Bronchopulmonary Dysplasia: A Review For The Pediatrician: AND Incidence

BRONCHOPULMONARY DYSPLASIA: A
REVIEW FOR THE PEDIATRICIAN
Bronchopulmonary dysplasia (BPD), or chronic lung disease of in-

fancy, is a pediatric illness that was unknown as recently as 25 years
ago. Since its description in 1967l it has emerged as a frequently
seen, unintended consequence of respiratory support of newborns.
The purpose of this presentation is to familiarize pediatricians with
this new, chronic respiratory illness. Current information regarding
the etiology, epidemiology, and pathophysiologv of BPD will be sum-
marized. The major focus will be the continuing pediatric manage-
ment of problems that relate specifically to bronchopulmonary dys-
plasia seen in these children after they leave tertiary care centers to
begin family and community life. No attempt is made to address the
multiple other issues regarding pediatric care of the “intensive care
nursery graduate.” For this information interested readers are re-
ferred to a recently published text developed specifically for that
purpose.2
Information about BPD is particularly relevant to pediatricians in
practice for two reasons. First, there is an increasing tendency to
discharge these patients earlier than has been done in the past. This
has come about both because of financial pressures and because the
home environment is widely believed to be superior to the hospital
environment in regard to developmental progress.3-5 Second, the in-
cidence of preterm birth is either stable or rising at the same time
that the survival of very small infants is improving.6’7 This will ulti-
mately lead to an increase in the number of former preterm infants
seen in pediatric practice. It can be expected that the frequency of
BPD seen by practicing pediatricians will increase in the future.
EPIDEMIOLOGIC, ETIOLOGIC, AND DIAGNOSTIC ASPECTS

OF BRONCHOPULMONARY DYSPLASIA
DEFINITION AND INCIDENCE
The incidence of BPD and its current prevalence are not known
with certainty. The incidence, or alternatively the risk, of the devel-
Curr Probl Pediatr, April 1989 177

opment of BPD is strongly related to gestational age or birthweight.
The risk is also greatly influenced by the presence or absence of the
respiratory distress syndrome (RDS).’ Retrospective studies of infants
with birthweights less than 1,500 gm (3 lb, 5 oz) have reported a 20%
to 40% incidence of BPD and for those with birthweights less than
1,000 gm (2 lb, 3 oz), an incidence of up to approximately 70% has
been reported.s-11 One recently published survey of eight neonatal
units performed between 1982 and 1984 involving 1,625 infants with
birthweights less than 1,500 gm produced the birthweight-specific
incidence data among survivors shown in Table 1.”
At present there are no formal diagnostic criteria for BPD. Several
definitions have been used, some more stringent than others, and
this diversity of definitions contributes to the variation in both inci-
dence figures and outcome data found in the current literature?” In
general, a prerequisite for the diagnosis of BPD would be a require-
ment for mechanical ventilation with supplemental oxygen admin-
istration in the neonatal period as treatment for an acute lung dis-
ease.” 8,’ The neonatal acute lung disease is most often RDS, but can
also be pneumonia, meconium aspiration, or persistent pulmonary
hypertension of the newborn. On less frequent occasions, infants
ventilated for apnea alone may progress to develop BPDe8 While
many neonates requiring such treatment recover without clinical
evidence of impaired lung function, others will exhibit continuing
impairment of gas exchange. Infants who at 28 days of age continue
to require supplemental oxygen and on examination have retrac-
tions, tachypnea, and inspiratory crackles with an abnormal chest
radiograph can be confidently diagnosed as having bronchopulmo-
nary dysplasia.’ Some infants diagnosed in this manner will improve
sufficiently prior to discharge to allow discontinuation of supple-
mental oxygen an&or various medications, while others will con-
tinue to require oxygen therapy and/or medications at home. This
illustrates the differences in severity of BPD remaining at the time of
TABLE 1.
Birthweight, gm % With BPD
701-800 76.1
801-900 68.8
901-1,000 46.4
l,OOl-1,250 26.0
1,251-1,500 12.9
Adapted horn Avery ME, Tooley WH, Keller
JB, et al: Is chronic lung disease in low
birth weight infants preventable? A survey
of eight centers. Pediatrics 1987; 792&30.
178 Curr Probl Pediatr, April 1989

discharge. However, it is important to be aware that even infants
sent home without supplemental oxygen and medications remain at
risk for some complications of BPD.13-*’
As with estimates of incidence, reported mortality rates in chil-
dren with BPD vary with selection criteria. Some authors have re-
ported mortality rates as low as ll%, while most series report a mor-
tality close to 30%.14’15 The vast majority of these deaths happen
during the initial hospitalization and are a consequence of progres-
sive respiratory insufficiency.13-15
ETZOLOGZC CONSIDERATIONS
No single etiologic explanation for the development of BPD has
found universal acceptance. Several possible “causes” have received
much attention: oxygen toxicity, trauma from the pressures gener-
ated during mechanical ventilation (so-called barotrauma), and the
presence of the endotracheal tube itself have all been thought by
various investigators to be important.2’8*12 It seems reasonable to say
at present that the “cause” of BPD remains unknown, and, in fact, a
single etiology may not exist. Rather, BPD may be the result of an
acute insult such as RDS, which requires certain therapeutic manip-
ulations such as high concentrations of inspired oxygen acting on
the substrate of an immature lung that is inherently susceptible to
injury.16 Susceptibility to injury may result from varying degrees of
surfactant deficiency, immature lung structure, and immaturity of
the pulmonary antioxidant systems.” l6 The importance of host fac-
tors is underscored by reports of a higher frequency of HLA-A2 an-
tigen and a higher frequency of a family history of atopic illness in
infants with BPD.17’18
In summary, BPD is a relatively new chronic pediatric pulmonary
illness whose occurrence is linked to premature birth and neonatal
lung disease. Its incidence is strongly related to low birthweight and
the presence of RDS. No single etiology is universally accepted at
present and multicausal explanations may provide the best frame-
work within which to proceed. The number of infants with this ill-
ness is likely to increase in the future unless prevention of prema-
ture birth is given priority in the health care system.
PATHOLOGY AND PATHOPHYSIOLOGY
Fortunately, only a minority of children with BPD come to post-

mortem examination. Such children usually represent the most se-
vere form of the disease. In this section pathology and pathophysi-
ology will be presented for each organ system affected.

