyzed further by stepwise logistic regression analysis.
Results Demographic Data Relating to Children Born Prematurely Of the 556 visually impaired children, 125 (23%) were born preterm. Seventy-three of the latter (58%) were male; 52 (42%) were female. The male-to-female ratio (1.44) was higher than that for the Finnish newborn population in general (1.05; P ⬍ 0.001) but does not differ significantly from that for the children born at full-term with visual impairment (1.68). Gestational age ranged from 23 to 36 weeks (median, 29 weeks), and birth weight ranged from 570 to 3820 g (median, 1360 g). Almost half (59/125) of the infants born preterm (47%) were of gestational age of less than 30 weeks. Sixty-eight of the 125 (55%) weighed less than 1500 g at birth (very low birth weight), and 31 (25%) weighed less than 1000 g at birth (extremely low birth weight). Fifteen of the 125 (12%) weighed 2500 g or more at birth. Eight were large for their gestational age.
Maternal Factors Related to Prematurity The percentages for young (less than 20 years; n ⫽ 27 [22%]) and older (more than 35 years; n ⫽ 42 [34%]) mothers of children born preterm differed considerably from the corresponding percentages for all women who gave birth in Finland (young mothers, 3%; older mothers, 13%). Only a few of the mothers had systemic disease during pregnancy. Three had diabetes mellitus, one had alcoholism, and one had a benign ovarian tumor. Thirty-six of the mothers had an infection during pregnancy. Medications (mainly antibiotics) during pregnancy were used by 15 of the mothers. The information on smoking (n ⫽ 5) and use of alcohol (n ⫽ 2) during pregnancy was self-reported, and it was assumed that more mothers fell into each of the two categories. All of the children of the mothers who had smoked had a handicap additional to visual impairment and were affected by at least one malformation.
Prenatal Period Prenatal disorders occurred in 89 cases (71%) of the infants born preterm, being more common in premature children than in children born at full term (P ⫽ 0.001; Table 1). Occurrence of a prenatal disorder did not correlate with the severity of visual impairment or the incidence of additional handicap.
Perinatal Period Thirty-seven of the 125 preterm births (30%) were by Cesarean section. This corresponds to the regular level in relation to premature births. The percentage in relation to all labors was 14%.4 Neonatal morbidity was high. Half of the infants had birth asphyxia according to low 5-minute Apgar scores (Table 1). Low 5-minute Apgar scores were most common in children with cerebral amblyopia (67%) and ROP (60%). Postnatal treatment of the preterm infants included mechanical ventilation (n ⫽ 61 [49%]), exchange blood transfusion (n ⫽ 17; [14%]), and surgery for patent ductus arteriosus (n ⫽ 6; [5%]), for hydrocephalus (n ⫽ 13; [10%]), and for other reasons (n ⫽ 5; [4%]).
Rudanko et al 䡠 Visual Impairment in Premature Children Table 1. Differences in the Incidences of Prenatal and Neonatal Disorders between Children Born Prematurely and Children Born at Full Term in Finland from 1972 through 1989
Prenatal and Neonatal Disorders
Premature (%)
Full term (%)
MantelHaenszel P Value
Pregnancies with prenatal disorders Multifetal pregnancy Infection Uterine hemorrhage Placental disorders Infants with neonatal disorders Birth asphyxia Respiratory disorders Hypoglycemia Infection Hyperbilirubinemia Cerebral hemorrhage
71 9 27 20 13 89 50 74 10 26 26 22
36 3 12 6 4 33 2 9 3 7 4 3
0.001 0.008 0.001 0.004 0.003 0.001 ⬍0.001 0.001 0.002 0.001 0.001 0.001
Table 2. Differences in the Conditions Present in Children Born Prematurely and at Full Term in Finland from 1972 through 1989 (Bivariate Analyses)
Parameters
Premature (%)
Full-term (%)
MantelHaenszel P Value
46 28 12 0 4 26 18 64 54 36 66
0 20 6 26 13 50 38 43 18 19 45
0.001 0.048 0.049 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001
70
40
0.001
Diagnoses associated with visual impairment ROP Optic atrophy Cerebral amblyopia Retinal dystrophy Congenital cataract Congenital malformations, all Ocular malformation Neurological sequelae Cerebral palsy Epilepsy Handicap other than visual impairment Blindness ROP ⫽ retinopathy of prematurity.
