Changing
Pattern
of Retinopathy
of
Prematurity:
A 37-Year
Clinic
Experience
A. H. Hoon,
MD, J. E. Jan, MD, M. F. Whitfield,
MD,
A. 0. McCormick,
MD, CM, D. P. Richards,
MSc,
and
G. C. Robinson,
MD
From the Department of Paediatrics, University of British Columbia, Visually Impaired Program, and Neonatal Follow-up Program, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
ABSTRACT. A retrospective analysis was done of
multi-disciplinary neurodevelopmental assessments in 70
chil-then who were legally blind because of cicatricial
retinop-athy of prematurity. The subjects lived in British
Colum-bia and were born during a 37-year period between 1951
and 1987. The purpose of the study was to investigate changes in the perinatal characteristics and to evaluate
the associated handicaps. All patients were assessed at
least once in the Visually Impaired Program, British Columbia Children’s Hospital. In the majority, the visual
loss was profound. Since 1951, blinding retinopathy of
prematurity has become a disease ofprogressively smaller
and less mature infants. Since 1981, it has been almost
entirely confined to infants of birth weight less than
1,000 g in British Columbia. The diagnosis of mild spastic
diplegia was made more commonly in patients born after
1980 but, despite the progressive reduction in birth weight
and gestational age during the study period, the number
of patients without other associated handicaps remained
constant (approximately 30%) during each successive
decade. Pediatrics 1988;82:344-349; retinopathy of
pre-maturity, blindness, handicap, very low birth weight.
Despite 40 years of medical progress, netrolental
fibroplasia, or retinopathy of prematurity, as it is
now called, continues to be a handicap among the
intensive cane nursery graduates.1 Silverman and
Flynn2 estimated that there were 10,000 cases
worldwide during the years 1943 to 1953 when
retinopathy of prematurity was seen in epidemic
proportions. With restrictions in the use of
supple-mentany oxygen, the prevalence of retinopathy of
prematurity decreased. It is again increasing despite
Received for publication Dec 27, 1987; accepted March 8, 1988.
Reprint requests to (J.E.J.) Visually Impaired Program, British
Columbia Children’s Hospital, 4480 Oak St, Vancouver,
British Columbia V6H 3V4 Canada.
PEDIATRICS (ISSN 0031 4005). Copyright © 1988 by the
American Academy of Pediatrics.
wide availability and use of better techniques for
surveillance of PA02.3’4 Phelps5 estimated that in
the United States in 1979 there were 546 infants
blinded from retinopathy ofprematunity in addition
to those affected by cicatnicial sequelae. Robinson
et al6 showed a slight increase in birth prevalence
rates for blinding retinopathy of prematurity in
British Columbia since the mid-1970s, although the
rates are well less than the epidemic numbers of
the 1950s.
There has been speculation concerning the
pos-sible risk factors related to the acute stages of the
disease.79 A few articles were written concerning
the neurodevelopmental outcome of infants with
blinding retinopathy of prematurity, but long-term
studies of trends have not been published
previ-ously.1#{176}3
The purpose of this retrospective study was to
investigate changes in the characteristics of
new-horns blinded by retinopathy of prematurity and in
the pattern and severity of associated handicaps of
children who were examined in the Visually
Im-paired Program of the British Columbia Children’s
Hospital since 1970.
PATIENTS AND METHODS
The Visually Impaired Program was established
in 1970 as a provincial assessment facility for blind
children in British Columbia. In 1985, the program
served a population of 2.7 million people, with a
delivery rate of 43,000 pen year, with one provincial
tertiary perinatal center at Grace and Children’s
Hospitals.
Within the Visually Impaired Program,
multidis-ciplinany patient assessments are done. The team
includes a pediatric neurologist (J.E.J.), an
psy-1951-1960 1961-1970 1971-1980 1981-1987
(n = 11) (n = 19) (n = 17) (n = 23)
Gender (No.)
Male 4 9 11 10
Female 7 10 6 13
Birth place (No.)
British Columbia 8 11 15 21
Other 3 8 2 2
Birth wt (g)
Mean 1,279 1,197 957 795
Range 737-1,644 850-1,616 580-1,134 580-1,200
Gestational age (wk)
Mean 29.7 29.5 28.1 25.6
Range 26-34 26-34 24-34 22-28
Last assessment (age in yr)
Mean 17.1 10.3 6.6 2.0
Range 13-22 3.5-17.5 3.5-10 0.3-5
chologist, a speech pathologist, a physiotherapist,
and an audiologist. Other specialties are involved
in individual cases. The referral of patients to the
Visually Impaired Program and the integration of
services received by the visually impaired are
facil-itated by the Canadian National Institute for the
Blind. Recently, coordinated assessments of new
infant patients with retinopathy of prematurity
have also been made with the Neonatal Follow-up
Program, British Columbia Children’s Hospital (M.F.W., A.H.H.).
