Article neonatology

Bronchopulmonary Dysplasia:
An Enduring Challenge
Yvonne E. Vaucher, MD,
Objectives After completing this article, readers should be able to:
MPH*
1. Describe the most common cause of chronic lung disease during infancy.
2. Explain the importance of a history of bronchopulmonary dysplasia throughout
childhood.
3. Identify infants at high risk for developing bronchopulmonary dysplasia.
4. List the adverse effects associated with postnatal corticosteroids.

Introduction
Despite clinical advances in antepartum, intrapartum, and neonatal care, bronchopulmo-
nary dysplasia (BPD) continues to challenge infants who have been in neonatal intensive
care units and their caretakers. BPD is the most common cause of chronic respiratory
disease during infancy and remains a major cause of long-term medical, pulmonary, and
neurodevelopmental morbidity, increasing the cost of health care and the utilization of
medical and educational resources throughout childhood.

Definition
BPD is a clinical diagnosis, defined by oxygen dependence for a specific period of time after
birth and accompanied by characteristic radiographic findings that correspond to anatomic
abnormalities. Thus far, a precise physiologic definition of BPD is lacking. As the clinical
presentation has evolved over the past 30 years, so has the definition. As originally
described by Northway in the 1960s, the diagnosis of classic BPD was based on progressive
radiographic changes in preterm infants who were treated for severe respiratory distress
syndrome (RDS) immediately after birth and had prolonged ventilator and oxygen
dependence. This form of BPD occurred in larger, relatively mature preterm infants, who
required treatment with high-pressure mechanical ventilation and high concentrations of
oxygen. Although the acute respiratory disease initially improved in these infants, oxygen
requirements increased 7 to 10 days after birth and persisted for at least 28 days. The
definition of BPD subsequently was modified by Bancalari to include preterm infants who
had less severe RDS that initially required short-term me-
chanical ventilation, but who also developed persistent respi-
ratory symptoms and an oxygen requirement for at least
Abbreviations 28 days after birth accompanied by radiographic abnormal-
BPD: bronchopulmonary dysplasia ities. The presentation of BPD continued to evolve with the
CLD: chronic lung disease advent of antenatal steroids and postnatal surfactant admin-
CP: cerebral palsy istration, which reduced the incidence and severity of RDS
ECMO: extracorporeal membrane oxygenation and increased the survival of extremely small, very immature
GER: gastroesophageal reflux infants (⬍30 weeks’ gestation or ⬍1,250 g birthweight).
IVH: intraventricular hemorrhage These infants had milder chronic pulmonary problems that
PCA: postconceptual age often resolved by discharge. Shennan noted that the need for
PFT: pulmonary function test supplemental oxygen until at least 36 weeks postconceptual
PVL: periventricular leukomalacia age (PCA) in these infants was much more predictive of later
RDS: respiratory distress syndrome pulmonary morbidity. He, therefore, recommended that
RSV: respiratory syncytial virus oxygen dependence at 36 weeks PCA, instead of 28 days
VLBW: very low-birthweight after birth, be used as a more clinically relevant definition of
BPD.

*Clinical Professor of Pediatrics, Division of Neonatology, University of California, San Diego, Calif.

