Eight-Year School Performance, Neurodevelopmental, and Growth Outcome of Neonates With Bronchopulmonary Dysplasia: A Comparative Study

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Eight-Year

School

Performance,

Neurodevelopmental,

and

Growth

Outcome

of Neonates

With

Bronchopulmonary

Dysplasia:

A Comparative

Study

Charlene MT. Robertson, MD, FRCP(C)*; Philip Charles Etches, MA, MB,

MRCP(UK), FRCP(C), DCH*; Edward Goldson, MDII; and Janis Mildred

Kyle, MEd

ABSTRACT. Eight-year outcome is reported for three

groups of preterm infants with bronchopulmonary

dys-plasia-group 1 with a birth gestation of 31 weeks

receiving supplemental oxygen until the equivalent of

36 weeks’ gestation, group 2 of the same gestation

receiv-ing supplemental oxygen to 28 days postnatal age but

not to 36 weeks gestational age, and group 3 with a

gestation of 32 weeks requiring supplemental oxygen

for >28 days-and for an individually matched preterm

neonatal comparison group and a term peer comparison

group for each bronchopulmonary dysplasia group. The

subjects all had parents whose mother tongue was

Eng-lish and were matched for gender, mother’s education,

and father’s socioeconomic status, and in the case of the

neonatal comparison groups they also were matched for

birth gestation and birth weight. Physical growth and

psychoeducational and school performance test scores

were similar for the three bronchopulmonary dysplasia

study groups with the exception of lower intelligence

quotient for those receiving supplemental oxygen for the

longest time. Children in groups 1 and 2 had outcome

scores similar to those of the neonatal comparison group and significantly below those of their peer comparison groups. On multivariate analysis for group 1 children,

61% of the variance of academic achievement was related

to lowest recorded pH, father’s socioeconomic status, and

lowest recorded Pao2. Compared with the peer groups,

the study groups continued to show academic delay when

the disabled children were excluded from analysis.

Al-though the duration of pulmonary disease affects

out-come, prematurity with and without chronic lung

dis-ease, along with adverse social factors, compromises the

outcome for low birth weight infants with a history of

bronchopulmonary dysplasia who have now reached

school age. Pediatrics 1992;89:365-372; bronchopulmonary dysplasia, prematurity, school performance, growth, neo-natal follow-up.

ABBREVIATIONS. BPD, bronchopulmonary dysplasia; SES,

socio-economic status; NICU, neonatal intensive care unit; MANOVA,

multiple analysis of variance; ANOVA, analysis of variance; ICH,

intracranial hemorrhage.

From the *University of Alberta, Edmonton, Alberta, Canada; jGlenrose

Rehabilitation Hospital, Edmonton; §Royal Alexandra Hospital, Edmonton; llHeaIth Sciences Center, University of Colorado and The Children’s Hos-pital, Denver.

Received for publication Mar 25, 1991; accepted Aug 8, 1991.

Reprint requests to (C.M.T.R.) Glenrose Rehabilitation Hospital, 10230-111 Aye, Edmonton, Alberta, Canada T6G OB7.

PEDIATRICS (ISSN 0031 4005). Copyright © 1992 by the American

Acad-emy of Pediatrics.

Bronchopulmonary dysplasia (BPD) was originally described as a complication of premature infants with

hyaline membrane disease treated with mechanical

ventilation,1 and it has continued to be a troublesome feature of neonatal intensive care. Although modern

techniques of respiratory management may have

re-duced the morbid consequences of mechanical

yen-tilation,2’3 the increasing survival of smaller and

smaller infants has produced a population with a

high incidence of BPD,38 and hence the long-term

consequences of this condition in terms of growth

and neurodevelopmental outcome have been subjects

of ongoing concern and study. Several short-term (up

to 2 years) outcome studies have found deficits in

growth and/or development among survivors of

BPD9’5 and have resulted in divided opinion about

whether this increased risk is independent of other

pennatal and neonatal events.’6 Long-term outcome

(up to 8 years) has documented growth failure but no

significant neurodevelopmental delay in BPD

survi-vors compared with a control group of premature

infants,17 and another recent study has determined

that the need for supplemental oxygen and chronic

lung disease by itself had little relation to preschool neurologic and cognitive outcome’8 We have recently

demonstrated in another group of high-risk preterm

neonates (small-for-gestational age) that adverse

long-term neurodevelopmental outcome is more a

function of prematurity itself than the specific

high-risk condition and that the major determinants of

outcome in the premature group are measured by

socioeconomic 19

In this paper we report the 8-year school

perform-ance, neurodevelopmental outcome, and growth of

neonates with BPD and oxygen dependency

com-pared with neonatal comparison groups matched for

gestational age, birth weight, gender, mother’s edu-cation, and father’s socioeconomic status (SES), and

also with term peer comparison groups matched for

gender, mother’s educational level, and father’s SES. All subjects, both study and comparison, had parents with English as their mother tongue, a factor which we believe to be very important in making long-term school performance comparisons.’9 Because abnormal pulmonary outcome up to 2 years of age has recently

been correlated with oxygen dependency at 36 weeks

gestational age rather than 28 days postnatal age,2#{176}

we examined two groups of neonates of 31 weeks’

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gestation or less, one of which met this anew” defi-nition of BPD, the other meeting only the traditional

definition, and also a third group of neonates of 32

weeks gestational age or greater who satisfied the

traditional 28-day criterion.