THE LUNGS
The Alveoli and Gas-Ewhanging Units
The architecture and function of the alveoli and alveolar septae
are greatly altered in BPD. Prominent features include fibrosis and
areas of emphysematous alveolar overdistention alternating with al-
veolar collapse.881g Pulmonary edema is also a consistent finding and
seems to result from either delayed lymphatic drainage, loss of pul-
monary capillary integrity, or both.8”g Fibrosis and pulmonary
edema both create poor pulmonary compliance and require the
child to generate high intrathoracic pressures in order to expand the
lungs.8’ ‘O,‘* This substantially increases the child’s work of breath-
ing.” ‘O Emphysematous regions of the lung receive excessive
amounts of ventilation but are poorly perfused. This situation also
increases the child’s work of breathing, as much of this ventilation
is “wasted.” Such regional overventilation leads to carbon dioxide
retention because it represents ventilation of physiologic dead
space.” Overdistended regions may be directly adjacent to areas of
partial or complete collapse. Collapse results in regional underven-
tilation, which leads to hypoxemia, because continued blood supply
to such areas represents a source of venous admixturez2 Children
generally attempt to compensate for these ventilation/perfusion ab-
normalities by means of an increased respiratory rate; this also con-
tributes to their increased work of breathing.8’20’ “I 23
The Small Conducting Airways

The small conducting airways are abnormal in children with BPD.
There is dysplasia of the respiratory epithelium and excessive mu-
cus production. Clearance of mucus by the ciliary system is im-
paired.= The muscular layer of the peripheral bronchioles is abnor-
mally hypertrophied and extends further down into the
tracheobronchial tree than would be seen in normal children.8”g’25
The effect of these changes is narrowing of the small airways, which
leads to increased resistance to airflow; this increased airway resis-
tance further increases the child’s work of breathing.10’26’27 The in-
creased thickness and extent of airway muscularization creates the
potential for further narrowing of peripheral airways through the
mechanism of bronchoconstriction.s’26’27 Indeed, several investiga-
tors have recently shown by the use of formal pulmonary function
testing that children with BPD do have reactive airways and that this
reactivity appears very early in their postnatal life.28-30 Inflammation
and increased mucus production along with bronchoconstriction
may result from exposure to inhaled irritants, allergens, or viral res-
piratory diseases.31’ 32 Events such as these not infrequently lead to
critical small airway narrowing with the child experiencing overt res-
piratory distress, coughing, wheezing, vomiting, and either cyanosis
180 Cum Probl Pediatr, April 1989

or a requirement for more oxygenz7 In this respect episodic exacer-
bations of BPD, as with viral infections, bear a very close resem-
blance to reactive airways disease or asthma.13’ 31-33
The Large Conducting Airways

Two recent reports indicate that the large airways are frequently
abnormal in children with BPD: tracheomalacia, bronchomalacia,
airway occlusion by growth of granulation tissue, and inspissation
of secretions have all been found.34J 35 Bronchomalacia is a recog-
nized cause of wheezing in pediatric patients and although rare as
a primary disorder is increasingly being recognized as contributing
to the difficulties of children with BPD.33 Bronchomalacia should be
suspected when wheezing and respiratory difficulty persist despite
optimal therapy for reactive airways disease.33
The Pulmonary Vasculature

The pulmonary arterioles in the lungs of children with broncho-
pulmonary dysplasia show abnormal muscular hypertrophy and ex-
tension of muscularization to distal levels of the vascular bed that
are not normally muscularized.8’ 1g,25J36As a consequence, the lu-
menal diameter of the small pulmonary vessels is decreased. This
results in a decrease in the overall cross-sectional area of the pul-
monary vascular bed and a concomitant rise in pulmonary artery
pressLlres.3640 In response to certain stimuli, most often alveolar hy-
poxia, the reactive pulmonary vasculature may constrict and further
acutely increase pulmonary arterial pressure. In the cardiac cathe-
terization laboratory, children with BPD have been seen to raise their
pulmonary artery pressure to systemic levels in response to mild
alveolar hypoxia. Conversely, children with elevated pulmonary ar-
tery pressures have frequently been found to reduce these pressures
after administration of modest amounts of supplemental oxy-
gen.3740
THE HJZART
Cardiac abnormalities are seen frequently in children with bron-

chopulmonary dysplasia and are believed to be secondary to the
lung disease. Direct hemodynamic measurements during cardiac
catheterization have consistently shown pulmonary artery hyperten-
sion.lO, 3740 This increase in pulmonary artery pressure is thought to
be due in part to destruction of a portion of the pulmonary capillary
network resulting in a decrease in the total cross-sectional area. The
decreased capillary area leads to increased resistance to flow and
thus to the increased pulmonary artery pressure. However, as stated
previously, a portion of the increase in pulmonary artery pressure is
usually reversible with the pulmonary vasodilator oxygen.3740 Those
Cum Probl Pediatr, April 1989 181

children who do not exhibit a decrease in their pulmonary artery
pressure in response to oxygen or vasodilators have a particularly
poor prognosis3g Generally, low-flow oxygen is all that is re-
quired to lower the pulmonary artery pressure to the extent that
such an elevation is reversible.3740 This implies that pulmonary
vasoconstriction is in part also responsible for the high pulmonary
artery pressure.
The presence of a high pulmonary artery pressure over long peri-
ods of time constitutes an excessive workload for the right ventricle.
Many children have electrocardiographic (ECG) patterns that indi-
cate either right ventricular hypertrophy or biventricular hypertro-
PhY.lO’ 31,4o Echocardiographic data have led to similar conclu-
sions.25’ 37 Cor pulmonale may be the ultimate consequence if
elevated pulmonary artery pressure is sustained over prolonged pe-
riods of time. It is significant that in the selected group of children
with BPD who come to autopsy, car pulmonale is a frequent find-
ing.lg
Recent observations, some as yet available in abstract form only,
indicate that patients with BPD who come to postmortem examina-
tion commonly have myocardial pathologic findings indicative of re-
peated episodes of ischemia and infarction.4143 Whether such epi-
sodes also occur in children whose lung disease is not so severe as
to preclude survival is at present a matter of speculation.
At presenf. there is only one therapeutic modality commonly used
to lower pulmonary artery pressure-increased concentrations of
inspired oxygen. As demonstrated by cardiac catheterization data,
alveolar hypoxia is a powerful stimulus for pulmonary vasoconstric-
tion that worsens pulmonary artery hypertension.3740 It would not
be reasonable to subject all children to invasive studies in order to
determine what inspired oxygen concentration produces for each
child the lowest pulmonary artery pressure. Therefore, the results
obtained from the published data have been extrapolated to routine
clinical use. In general, children will have their lowest pulmonary
artery pressure when their inspired oxygen concentration is ad-
justed so as to maintain their arterial hemoglobin saturation greater
than 90% at all times.3740
Patients with bronchopulmonary dysplasia have a requirement for