Pediatrics in Review Vol.23 No.10 October 2002 349

neonatology bronchopulmonary dysplasia

Some very low-birthweight (VLBW), extremely pre- Term and near-term infants also are at risk for BPD
term infants born between 23 and 28 weeks’ gestation following severe respiratory failure treated with very high
and weighing less than 1,250 g develop increasing oxy- oxygen concentrations, mechanical ventilation, and ex-
gen requirements 1 to 2 weeks after birth, even without tracorporeal membrane oxygenation (ECMO). BPD oc-
preceding lung disease, mechanical ventilation, or oxy- curs in up to 27% of term or near-term infants who have
gen therapy. This form of atypical BPD is reminiscent of very severe primary respiratory disease (ie, RDS, meco-
Wilson-Mikity disease that was described contemporane- nium aspiration, pneumonia, sepsis) and in up to 50% of
ously with classic BPD. The clinical onset of atypical BPD those who have underlying pulmonary hypoplasia (eg,
is characterized by a delayed, gradual increase in oxygen congenital diaphragmatic hernia) and are treated with or
dependence, milder symptoms overall, and more rapid are eligible for ECMO.
resolution of symptoms and weaning to room air. The Advances in neonatal care have decreased the inci-
term chronic lung disease (CLD) often is used instead of dence of BPD only in larger, more mature preterm
BPD to denote persistent pulmonary insufficiency and infants. The risk of BPD in VLBW infants is not reduced
oxygen requirement beyond 36 weeks PCA regardless of by antenatal steroids, surfactant administration, or any
the cause or need for mechanical ventilation. specific type of respiratory support (eg, conventional
Defining BPD by the need for supplemental oxygen ventilation or high-frequency ventilation), although the
alone at a specific point in time does not take into disease is less severe than in the past. However, there are
account different parameters for oxygen use or adjunc- substantial differences in the incidence of BPD between
tive therapies, such as diuretics,
fluid restriction, bronchodilators,
or steroids, that affect the need for
supplemental oxygen. Conse-
quently, it is difficult to determine
accurately the incidence and prev-
The risk of bronchopulmonary dysplasia
(BPD) is multifactorial— duration of
alence of BPD or to compare
treatments or outcomes among
mechanical ventilation and oxygen
different neonatal centers. administration, infections, and low
birthweight are most important, but term
Epidemiology
The risk of BPD is multifactorial. infants treated with high oxygen
It is related directly to the severity
of the initial lung disease (most
concentrations are also at risk.
often RDS) and the duration of
mechanical ventilation and oxygen administration. BPD individual neonatal units, suggesting that the overall
is related inversely to birthweight and gestational age, approach to respiratory support is important. Centers
with the smallest, sickest, most immature infants being at that emphasize “gentle” ventilation that minimizes lung
highest risk. The increased susceptibility of the very injury (eg, permissive hypercapnea, lower airway pres-
preterm infant may reflect the anatomic, developmental, sures, avoidance of intubation or early extubation) have
and reparative immaturity of the neonatal lung at the substantially lower rates of BPD. Vitamin A, known to
time of lung injury. The risk of BPD is also increased by protect epithelial integrity and promote normal cell dif-
a hemodynamically significant patent ductus arteriosus, ferentiation and growth, is associated with a small, but
postnatal sepsis, antenatal maternal infection (eg, chorio- significant decrease in the risk of BPD when administered
amnionitis), and maternal or neonatal colonization with parenterally immediately after birth. Postnatal dexa-
Ureaplasma histolyticum. In the case of maternal infec- methasone has been reported by some to decrease oxy-
tion, it is postulated that circulating maternal cytokines gen dependence at 36 weeks after birth, but serious
gain access to the fetal circulation and injure fetal tissues, short- and long-term complications preclude routine
including lung and brain, thereby increasing the risk of use. Prevention of BPD remains elusive, ultimately de-
BPD as well as brain injury. Although some studies pending on avoiding or delaying premature delivery
report an association between a family history of atopy or whenever possible, reducing antenatal and postnatal in-
asthma and BPD, others have failed to confirm this fections, and minimizing postnatal exposure to noxious
relationship. agents, such as intubation, oxygen, and ventilation. It is