Ophthalmologic operations were carried out on 28 of the 125 children born prematurely (22%). Retinal cryotherapy was undertaken in 11 cases. The operation was for congenital cataract in six cases, congenital glaucoma in three cases, retinal detachment in seven cases, and ptotic eyelids in a single case. Cryotherapy was performed for ROP in nine cases and for complications of congenital cataract and persistent hyperplastic primary vitreous in a single case each. All cryotherapy occurred in the 1980s, in 8 of the 11 cases (73%) in the latter half of the 1980s.
Parameters Related to General Infant Health Ocular malformation was much rarer in the children born prematurely with visual impairment than in the full-term children with visual impairment. Neurologic sequelae and existence of other handicap were considerably more common in the children born prematurely (Table 2). Motor impairment developed in 69 (55%), mental impairment in 66 (53%), and both in 44 (35%) of the children born prematurely. Hearing was affected in nine children (6%).
Visual Impairment and Ophthalmologic Diagnoses Blindness was significantly more common in the children born prematurely (Table 2), and in male (50/125; 58%) than in female children (37/125; 42%). Blindness was most common in infants with extremely low birth weight (⬍1000 g; Table 3). Visual impairment developed before birth in 26 cases (21%) and was related to the prematurity itself in 99 cases (79%). Most of the ophthalmic disease in the children born prematurely was retinal and neuro-ophthalmologic (Table 4). The risk factors primarily associated with visual impairment in the children born prematurely were very low birth weight (⬍1500 g; P ⫽ 0.001) and low gestational age (⬍30 weeks; P ⫽ 0.007). Other factors found by means of logistic regression analysis to be significantly associated with visual impairment in the prematurely born children were occurrence of respiratory disorders (odds ratio [OR], 8.96; 95% confidence interval [CI], 4.91–16.43; P ⬍ 0.001), hyperbilirubinemia (OR, 6.40; CI, 2.60 –15.73; P ⬍ 0.001), birth asphyxia (OR, 3.82; CI, 2.10 – 6.95; P ⬍ 0.001), prenatal infection (OR, 2.15; CI, 1.05– 4.40; P ⬍ 0.05), and duration of mechanical ventilation (P ⬍ 0.05). Retinopathy of prematurity was significantly more common when mechanical ventilation continued for more than 2 weeks (Mann–Whitney U test).
Table 3. Visual Impairment (World Health Organization Categories) in Children Born Preterm in Finland from 1972 through 1989, by Birth Weight (International Classification of Diseases, World Health Organization, 1980) Birth Weight ⬍1000 g (n ⫽ 31; 25%)
1000–1499 g (n ⫽ 37; 30%)
Categories of Visual Impairment
n
%
n
%
n
%
n
%
WHO 1 (moderate; VA, ⬍6/18–6/60) WHO 2 (severe; VA, ⬍6/60–3/60) WHO 3 (profound; VA, ⬍3/60–1/60) WHO 4 (nearly blind; VA, ⬍1/60– LP) WHO 5 (blind; NLP) WHO 9 (blind; unknown degree) Low vision (WHO 1–2) Blind (WHO 3–5 and 9) All categories
3 0 0 13
10 0 0 42
7 3 3 12
19 8 8 32
22 3 8 8
39 5 14 14
32 6 11 33
26 5 9 26
12 3 3 28 31
38 10 10 90 100
8 4 10 27 37
22 11 27 73 100
4 12 25 32 57
7 21 44 56 100
24 19 38 87 125
19 15 30 70 100
1500 g or more (n ⫽ 57; 45%)
All Birthweights (n ⫽ 125; 100%)
LP ⫽ light perception; NLP ⫽ no light perception; VA ⫽ visual acuity; WHO ⫽ World Health Organization.
