Province-Based
Study
of Neurologic
Disability
Among
Survivors
Weighing
500
Through
1249
Grams
at Birth
Charlene Robertson, MD, FRCP(C)*; Reginald S. Sauve, MD, FRCP(C4; and Heather E. Christianson, BA
ABSTRACT. Background. As the mortality of children
weighing 500 through 1249 g at birth decreases, the
pub-lished rates of neurologic disability among survivors have
caused concern. Outcome information from a
province-based study in which perinatal/neonatal regional care is
well developed and includes high-risk identification,
early referral, organized transport, and outreach
educa-tion, provides data from a Canadian source for
compari-son with epidemiologic reports.
Methods. Neurologic disability rates among 2- to
3-year-old survivors weighing 500 through 1249 g at birth
is provided based on all live births/neonatal survivors/
1-year survivors born in Alberta, Canada to Alberta
residents in 1990.
Results. Corrected survival to 1-year was 163 of 229 or 71% of live births of the total group weighing 500 through
1249 g. Of 168 live births, 143 or 85% weighing 750
through 1249 g, free from lethal anomalies, survived.
Based on 1-year survival, disability rates were: cerebral
palsy, 67/1000; vision loss (acuity in the best seeing eye
after correction, <20/60), 12/1000; neurosensory hearing
loss (loss of 30 dB binaurally), 12/1000; and trainable/
profound mental retardation, 18/1000. No survivor had a
convulsive disorder. No vision loss or mental
retarda-tion as defined by this study occurred in survivors of
750 g. All children with cerebral palsy were or were
projected to become ambulatory.
Conclusions. Neurologic disability among small
pre-term surviving infants can occur less frequently than
sug-gested by published reports. We believe this provincial
study supports the value of well developed regional
pen-natal programs. Pediatrics 199493:636-640; mortality,
neurologic disability, survivors, regional perinatal
pro-gram.
Population-based information on very low birth
weight infants born in North America is needed for
comparison with information collected in other
geo-graphic areas of the developed world.#{176}
Epidemio-logic studies from Sweden, the United Kingdom,
Ire-land, Holland, and Western Australia report that
cerebral palsy prevalence among preterm children
in-creased from the early-1970s to the mid-1980s.
Al-though all studies report improved group survival,
some report that children born more recently with
From the *Department of Pediatrics, The University of Alberta, *Neonatal
Follow-up Clinic, Glenrose Rehabilitation Hospital, Edmonton, Alberta, the
Departments of Pediatrics and Community Health Sciences, The
Univer-sity of Calgary, the $Perinatal Follow-up Clinic, and the §Perinatal
Fol-low-up Program, Alberta Children’s Hospital, Calgary, Alberta, Canada.
Received for publication Jun 25, 1993; accepted Sep 9, 1993.
Reprint requests to (C.M.T.R.) Neonatal Follow-up Clinic, Glenrose
Reha-bilitation Hospital, 10230 111 Ave. Edmonton, Alberta, T5C 0B7, Canada.
PEDIATRICS (ISSN 0031 4005). Copyright © 1994 by the American
Acad-emy of Pediatrics.
cerebral palsy are more severely handicapped, have
more complex disabilities, and more frequently have
spastic hemiplegia or quadriplegia than children born
earlier.”9’10 The increase of the prevalence of vision
loss associated with retinopathy of prematurity
re-ported among the smallest very low birth weight
sur-vivors is thought to be primarily a function of
increas-ing lowest birth weight-specific survival.1115
Publications from regional programs within Canada
have reported a trend of improved outcome among
survivors weighing 500 through 1250 g at birth and
have linked these results to well developed regional
perinatal programs.119 The objectives of this report
are to provide survival and neurodevelopmental
disability rates for preterm infants weighing 500
through 1249 g at birth for a province-based birth
cohort and to compare these data with other
epide-miologic studies.
METHODS
Since the 1960s, all births to Alberta residents of 20 weeks’
gestation and/or 500 g birth weight have been prospectively
recorded by the Reproductive Care Committee of the Alberta
Medical Association through the use of hospital birth records,
mortality studies by individual chart reviews, and information
from the Department of Vital Statistics of the Province of Alberta.