350 Pediatrics in Review Vol.23 No.10 October 2002


possible that for the most immature infants, even expo-
sure to room air is injurious.
As noted previously, the incidence of BPD depends
on the definition used. Fewer than 50% of extremely
preterm infants who require supplemental oxygen at
28 days after birth remain oxygen-dependent at 36 weeks
PCA, and fewer still remain oxygen-dependent at
42 weeks PCA. For all VLBW neonates (⬍1,500 g at
birth), the incidence of oxygen dependence at 28 days is
about 30% to 50%; at 36 weeks PCA, the incidence of
oxygen dependence in these same infants falls to 4% to
30%. For VLBW infants who require mechanical ventila-
tion and surfactant, approximately 60% are oxygen-
dependent at 28 days, and 30% remain oxygen-
Amoderate
large number of infants who have
or severe BPD require home
oxygen for an extended period.
dependent at 36 weeks PCA. In some series, up to one
third of VLBW infants have the milder form of atypical
BPD. Because the incidence of BPD is highest in the
most premature and lowest birthweight infants and be-
cause more of these very immature neonates now survive,
the total number of children living with BPD is increas-
ing, albeit in a clinically less severe form than seen previ-
ously.
Pathogenesis
BPD appears to be the final common path of lung injury.
Initially it was believed to be the consequence of direct
trauma from mechanical ventilation and oxygen toxicity.
As the clinical presentation of BPD has changed and
oxygen dependence has developed in the absence of RDS
or initial oxygen exposure, inflammation has emerged as
the central disease process. Anatomic and developmental
immaturity modify the lung’s response to trauma and
inflammation. Evidence of an inflammatory response
that accompanies RDS, including activated inflammatory
cells, inflammatory mediators, and cytokines, persists in
infants who develop BPD.
Barotrauma and volutrauma from mechanical ventila-
tion may injury airways and lung parenchyma directly
and indirectly. Intubation traumatizes local tissue sur-
faces, destroys normal ciliary action, and introduces
pathogens and exogenous gases directly into the airway.
neonatology bronchopulmonary dysplasia
Air leaks (eg, pulmonary interstitial emphysema) further
disrupt lung tissue. Oxygen exposure generates toxic free
radicals that cause acute tissue injury, incite inflamma-
tion, and inhibit normal repair and development.
Developmentally immature lung tissue may be both
more susceptible to injury and less effective at tissue
repair. At autopsy, infants dying of BPD have evidence of
abnormal lung morphology and development, with de-
creased alveolarization and septation. Ultimately, BPD
must be “outgrown.” As airways become larger, alveo-
larization proceeds, and the previously injured lung rep-
resents a smaller proportion of total lung volume. Fortu-
nately, alveolar growth continues up to 5 years of age,
allowing most infants who have BPD to recover clinically
even though pathologic and radiologic
abnormalities often persist into adult-
hood.
Clinical Aspects
BPD results in chronic respiratory insuf-
ficiency and prolonged oxygen depen-
dence for many weeks or months. Clin-
ical manifestations include tachypnea,
retractions, wheezing, and rales.
Ventilation/perfusion mismatch and increased physio-
logic dead space result in hypercapnia and hypoxemia.
The risk of superimposed infection is increased. For all
forms of BPD and CLD, oxygen requirements begin to
increase at the end of the first week after birth, reaching
a stable plateau by the beginning of the third week.
Clinical exacerbations occur in association with pulmo-
nary edema, superimposed infection, or right heart fail-
ure.
Northway described four distinct radiographic stages
of BPD: I-RDS, II-diffusely hazy, III-diffusely bubbly,
interstitial pattern, and IV-hyperaeration, focal hyperlu-
cency, alternating strands of opacification. These stages
correspond to a pathologic progression from acute RDS
to interstitial and airway edema, inflammation, and squa-
mous metaplasia and finally to areas of emphysema,
fibrosis, and atelectasis and increased peribronchiolar and
perivascular smooth muscle. Milder or atypical BPD is
radiographically less severe, with diffuse haziness or in-
terstitial prominence, often with normal inflation, and
less severe anatomic abnormalities.
Bronchospasm, episodes of cyanosis, and chronic hy-
poxemia often accompany BPD. Early pulmonary func-
tion abnormalities in infants who have BPD include
decreased lung compliance, ventilation perfusion mis-
match, and increased lung volume, airway resistance, and
air trapping.
Pediatrics in Review Vol.23 No.10 October 2002 351
neonatology bronchopulmonary dysplasia
Table 1. Therapeutic Goals and Adverse Effects of Treatment
Goal Treatment
2Lung water Fluid restriction
2Pulmonary edema Diuretics
Corticosteroids
2Airway hyperreactivity Bronchodilators
2Pulmonary hypertension Maintain oxygen saturation >92%
2Inflammation Mast cell stabilizers (eg, cromolyn)
Corticosteroids
2Gastroesophageal reflux Metoclopramide
Antacids
1Oxygen delivery Supplemental oxygen
Packed red blood cell transfusion
Erythropoietin
1Growth Hypercaloric, fortified feedings
(24 to 30 kcal/oz)
Maintain oxygen saturation >92%
Clinical improvement in BPD usually is heralded by
improvement in somatic growth. Infants who develop
BPD are at increased risk of patent ductus arteriosus,
sepsis, intraventricular hemorrhage (IVH), retinopathy
of prematurity, and death.
Management
The treatment goals of BPD focus on relieving respira-
tory symptoms, improving lung function, minimizing
ongoing lung injury, reducing inflammation, maintain-
ing adequate oxygenation, and facilitating lung growth.
BPD itself, as well as the treatment regimens used to
improve respiratory function, results in an assortment of
associated problems (Table 1). Although diuretics can
reduce pulmonary edema and oxygen requirements, they
also cause electrolyte depletion, bone loss, and nephro-
calcinosis. High-dose systemic corticosteroids facilitate
extubation and decrease neonatal respiratory support
and oxygen exposure. However, these short-term bene-
fits are achieved at the expense of serious neonatal com-
plications (eg, hyperglycemia, hypertension, intestinal
perforation, infection), poor brain and somatic growth,
and substantially worse neuromotor and developmental
outcomes, including cerebral palsy (CP), in early child-
hood. Postnatal corticosteroids have not been shown to
convey any long-term respiratory benefit. It is not known
whether the deleterious effects of systemic steroids are
related to the specific type of steroid administered, the
pharmacologic doses used, or the duration of treatment.
Although aerosolized steroids are associated with fewer
352 Pediatrics in Review Vol.23 No.10 October 2002
Adverse Effects
Caloric restriction
Naⴙ, Kⴙ, Caⴙⴙ loss; osteopenia; rickets; fractures;
nephrocalcinosis; cholelithiasis
Hyperglycemia, hypertension, infection, gastrointestinal
perforation, poor brain and somatic growth, cerebral
palsy
Tachycardia, irritability
See above
1Infection risk
Ongoing oxidant injury
Donor blood exposure
Insufficient free water, prerenal azotemia, hypernatremic
dehydration
complications, they are also less effective therapeutically.
Randomized, controlled trials are needed to define the
role, if any, of postnatal steroids or other anti-
inflammatory agents. Because of concerns about short-
and long-term adverse effects, it is recommended that
postnatal steroids be used only in exceptional clinical
circumstances (eg, severe respiratory failure with maxi-
mal ventilatory and oxygen support). It is possible that
the treatments used to reduce oxygen dependence may
be more detrimental to the infant than oxygen itself and
that the efforts to reduce oxygen dependence are mis-
guided.
Discharge and Home Care
A nurturing home environment improves physical
growth and psychosocial development. Infants who have
BPD should be discharged from the hospital to consis-
tent caretakers as soon as feasible. This often necessitates
continuing complex treatments at home, including oxy-
gen, hypercaloric feedings, fluid restriction, diuretics,
bronchodilators, and cardiorespiratory monitors. Medi-
cal treatment and home oxygen therapy may be needed
for many months or even years. The abrupt transition
from intensive care to the home is difficult for families
and requires comprehensive parent education before dis-
charge and ongoing psychosocial and medical support.
A specific plan must be in place at discharge, including
how the parent will monitor the infant’s respiratory
status, when to provide extra oxygen, which physician to
call when respiratory problems arise, and when to call for