Subjects

METHODS

BPD Study Groups. Three preterm study groups received

supple-mentary oxygen. The entry criteria for the three study groups

included the following: (1) BPD study group 1-subjects with a

gestational age of 3 1 weeks or less who received continuous

sup-plementary oxygen until their age exceeded the equivalent of 36

weeks’ gestation; (2) BPD study group 2-subjects with a

gesta-tional age of 3 1 weeks or less who received supplementary oxygen

for more than 28 days but not to the equivalent of 36 weeks’

gestation; (3) BPD study group 3-preterm subjects of 32 or more

weeks’ gestation receiving continuous supplementary oxygen for

more than 28 days. All BPD study infants were treated with

mechanical ventilation after initial resuscitation, at least within the

first week of life, and had radiographic evidence of BPD defined

by areas by hyperlucency interspersed with atelectasis and

pul-monary scarring according to standard definition.’ Gestational age

was determined by Dubowitz assessment.2’ Eligible children were

part of a prospective study of neonatal intensive care unit (NICU)

survivors cared for in the two tertiary care units (University of

Alberta and Royal Alexandra Hospital) of the Northern and Central

Alberta Regional Perinatal Program and enrolled in the long-term

Neonatal Follow-up Clinic of the Glenrose Rehabilitation Hospital

(Edmonton, Alberta, Canada). Forty-seven children (21, 15, and

1 1, in groups 1, 2, and 3, respectively), of whom 34 were boys and

who constituted 92% of those meeting the study entry criteria,

were assessed at 8 years of age between the years 1983 and 1987.

The parents of the children used English as their mother tongue.

None of the children had dysmorphic features, syndromes, or

chromosomal disorders known to be associated with developmental

delay. None required an intracranial shunt procedure for

hydro-cephalus and none had major intracranial hemorrhage diagnosed

clinically (routine screening imaging techniques were not employed

during the time of their neonatal care).

Comparison Subjects. There was one matched neonatal group

and one matched peer group for each of the three study groups.

Individually matched subjects constituted the three preterm

neo-natal comparison groups. While 62% of these children were treated

with varying durations of mechanical ventilation, none required

supplementary oxygen for 28 days and all had normal chest

roent-genographic results prior to the termination of oxygen therapy. The

gestational age for each child was determined by Dubowitz

assess-ment and was within 2 weeks of the mother’s dates. Each group

of matched neonatal comparison children (21, 15, and 1 1,

respec-lively) was selected from surviving children receiving care in the

same NICUs at the same time and enrolled in the same follow-up

program and for the same duration as the study children. These

children were subject to the same exclusions as the children of the

BPD study groups. Parents of all the matched children had English

as their mother tongue. The children were matched for mother’s

educational grade level, father’s Blishen SES22 (highest index

al-lowed based on past employment if father was unemployed at the

time of testing), and gender, as well as gestational age (within 2

weeks) and birth weight (within 200 g).

The three peer comparison groups comprised of 47 children (21,

15, and 1 1 for each group) of parents with English as their mother

tongue. They were matched to the study subjects for gender,

mother’s educational grade level, and father’s SES. They were

selected from an established peer group of 155 previously described

children who were from various locales and socioeconomic groups,

attended regular school, according to their parents’ questionnaire responses had birth weights >2500 g and gestation ages >37 weeks,

and as neonates had been cared for in well-baby nurseries.23

Approval for the testing was obtained from school authorities.

Parents of individual children signed written consents before

test-ing.

Procedure

The procedures for the measurements of growth and recording

of illnesses and hospitalizations have been previously reported.’

The procedures for and details of tests used for the 8-year

neuro-developmental, psychoeducational, and school performance testing

have been previously reported.23 Briefly, at the age of 8 years,

study children were individually assessed in English by a

devel-opmental pediatrician (C.M.T.R.), nurse, certified psychologist,

au-diologist, and reliability-tested educator. The assessors, other than

the physician, were unaware of the neonatal history details.

Inde-pendent diagnoses for the physically disabled children at 8 years

of age were obtained from a pediatric physiatrist and the clinic’s

pediatrician (C.M.T.R.). Conditions considered to be a disability

have been previously documented,’923 and for this study include

cerebral palsy, visual impairment (acuity <20/60), legal blindness

(acuity <20/200), cognitive delay (intelligence quotient >3 SD

below the mean on standardized testing), convulsive disorder, and/

or neurosensory hearing loss requiring amplification.

Psychoeducational and School Performance Tests

The psychoeducational and school performance tests, as

previously reported,23 included the Wechsler intelligence scales,24

the Peabody Picture Vocabulary Test,25 and the Developmental

Test of Visual-Motor Integration.26 The level of school performance

was measured by the McCracken Standard Reading Inventory,27

the Edmonton Spelling Abilities Test,28 and KeyMath Diagnostic

Arithmetic Test.29 School performance tests for reading, spelling,

and arithmetic were scored as the grade level achieved compared

with the expected grade level for chronologic age and birth date.