Within these gestational age and birth weight parameters, all
births including stillbirths, delivery room deaths, and death of
nontransferred infants are registered. Since the mid-1970s, this
information about newborns weighing 500 through 1249 g at birth
has been incorporated annually into the databases of the two
Regional Perinatal Programs in the Province of Alberta. For the
purpose of this study, information was extracted on stillborn and
live born children weighing 500 through 1249 g born in 1990 in
Alberta (661 185 km2 or 255 285 square miles in size, population
2 469 621) to Alberta parents, with total births to Alberta parents
numbering 42 601.
In 1990, 48% of the population lived in one of two metropolitan
areas where the tertiary care facilities are located. Newborns of
less than 37 completed weeks gestation made up 6.7% of live
births; newborns born to teenage mothers, 10%. The use of
supple-mental surfactant began in this province in 1988.
Obstetrical/newborn care in the province is provided by 75
level I (primary) care hospitals, 8 level II (intermediate) care units,
and 3 level III (tertiary) care units. Primary care documentation of
obstetrical risk factors and referral of all pregnancies above low
risk has been increasing during the past two decades)6172’
Ag-gressive care of very low birth weight newborns and early
mater-nal and/or neonatal transfer is strongly encouraged. The method
of referral to one of three tertiary care hospitals (Royal Alexandra
Hospital and University of Alberta Hospitals in the North, and the
Foothills Hospital in the South), subsequent referral for neonatal
follow-up to one of two multidisciplinary clinics (Glenrose
Reha-bilitation Hospital in the North and Alberta Children’s Hospital in
the South), method of follow-up, and criteria for disability have
been described previously.169720 Briefly, 96% of survivors born in
1990 received follow-up to a minimum of 2 years. Developmental
pediatricians not involved in the initial care assessed the children,
fol-RESULTS
The 1-year province-based survival of all newborns
500 through 1249 g birth weight born in Alberta was
68%; corrected 1-year survival, 71%. Background
in-formation is provided in Table I. Lethal anomalies
included hypoplastic lungs, idiopathic hydrops
fe-talis, multiple anomalies, Trisomy 18, and
compli-cated anal stenosis. Of the 9 newborns dying after 28
days, all but two died before hospital discharge, and
these two died of sudden infant death syndrome and
were not known to have disabilities. There were no
deaths after I year of age to the time of writing.
Cor-rected 1-year survival was 85% for the 168 live born
infants with a birth weight 750 g.
Disability was diagnosed in 14 (8.5%) of 163
chil-dren (Table 2). By age 2 years, no vision loss, mental
retardation, or convulsive disorder as defined by this
study occurred in survivors weighing 750 g at birth.
Two children of 749 g birth weight had three
dis-abilities each; both had legal blindness secondary to
retinopathy of prematurity. Cerebral palsy occurred
more frequently in survivors weighing 750 g at birth
than in those in the lower birth weight group. One
multiply disabled child had neurosensory hearing
loss of 50 to 60 dB as one of his disabilities.
Only the spastic syndrome forms of cerebral palsy
occurred: 46/1000 live born infants weighing 500
through 1249 g at birth, 64/1000 neonatal survivors,
and 67/1000 1-year survivors. One child with cerebral
palsy was multiply disabled with blindness and
men-tal retardation. The remaining 10 children with
cere-bral palsy who weighed 750 through 1249 g at birth
had a single disability (Table 2). No child with
cere-bral palsy had a congenital anomaly. All children
with cerebral palsy now sit independently, and walk
or are expected to become ambulatory (Table 3). One
blind/deaf/retarded child without cerebral palsy
will likely become dependently disabled. (His mother
had a history of alcohol abuse.)
DISCUSSION
This is the first total province- or state-based study
in North America of greater than 1-year outcome of
preterm infants weighing 500 through 1249 g at birth.