emergency transport. Acute respiratory exacerbations are
likely and can be life-threatening. Valuable time will be
lost unless the parent knows when and who to call for
help.
Parents need to be aware of the high risk of superim-
posed respiratory infection and rehospitalization despite
optimal care and appropriate precautions. Understand-
ing the rationale for their infant’s treatment regimen (eg,
hypercaloric feedings, fluid restriction, medications, ox-
ygen, monitors, immunization, respiratory syncytial virus
[RSV] prophylaxis), the anticipated time course of treat-
ment, and the need for close medical follow-up encourages
compliance and helps the parents cope with the inevitable
ups and downs that accompany slowly improving BPD.
Home cardiorespiratory monitors are recommended
for children receiving oxygen at home. Oxygen satura-
tion should be monitored intermittently to detect unsus-
pected periods of hypoxemia, especially during both
activity and sleep, until supplemental oxygen, fluid re-
striction, or medications no longer are needed to main-
tain adequate oxygenation. Continuous oximetry rarely
is needed, except for children who have severe disease
and require frequent changes in oxygen delivery
throughout the day to maintain adequate oxygen satura-
tion. Oxygen, medications, and fluid restriction each
should be weaned slowly, one at time, to be sure that
changes in treatment are well tolerated. Children who
have BPD and are discharged from the hospital on oxy-
gen or medications should be followed closely by pedi-
atric pulmonary specialists in addition to their primary
pediatrician until the disease has resolved clinically.
Nutrition
Optimal nutrition, including sufficient energy, substrate,
and vitamins, is essential for lung growth and repair.
Malnutrition has deleterious effects on both lung func-
tion and size. Children who have BPD often grow poorly
due to increased rates of energy expenditure, increased
nutrient and caloric requirements, and suboptimal nutri-
tion. Feeding intolerance, gastroesophageal reflux
(GER), oral aversion, fluid and caloric restriction, hypox-
emia, recurrent infection, and rehospitalization all make
feeding difficult and contribute to growth failure. Poor
weight gain may be a sign of unsuspected hypoxemia,
especially at night when oxygen saturation falls during
sleep. Therapeutic strategies must focus on limiting ca-
tabolism, promoting an anabolic state, and providing
extra calories and nutrients necessary for tissue repair and
growth. After discharge, children who have BPD con-
tinue to need extra calories and nutrients to “catch up”
neonatology bronchopulmonary dysplasia
and to sustain normal growth. Extra nutrition support
may be required for at least 1 year PCA.
Individual nutrients hypothesized to be important in
the prevention or treatment of BPD include inositol;
fatty acids; carnitine; cysteine; and vitamins A, C, and E.
Thus far, only parenteral vitamin A, administered shortly
after birth, has been shown to have a small, specific
benefit in reducing the risk of BPD. Providing sufficient
energy and nutrients as soon as possible is essential.
Beginning parenteral nutrition with protein, fat, carbo-
hydrate, vitamins, and minerals within 24 to 48 hours
after birth limits protein loss, minimizes catabolism, pre-
vents essential fatty acid deficiency, and provides vitamins
and trace elements. Early initiation and establishment of
enteric feeding allows higher caloric intake with less fluid
intake.
Use of human milk improves utilization of nutrients
and confers specific immunologic advantages to the in-
fant who has BPD. However, fortification of human milk
is required to provide adequate protein, calories, and
minerals to all infants whose birthweights are less than
1,500 g. Preterm adapted formula is an alternative if
human milk is unavailable for VLBW infants. Both forti-
fied human milk and preterm adapted formula provide
nutritionally balanced, calorically dense feedings that can
be increased up to 30 kcal/oz when fluids are restricted
to reduce lung water and pulmonary edema. Enriched
feedings may be needed for many months. Even in
healthy VLBW infants who do not have chronic disease,
the use of preterm adapted formulas until 9 to 12 months
PCA appears to improve long-term growth. Frequent
assessment of growth parameters, including length and
head circumference, as well as weight is necessary to
assure that nutrition requirements for growth are being
met adequately.
Prognosis
Postdischarge complications related to BPD are shown
in Table 2. When pulmonary outcome initially was de-
scribed for infants who had classic BPD, 24% continued
to have respiratory symptoms as adolescents and young
adults. Although less severe BPD is associated with a
better long-term outcome, children who have BPD still
have twice the risk of developing wheezing or asthma or
lower respiratory tract infections, and of being rehospi-
talized due to respiratory illness during infancy and early
childhood compared with gestational age-matched pre-
term infants who do not have BPD. In several reports,
50% of all VLBW children who had a history of BPD had
been rehospitalized in the first 12 to 24 months after
birth, and 50% had a history of wheezing or asthma at
Pediatrics in Review Vol.23 No.10 October 2002 353
neonatology bronchopulmonary dysplasia