Children with school performance of 1 year below expected grade

level for one or more of reading, spelling, or arithmetic were classed

as academically delayed. In addition to the specific tests, each

child’s teacher, who was unaware of the neonatal status of the

children and of this study, was asked whether the classroom was

a regular or special one and whether the child received resource

room help. The teacher also completed a checklist behavior rating

scale, the Davids Scale of Hyperkinesis.3#{176}

Information from the comparison peer group on identical school

performance and psychoeducational tests was compared with that

for the preterm groups. Assessors were aware that the peer group

children were not in the neonatal follow-up groups.

Data Handling

Statistical analyses were performed on the data from 141

chil-dren. There were 21 children in BPD study group 1, 15 in BPD

study group 2, and 1 1 in BPD study group 3. Thus, there were 47

study children in three BPD groups, 47 matched neonatal

compar-ison children, and 47 matched term peer comparison children,

giving a total of nine groups. The Cochran Q Test for repeated

measures was employed to test group differences on noncontinuous

variables. For continuous variables, multiple analysis of variance

(MANOVA) for repeated measures using Wilks’ lambda method3’

was used to examine the significance of difference in means for

the various subgroups. One overall two-way repeated-measures

MANOVA for all psychoeducational and school performance

out-come variables simultaneously was done prior to univanate

analy-sis, to determine overall significance. Scheff#{233} multiple comparison

of means was calculated in the context of the entire analysis. If the

MANOVA was significant then individual univariate significance

levels are reported for each of the MANOVAs for each of the

outcome variables using Scheff#{233} comparisons to determine the

location of the significance. The level of significance used was .05

unless otherwise indicated. The Geisser-Greenhouse Method of

adjusting for nonhomogeneity of variance was used.3’ Comparisons

of the three BPD study groups (not including matched groups)

were done using one-way analysis of variance (ANOVA).

Descrip-five variables and variables used to individually match the children

were entered into stepwise multiple regression analysis to

demon-strate combinations of variables that work together to predict school performance.

RESULTS

The original cohort of prospectively identified high-risk infants included 466 consecutively admitted

(3)

less, of whom 242 (52%) died-228 in hospital and 14 after discharge (one with chronic pulmonary in-sufficiency due to BPD); 48 (10%) were lost to follow-up (28 after 31/2 yeaIS of age; 5 with cerebral palsy

and 5 others without physical disability but with

cognitive scores below average, that is, >1 SD below the mean on standardized testing); leaving 176 (38%)

subjects who survived and were followed to 8 years

of age and from whom the children studied in this

paper were chosen. Fifty-one of the 1 76 subjects

assessed at 8 years of age received mechanical venti-lation for at least several days and supplementary oxygen for >28 days. Of these 51, fifteen were ex-cluded from further analysis for this study: 9 because

their parents used English as a second language and

6 because of severe neurologic complications of

intra-cranial hemorrhage (ICH). These 6, who require

spe-cialized institutional or group home care, were evenly distributed in BPD groups 1 and 2; 3 had had neonatal

intracranial shunts and were severely disabled and 3

others were profoundly disabled following gross

neo-natal ICH. These disabled children could not be

as-sessed, leaving 36 subjects in BPD study groups 1 and 2 for this study.

In addition, during the same years, 13 premature

children with gestational ages of 32 weeks or more,

whose parents’ mother tongue was English and who

were free from intracranial shunts or clinically

diag-nosed ICH, received supplementary oxygen for

greater than 28 days and were discharged alive from

the NICUs. Two of these were lost to follow-up and

the remaining 1 1 seen at age 8 years were the children

selected for BPD study group 3.

Table 1 displays the variables used to match the

preterm study groups receiving long-term

supple-mentary oxygen with the comparison groups. BPD

study group 1 did not differ from BPD study groups

2 and 3 other than for the requirement of longest

duration of supplementary oxygen (mean of 80 days).

BPD study group 3 subjects differed from BPD study

groups 1 and 2, demonstrating greater birth measure-ments reflecting their greater gestational age. All BPD

study groups required more supplementary oxygen

and included more children with patent ductus

arter-iosus than their corresponding neonatal matched

groups. BPD study groups 1 and 3 remained in the

NICU longer. Four of the BPD study children and

two of the matched neonatal comparison children

had birth weights <10th percentile compared to

standard curves.33

At age 8 years no significant differences were found

on growth and health variables between the three

BPD

study groups (Table 2). There was no significant

gender effect. Children of BPD study groups 1 and 2

(with a gestational age of 3 1 weeks) did not differ in their weight and height from those of their matched

neonatal comparison groups. However, children in

the greater gestational age BPD study group 3 were

lighter and had less subcutaneous tissue than those

of their corresponding matched neonatal group. The

mean percentile of weight for all preterm children

was as follows: boys 32.2, girls 30.9; height: boys

36.9, girls 40.9 when plotted on standard growth

curves.34 All groups of preterm children were shorter

and lighter than the matched term peer comparison

group. There were no significant differences in the

proportions of disabled children among the preterm

groups, although those in BPD study group 1 with

the longest duration of oxygen therapy had the high-est percentage of disability (8/21; 38%).

Classroom teachers of the children at 8 years of age

reported that 48% of those children in BPD study

group 1, 38% of their matched neonatal comparison

group, and 19% of their peer group were receiving

school resource room help or attending special class for disabled children at the time of the study. Forty percent of BPD study group 2, 47% of their matched

neonatal comparison group, and 7% of their

corre-sponding peer group received resource room help or

attended special class according to teacher report.