A total of 70 patients with retinopathy of
pre-maturity (34 boys and 36 girls) were studied; they
had visual acuity of 20/200 or less in the better eye
with connection. Of these, 55 patients were born in
British Columbia and 15 patients were born
else-where. Single-occasion assessment was made of 42
patients; 28 were assessed more than once. In
pa-tients seen several times, the most recent
evalua-tion was used in determining neunodevelopmental
outcome. Of the 70 patients, 11 wene bonn between
1951 and 1960, 19 between 1961 and 1970, 17
be-tween 1971 and 1980, and 23 in the 7-year period
from 1980 to 1987. Although the majority were
assessed during childhood, some of those born
be-fore 1960 were seen as young adults. Results of
neunodevelopmental assessments of patients born
after 1981 may not yet reflect ultimate outcome,
because many of these patients were less than 3
years of age.
A battery of standardized, age-appropriate
psy-chologic tests suitable for visually impaired children
were administered by the developmental
psycholo-gist, who had extensive experience in testing
visu-ally impaired children. A description of the
psy-chologic assessment of blind children as it is done
in our clinic has been published elsewhere.”
Although the patient population represents
nearly all infants with blinding retinopathy of
pre-TABLE 1. Demographic Data
Demographic Data
maturity bonn in British Columbia during the last
17 years, the ascertainment prior to this period is
less complete. The influence of emigration,
decreas-ing neonatal and postnatal mortality, the changing
practice of institutionalizing severely handicapped
infants, and other epidemiologic factors were not
considered. Therefore, this is not an accurate study
of incidence or prevalence in a geographically
con-fined area but a profile of clinic population
through-out a prolonged period of time. Nevertheless, we
believe that the data are valuable and that they
merit publication.
RESULTS
Details of the study population by decade of birth
are given in Table 1. There was a progressive
de-crease in birth weight and gestational age from the
1950s to the 1980s. Only two infants of 22 born
after 1980 had a birth weight greater than 1,000 g.
Growth failure in weight, length, and head
circum-ference was a common finding (Table 2).
Hydro-cephalus developed in one child from the 1971 to
1980 and two patients from the 1981 to 1987
pe-nods. Head growth appears to have been more
appropriate in those born in the 1980s, but a greaten
proportion of infants were underweight and of short
stature. These findings parallel the growth
prog-nosis of sighted infants born in the same decade
and within the same birth weight cohort (MF
Whit-field Neonatal Follow-up Program, British
Colum-bia Children’s Hospital, Vancouver, Canada, 1987).
In Table 3, details of visual function are shown.
There was a progressive reduction in the proportion
of patients who had light perception only on no
vision. Some of these children were young, however,
and may yet develop later cicatnicial sequelae
TABLE 2. Growth Failure in Weight, Height, and Head Circumference*
Characteristics 1951-1960
(n = 11)
1961-1970
(n = 19)
1971-1980
(n = 17)
1981-1987
(n = 23)
Wt 1 3 6 5
Height 1 2 7 6
Microcephaly 2 4 3 2
* Results are given in numbers of patients. Measurements of weight and length were
compared to National Center for Health Statistics percentiles!5 Growth failure in weight
and length was defined as a measure less than the fifth percentile. Microcephaly was
defined as a head circumference more than 2 SD less than the mean for sex and age.
TABLE 3. Residual Vision*
Vision 1951-1960
(n = 11)
1961-1970
(n = 19)
1971-1980
(n = 17)
1981-1987
(n = 23)
20/200-20/400 1 3 7 4
20/400 to perception 1 2 1 9
of hand movement
Light perception 4 8 9 9
None 5 6 0 1
* Results are given in num
hers of patients.
the children of school age were Braille- rather than
print-readers.
The results of the neurologic examination are
given in Table 4 and results of developmental and
psychologic assessments are presented in Table 5.