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Ophthalmology Volume 110, Number 8, August 2003 Table 4. Main Diagnosis, Handicaps Other than Visual Impairment and Blindness in Children Born Preterm in Finland from 1972 through 1989 in Relation to Birth Weight Birth Weight ⬍1000 g (n ⫽ 31; 25%)
1000–1499 g (n ⫽ 37; 30%)
1500 g or more (n ⫽ 57; 45%)
All Birthweights (n ⫽ 125; 100%)
Parameters
n
%
n
%
n
%
n
%
All ophthalmic diagnoses ROP Optic nerve atrophy Cerebral amblyopia Cataract, congenital Other ophthalmic diagnoses Cerebral palsy Epilepsy Multiple handicap Blindness
31 30 1 0 0 0 8 7 15 28
100 97 3 0 0 0 26 23 48 90
37 21 7 5 2 2 20 10 23 27
100 56 19 14 5 6 54 27 62 73
57 6 27 10 3 11 39 28 45 32
100 11 47 18 5 19 68 49 79 56
125 57 35 15 5 13 67 45 83 87
100 46 28 12 4 10 54 36 66 70
ROP ⫽ retinopathy of prematurity.
In all of the infants born at less than 26 gestational weeks (n ⫽ 9), ROP developed, but in none of the infants (n ⫽ 34) born after 32 gestational weeks did it develop (Fig 1). The correlation of gestational weeks categorized in this way was negative in relation to the other ophthalmic conditions, neurologic sequelae, and occurrence of handicap other than visual impairment in the children born prematurely. Cryotherapy was undertaken in 9 of 57 children with ROP (16%), and the remaining 48 of 57 children (84%) were left untreated. Of the 48 not treated, 40 (83%) were blind. Of the nine children with ROP who underwent cryotherapy, eight (89%) were blind and one was partially sighted.
Incidence and Nature of Visual Impairment in Infants Born Prematurely from 1972 through 1989 The prevalence of visually impaired children born prematurely in the Finnish population of the corresponding age (n ⫽ 1,138,326) was 11 in 100,000 children. The corresponding statistics for ROP, optic atrophy, and cerebral amblyopia were 5, 3, and 1, respectively. The mean annual incidence of preterm children with visual impairment did not change between the 1970s and 1980s, with the exception of a relative increase in prematurely born blind children. Preterm children with different diagnoses of visual impairment differed markedly in other respects, too (Table 5).
Discussion
Figure 1. Main ophthalmologic diagnoses in visually impaired preterm children by gestational age.