Sixty-four percent of BPD study group 3, 28% of the

corresponding neonatal group, and 36% of their

cor-responding peer group had similar reports.

The overall MANOVA group effect for

psychoed-ucational and behavioral test score results was not

significant, that is, there were no differences between

the BPD study groups on these outcome variables as

a group. Univariate one-way ANOVA results for

intelligence quotient demonstrated a lower score for BPD study group 1, while receptive vocabulary

was lower for both BPD study groups 1 and 3. The

MANOVA matching effects were significant: BPD

study groups 1 and 2 and their matched neonatal

groups had significantly lower mean scores overall

on psychoeducational and school performance testing and higher ratings on the Davids Scale of Hyperki-nesis than the peer groups (Table 3)-Scheff#{233} multi-ple comparisons indicated that this was particularly

true for the BPD study group 1 children and their

matched neonatal group and that many of the

mdi-vidual scores for BPD study group 2 and their

matched neonatal group did not differ from their peer group. BPD study group 3 children had significantly

poorer mean scores on intelligence quotient and

hyperactivity than both their corresponding matched

neonatal group and their matched peer group (Table

3). Results were not affected by gender. The

percent-age of academic delay (delay in one or more of

reading, arithmetic, or spelling scores) in the

corn-bined BPD study group and the combined matched

neonatal comparison group was significantly greater

than that in the combined matched peer comparison

group: 24 (5 1

%)

and 22 (47%) vs 9 (19%), Cochran

Q

Test 20.0, df 2, P < .001. There were no significant differences in percentage of academic delay between

each of the three BPD study groups (57% vs 40% vs

55%) or between each study group and its matched

neonatal comparison group.

Further outcome analyses were done using only

those children from the three BPD study groups who

were not disabled and their corresponding matched

children from the peer group. When the scores of the

nondisabled children from each of the three BPD

study groups were compared, there were no

differ-ences in means or standard deviations. When the

scores from the 36 nondisabled children from all three

BPD

study groups combined were compared with

those of their matched subjects from the peer groups,

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TABLE 1. Means and Standard Deviations/Percentages for Descriptive Variables for Three Preterm Bronchopulmonary Dysplasia

(BPD) Study Groups, Three Matched Neonatal Comparison Groups, and Three Matched Peer Comparison Groups*

Variable BPD Study Comparison Groups BPD Study Comparison Groups BPD Study Comparisons Groups

Group 1 Group 2 Group 3

(n = 21) Neonatal 1 Peer 1 (n = 15) Neonatal 2 Peer 2 (n = 1 1) Neonatal 3 Peer 3

(n=21) (n=21) (n=15) (n=15) (n=11) (n=11)

Continuous, mean (SD)

Gestation, wkt 29.3 (1.2) 30.0 (1.3) >37 28.7 (1.8) 29.1 (2.1) >37 33.2 (1.6) 33.4 (1.6) >37

Birth weight, kg 1.2 (0.3) 1.2 (0.2) >2.5 1.1 (0.2) 1.1 (0.2) >2.5 1.7 (0.6) 1.7 (0.5) >2.5

Birth length, cm 38 (3) 38 (3) ... 38 (2) 38 (2) ... 43 (4) 42 (4) ..

Birth head circumference, 26 (2) 27 (2) ... 26 (2) 26 (2) .. . 29 (3) 29 (3) ...

cm

Mother’s antepartum risk 6 (4) 5 (3) ... 7(4) 6 (5) ... 5 (2) 4 (3) ...

score32

Neonatal intensive care 1 15 (49) 69 (32) ... 88 (29) 75 (20) ... 108 (56) 39 (18) ..

unit, d

Supplementary oxygen, d 80 (184 9 (9) ... 34 (6) 11 (9) .. . 48 (10) 4 (5) ..

LowestrecordedPao2 32(6) 39(14) .. . 33(11) 40(13) .. . 27(8) 35(11) ...

Admission hemoglobin, 16 (2) 17 (1) ... 15 (2) 15 (2) ... 16 (3) 16 (4) ...

mg/100 mL

Lowest recorded pH 7.2 (0.08) 7.24 (0.07) ... 7.2 (0.05) 7.3 (0.06) ... 7.2 (0.08) 7.3 (0.05) ...

Mother’s education grader 12.1 (1.5) 12.0 (1.3) 12.0 (1.4) 11.3 (1.2) 11.6 (1.0) 11.6 (1.1) 11.6 (1.3) 11.5 (0.5) 11.5 (1.0)

Father’s Blishen indext 46 (14) 44 (14) 46 (16) 43 (16) 43 (15) 42 (15) 41 (14) 42 (15) 41 (13)

Noncontinuous, no. (%)

Gender, malet 14 (67) 14 (67) 14 (67) 10 (67) 10 (67) 10 (67) 10 (91) 10 (91) 10 (91)

Sibling order, first 8 (38) 9 (43) 9 (43) 6 (40) 6 (40) 6 (40) 6 (54) 5 (46) 4 (36)

Born in tertiary hospital 14 (67) 15 (73) . .. 5 (33) 12 (80) ... 6 (56) 5 (46) ...

Apgar score at 1 mm, 3 7 (33) 9 (43) . .. 10 (67) 4 (27) ... 2 (18) 5 (46) ...