The overall incidence of mental retardation was
34%. These results also show that from 1951 to
1980 there was no change in the proportion of
children who were mentally retarded. However,
Sufficient data are not yet available regarding the
new survivors of ultraintensive neonatal care (born
after 1980) to provide a clean prediction of their
later functioning. Speech and language problems,
learning difficulties, and psychiatric problems are
detailed in Table 6. A total of 19 (26%) patients
had severe behavioral problems. Seven were
re-ferned to psychiatric and five to special treatment
facilities. Many of these children exhibited marked
autistic-like behavior. The overall spectrum of
handicaps present in addition to visual impairment
is given in Table 7. A total of 26% of patients had
cerebral palsy. Seven infants born prior to 1980 and
seven born after 1980 had spastic diplegia. Three
children had other types of cerebral palsy and one
child bonn between 1960 and 1970 acquired his
hemiplegia secondary to severe dehydration at 4
years of age. The majority of children with spastic
diplegia were mildly affected. Seizures, hearing loss,
learning disabilities, and speech and language
dis-orders are included as other disorders.
A seizure disorder was present in 14 (20%)
chil-dren, four of whom had seizures confined to the
newborn period. As part of another study,16 26
EEGs were obtained in 20 children with
retinopa-thy of prematurity. These records were located and
reassessed. Fourteen records showed either
occipi-tal #{244}-waves or spikes, which were associated in 12
patients with CT evidence of peniventniculan
leu-comalacia.
Of the 62 children who had hearing assessments,
seven (11%) patients had sensonineunal hearing
loss. In two patients the bilateral hearing loss was
profound and in two others it was mild. Three
children had mild unilateral hearing loss. The cause
was unclear in all. There was no change in the
incidence of permanent hearing impairment with
time throughout the study period. The proportion
of children free of additional handicaps remained
approximately 30% throughout the study (Table 7).
The 15 patients who were not bonn in British
Columbia but were evaluated in the Visually
Im-paired Program received their peninatal care in
various North American centers. Three children of
11 had no additional handicaps.
DISCUSSION
This study provides a unique panorama of
changes occuning in patients with blinding
retinop-athy of prematurity during a 37-year period. The
study period spans the era of liberal, uncontrolled
oxygen use (early 1950s), drastic curtailment of
oxygen use after the first cooperative study (early
1960s in Vancouver)’7 leading to availability of
methods for measuring arterial partial pressure of
oxygen in small blood samples, and arterial
cathe-tenization in the later 1960s and early 19705.18 It
also includes the introduction and subsequently
ready availability of tertiary negionalized perinatal
care in the 1970s and 1980s, supported by major
technologic advances such as continuous oxygen
TABLE 6. Speech, Language, and Psychiatric Disorders*
1951-1960 1961-1970
(n=11) (n=19)
1971-1980 1981-1987
(n = 17) (n = 23)t
Speech and language 1 0 3
Learning 2 3 5
Psychiatric 4 3 8
0 0 4
* Results are given as numbers of patients.
t Of these, 12 children were too young for accurate evaluation.
TABLE 7. Overview of Associated Handicaps*
1951-1960 1961-1970 1971-1980 1981-1987
(n = 11) (n = 19) (n = 17) (n = 23)
Handicap (No. of children)
Mental retardation 4 4 6 5
Cerebral palsy 3 5 2 8
Psychiatric 4 3 8 4
Other 5 12 11 10
No.(%)ofhandicapped 8(73) 12(67) 12(71) 11/15t(73)
children
fully assessed for
TABLE 4. Neurologic Examination*
Examination
Results
1951-1960
(n = 11)t
1961-1970
(n = 19)
1971-1980
(n = 17)
1981-1987
(n = 23)
Normal 3 6 3 8
Borderline 3 4 9 4
Abnormal 4 91: 5 11
* Results are given as numbers of patients. Borderline abnormal results included mild
hypotonia and impaired coordination. Abnormal findings were most commonly, but not
always, due to spastic diplegic cerebral palsy.
t In one child, the examination was not done by a neurologist.
:1:
Includes one child who at 4 years of age became hemiplegic.TABLE 5. Developmental Delay and Psychologic Assessment*
Developmentaland
Psychologic Assessment
1951-1960
(n = 11)
1961-1970
(n = 19)
1971-1980
(n = 17)
1981-1987
(n = 23)
Early developmental delay 8 12 10 10
Formal IQ testing
Above average 0 1 2 0
Average 7 14 9 3
Mental retardation 4 4t 6 5
* Results are given as numbers of patients. For analysis purposes, above-average
intelli-gence was defined as a global IQ greater than 110 and mental retardation as an IQ of 70
or less. Developmental delay was noted in children younger than 2#{189}years and too young
for formal psychologic assessment who were slower than average in reaching childhood
milestones.
t One child, in whom brain damage was apparent at 4 years of age, was included.