calories that exceeds that found in children who do not have BPD
by about 25% .” Growth failure, defined as weight less than the third
percentile, is frequently present in infants with BPD at the time of
discharge from the intensive care nursery.15’20’44 Some children with
BPD will be able to grow well with a supranormal caloric intake,
while others will exhibit growth failure despite a high intake of cal-
1.92 Curr Probl Pediatr, April 1989

ories. 15220244 There is very little specific information available regard-
ing the nutritional requirements of children with BPD.
Careful study of these children has produced some significant
findings. First, children with BPD and growth failure exhibit a resting
oxygen consumption, and thus a caloric expenditure, which is in-
creased in comparison to either children without BPD or children
with BPD but without growth failure.45 The total resting caloric ex-
penditure in children with BPD and growth failure is increased in
proportion to the severity of derangement of their pulmonary me-
chanics .‘I, 46 However, the increase in total work of breathing has
been found not to be sufficient to account for the entire observed
increase in caloric expenditure.45,46 Thus, other mechanisms in ad-
dition to unfavorable pulmonary mechanics are operating to in-
crease the caloric requirements of children with BPD. As yet these
other mechanisms remain to be elucidated. Recent investigation of
infants with BPD and growth failure found both increased resting
metabolic demands and decreased serum prealbumin values in
these patients. The authors interpreted these findings as evidence
for a state of protein-calorie malnutrition.45
Published data indicate that approximately 35% of children with
BPD who survive to be discharged will exhibit some degree of
growth failure.15 Growth in children with BPD is probably best mon-
itored by serial determination of weight, height, and head circumfer-
ence plotted on a Babson fetal-infant growth chart. This chart com-
pensates for the infant’s preterm birth. Its use is the general practice
of neonatal follow-up groups. Such correcting of age for preterm
birth is recommended for the first 24 months of life.4
In general the growth pattern of children who exhibit growth fail-
ure with BPD can be described in three phases. During the first
phase patients grow slowly (i.e., the slope of the growth curve is less
than that of a normal growth curve) and generally are below the
third percentile for weight. Length and head circumference are rel-
atively spared (although still compromised) and may typically be be-
tween the fifth and 25th percentile.44 When the child’s pulmonary
function improves there is usually a significant increase in the
growth velocity, which may be called “catch-up” growth.‘5,47 If the
child continues to do well then the period of catch-up growth leads
to crossing of percentiles and subsequently to the third phase,
which is one of growth along a typical growth curve.44 Whether these
children ultimately attain the full genetic potential for stature is not
clear at the present time.
THE BBAlN
It is at present uncertain whether the neurologic and developmen-

tal abnormalities that sometimes occur in children with broncho-

pulmonary dysplasia are related to their lung disease per se or to
the preterm birth and multiple perinatal insults that characterize
the early lives of these children. However, definite abnormalities of
respiratory control have been described in infants with BPD and
these seem to be unique to this population.48 Recent evidence indi-
cates that infants with BPD who have adequate arterial oxygen sat-
uration while awake may regularly exhibit profound arterial desatu-
ration during sleep and feeding.48 This implies an abnormality in
control of respiration. Moreover, these same investigators have pre-
sented data that indicate that the central nervous system (CNS) hy-
poxic arousal response is abnormal in perhaps two thirds of chil-
dren with BPD. On hypoxic challenge in the laboratory these
children were found to arouse predictably but subsequently to ex-
hibit prolonged apnea and bradycardia.48
The combined findings of frequent hypoxic episodes during sleep
and an abnormal hypoxic arousal response strongly imply altered
CNS function in the area of control of respiration. Such abnormali-
ties may explain the increased incidence of unexpected, unex-
plained death that has been described in this population of in-
fants.@ 5o
The case presentation below serves to illustrate the typical course
of a child who develops bronchopulmonaty dysplasia.
CASE PRESENTATION
JG was the 930~gm product of a 28-week gestation born to a
mother who had continued to smoke one pack of cigarettes per day
during her pregnancy. The gestation was uncomplicated until the
day of delivery, when a large abruptio placentae occurred. The infant
was delivered by emergency cesarean section and Apgar scores were
recorded as 3 at 1 minute and 9 at 5 minutes of age. Shortly after
birth the newborn developed progressive respiratory difficulty ne-
cessitating mechanical ventilation with high concentrations of in-
spired oxygen. Severe RDS developed and the newborn required me-
chanical ventilation with increased concentrations of inspired
oxygen (Fig 11 for several weeks. Pulmonary air leak syndrome with
unilateral pulmonary interstitial emphysema and pneumothorax
complicated the infant’s course. She also experienced persistent pa-
tency of the ductus arteriosus, which became significant on the sec-
ond day of life. Closure with indomethacin was temporally related
to improvement in her respiratory status. Insertion of a Broviac cath-
eter central line was required for venous access and parenteral nu-
trition. This was ultimately complicated by both thrombosis and
Staphylococcus epidermidis infection. During the second week of the
child’s course, when improvement in pulmonary function and chest
radiograph were expected, she did not improve. Her pulmonary sta-
184 Cur-r Probl Pediatr, April 1989