Mechanical ventilation after 21 (100) 15 (71) . .. 15 (100) 10 (67) ... 11 (100) 4 (36) ...

initial resuscitation

Patent ductus arteriosus 17 (814 6 (29) . .. 13 (87) 4 (27) .. . 8 (73) 3 (27) ...

Neurologic examination at 14 (674 4 (19) .. . 9 (60) 5 (33) ... 9 (82) 4 (36) ..

discharge, abnormal

aBPD study group I : gestation 31 weeks, supplementary oxygen >36 weeks’ gestation; BPD study group 2: gestation 31 weeks,

supplementary oxygen >28 days of life; BPD study group 3: gestation 32 weeks, supplementary oxygen >28 days of life.

t Five variables used for matching comparison groups with BPD study groups.

: P < .01 (multiple analysis of variance with Scheff#{233} multiple comparison and Cochran Q test) denotes significant matching effect’BPD

study group result is significantly different from that of the corresponding neonatal matched group.

§ P < .001 (analysis of variance) denotes significant effect: BPD study group mean is significantly different from those of the other. BPD

study groups.

the mean test scores were lower in all areas (Table 4). Eighteen (50%) of the 36 nondisabled children of the

combined three BPD study groups demonstrated

ac-adernic delay compared with 19% of the combined

matched peer groups. Forty-four percent (16/36) of

the nondisabled preterm neonatal comparison group

of children had academic delay.

Stepwise multiple regression analysis for the

de-pendent variable of academic level (average of read-ing, spelling, and arithmetic levels) was completed

for the 21 BPD study group 1 children. Those

vari-ables from Table 1 with a significant correlation (r)

(P <

.05)

to lower academic level included lowest recorded pH (r = .55, P =

.005),

more older siblings

(r =

.50,

P = .01), lower father’s SES (r = .46, P =

.02),

and lowest recorded Pao2 (r = .44, P =

.02).

The

multiple correlation coefficient (R) for the

combina-tion of variables predicting academic level was .82

(step 1, lowest recorded pH, adjusted R2 = .26; step 2, father’s SES, adjusted R2 =

.50;

and step 3, lowest

recorded Pao2, adjusted R2 = .61).

When the 8 disabled children were excluded from

BPD study group 1, the data from the remaining 13

children could not be effectively assessed by multiple

regression because of the small number. However,

significant individual correlations (r) (P < .05) were as follows: gender (r = .5 1, P = .00 1), mother’s level

of schooling (r = .42, P = .006), and lowest recorded

pH(r= .38,P= .01).

DISCUSSION

This study demonstrates the complexity of theyari-ables contributing to the outcome of preternvinfants requiring prolonged supplemented oxygen during the newborn period. The results are instructive as ‘they come from one of the few school-age outcome studies that have attempted to take into consideration ether complications of prematurity and social issues. that

could confound the outcome for these children. The

results clearly show the ongoing problems of. these

preterm children. However, this group of chil#{231}lren, reported after the completion of 8 years of follow-up, are not representative of the smallest or the sickest

infants now surviving the newborn period. ,Thus,

these results must be viewed in this context rather than be generalized to all infants with chronic lung

disease cared for today, of whom many were,born

several weeks earlier. We expect that this paper will be of interest in future years in a historical sense, as the story of BPD unfolds; hence, comprehensive iden-tification of variables is included.

While the percentage of outcome data avail4ile at

age 8 years for the BPD study children meeting the

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TABLE 2. Means and Standard Deviations/Percentages for Repeated Me

Preterm Bronchopulmonary Dysplasia (BPD) Study Groups, Three Matched

Comparison Groups*

asures of 8-Year Growth and Health Variables for Three

Neonatal Comparison Groups, and Three Matched Peer

Variable BPD Study Comparison Groups BPD Study

Groupi Neonatal 1 Peer 1 Group2

(n=21) (n=21)

Comparison Groups

Neonatal 2 Peer 2

(n=15) (n=15)

BPD Study Comparison Groups

Neonatal 3 Peer 3

(n=11) (n11)

Continuous, mean (SD)

Weight, kg 23 (5) 23 (4) 27 (3) 24 (5)

Length, cmt 120 (8) 122 (7) 127 (7) 124 (7)

Head circumference, cm 50 (2) 51 (2) ... 52 (1)

Tricepsskinfold,mm 7.7(4.2) 6.7(2.3) ... 6.6(2.9)

Subscapular skinfold, mm 6.1 (3.7) 4.7 (1.7) ... 5.3 (3.7)

Illnesses requiring doctors’ 22 (10) 18 (14) ... 26 (14)

attention (discharge to 8

y)

Hospitalizations (discharge 3 (2) 2 (3) ... 3 (3)

to 8 y)

Noncontinuous, no. (%)

Disabled (child has 1 or 8 (38) 6 (27) 0 (0) 2 (13)

more of)

Cerebral palsy 3 (14) 5 (24) 0 (0) 2 (13)

Legal blindness 2 (10) 0 (0) 0 (0) 0 (0)

Visual impairment I (5) 1 (5) 0 (0) 0 (0)

Deafness 1 (5) 1 (5) 0 (0) 0 (0)

Severe or profound retar- 3 (14) 1 (5) 0 (0) 0 (0)

dation

23 (3) 28 (4)

123 (6) 128 (7)

51 (2) . ..