:1:
Of these, 15 children were too young to have formal psychologic testing.Disorders
* Some children had more than one handicap.
t Eight children were 13 months of age or younger and could not be
mental retardation and learning disabilities.
oximeten) and major improvements in ventilator In each of the four decades, approximately 30%
and incubator design and reliability. of the patients had no additional handicaps. The
One of the most striking findings in this study remaining 70% had a wide spectrum of disabilities
was a confirmation that the birth weight of the including cerebral palsy, mental retardation,
deaf-study children with retinopathy of prematurity has ness, and learning and psychiatric difficulties. In a
progressively decreased during the study period. survey of all causes of congenital blindness
includ-Clearly, most premature infants who developed net- ing retinopathy of prematurity in British Columbia
inopathy of prematurity in recent years would have from 1945 to 1984, Robinson et al6 reported that
handi-caps. Since 1960 however, the proportion of
chil-dren without additional handicaps has increased to
5o%#{149}6When searching for neurologic handicaps, it
is important to assess children beyond infancy.
Indeed, Gillman and Goddard’9 noted an increasing
number of additional handicaps in 77 legally blind
children as they grew toward maturity.
The overall incidence of mental retardation
(30%) in our clinic population is similar to that
reported by other authors.”9’2#{176} It is well recognized
that retinopathy of prematurity itself does not lead
to mental retardation; many of the patients in this,
and in other studies, have normal or superior
intel-ligence.2#{176}
The percentage of patients with abnormal
neu-rologic findings did not change during the study
period, but the incidence of spastic diplegia
in-creased. The diplegia was usually mild, affecting
the legs mainly, but permitted ambulation. The
increase in spastic diplegia correlated with the
pro-gressive reduction in birth weight of the infants
blinded by retinopathy of prematurity.2’
During the last two decades, there have been
more children in the retinopathy of prematurity
study with residual vision than before, but these
younger subjects remain at risk for late
complica-tions such as retinal detachment or glaucoma.22 The
severity of visual loss in patients with retinopathy
ofprematunity reflects the inability of modern
med-icine to control the progression of this ocular
dis-order that can be readily diagnosed in the acute
stage. The incidence of sensonineural hearing loss
among graduates of the neonatal intensive care unit
whose birth weight was less than 1,500 g is reported
to be between 2% and 10%, but in most cases there
is no clear causitive factor.23 Unilateral on bilateral
sensonineural hearing loss was present in 7 (11%)
of the children in our study, two of whom were
classified as deaf-blind.
More than one quarter of the patients exhibited
severe behavioral problems. The association of
au-tistic behavior and children with retinopathy of
prematurity is well documented in the literature.24
This is thought to be related to CNS injury rather
than to environmental deprivation, and it is not as
prominent in children with most other ocular
le-sions.24 The numbers in this report and the young
age of the most recent patients do not permit any
comment about trends.
The EEGs of children with retinopathy of
pre-maturity have been studied.25’26 The records of these
individuals frequently show posterior #{244}-activity
with or without occipital spikes. The presence of
peniventnicular leukomalacia appears to explain
these changes.’6 The records ofblind children
with-out any additional neurologic deficits do not show
these abnormalities, and the generation of
a-rhythm is affected only when the visual loss is severe, at the level of finger counting on less.’6
Large-trend studies of children with blinding
ret-inopathy of prematurity such as ours have not been
published before. It has repeatedly been emphasized
in the literature that the results of follow-up studies
concerning very low birth weight infants cannot be
accurately compared. Important variables include
the time of publication, duration of follow-up,
pre-natal care, prematurity and birth weight of the
infants, birthplace (ie, whether newborn was born
in or transported to the peninatal center), and social
and economic factors. Nevertheless, although by
selection all of our patients were blind, only 30%
were free from additional neurologic handicaps. In
contrast, in follow-up studies of very low birth
weight, sighted infants, fewer than one third had
one or more additional neunologic handicaps.273’
This clearly suggests that the majority of infants
with blinding retinopathy of prematurity are
ex-posed to more severe neurologic insults than their
sighted contemporaries.
In summary, this retrospective analysis confirms
that, because of modern intensive care techniques,
blinding retinopathy of prematurity has become a
disease primarily affecting infants smaller than
1,000 g. The study clearly shows that despite the
downward change in birth weight and gestational
age, the number of survivors without associated
handicaps has remained constant (approximately
30%) throughout nearly four decades. However,
mild spastic diplegia has increased as a result of
lower birth weight and shorter gestational age of
affected patients. Finally, the visual loss is profound in the majority of patients with severe retinopathy of prematurity.
In the 1980s, the increasing survival of infants of
less than 1,000-g birth weight may cause a
signifi-cant increase in the absolute numbers of very low
birth weight infants blinded by retinopathy of
pre-maturity. By the end of the decade, this will further
strain the services that support visually impaired
and handicapped individuals.
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