FIG 1.
Serial chest radiographs of infant in first case presentation, A, radiograph during first day
of life showing the reticulogranularity and air bronchograms that are characteristic of RDS.
B, film during second week of life when left-sided pulmonary interstitial emphysema and
right upper lobe atelectasis developed. C, the child’s radiographs gradually evolved to
show diffuse, bilateral atelectasis that appears as perihilar haze in this film. D, the typical
radiolucency, perihilar, and upper lobe streaking found in BPD.
Curr Probl Pediatr, April 1989

tus remained stable, but her chest radiograph showed diffuse atelec-
tasis and did not change significantly during the next 2 weeks. At 28
days of age when the infant continued to exhibit tachypnea, retrac-
tions, and crackles on examination, continued to require supple-
mental oxygen and still had an abnormal chest x-ray, the diagnosis
of BPD was made.
Management of the infant’s BPD included efforts to optimize her
nutritional status and continued mechanical ventilation with in-
creased inspired oxygen as supportive measures. Pharmacologic
therapy included aminophylline, which was intended to improve
pulmonary compliance, increase diaphragmatic strength, and de-
crease resistance to airway flow. The diuretics, spironolactone and
chlorothiazide, were given to improve pulmonary mechanics by de-
creasing pulmonary edema. At the age of 6 weeks she was given
dexamethasone for 5 days to improve pulmonary compliance. Dur-
ing this period her requirement for respiratory support fell from 80%
oxygen with a mean airway pressure of 13 cm H,O to 33% oxygen
with a mean airway pressure of 5 cm H,O. As her condition im-
proved she was able to tolerate enteral feedings and by 6 weeks of
age no longer required the support of parenteral nutrition. She was
removed from mechanical ventilation at the age of 7 weeks.
The infant’s postventilator course was significant for the presence
of tachypnea with a respiratory rate of 60 to 80 beats per minute,
intercostal retractions, end inspiratoty crackles on auscultation of
the chest, and a persistent requirement for supplemental oxygen.
Her growth was suboptimal for several weeks. She continued to re-
quire aminophylline and diuretics. She also required nasal cannula
oxygen at 1.0 Wmin to maintain an oxygen saturation greater than
90% at all times as measured by pulse oximetry. In addition, her
management included feedings of hypercaloric formula made to 30
calories/ounce. Ultimately, her growth began to improve coincident
with the resolution of her clinical findings of lung disease.
Presently the infant is at home and continues to do well. She still
requires home oxygen therapy as well as diuretics. A recent chest
radiograph is shown in Figure 1. Her growth has crossed percentiles
and she now grows along the 15th percentile. Follow-up has shown
normal neurodevelopmental findings to date.
ASPECTS OF BPD AT DARTMOUTH-HITCHCOCK MEDICAL

CENTER AND OTHER CENTERS
INCIDENCE
As stated earlier, there are wide discrepancies among incidence
reports of bronchopulmonary dysplasia, with reported rates from
6% to 62% .1”51’52 This does not necessarily reflect a real differ-
ence among institutions, but may depend on the definition of
BPD (the numerator) and the population considered to be at risk
(the denominator). The population at risk for BPD has been de-
fined in several ways: (1) all newborns, (2) newborns admitted to
a neonatal intensive care unit, (3) newborns who require ventila-
tory support, (4) newborns with RDS, (5) newborns less than
1,500 gm birthweight, or (6) newborns weighing less than 1,500
gm surviving 28 days.“’ ” It should be apparent that as the popu-
lation under consideration becomes smaller, the incidence of
BPD will appear to become larger. Horbar et a1.53 surveyed 11
neonatal intensive care units and found an average incidence of
BPD equal to 25.6% of all infants of birthweight 701 to 1,500 gm.
Bronchopulmonary dysplasia occurred in 30% of those who sur-
vived the first 28 days. The incidence in our institution is com-
parable to the previously cited study. In a six-year period from
1982 to 1987, the incidence was 22.5% of all infants less than 1,500
gm, and 29.4% of those who survived 28 days.54
MORTALITY
Infants with BPD are at a significantly higher risk of dying in in-

fancy than premature infants without BPD. Mortality rates have been
23% to 40% in various series.15,3g,47,55,56 The cause of death is most
often progressive respiratory failure, severe pulmonary artery hyper-
tension, and car pulmonale.8’ 3s Werthammer4’ found the incidence
of sudden infant death among BPD children to be seven times the
incidence in the general population. These events have been attrib-
uted to several causes. Perlmann56 noted marked hypochloremia in
the BPD infants who died compared with the survivors. This has not
been confirmed in other studies.57 Little et al.43 demonstrated mul-
tiple areas of ischemic cardiac infarcts on autopsy in several cases
of sudden death. Death may also be related to CNS events. Ellisor?’
described a syndrome of severe CNS deterioration, progressive ap-
nea, and death among infants with chronic lung disease who re-
mained ventilator-dependent. Autopsy in these cases showed gliosis
of the brain stem. Campbel15’ described five infants with progressive
cerebral deterioration and death, and thought this course was re-
lated to the course and treatment of BPD.
Data from our institution show a mortality rate of 25% among all
infants with BPD from January 1980 through June 1988 (124 patients,
31 deaths). For five of these infants death was a sudden unexpected
event and one of these occurred at home after discharge.54 This is
consistent with the findings of several others who have reported that
death usually occurs during the initial hospitalization.14’15
Cur-r Probl Pediatr, April 1989 187

ETIOLOGZC FACTORS
As stated earlier, the most common respiratory disorder preceding
BPD is RDS.8’60 In reviewing 124 infants with BPD in our institution,
100 (80.6%) had RDS, 16 (13%) had pulmonary insufficiency, and
eight (6.4%) had other respiratory illnesses.54 There were often con-
founding factors complicating the course of recovery from the initial
respiratory illness, most commonly sepsis and persistent sympto-
matic PDA. In our institution between 1982 to 1987, the incidence of
a symptomatic patent ductus arteriosus (PDA) in BPD patients less
than 1,500 gm was 70.8%. The incidence of symptomatic PDA in
non-BPD infants weighing less than 1,500 gm during the same pe-
riod was 10.1% .54
Males are more susceptible to the development of BPD than fe-
males.53 The overall F-M ratio in our population of infants diagnosed
as having BPD was 1: 1.5 (49/75). Males are more likely to die of the
disease, as the F-M ratio in the survivors increased to 1: 1.3 (40/53).
The average birthweight of females with BPD was 967 gm (range,
550-2,320), as opposed to 1,440 gm (range, 460-3,120) in the males.
The average gestational age was 27.1 weeks (range, 24-37) in the fe-
males, 30 weeks (range, 2342) in the males.54
HOME OXYGEN THERAPY