6.7(3.0) .. . 5.1 (2.4) ...

21 (14) ...

3 (4) . ..

4 (27) 0 (0)

3 (20) 0 (0)

0 (0) 0 (0)

1 (7) 0 (0)

0 (0) 0 (0)

22 (5) 25 (4) 27 (6)

124 (5) 125 (5) 128 (5)

51 (2) 53 (1) ..

4.7(1.8) 8.2(4.6) ...

4.0 (1.3) 5.8 (3.1) ...

18 (16) 15 (12) ...

3 (3) 2 (1) ..

1 (9) 1 (9) 0 (0)

0 (0) 0 (0) 0 (0)

1 (9) 1 (0) 0 (0)

0 (0) 0 (0) 0 (0)

1 (9) 0 (0) 0 (0)

* BPD study group 1: gestation 31 weeks, supplementary oxygen >36 weeks of gestation; BPD study group 2: gestation s31 weeks,

supplementary oxygen >28 days of life; BPD study group 3: gestation 32 weeks, supplementary oxygen >28 days of life. Many peer

group values are missing.

tP <. .01 (multiple analysis of variance) denotes significant matching effect: BPD study group means and those of the matched neonatal

comparison groups are significantly different from those of the matched peer comparison groups.

P < .01 (multiple analysis of variance) with Scheff#{233} multiple comparisons) denotes significant matching effect: BPD study group

measurement is significantly different from that of the corresponding matched neonatal group.

used.-the overall MANOVA approach. Although the

numbers are small, detailed matching of the three

different BPD study groups with both preterm

chil-dren .receiving care in the same tertiary NICUs and

follow.up program and term children from the

corn-munity .gives this study a unique, albeit somewhat

compMcated, perspective. The favorable mean

intel-lectuaLtest score of the community children indicates

that those children with whom NICU survivors

corn-pete .kt the regular school system are very cap-able children, as we have previously discussed.19’23

This study has attempted to put the 8-year test

results.of the children of 31 weeks’ gestation at birth

into perspective by providing the overall outcome of

that entire consecutively admitted population of

chil-dren that received initial neonatal care through this

regional program. It is accepted that the gestational age based on clinical examination for all 466 children may not.ttave been entirely accurate; however, it was universally available and this was not the case for all mother’s dates.

The. interpretation of the most conservative statis-tical aRalysis used to determine the results of this study (ie, the overall two-way repeated-measures

MANOVA for all psychoeducational and school

per-formance outcome variables simultaneously) shows

that those children of 31 weeks’ gestation with BPD

and their matched neonatal groups perform less well

than their corresponding comparison peer groups.

Thus the long-term neurodevelopmental outcome

and school performance of preterm neonates

requir-ing prolonged supplemental oxygenation is, to a great extent, as much a function of prematurity as of this specific condition, findings that are similar to those

of Sauve and Singhal.’7 However, using a less

con-servative, but more specific and common analysis

(ANOVAs), small differences were seen between

groups showing that pulmonary problems made some

difference to outcome. For neonates of 31 weeks’

gestation with oxygen dependency at 36 weeks or

more gestational age (BPD study group 1), the 8-year

intelligence quotient was less than that of those

chil-dren requiring oxygen to 28 days postnatal age (BPD

study group 2), but other results were similar and

similar to their matched preterm neonatal comparison

groups. This same group (BPD group 1) had more test

scores that were below their corresponding matched

peer group than those children in BPD study groups

2 and 3 when compared with their matched peer

groups. Analysis of variance also determined that for

children of 32 weeks’ gestation, prolonged

supple-mental oxygen identified those infants as a BPD group

with some psychoeducational scores below their

matched preterm neonatal comparison group. This

BPD

study group 3, with the greatest gestational age,

is comparable with Northway and coworkers’ original

population of larger preterm infants with BPD who

demonstrated delayed school progress compared with

preterm and full-term controls.35

While there were differences in duration of oxygen

supplementation between groups whose gestation

was 31 weeks, this distinction had little effect on

outcome. Thus, the differences seen in the 2-year

pulmonary outcome between old- and new-definition

BPD populations2#{176} did not translate into

psychoedu-cational differences at age 8 years. The higher

pro-portion of disability in the BPD group with the longest

duration of supplemental oxygen was not

(6)

TABLE 3. Means and Standard Deviations for 8-Year Psychoeducational Scores and the Davids Rating Scale of Hyperkinesis for the

Three Preterm Bronchopulmonary Dysplasia (BPD) Study Groups, Three Matched Neonatal Comparison Groups, and Three Matched Peer

Comparison Groups*

Variable BPD Study Comparison Groups BPD Study Comparison Groups BPD Study Comparison Groups

Group I Group 2 Group 3

(n = 21) Neonatal 1 Peer 1 (n = 15) Neonatal 2 Peer 2 (n = 1 1) Neonatal 3 Peer 3

(n=21) (n=21) (n=15) (n=15) (n=11) (n=11)

IQ score: full-scale 88 (21411 97 (204 115 (10) 103 (15) 96 (154 115 (10) 94 (25) 106 (13) 113 (12)

Visual-motor integration 6.2 (3)1 7.1 (34 10.2 (2) 7.5 (2) 6.8 (3) 9.2 (3) 6.5 (3) 8.7 (3) 8.5 (2)