with a longer duration of intubation, larger endotracheal

BPD: Related Medical
Table 2. tubes, increased numbers of intubations, higher initial
mean airway pressure, clinically severe BPD, and lower
Problems After Discharge gestational age. Two thirds of these infants had respira-
Respiratory tory symptoms during infancy, abnormal vocalization
(eg, stridor, aphonia, or hoarseness), and apnea. Death
Bacterial and viral pneumonia
Bronchitis after discharge home is less common than previously, but
Aspiration it occurs in up to 6% of infants who have BPD, usually
Reactive airway disease, wheezing due to cardiopulmonary complications.
Exercise intolerance Pulmonary function test (PFT) abnormalities are
Otitis media
found consistently in school-age children who have a
Acute life-threatening event
Sudden infant death syndrome history of BPD. These abnormalities include decreased
Tracheomalacia forced vital capacity, forced expiratory volume, and
Subglottic stenosis forced expiratory flow and increased residual volume.
Death Laboratory evidence of expiratory airflow obstruction
Cardiovascular and gas trapping persist throughout childhood, even
Systemic hypertension among clinically asymptomatic children. The severity
Pulmonary hypertension and persistence of the PFT abnormalities and exercise
Cor pulmonale intolerance correlate with the duration of mechanical
Congestive heart failure ventilation, oxygen therapy, and treatment. Except for
Gastrointestinal increased airway resistance, PFT abnormalities usually
Gastroesophageal reflux improve by 7 to 11 years of age and resolve by early
Oral aversion adulthood. At least 50% of children who have a history of
Feeding intolerance BPD have laboratory evidence of bronchial hyperreactiv-
Slow weight gain ity, even without a clinical history of wheezing or reactive
Failure to thrive airway disease. Radiographic abnormalities (eg, hyperlu-
Other cency, bullae, multiple fibrotic strands, and atelectasis)
Osteopenia, rickets, fractures also persist throughout childhood. Despite the abnormal
Renal stones, gallstones results of PFTs and chest radiographs, most children
Nephrocalcinosis have normal exercise tolerance by late childhood. The
long-term effect of BPD on pulmonary response to re-
spiratory irritants, pulmonary function, and respiratory
mid-childhood. RSV prophylaxis during infancy has disease in later life is unknown, especially with respect to
been shown to halve the risk of hospitalization for RSV the risk of chronic obstructive pulmonary disease. Fami-
and to reduce both the length of stay and the duration of lies and children should be counseled to avoid tobacco
oxygen therapy if the infant is hospitalized. GER, which use, second-hand smoke, and other respiratory irritants.
is common in preterm infants, contributes to acute and Catch-up growth is delayed in infants who have BPD.
chronic airway inflammation, edema, aspiration pneu- Poor somatic growth may reflect insufficient food intake
monia, and feeding difficulties. to meet metabolic or energy needs or chronic oxygen
Approximately 25% of infants who have BPD have a desaturation, especially during sleep. Although adoles-
transient recurrence or worsening of apnea following cents and young adults who have a history of classic BPD
initial immunization. This risk appears to decrease with were smaller than controls in one study, their growth still
subsequent immunizations. The risk of an acute life- was within the normal range. More recent studies of
threatening event (20%) or of sudden infant death (3%) is children who have milder BPD do not demonstrate
higher in VLBW infants who have BPD. Fortunately, the significant differences in height and weight at school age
small number of affected children who require tracheos- compared with preterm controls who did not have BPD,
tomy due to airway obstruction or the need for pro- although children who had BPD do tend to have lower
longed ventilation is decreasing steadily. However, lean body mass and lower bone mineral content.
moderate-to-severe airway compromise by tracheomala- Recurrent episodes of hypoxemia and cyanosis may
cia and subglottic stenosis has been found by bronchos- lead to pulmonary hypertension, cor pulmonale, and
copy in 27% of infants who have BPD and is associated heart failure. Systemic hypertension occurs in 6% to 11%