Twenty-three percent of visually impaired children in the population studied were born prematurely. The incidence of visual impairment among prematurely born children was at the same level as in other Nordic countries except Denmark, where a higher incidence has been recorded.5 The incidence of visual impairment was higher in male infants, as previously reported.6
Table 5. Characteristic Findings and Conditions Discovered in Preterm Children with Visual Impairment Born in Finland from 1972 through 1989 Diagnoses
Parameters
Retinopathy of Prematurity (n ⫽ 57)
Optic Atrophy (n ⫽ 35)
Cerebral Amblyopia (n ⫽ 15)
All diagnoses (n ⫽ 125)
Prevalence of visual impairment for 100,000 children Blindness (%) Male-to-female ratio Median gestational age (wks) Median birthweight (g) Low 5-minute Apgar score 0–6 (%) Mechanical ventilation (%) Cerebral palsy (%) Epilepsy (%) Multiple handicap (%)
5 83 1.11 27 930 60 70 26 12 46
3 66 2.18 32 1850 34 37 94 69 97
1 80 1.14 33 1850 67 47 100 73 100
11 70 1.44 30 1360 50 49 54 36 66
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Rudanko et al 䡠 Visual Impairment in Premature Children Prenatal and perinatal disorders were common in the children born prematurely. Prenatal maternal infection, for example, bacterial vaginosis or urinary infection, may have triggered some of the preterm births and consequently created a risk of visual impairment and other disability. Neonatal morbidity was substantial, and most of the infants born prematurely had risk factors (i.e., respiratory disorders, birth asphyxia, and hyperbilirubinemia) for brain damage and retinopathy. Retinopathy of prematurity, optic atrophy, and cerebral amblyopia were the main diagnoses associated with visual impairment in the children born prematurely. Retinopathy of prematurity was the most common diagnosis in relation to the smallest and most immature newborn children. Apart from ROP, the proportion of neuro-ophthalmologic disease (40%) with high occurrence of blindness, cerebral palsy, epilepsy, and multiple handicap was noteworthy. The relationship between optic atrophy and cerebral amblyopia may not reflect reality, because cerebral amblyopia was not a diagnostic term in general use at the time, and some cases that now would be so categorized might have been classed as instances of optic atrophy. What causes ROP is not yet fully understood. Apart from immaturity, several factors have been found to be associated with ROP. These factors mainly are involved in a chain reaction of hypoxia, reperfusion, hyperoxia, and ischemia.7–9 In this study, mechanical ventilation was found to be associated with ROP, although treatment for two weeks was found to be relatively safe. Ja¨ rvenpa¨ a¨ et al10 (1991) in Finland and Friedman et al11 (2000) in the United States have reported that oxygen therapy for more than 30 days was associated with ROP. Teoh et al12 (1995) in Malaysia calculated that every day in a ventilator increases risk of ROP by 1.156 times, and that oxygen therapy for more than 30 days results in a more than 90% chance of ROP. However, modern neonatal intensive care, including surfactant treatment, has altered considerably the need for mechanical ventilation. Results from the presurfactant era therefore may have little relevance to current circumstances. In the 1970s and 1980s, the incidence of ROP stage 3 to 5 varied between 2.5% to 20%, and the rate of severe visual impairment or blindness ranged between 2.5% to 10% in the Nordic preterm population with very low birthweight (⬍1500 g).13–15 Threshold ROP was rare in those born weighing ⬎1500 g, as we also found. Retinopathy of prematurity was diagnosed in this study only in 0.01% of children born prematurely weighing ⬎1500 g. For those born weighing ⬍1500 g, the corresponding percentage was 8%, and for those born weighing less than 1000 g, it was 11%. These percentages are lower than those reported in several other studies; for example, 30% in relation to children born at the end of the 1970s in the United States weighing ⬍1000 g, 26% in relation to children born between 1977 and 1984 in Australia weighing ⬍1000 g, and 18% in relation to children born between 1985 and 1992 in Australia weighing ⬍1000 g.16,17 In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity carried out in the United States from 1986 to 1987, threshold ROP affected 9% of infants born weighing ⬍1000 g.18 The introduction of ocular cryotherapy in 1972 and,