The dependence on medical technology and specialized nursing
care for an extended period of time usually commits infants with
BPD to prolonged hospitalization, in neonatal or pediatric intensive
care units. This has a major impact on the medical institutions, care
takers, the family and society, and of course, the infant itself. A gen-
eral trend in health care today is towards outpatient care and home
care of chronically ill patients in order to conserve health care re-
sources. Several centers have started programs for discharge of BPD
infants while still dependent on supplemental oxygen, cardiorespi-
ratory monitors, and in some instances, home ventilators.4’61,62
Our institution has had a structured program for home oxygen
treatment since 1982. By June 1988, our BPD population consisted
of 110 infants. Fifty-two infants have been discharged on home oxy-
gen; one was also discharged on a home ventilator. An additional 58
infants were diagnosed with BPD during this period. Twenty-eight
of these died and 24 infants were weaned off oxygen before they
were ready for discharge for other reasons. Six infants in this cohort
are still hospitalized. The average duration of home oxygen was 123
days for the 42 children who were weaned.54

FINANCZAL, IMPACT OF BRONCHOPULMONARY DYSPLASIA
The accumulated medical expenses for an infant with BPD fre-
quently exceed $100,000. Most of this cost is generated during the
initial hospitalization in the intensive care unit. McAleese et aL3 cal-
culated an average hospital cost of $142,000 for 37 infants with BPD.
The cost of nonintensive hospital care in stepdown units or local
hospitals while the infant is convalescing is also substantial, and
much can be saved by early discharge with specialized medical care
at home. McAleese3 calculated the projected cost of extended hos-
pital stay for the duration of oxygen therapy and compared this with
the cost of earlier discharge on a home oxygen therapy program.
Results showed a savings of $68,000 per child discharged on home
oxygen. Early discharge, on the other hand, may create additional
stress and expenses for the family, because the primary responsibil-
ity for the infant’s care is shifted to them.63 Expenses not covered by
insurance must be paid for by the family, and care of a child with
special needs is a major problem. Often one of the infant’s parents
will discontinue paid employment in order to stay home to care for
the infant. This leads to loss of income, and sometimes loss of health
insurance benefits as well. Most of the cost savings accrued by early
discharge benefits the third-party payers, but more health insurance
programs are now willing to support both extended outpatient ex-
penses as well as specialized home nursing care in order to encour-
age early discharge and at the same time minimize the burden on
the family.3
DISCHARGE PLANNING AND NURSE COORDINATOR

CRITERIA FOR DISCHARGE AND PREDZSCHARGE ASSESSMENT
The concept of early hospital discharge for the infant with BPD is
appealing for a number of reasons. As has been mentioned, the use
of low-flow oxygen at home can reduce the cost of health care sub-
stantially.3 Bonding and emotional attachment between the infant
and the family are facilitated, as are developmental and social skill~.~
Discharge from the hospital eliminates the risk of nosocomial infec-
tion.
Appealing as it may be, home care involving low-flow oxygen is
not appropriate for every infant with BPD. A number of areas must
be examined before a child with BPD can be considered a candidate
for home management. These areas, discussed individually in the
following paragraphs, are (1) stability of the child’s medical condi-
tion, (2) parents’ attitude about, and confidence in, their ability to
care for their child at home, (3) availability and adequacy of com-
munity-based support services.

Medical Stability
The overall demands of the infant’s medical care, including the
requirement for low-flow oxygen, medication schedule, feeding rou-
tine, and equipment needs, warrant careful review. The fewer the
requirements the more likely it is that home care will be successful.
The general clinical course should preferably be one of gradual im-
provement, or at least stability. Home care is not appropriate for the
child who frequently needs acute assessment or treatment for re-
peated complications or episodic deteriorations.
Medical stability is a subjective judgment; suggested minimal pre-
requisites follow: first, qxygenation must be carefully documented,
including assessment in different states, such as quiet activity, active
sleep, and quiet sleep. It is a general recommendation37-40 as well as
our practice to maintain oxygen saturation, as determined by pulse
oximetry, greater than 90% in all states. Under most circumstances,
in order to be considered for discharge on low-flow oxygen, the ox-
ygen flow required to achieve this should not be greater than 1.0 W
min delivered by nasal cannula.
The next consideration is the infant’s weight gain. It would be op-
timal to have all patients exhibiting catch-up growth at the time of
discharge; however, this would be nearly impossible to achieve in
practice. As a compromise, prior to discharge, the infant’s weight
gain should be adequate to maintain growth along a growth curve
that parallels the fifth percentile. Many of these infants will be slow
or problem Teeders. An infant whose growth is less than optimal may
be discharged if a feeding plan, which is mutually agreeable with the
health care staff and the family, is established.
The infant’s medication regimen andfeeding plan, which will gen-
erally consist of bronchodilators, diuretics, special formulas, special
feeding techniques, or some combination of these, must be applica-
ble to the home setting. The chances of successful home care can
be increased by following several guidelines. First, medications
should be administered as infrequently as possible. Generally, four-
times-daily dosing is the maximum which can be reasonably ex-
pected of a family, and less is certainly desirable. Second, the avail-
ability of prescribed medications, as well as their dosage form, at a
conveniently located pharmacy should be verified prior to discharge.
Third, a demonstrated ability of the responsible family members to
administer the medications properly is required. In addition, par-
ents should have a working knowledge of the intended therapeutic
effects, possible side effects, and toxicities of the medications to be
given to the infant at home. It is very important that no changes be
made in an infant’s medications within the 3 days prior to discharge
home.
Similar considerations apply in regard to an infant’s formula prep-
aration and feeding schedule. A formula and schedule that produce

acceptable weight gain must be found prior to discharge. Parents
should demonstrate competence in both formula preparation as
well as in actual feeding skills. This is important because infants
with BPD are often discharged on specially prepared formulas with
increased caloric density. These infants are frequently noted to be
difficult to feed and parents must be able to interpret their infant’s
cues in order to feed them with consistent success. Failure to do
this may result in frustration for the parents as well as growth failure
for the child. As with an infant’s medication regimen, no changes in
formula composition or feeding plan should be made less than 3
days prior to discharge.
Infants are not discharged until they are apnealfree, having out-
grown any apnea of prematurity. However, for reasons to be dis-
cussed shortly, we and most other BPD follow-up programs rou-
tinely employ cardiorespiratory monitoring at home for children
who are discharged on low-flow oxygen therapy.4 In healthy chil-
dren, the pneumogram has been shown not to be a reliable indicator
of babies at risk for sudden infant death syndrome and a 1987 Na-
tional Institutes of Health consensus conference has discouraged
the use of the pneumogram for this purpose.64 Similarly, there are
no data to demonstrate that the pneumogram is helpful in selecting
children with BPD who are at risk for unexpected death.
Parental Attitude and Preparedness