354 Pediatrics in Review Vol.23 No.10 October 2002


of infants, often is not evident until after discharge, and
may progress to left heart failure if unrecognized and
untreated. Although nephrocalcinosis usually disappears
after diuretics are discontinued, it may persist and can be
associated with abnormalities of renal function. Renal
calcifications should be followed by renal ultrasonogra-
phy until resolution. Children who have BPD also are at
increased risk for otitis media, bronchitis, hearing loss,
and visual impairment. Inguinal hernias are twice as
common among VLBW preterm infants who have BPD
(23% versus 12%), and the hernias often enlarge progres-
sively, sometimes to dramatic proportions. Inguinal her-
nias may be associated with discomfort and irritability
and should be repaired as soon as feasible before dis-
charge to home.
Neurodevelopmental outcome is multifactorial, being
most strongly influenced by neonatal brain injury (eg,
IVH, periventricular leukomalacia [PVL]), gestational
age or birthweight, race, socioeconomic status, and pa-
When the outcome is controlled for
other important predictors of
neurodevelopment, BPD independently
accounts for adverse outcome, primarily in
neuromotor function.
rental education. In general, neonatal issues (eg, severity
of neonatal disease, birthweight, or gestational age) are
better predictors of short-term outcome at fewer than 24
months PCA, and long-term outcome is determined by
external influences, such as socioeconomic status and
parental education. The ability to assess neurodevelop-
mental outcome accurately changes over time as diag-
nostic capabilities improve and the child’s own develop-
mental repertoire expands. The evaluation of outcome in
children who have BPD is confounded by the varying
definitions of BPD, the changing clinical presentation of
BPD and neonatal care over time, small sample size, and
selection bias. Many studies, especially at school age,
exclude children who have severe disabilities.
At any postnatal age examined thus far, neurodevel-
opmental outcome is affected adversely by BPD. When
outcome is controlled for other important predictors,
such as gestational age, birthweight, brain injury (IVH
and PVL), race, gender, socioeconomic status, and pa-
neonatology bronchopulmonary dysplasia
rental education, BPD independently accounts for ad-
verse outcome, primarily in areas of motor function.
Neurodevelopmental outcome, as with medical and pul-
monary outcome, is predicted better by the need for
supplemental oxygen at 36 weeks PCA rather than at
28 days after birth. Long-term outcome studies of more
immature, less severely ill preterm infants born in the
1990s, after the routine use of antenatal steroids and
surfactant, are just beginning to appear. Although ante-
natal steroids have been associated with a decreased risk
of severe IVH and CP during this decade, postnatal
steroids, widely used simultaneously, have been associ-
ated with an increased risk of neuromotor problems,
including CP. It is, therefore, possible that neurodevel-
opmental outcome for these children actually may be
worse than previously described.
BPD is specifically associated with an increased risk of
neuromotor abnormalities. Studies of children born in
the 1980s reported that those who had BPD had a similar
incidence of CP (6% to 13%) and a
higher risk of overall disability (40% ver-
sus 23%) compared with preterm con-
trols. Progressive brainstem deteriora-
tion and cerebral encephalopathy as well
as an extrapyramidal movement disor-
der associated with restless, chorealike
limb movements and oral-buccal-
lingual dyskinesia have been described
during infancy in children who had very
severe BPD. These infants had pro-
longed hospitalization, frequent and
persistent episodes of hypoxemia, recur-
rent respiratory decompensation, or heart failure. In
infants who have less severe BPD, gross motor delay
frequently is observed during infancy. The motor delay
resolves concomitantly with improvement in respiratory
symptoms, exercise tolerance, and somatic growth. In
these children, developmental progress usually is pre-
served better in those areas of development less depen-
dent on large muscle strength, such as adaptive, lan-
guage, fine motor, and personal/social domains.
Follow-up studies of school and academic perfor-
mance in middle childhood have compared children who
have a history of milder BPD born in the 1980s with
preterm controls. Those who had a history of BPD were
more likely to require special school resources or classes
(48% versus 38%), to have academic delay (51% versus
47%), and to have poorer math, reading, and spelling
skills. They also had more adverse neuropsychological
and educational outcomes, including lower verbal and
performance IQs, increased hyperactivity, and worse fine
Pediatrics in Review Vol.23 No.10 October 2002 355
neonatology bronchopulmonary dysplasia