Although this is a numerically small study, it
pro-vides recent population-based mortality and
neuro-logic morbidity information that can be compared
with other epidemiologic and/or geographically
de-fined studies.’18’19’#{176} Survival of infants of 750
through 1249 g at birth was 85% in this study, higher
than most reports; however, for those 500 through 749
TABLE 1. Background Information on a Province-Based Birth Cohort Weighing (500 through 1250 Crams at Birth)
Variables Birth Weight Croups, n Total Croup,
N
500-749 g 750-999 g 1000-1249 g
Total births 113 90 121 324
Stillbirths 50 18 15 83
Live births 63 72 106 241
Neonatal deaths
Associated with lethal malformations 2 2 8 12
Other causes 37 9 11 57
Corrected neonatal survival (rate) 24 (39%) 61 (87%) 87 (89%) 172 (75%)
Deaths >28 d, before I y 4 2 3 9
Corrected 1-year survival (rate) 20 (33%) 59 (84%) 84 (86%) 163 (71%)
low-up clinics, independent diagnoses for the physically disabled
children at 2 to 3 years of age were obtained from a pediatric
physiatrist (North) or child neurologist (South). At adjusted age 2
years or younger, the Mental Development Index of the Bayley
Scales2’ was determined; if a ceiling was obtained or if the child
was >2 years adjusted age, the Stanford-Binet Intelligence Scale
was used to obtain an intellectual quotient. For the purpose of this
study, children with scores >3 SD less than the mean of published
standardized data were categorized within the mental retardation
range. Categorizing of disabled young children fluctuating within
the lowest cognitive range is difficult, and the case-conference
judgment of the entire clinic assessment team was used to assist in
making this categorization, as described previously.23 Although
children with Mental Developmental Indices of 2 to 3 SD below
the mean are functioning within the delayed range, they have not
been labeled as disabled in this study. Level of motor function was
determined by the Psychomotor Development Index of the Bayley
Scales,21 the Peabody Developmental Motor Scales,24 and/or the
Test for Cross Motor Reflex Development/s Conditions
consid-ered to be a disability were consistently defined by standard
pro-tocol and included cerebral palsy, visual loss (acuity in the best
seeing eye after correction, <20/60) including legal blindness
(cor-rected acuity, <20/200), cognitive delay (mental development
in-dex or intelligence quotient >3 SD below the mean on
standard-ized testing), convulsive disorder requiring anticonvulsants for
seizure control, or any neurosensory hearing loss (loss of 30 dB
binaurally))6”7 All children were tested by certified audiologists,
initially by newborn screening; they were subsequently tested
repeatedly in a sound booth and/or by brainstem audiological
evoked response testing to ensure either normal binaural or, if
possible, bilateral hearing, or to determine the degree of
neuro-sensory hearing loss. All children with a developmental delay or
disability were given the opportunity to have early intervention
by trained therapists.
The definition of cerebral palsy used is that of Bax, “A disorder
of movement and posture due to a defect or lesion of the immature
brain,”26 r095 along with more recent guidelines by Levine using at
least four of six clinical motor abnormalities leading to a
constel-lation of findings of the cerebral palsy syndrome.27 Creat care was
taken in mild or so-called threshold cases28 as there are no
ac-cepted minimal diagnostic criteria for cerebral palsy. For the
pur-pose of this report, suspect cases were included as cases.
The incidence of disability is defined as the percentage of
dis-ability among I -year survivors. Cerebral palsy rates based on live
births and neonatal survivors are given to provide an opportunity
to compare rates with those in other countries. Complexity of
disability is determined by the number of disabilities per child;
two or more disabilities diagnosed in a single child renders that
child multiply disabled. The severity of diagnosis was determined
by individual diagnosis and, for cerebral palsy, the level of gross
motor function of the child. Being ambulatory referred to
inde-pendent walking; projected future ambulatory status was
deter-mined by independent sitting at less than 2 years.29 All children
with syndromes and/or central nervous system malformations
with a known association with developmental delay or those
known to have a central nervous system insult after neonatal
intensive care discharge were documented and then were
ex-cluded from the lists of disabled, hence producing ‘corrected’
rates.