Receptive vocabulary 88 (18) 91 (18) 102 (11) 102 (11)11 97 (16) 109 (13) 86 (21) 108 (11) 106 (8)

School performancet

Readinglevel -l.6(1.9)t -(o)t +0.5(1.3) -0.7(1.3) -0.8(1.7)t +0.6(1.1) -1.3(1.8) -0.3(1.6) -0.1(1.2)

Spelling level -1.1 (1.8)t -0.8 (1.5) +0.1 (0.7) -0.7 (0.7) -0.6 (1) +0.2 (0.7) -1.1 (1.7) +0.1 (1) -0.4 (0.7)

Arithmeticlevel -1.3(1.7)t -1.0(1.1)t -0.1(1.1) -0.7(0.9) -1.0(0.9)t +0.1(0.8) -1.3(1.4) -0.7(0.9) -0.4(0.4)

Hyperactivity rating 21 (5)t 22 ()t 15 (7) 20 (54 20 (4)1 14 (8) 23 (5)* 18 (5) 15 (6)

31 weeks,

* BPD study group 1: gestation 31 weeks, supplementary oxygen >36 weeks of gestation; BPD study group 2: gestation

supplementary oxygen >28 days of life; BPD study group 3: gestation 32 weeks, supplementary oxygen >28 days of life.

t School performance is expressed as grade level above (+) or below (-) grade level expected for age.

t P < .001 (multiple analysis of variance with Scheff#{233} multiple comparison) denotes significant matching effect: BPD study group and/or

matched neonatal comparison group mean is significantly different from that of the matched peer comparison group.

§P < .05 (multiple analysis of variance with Scheff#{233}multiple comparison) denotes significant matching effect: BPD study group mean is

significantly different from that of the corresponding matched neonatal group.

IIP< .05 (analysis of variance) denotes significant effect: BPD study group mean is significantly different from those of other BPD study

groups.

TABLE 4. Multiple Analysis of Variance for Repeated Measures of 8-Year Psychoeducational

Outcome Variables and School Performance and the Davids Rating Scale of Hyperkinesis for the 36

Nondisabled Children of the Bronchopulmonary Dysplasia (BPD) Study Groups and Their Matched

Peer Group*

Variable Combined BPD Study Combined Matched

Groups (Nondisabled) Peer Group

(n=36) (n=36)

IQ score

Full-scale 101 (13) 114 (10)t

Verbal 101 (13) 111 (11)t

Performance 100 (12) 115 (10)t

Visual-motor integration 7.5 (1.9) 9.5 (2.4)t

Receptive vocabulary 97 (12) 105 (12)t

School performance

Reading level -0.8 (1.3) +0.3 (1.1)t

Spelling level -0.6 (0.9) +0.0 (0.6)t

Arithmetic level -0.7 (0.8) -0.1 (0.6)t

Hyperactivity rating 21 (5) 13 ()t

* Data are expressed as mean followed by standard deviation in parentheses.

t P < .001 denotes significant difference between groups in univariate F test following significant overall multiple analysis of variance.

cantly greater than the proportion of the other BPD

groups; however, the numbers were small, possibly

affecting significance levels. All preterm children with

BPD, whether determined by new or old definition,

did less well than their term matched peer comparison

groups. This was true although none of the study

children required a shunt procedure for hydrocepha-lus and none had clinically diagnosed ICH; however, lesser degrees of ICH would likely have been present

in some children. Large percentages of all preterm

children, both BPD and neonatal comparison groups,

demonstrated academic delay on testing and were

receiving resource room help or were attending

spe-cial classes. These findings were much less marked, as might be expected, in the larger healthier preterm

infants (neonatal comparison group 3). School

per-formance scores continued to be delayed when the

children with developmental disabilities were

ex-cluded.

Growth and frequency of postnatal illnesses and

hospitalizations in the BPD study groups of 31

weeks’ gestation and their matched preterm neonatal

comparison groups were similar. For children with a

gestation of 32 weeks, those with oxygen for >28

days had a lower mean weight and less subcutaneous tissue (triceps) than their matched neonatal

compari-son group. Eight-year height and weight of all

pre-term children was significantly less than those of the

peer group children in this study and the mean

per-centiles achieved suggest a lack of 8-year catch-up growth in contrast to that described in the follow-up of healthy very low birth weight populations,36’37 but similar to that reported in other long-term studies of children with chronic lung disease.’7’35 Regrettably

this study cannot relate 8-year pulmonary function

studies to other outcome measures; however, airway

obstruction and lowered oxygen saturation at

maxi-mum workload have been reported in both those

children who have had BPD and others who have

received artificial ventilation as neonates38 and may explain growth lag in this population. Differences in reported pulmonary outcomes2#{176} between those in-fants of 31 weeks’ gestation requiring supplemental

(7)

gestation and those requiring supplemental oxygen to 28 days could not be confirmed by this study.