Table 3. Timeline of Pediatric Care for the Child Who Has BPD
Discharge312 months 132 years 235 years 5315 years
Provide close medical Provide medical Provide medical supervision Provide ongoing developmental
supervision supervision Coordinate care assessment
Coordinate care Coordinate care Perform neurodevelopmental Provide educational testing
Maximize nutrition Monitor growth examination yearly Provide intervention as needed
Fortify feedings Perform neurodevelopmental Provide educational Provide medical surveillance
Monitor growth examination intervention Provide counseling about
Wean oxygen slowly Provide early education Provide preschool experience smoking
Wean medications support Provide psychosocial support Provide psychosocial support
Provide routine immunization Provide psychosocial support
Provide respiratory syncytial Avoid rehospitalization
virus (RSV) prophylaxis Provide RSV prophylaxis
Provide parent education Provide routine
Provide psychosocial support immunization
Perform neurodevelopmental Provide influenza
examination immunization
Prevent rehospitalization

motor function, receptive vocabulary, visual-perceptual
integration, and memory. At 9 to 10 years of age, 71% of
the children who required oxygen at home for more than
1 month after discharge from the neonatal intensive care
unit have been reported to have suspect or abnormal
findings on neuromotor examinations, including senso-
rimotor difficulties, eye-hand incoordination, poor pos-
tural stability, poor motor coordination (“clumsiness”),
or motor difficulties. The severity of BPD (ie, duration of
hospitalization and oxygen therapy, severity of PFT ab-
normalities) and lower socioeconomic status were the
only independent predictors of these neurologic abnor-
malities. Such neuromotor and neurobehavioral abnor-
malities would be expected to have adverse effects on
school performance.
The outcomes of children who have had the more
recent, less severe forms of BPD are similarly concerning.
A well-controlled study in VLBW children who received
antenatal steroids and surfactant noted that those who
had a history of BPD were more likely than preterm
controls to have mental (21% versus 11%) or motor (20%
versus 9%) retardation at 3 years corrected age. Of the
multiple risk factors examined, only BPD and the neuro-
logic risk score, reflecting the severity of neonatal brain
injury, independently decreased standardized motor
scores on the Bayley Scales of Infant Development (BPD:
⫺12 points, neurologic risk: ⫺14 points). In contrast,
cognitive function was predicted independently by neu-
rologic risk, minority race, and social class, but not by
BPD. In this same group, after controlling for IQ, BPD
adversely affected preschool language outcome and was
associated with both receptive language impairment and
poorer expressive language skills. The physiologic basis
for the adverse effect of BPD on neurodevelopmental
outcome is unknown, but prolonged and recurrent hy-
poxemia, malnutrition, lack of specific nutrients, toxic
effect of drug therapies, and lack of appropriate environ-
mental stimulation all may play a part in altering brain
growth, development, and function.
BPD is an excellent marker for high neurologic, de-
velopmental, and academic risk throughout childhood
that identifies children who require longitudinal neuro-
developmental evaluation. Although most neurodevel-
opmental follow-up programs, government funding, and
intervention services are focused primarily on infants and
young children, the most profound developmental ef-
fects of BPD or prematurity in general appear during the
school years. Because many of the neurodevelopmental
abnormalities associated with BPD are subtle and not
readily evident, high-risk children who have a history of
BPD are served best by standardized, comprehensive
preschool and school-age assessments performed by ex-
perienced personnel.
Summary
Children who have BPD need a readily available, consis-
tent primary pediatric care clinician to coordinate medi-
cal and developmental care from neonatal intensive care
unit discharge to adulthood (Table 3). Initial goals in-
clude promoting optimal growth, ensuring adequate
oxygenation, preventing infection by RSV immunopro-
phylaxis and immunization, assuring appropriate devel-