The study subjects included 324 subjects, that is, all births
weighing 500 through 1249 g born in 1990 in Alberta, Canada to
Alberta residents. Of the 241 infants born alive, 90% were born at
TABLE 2. Incidence and Complexity of Specific Neurologic Disability at 2 to 3 Years of
through 1249 g at Birth Born in Alberta, Canada to Alberta Residents in 1990
Age Among 1-Year Survivors Weighing 500
Variables Birth Weight Croups, n Total Croup,
N
500-749 g 750-999 g 1000-1249 g
1-y survivors 20 59 84 163
Follow-up to 2+ y 20 57 80 157
Disabled survivors (%) 3 (15%) 6 (10%) 5 (6%) 14 (8.5%)
One or more of
Cerebral palsy I 6 4 11 (6.7%)
Vision loss 2 (1.2%)
Visual impairment 0 0 0
Legal blindness 2 0 0
Hearing loss (neurosensory) 1 0 1+ 2 (1.2%)
Mental retardation 3 0 0 3 (1.8%)
Convulsive disorder 0 0 0 0 (0%)
Multiply disabled 2 (10%) 0 0 2 (1.2%)
* Ceneral moderate loss requiring amplification.
t Midfrequency moderate loss, normal high frequency hearing, not requiring amplification at this time.
TABLE 3. Complexity and Severity of Specific Neurologic Disability at 2 t
through 1249 g at Birth Born in Alberta, Canada to Alberta Residents in 1990
o 3 Years of Age Among 1-Year Survivors eighing 500
Disability Cross Motor Ambulatory Yes/
Delay, mo* Futuret/No
Birth Weight Croups Total
500-749 g 750-999 g 1000-1249 g
(n = 20) (n = 59) (n = 84)
Single disability
Spastic diplegia 6 Yes 0 2 1 3
Spastic diplegia >6 to 9 Yes 0 2 0 2
Spastic hemiplegia 6 Yes 0 1 1 2
Spastic quadriplegia 6 Yes 0 1 1 2
Spastic quadriplegia >6 to 12 Future 0 0 1 1
Mental retardation 6 Yes I 0 0 1
Deaf (moderate low frequency) 6 Yes 0 0 1 1
Multiple disabilities
Spastic diplegia, legal blindness, >6 to 12 Future 1 0 0 1
mental retardation
Mental retardation, legal blindness, >18 No 1 0 0 1
deaf (moderate)
3 6 5 14
* For tests of level of motor function see text.2I24n
1Future refers to projected ambulatory status because of the presence of independent sitting before 2 years of age.29
g at birth, survival was in the commonly reported
range of about 30% to 45%.#{176}Most current reports give
cerebral palsy rates for preterm infants weighing
1500 g at birth as 80 to >100 per 1000 neonatal
survivors,13’9 with rates for those weighing <1000 g
at birth at the higher end of this range.9 Cerebral palsy
rates in this study are not statistically different than
other published epidemiologic studies, although
birth weight groups are not directly comparable in
many cases. The cerebral palsy rate in this study for
preterm infants of 500 through 1249 g birth weight is
46/1000 live births; a recent meta-analysis of
hospital-and region-based studies of preterm infants weighing
1500 g at birth reported 77 children with cerebral
palsy per 1000 live births.31 A cerebral palsy rate of
64/1000 neonatal survivors compares favorably with
other reports3’6’9’2 and with a recent report from
Northern Alberta of 93/1000 neonatal survivors for
children born in 1988 to 1989 and 157/1000 neonatal
survivors for children born in 1978 to 1979.17
Unfor-tunately the cerebral palsy rate in preterm infants
con-tinues to be much higher than the rate for the general
population.
Although an increased severity and complexity of
disability of very low birth weight survivors with
ce-rebral palsy has been reported,9”#{176} this was not
con-firmed by this study. Ten of eleven children with
ce-rebral palsy had this disability as a single finding. All
children with cerebral palsy were, or are projected to
become ambulatory according to our previous
crite-na.29 Three had gross motor levels of function within
average range for age, and 6 of the I I had spastic
diplegia. The recently reported predominance of
spastic hemiplegia or increased incidence of spastic
quadriplegia was not noted. If the clinical diagnosis
of cerebral palsy is to be used by epidemiologists for
population comparisons and as an outcome measure
in medical audits, then the question of the threshold
of diagnosis or minimal criteria for diagnosis must be
addressed. The threshold a child has to cross to be
given a diagnosis of cerebral palsy is of paramount
importance in estimating the frequency of cerebral
palsy.28 A further definition of minimal criteria for
diagnosis of cerebral palsy would be most useful to
follow-up clinics. Cerebral palsy rates of this study
group are likely to be an overestimate of the rates
when this group reaches an older age as reported
previously.33’