Stepwise multiple regression for academic level for

BPD study group 1 showed that academic

achieve-ment was related to the combination and interaction

among the following variables: lowest recorded pH,

father’s SES, and lowest recorded Pao2 (adjusted R2

= .61). That is, low scores on these variables tended

to be associated with poor academic outcome. Even when the disabled children were excluded, the lowest

recorded pH level still contributed to outcome. The

role of acidosis as measured by lowest recorded pH

correlated with poor outcome even in the nondisabled

children and coincides with a strong association of

neonatal acidosis (presumably as a reflection of the

severity of pulmonary disease) and cognitive delay

previously described in children with BPD.39 Social factors as measured by the variables father’s

SES and mother’s education achievement appear to

play a role in the school performance of this

population as in other populations of high-risk

in-fants.19 The mean father’s Blishen socioeconomic

score for the groups of study subjects and hence for

their matched comparison groups was found to be at

the midpoint of this Canadian index, which is based

on father’s education, income, and employment as a

prestige factor and is ranked from <20 to >75.22 The

children of this study came from homes representing all social levels, not particularly from homes

consid-ered to be from lower SES levels. We, at this time,

are not reporting on risk factors related to parents’

behavior that have been recently reported as a

pri-mary predictor of outcome in another population of

preterm children with chronic lung disease.’8

How-ever, the children in this study were closely monitored and there was no evidence of physical abuse or major neglect of any of the preterm children that could have overtly affected their long-term outcome. In another

study we have found less attachment of parents for

children who have received prolonged oxygen

ther-apy as infants compared with other NICU survivors.40

Thus both adverse medial and social factors

strongly influenced school outcome for these children

who were medically compromised in the newborn

period as has been reported previously.444 The find-ings of this study are consistent with some studies reported in the literature but not with others. Skid-more et al’5 have reported an increased risk of cerebral

palsy and other neurodevelopmental problems

among low birth weight infants with chronic lung

disease. They determined that among infants with

birth weights 1500 g the combination of chronic

lung disease and ICH along with low SES all contrib-uted to explaining the poor outcome. They also noted that those infants with mild to moderate lung disease,

who did not have a high incidence of ICH and other

disabilities, were indistinguishable from healthy peers at 2 years of age. Hunt et al,4’ in an 8- and 1 1 -year

follow-up of children with birth weights 1500 g,

found that when they dichotomized their population into those infants with no problems in the perinatal period and those with moderate to severe problems,

and divided the parents into those with high and

those with low education, then there were differences

in outcome. Children with moderate to severe

peri-natal problems as a group did worse than children

without those problems. Moreover, when low parent

education was added to the analysis, the childrens’

outcome was even worse. The authors excluded those

children with significant disabilities from the overall analysis. Leonard et al’8 suggested that respiratory

problems in the 1250-g infant evaluated at an

av-erage of 60 months had no significant effect on

out-come while environmental stresses did. The results

presented in these papers emphasize the effect of the

social environment as described by Escalona42 and

Sameroff et al.44

The adverse effects of prematurity were described

by Klein et al,45 who reported that the developmental

and academic achievement at 9 years of age of

chil-then with birth weights 1500 g was significantly

below that of full-term children of the same age and SES. Similar findings were reported by Eilers et al46 in a group of children evaluated at 5 to 8 years with

birth weights 1250 g. These authors found that more

than 50% of their subjects (including the disabled)

required more special education efforts than the

gen-eral school population.

With respect to the long-term effects of early pul-monary problems in premature infants, the literature

is discordant. An early report from England showed

that very low birth weight school-age children born

in the late 1960s and early 1970s actually did better

if they had respiratory distress in the newborn period

compared with those who did not.47 Two more recent

studies found no significant neurodevelopmental

de-lay in BPD survivors compared with other preterm

infants,17”8 and another recent study from Hungary

reported that those extremely low birth weight

sur-vivors who required more oxygen therapy in the

neonatal period did less well at school age.48 Our

study confirms that children with low birth weight

generally do less well academically at 8 years of age than the term peer comparison children. It suggests

the history of prematurity rather than chronic lung

disease is the major medical factor in determining outcome, although respiratory variables play a role in

the more severely affected children. These findings

can probably be extrapolated to older schoolchildren,

as several long-term studies suggest that the 1 1- or

14-year outcome of preterm children does not vary

greatl1 from the 8-year psychoeducational

find-ings.4

These results have important implications. The

sub-jects evaluated did not include the most

neurologi-cally compromised infants, nor did the study include

subjects with a gestational age at birth of about 4

weeks earlier as would be the case today. These

results cannot be generalized to the current

popula-tion of extremely low birth weight infants. However,

it is apparent that for the smaller preterm infants of

our study, prematurity with and without chronic lung

disease, along with adverse social factors,

compro-mises the outcome for low birth weight infants even

when disabled children are excluded from analysis.

For somewhat larger preterm infants, chronic lung

disease effects could be seen. By implication, the

smaller the baby and the more severe the

(8)

tions of prematurity, the less optimal will be the outcome. Drawing on the results of this study as well as others, it would appear that the current task before us is to prevent prematurity, so far as is possible. When this is not possible, the goal must be to mini-mize the complications of preterm birth and enhance

the environments in which these small babies will be

reared.

ACKNOWLEDGMENTS

Financial support for this research was provided by the Northern

and Central Alberta Regional Perinatal Program and the Glenrose

Rehabilitation Hospital, Edmonton, Alberta, Canada.

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Pediatrics

Charlene M.T. Robertson, Philip Charles Etches, Edward Goldson and Janis Mildred Kyle

Neonates With Bronchopulmonary Dysplasia: A Comparative Study