Parental attitude is of prime importance in successfully managing
the oxygen-dependent child at home. Initially, many parents display
a lack of confidence in their ability to provide safe care at home.
When faced with the alternative of continuing hospitalization, how-
ever, most parents decide to take their infant home as soon as pos-
sible, even if it means the infant will require supplemental oxygen at
home. Prior to discharge, a detailed family assessment is done to
determine whether the family structure, employment situation, liv-
ing quarters, and community support systems are such that suc-
cessful home care is likely. It must be recognized by professional
staff that home care places extraordinary demands on the family
and may be unwise and unsuccessful in certain circumstances. The
goal of a predischarge assessment is to identify situations where the
risk of failure is high.
Although the psychosocial situation is critical, the physical envi-
ronment is also important. Reasonable proximity and access to rou-
tine and emergency medical care is essential. Also essential is the
availability of telephone and transportation. The home must be able
to accommodate the necessary medical equipment. A situation in
which the child would be repeatedly exposed to cigarette smoke or
other airway irritants is not appropriate for the child with BPD. Like-
wise, placement in a day care situation with the subsequent in-

creased risk of respiratory infection is not advisable for the child
with BPD.65
In certain cases financial considerations may preclude home care.
Even though total direct health care costs are reduced with early
discharge, the indirect costs of transportation, special formulas, care
of other children, and lost wages may warrant delaying discharge in
individual instances.
Community-Based Support Services

It is difficult for excessively stressed families to meet the special
needs of their infant. Poor compliance with recommended manage-
ment often occurs and results in less than satisfactory recovery. The
goal in utilizing community support services (e.g., Early Intervention,
Visiting Nurse Association, nursing home care, respite care) is to
supplement the family’s ability to function and prevent exhaustion
of family members. Prior to discharge and as part of the discharge
planning process, an attempt is made to determine which services
will increase the chances for successful home care and whether
these services would be available for the family. If needs and avail-
ability match, the services required are mobilized prior to the day of
discharge.
TRANSITIONAL CARE
Once discharge readiness is established, the transition from hos-
pital to home care begins. Successful home care depends, to a de-
gree, on a smooth transition. This transition will involve: (1) estab-
lishing a daily care routine for the parents, (2) discharge teaching, (3)
identifying and assessing an equipment vendor, (4) identifying emer-
gency services, (5) obtaining baseline medical data, and (6) arranging
for medical follow-up.
DaiIy Care Routine

The establishment and implementation of a care routine applica-
ble to the home situation prior to discharge is of paramount impor-
tance. This routine (amount of oxygen administered, feeding com-
position and schedule, medications and dosages) should not be
altered within the three days prior to discharge. Parents should be
required to room-in with their infant for 24 to 48 hours. During this
time they should assume total care so that they have a thorough
understanding of the child’s care. This may help alleviate fears as to
their ability to assume responsibility for their child at home.
Discharge Teaching
There are five general areas in which families need to receive in-
struction: (1) diagnostic and prognostic aspects of BPD, (2) safe and

TABLE 2.
Outline of Discharge Teaching
Diagnosis and prognosis of BPD

Equipment
Cardiorespiratory monitor
Oxygen
Tanks-gas or liquid
Flowmeter
Nasal cannula placement
Thermometer
Nebulizer/compressor for delivery of inhaled medications
Suction machines/devices
Rationale for therapeutic intervention
Medication effects and side effects
Nutritional requirements/feeding schedule
Chest physical therapy
CPR
Assessment skills
Signs and symptoms of cardiorespiratory compromise
Feeding problems
Signs and symptoms of side effects
Developmental intervention
Comforting
Handling
Appropriate anticipatory guidance
Special feeding plan
appropriate use of equipment, (3) rationale for the various therapeu-

tic interventions, (4) assessment skills, and (5) developmental inter-
vention. These are detailed in Table 2.
Zdentiflcation and Assessment of OFygen Equipment Vendor

Home care companies and vendors have begun to compete for the
home oxygen market. To ensure quality care and minimize frustra-
tion for the family we have adopted minimum standards for vendor
service; these are delineated in Table 3.
TABLE 3.
Minimum Standards: Oxygen Equipment Vendor
ZChr/day call response system

Responds to all patient inquiries within 2 hours (unless clearly identified by parent as a
nonemergency call).
Qualified, professional staff: certified respiratory therapists and/or registered nurses
Experience with infants
Appropriate equipment: low-flow oxygen meters, appropriate-sized nasal cannula
Will demonstrate equipment to family and additional care providers on request and without
additional fees

Identification of Emergency Services
For children requiring supplemental oxygen therapy, it is good
practice to notify emergency public support services, including tele-
phone and electric companies and an ambulance company, of the
child’s presence in the community. In special situations it may be
advisable to provide emergency rooms that would be involved with
care of the infant with written, organized advice or protocols regard-
ing emergency management.
Baseline Medical Data

In order to aid in monitoring progress and in assessing any acute
illness after discharge, certain baseline data obtained at or just be-
fore discharge are important. A physical examination with weight,
recumbent length, head circumference, and vital signs, including
systemic blood pressure, should be performed. The data should be
recorded and any abnormalities on examination clearly noted. Oxy-
genation status should be documented. As previously stated, the
pulse oximeter saturation should be measured at rest, while sleep-
ing and during feeding and the amount of oxygen being delivered to
achieve those saturations noted. Oxygen saturation obtained in
room air can serve as a helpful baseline to monitor future progress.
Further discharge laboratory data consist of a capillary or arterial
blood gas determination for pH and Pcoz, chest radiograph, hemo-
globin and,hematocrit, serum electrolytes, and an ECG. Other inves-
tigations such as anticonvulsant or theophylline blood levels may be
indicated in certain patients.
Arranging Medical Follow-Up