To our knowledge this is the first report in the
of preterm survivors weighing 750 through 1249 g
who are free of visual impairment or legal
blind-ness. Based on 1-year survival rates, for the total
co-hort, vision loss was 12/1000, and neurosensory
hearing loss, 12/1000. Both rates are below
previ-ously reported rates.11’3’17’#{176}’35-1#{176}
No study child required anticonvulsants after
dis-charge from the neonatal intensive care units. Three
children had mental retardation within the trainable/
profound range at time of testing. Because of the
severe mental delay of one blind/deaf child it is
pro-jected that he will become a dependently
handi-capped older child or adult. Limited mental function
as a criterion for categorizing a dependently
handi-capped child was determined by a previously used
scale.17’18 In this study, overall cognitive development
has not been reported in more detail because of lack
of prediction of future scores for children <3 years.41
At the tested age, three additional children were
found to have cognitive development between 2 and
3 SD below the mean on standardized testing.
How-ever, for young children scores in this range may
re-flect environmental rather than neonatal illness
causes, and hence may not be a good outcome
vari-able for this type of study. Fewer children have
trainable/profound mental retardation in this study
than in previous studies from Alberta.16’17’2#{176}There has
been no attempt in this paper to address
school-related skills of preterm children.
In this province there has been an overall
educa-tional effort at all levels of health care to use the
re-gional perinatal programs as they were intended with
an emphasis on early prenatal care, risk identification, and referral according to risk. In spite of the location
of the patients’ homes a distance away from tertiary
care facilities for more than half of the parents of these
small infants, and long transport distances, 90% of
mothers were delivered of their newborns at one of
three tertiary hospitals. This is an increase from the
81 % of a provincial cohort delivered in a tertiary unit
in 1986.20 We believe the organization of the regional
peninatal programs and good antenatal and intensive
peninatal/neonatal care, as well as relatively good
so-cial circumstances, have contributed to the improved
outcome of very low birth weight infants in this
prov-ince.16’17’2#{176}
This
care includes prenatal classespro-vided by 27 public health units, as well as by
hospi-tals, peninatal outreach educational programs, and
universal medical care. This paper provides
demo-graphic and geographic data so that comparisons can
be made with other locales. It is recognized that due
to differences in population backgrounds the ability
to generalize these results may be limited.42
It has been almost 30 years since the creation of
comprehensive programs for neonatal care.42
Cradu-ally regionalized care for high-risk mothers and
new-borns developed, centralizing the expert care and
in-corporating a transfer system of mothers and/or
newborns to tertiary care centers. There is good
evi-dence that this care has contributed to improved
sun-viva! of very low birth weight newborns.47 By
add-ing information on morbidity, we believe this paper
points out the value of organized, all encompassing
regiona!ized peninatal care in a large geographic area.
Perhaps this information will be useful to those who
have concerns about the evolution of comprehensive
neonatal care programs.42’48
This paper provides a province-based study of
out-come of low birth weight infants without selection
bias and with good follow-up. The results provide for
some optimism about the outcome of these infants.
However, we must continue striving to lessen the
dis-ability rates among preterm infants. We believe the
information will be useful to those responsible for
or-ganizing care for very low birth weight infants, those
interested in regionalization of medical care and
health care access, and agencies involved in chronic
health care provision.
ACKNOWLEDCMENTS
This study was made possible because of the organization and structure of Alberta’s Perinatal Programs. We gratefully acknowl-edge the direction from and support by Dr P.C. Etches, Chairman,
Reproductive Care Committee, Alberta Medical Association.
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47. Cordero R, Backes CR, Zuspan FP. Very low-birth weight infant, I:
influence of place of birth on survival. Am IObstet Gynecol. 1982;143: 533-537
48. Blackman JA. Neonatal intensive care. Is it worth it? Developmental
sequelae of very low birthweight. Pediatr Clin North Am. 1991;38:
1497-1511
HARSH WORDS OF THE FOUNDER OF INDEX MEDICUS
Nine-tenths at least, of it [the medical literaturel becomes worthless, and of no
interest, within ten years of its publication, and much of it is so when it first
appears.
John S. Billings (in 1887). Quoted in: Taylor CR. Creat Expectations. The reading habits of year II medical
students. N Engl IMed. 1992;326:1436-1440.