subsequently, retinal laser therapy have improved markedly the prognosis in cases of ROP in general. The improvement has been most marked from the 1980s onward.19 –23 A screening program for ROP (A Joint Statement of the American Academy of Pediatrics, the American Association for Pediatric Ophthalmology and Strabismus, and the American Academy of Ophthalmology) was adopted in Finland in the mid-1980s for children born weighing ⬍1500 g and children born at gestational age less than 30 to 34 weeks. The recommendations were also modified further. For example, threshold ROP had to be treated within 72 hours of diagnosis. A reduction in unfavorable outcome in cases of ROP of some 50% was seen. By the end of the 1980s, it was possible theoretically, by means of cryotherapy and laser therapy, to prevent progression of threshold ROP to stages 4 to 5 in more than 75% of cases. During the 1990s, further improvement of cryotherapy and laser therapy has led to success rates exceeding 90%, even in cases of severe posterior ROP. Results of vitreoretinal surgery for stages 4 to 5 have, however, remained poor.24,25 However, this study covered the most severe recorded cases of visual impairment. Only 9 of 57 children (16%) with ROP had been treated with cryotherapy, and one of them was saved from blindness. Cortical cells and other central visual pathways are especially vulnerable to acidosis and hypoxia during their intensive development between the sixth and eighth months of gestation, and in the perinatal period in cases of preterm birth. Cerebral injuries leading to hydrocephalus, periventricular leukomalacia, cerebral palsy, epilepsy, and other neurologic sequelae correlate with the degree of infant immaturity and metabolic activity at birth.3,26 Those injuries are more common causes of severe visual impairment accompanied by cognitive and motor disabilities than generally assumed. In a Swedish study, brain malformations and hypoxic–ischemic encephalopathy were the main causes of visual deficits in children born prematurely and screened for ROP.27 In Finland, periventricular leukomalacia was found in 32% of infants of birth weight ⬍1750 g.28 In this study, the incidence of neuro-ophthalmologic visual impairment was notably high (40%). During the 1990s, according to the Register of Visual Impairment, it was even higher (56%).29 There was no decrease in the incidence of visual impairment associated with prematurity in Finland from the 1970s through the 1980s. Retinopathy of prematurity was by far the most common diagnosis in cases of visual impairment and blindness associated with premature birth. Its incidence increased as the consequence of higher survival of infants of extremely low birth weight. The pattern has been similar in other countries.30 No reduction in incidences of ROP and severity of forms of visual impairment was reported in relation to Finland until the 1990s. Records relating to children with extremely low birth weight born between 1996 and 1997 were studied by Tommiska et al (2001).31 Retinopathy of prematurity was found only in infants born at gestational age less than 28 weeks. Retinopathy of prematurity of stages 3 to 5 was recorded in 19 of 211 children (9%). Two children with extremely low birth weight born in Finland during this period (gestational age, 25 weeks; birth weight, 880 g; and gestational age, 24 weeks; birth weight,
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Ophthalmology Volume 110, Number 8, August 2003 710 g) are recorded in the Finnish Register of Visual Impairment. This corresponds to an incidence of visual impairment associated with a diagnosis of ROP of 4% to 9% in 536 children with extremely low birth weight born in Finland (Finnish Perinatal Statistics), lower than the 11% for the 1970s and 1980s. The data from the 1990s in the Finnish Register of Visual impairment reveals a marked change in the incidence and characteristics of visual impairment in children born prematurely.29 The percentage of children born prematurely with visual impairment increased in the 1990s, but the percentage of children born prematurely who were blind remained at the level it was in the 1980s. Retinopathy of prematurity became a less common diagnosis in relation to visual impairment or blindness (35% of cases). The severity of ROPrelated visual impairment also decreased. Neuro-ophthalmologic disease became the most common disorder in relation to children born prematurely and visually impaired (56% of cases). The causes of prematurity and factors associated with it are not thoroughly understood, and the prevention of preterm birth itself has been difficult. However, rapid improvement in perinatal care has resulted in a higher survival of children with extremely low birth weight. Concern has been expressed about whether this is resulting in increases in incidences of disability.32 This study provides baseline information about visual impairment in children born prematurely before the surfactant period, when laser therapy of ROP was also uncommon. Compared with the results from 1996 and 1997 and with several other reports from industrialized countries, the risk of ROP appears to have decreased since the 1980s, despite the increase in survival rates of premature infants.33–36 However, the results of this study indicate that higher survival rates in relation to preterm children are associated with higher incidences of children with optic nerve atrophy, cerebral visual impairment, severe neurologic sequelae, and multiple handicap. More epidemiologic studies are needed to determine the success of attempts to prevent retinopathy and lesions in central visual pathways. Data in national registers of visual impairment are therefore very valuable and need to be assessed in combination with data from other registers. Reliable national registers are crucial in this connection.
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