As a result of the complicated neonatal course experienced by
children who develop BPD, it is not unusual for several pediatric
subspecialists to be involved in their care. Additionally, these chil-
dren require primary pediatric care in their own locality. It is possi-
ble to avoid fragmentation of a child’s medical care when each care
provider’s roles and responsibilities have been defined and agreed
on prior to discharge. Generally, the BPD follow-up team, because of
their location at a tertiary center, can most conveniently coordinate
visits to multiple subspecialists when this is required. Private physi-
cians, because of their geographic proximity and availability, are gen-
erally best suited to provide anticipatory guidance, immunizations,
and assessment during the intercurrent illnesses seen in these chil-
dren.
Specific details of a child’s care, such as who will monitor the
need for continued use of oxygen and adjustment of medications
related to the child’s BPD, are probably best decided on a case-by-
case basis for each child. In any case, discharge should not occur

until medical follow-up plans are decided on and are arranged in
detail.
THE ROLE OF THE NURSE COORDINATOR

Successful home care is dependent on the efforts of a multidisci-
plinary team, as the needs of an individual family and their infant
vary and are often complex. The nurse coordinator is the key in
building a program to support care of oxygen-dependent children at
home. The coordinator begins preparation while the infant is still in
the hospital by presenting the BPD infants to a multidisciplinary
team, which includes representatives of child development, social
work, and nursing. At Dartmouth-Hitchcock Medical Center (DHMC)
the infants are followed up on a biweekly basis by the nurse coor-
dinator with reviews of their medical status and nursing care plans
during their ongoing hospitalization. In this forum, psychosocial and
financial needs that must be addressed prior to discharge are dis-
cussed. For example, these meetings provide an opportunity to iden-
tify the need for regular home nursing care, respite care, or more
intense efforts at parental education. When such needs are identi-
fied, a plan is generated and it is the responsibility of the nurse
coordinator to ensure that the plan is implemented and that follow-
ing discharge any needed adjustments are made.
Infants with BPD who remain oxygen-dependent may be dis-
charged from a tertiary center either directly home or transferred to
another hospital more proximate to their home. The role of the
nurse coordinator varies somewhat with either of these possibilities.
If the infant is discharged directly home, the nurse coordinator
maintains contact with the family by telephone, home visits, and at
clinic visits. When an infant is transferred to another hospital the
nurse coordinator also serves as an educational resource for staff
who may not be familiar with BPD. In either type of discharge, the
coordinator remains available as a consultant to the family directly
as well as to community-based professionals. The nurse coordinator
refers problems to appropriate departments as they arise. In the po-
sition of case manager, the nurse coordinator has knowledge and
experience regarding all aspects of family care and in this manner
becomes a resource to the family as well as to the staff.
SUPPORT SERVICES FREQUENTLY REQUIRED

Respite Care
Respite care is care provided by a non-family member for the pur-
pose of relieving the parents for some period of time. It is distinct
from home nursing care in that it is provided at infrequent intervals

and does not require a level of skill beyond that of the parents. Par-
ents commonly request respite care. Insurance companies that have
case management programs will occasionally pay for respite care,
particularly if the child’s care is complex and the respite is viewed
as reducing the potential for rehospitalization. Visiting and public
health nurses are a potential resource, particularly in identifying vol-
unteer respite services or local funds set aside for families. Although
the need for respite care is great, the resources are limited and fam-
ilies who have supportive friends and family members tend to find
these latter groups the best resource in providing a break from the
constant care of their child.
Professional Home Nursing Services

Occasionally the care of an infant with BPD is so complex and
intense that its proper execution constitutes skilled nursing care.
Examples of this might include children with gastrostomy tubes,
children requiring very frequent chest physiotherapy or inhalation
treatments, children requiring tracheostomy care with suctioning,
and/or those whose respiratory status is precarious. It is unreason-
able to expect parents alone to provide skilled nursing care 24 hours
a day; professional help must be employed. The number of hours of
nursing support and arrangement of the time of day for these ser-
vices are individually identified. It is within the role of the nurse
coordinator to evaluate the home care staffs knowledge of infants
with BPD and provide necessary consultation and training.
Early Intervention and Developmental Care

There is a body of literature to suggest that early and ongoing
developmental care for infants at risk will result in improved out-
come.5 At DHMC there is a developmental team for inpatient con-
sultation and management of these issues. This same team is avail-
able to work with community early intervention staff after discharge.
This team also participates in the regular BPD clinic visits with on-
going developmental assessments.
Parent Support Groups

There is documentation of the benefits of parent support groups
for families of medically fragile and developmentally delayed infants
and children.5 In our own experience, families can provide support
to each other that is unequalled by professional efforts. Goals of par-
ent support groups include alleviation of psychosocial stress, relief
from a sense of isolation, and the sharing of information and expe-
riences. Lobbying efforts to obtain increased state and federal sup-
port for families who deal with these infants has also originated in
settings of this kind.