356 Pediatrics in Review Vol.23 No.10 October 2002


opmental evaluation and support, and helping the family
cope with the physical and psychological difficulties of
caring for a medically fragile child. The primary care
practitioner who is cognizant of potential neurodevelop-
mental, behavioral, and educational risks will be a valu-
able advocate, helping assure that appropriate psychoso-
cial and educational assessments are performed and that
appropriate school and interventional resources are made
available throughout childhood. Despite their early
physical difficulties and increased neurodevelopmental
risks, most children who have BPD have an excellent
prospect of becoming well-functioning, healthy adults
who are satisfied with their quality of life and are able to
contribute positively to their families and society.
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Pediatrics in Review Vol.23 No.10 October 2002 357
neonatology bronchopulmonary dysplasia

PIR Quiz
Quiz also available online at www.pedsinreview.org.

6. A 12-hour-old male infant born to a 22-year-old woman after 28 weeks’ gestation presents with
respiratory distress. The infant weighed 800 g at birth and has been receiving supplemental oxygen.
Findings on the physical examination are consistent with a gestational age of 28 weeks. The respirations
are 60 breaths/min, heart rate is 140 beats/min, rectal temperature is 96.8°F (36°C), and blood pressure is
50/30 mm Hg. Grunting and intercostal retractions are noted. Umbilical artery blood gas shows a pH of
7.28, PCO2 of 46 torr, and PO2 of 64 torr under 100% oxygen hood. Chest radiography shows diffuse
reticulogranular opacification with air bronchograms. Which of the following is most likely responsible for
this infant’s illness?
A. Bacterial pneumonia.
B. Oxygen toxicity.
C. Primary pulmonary hypertension of newborn.
D. Surfactant deficiency.
E. Transient tachypnea of newborn.

7. Immediately after birth, parenteral administration to a preterm infant of which of the following is
associated with a decreased incidence of bronchopulmonary dysplasia?
A. Vitamin A.
B. Vitamin B12.
C. Vitamin C.
D. Vitamin D.
E. Vitamin K.

8. A 4-month-old preterm female infant is dependent on oxygen after treatment of respiratory distress
syndrome (surfactant deficiency) and bronchopulmonary dysplasia that required mechanical ventilation for
2 months. She is being discharged from the hospital. Which of the following statements about prevention
of infections is true?
A. Bacillus Calmette-Guérin vaccination should be administered prior to discharge.
B. Live vaccines are contraindicated.
C. Palivizumab should be administered during the RSV season until 2 years of age.
D. Penicillin prophylaxis should be administered until 1 year of age.
E. Pertussis vaccine should be administered at half the usual dose.

9. A 6-month-old boy is being followed for bronchopulmonary dysplasia. He was born preterm after
30 weeks’ gestation and weighed 980 g. The neonatal course was complicated by respiratory distress
syndrome (surfactant deficiency) and grade 1 intraventricular hemorrhage. He also required indomethacin
treatment for patent ductus arteriosus. He was discharged from the hospital at 4 months of age weighing
2.1 kg. He has continued to be oxygen-dependent, requiring 0.25 L by nasal cannula. His diet consists of
18 oz (24 kcal/oz) infant formula every day. Physical examination shows an alert, interactive infant whose
respirations are 40 breaths/min, heart rate is 120 beats/min, and weight is 3.4 kg. He is slender and has
little subcutaneous fat. The chest is clear to auscultation, and findings on the abdominal examination are
normal. Of the following, the most likely reason for the infant’s poor weight gain is:
A. Cor pulmonale.
B. Growth hormone deficiency.
C. Inadequate caloric intake.
D. Renal dysfunction.
E. Thyroid dysfunction.

358 Pediatrics in Review Vol.23 No.10 October 2002