FOLLOW-UP OF INFANTS WITH BRONCHOPULMONARY
DYSPLASIA
FOLLOW-UP AT THE TERTIARY CARE CENTER
No generally agreed upon guidelines exist for the follow-up of in-
fants with BPD. Many infants, particularly early in their posthospital
course, require very frequent follow-up visits. In other cases where
problems are less severe, only infrequent return appointments to the
tertiary care center are needed. At DHMC, we see all BPD patients in
our Transitional Long-Term Care (TLC) clinic within 1 to 2 weeks
after discharge. At the initial visit, we check to see that arrangements
discussed under “Transitional Care” have gone smoothly, and sort
out any problems with pharmacies, equipment, or vendors. The rou-
tines of home care, including feeding, sleeping, oxygen delivery, and
medication administration are reviewed and evaluated. Often, subtle
differences in care techniques or environment can influence the
child’s status considerably. Unless, specific problems are identified
that dictate a change in therapy, we make it our policy that no alter-
ations in the care routine are made at the initial clinic visit.
The frequency of subsequent return visits to the TLC clinic at
DHMC varies with the degree of illness and the intensity of treat-
ment required. As a minimum most children receiving home oxygen
therapy are seen monthly for 6 months after discharge and then
every 2 months until oxygen is discontinued. If they are no longer
on supplemental oxygen but still receiving diuretics, we see them
every 1 to 2 months. In those whose only regular medication is bron-
chodilators, visits are scheduled every 4 to 6 months. Whenever any
significant change is made in the treatment regimen (e.g., lowering
or discontinuing oxygen or other medications), the patient is seen
again two weeks later. Follow-up visits with primary care providers
are generally in addition to the TLC clinic visits. When patients no
longer require oxygen and long-term medications, we continue to
see them every six months to once a year.
The content of a visit to our TLC clinic naturally varies from pa-
tient to patient, but certain parameters are evaluated at every visit.
The interim history seeks to discover any medical complications but
also looks for any family, social, economic or emotional changes, or
problems. Comments or concerns of primary physicians, social
workers, or visiting nurses are reviewed. As growth may be the single
best indicator of adequate treatment, the physical assessment al-
ways includes an accurate weight, recumbent length, and head cir-
cumference. All are plotted on an appropriate growth chart for lon-
gitudinal comparison. Vital signs including blood pressure are taken
at each visit. A general physical examination that pays particular at-
tention to the cardiorespiratory system is always performed. In ad-

dition to a thorough history and examination, other parameters are
monitored serially in the infant with BPD. These are discussed as
follows.
Oxygenation
Long-term oxygen supplementation at home requires careful
monitoring and cautious weaning. Currently, pulse oximetIy pro-
vides the best means of assessing the adequacy of oxygen ther-
apy.@’ 67 Oxygen saturation should be measured at least once
monthly as long as the child is stable or improving. More frequent
measurements are indicated if the child is unstable or in the event
of an acute illness. Testing generally requires 20 to 30 minutes in the
clinic setting to assure stability of oxygenation. We routinely record
the saturation on the current oxygen flow rate, at one or two lower
flow rates, and on room air. The room air measurement in particular
can be helpful in monitoring improvement in pulmonary status over
time. Although in the clinic testing is generally performed during
quiet wakefulness, not infrequently recording the saturation during
sleep or feeding is indicateds4
Chest Radiographs
Because chest x-ray improvement lags behind clinical improve-
ment in BPD, chest x-rays can remain abnormal for years.68 The
x-ray findings are continually evolving; therefore chest films are ob-
tained periodically to establish new baselines. This is especially im-
portant to prevent overinterpretation of abnormalities during acute
respiratory illnesses. We repeat a chest x-ray every six months until
normal and thereafter only when clinically indicated.
Carbon Dio;uide Tension

Some infants discharged with BPD have persistent elevation of
Pco,.6g As with the chest radiograph, periodic arterial or capillary
Pco, determinations are important to provide a baseline for compar-
ison during acute illnesses. If the discharge Pco, is elevated, we re-
peat the measurement at 2-month intervals until normal.
Electrocardiogram
Cardiac abnormalities are frequent in BPD. Right and/or left ven-
tricular hypertrophy has been noted on ECG tracings.10831’40 Such
ECG changes may indicate that the child is experiencing episodes
of hypoxia that have not been apparent during oxygen monitoring
in the clinic. Electrocardiograms are followed up every two months
until they are normal and the child has been off supplemental oxy-
gen for six months. Persistent or progressive abnormalities may in-
dicate the need for further studies such as echocardiography or car-
diac catheterization.

Laboratory
We recommend that the hemoglobin and hematocrit be checked
monthly until consistently within the normal range for age. Serum
electrolytes and a urinalysis should be obtained monthly as well in
all infants on diuretic therapy. Changes in clinical status or dosing
may warrant more frequent measurements.
Most often the serial follow-up investigations are obtained at the
tertiary care center. However, because travel with infants on supple-
mental oxygen can be difficult and anxiety-producing, it is some-
times more convenient to have the studies done by the primary care
provider when needed between scheduled return visits to the BPD
follow-up clinic. Also, as much as possible, we try to coordinate re-
turn visits to the various specialists at the medical center to decrease
the need for travel and improve compliance with follow-up recom-
mendations.
Immediately following each visit to our TLC clinic, a letter review-
ing history, physical findings and laboratory data, impressions and
recommendations for treatment and future follow-up is generated
and promptly forwarded to the private physician. The need for good
communication plus consistent advice and recommendations can-
not be overemphasized in the care of these often complicated and
difficult patients. For our own purposes, we have found it useful to
keep a flow chart with essential information on each patient sepa-
rate from the general medical chart. This allows quick and easy ac-
cess to pertinent information.
FOLLOW-UP BY PRIMARY CARE PROVIDERS

It is the responsibility of the tertiary care center to communicate
to the primary care provider, prior to the child’s hospital discharge,
the details of the infant’s neonatal course, feeding plan, medications,
oxygen therapy, and long-term management plan. The initial visit to
the primary care physician should be within the first week of hos-
pital discharge to acquaint the physician with the family and vice
versa. This early visit allows the physician to review the history and
current treatment and to perform a baseline physical examination.
Subsequent visits should be weekly for the next four to six weeks
and then every two weeks until the clinical course is stable and the
family is coping well and is comfortable with the various physical
and emotional demands of home care. If everyone is doing well, vis-
its can be scheduled every four weeks until the patient is off oxygen,
diuretics, and special formulas. Less frequent follow-up should be
needed thereafter unless complications arise. The child with BPD is
at increased risk for a variety of problems (see Table 4) and aware-
ness of these is essential.
The infant with a prolonged course of BPD is usually behind on
Curr Probl Pediafr, April 1989 199

Anticipated Problems in
Bmnchopulmonary Dysplasia
Poor growth
Feeding difficulty
Gastroesophageal reflux
Aspiration
Recurrent respiratory infections
Otitis media
Reactive airways disease
Upper airway obstruction
Pulmonary hypertension, COT pulmonale
Sudden death
Systemic hypertension
Hernia
Developmental delay
Vision impairment
Hearing impairment
Risk for child neglect or abuse
immunizations when discharged to home and proper vaccination

becomes the responsibility of the primary care provider. Current rec-
ommendations are to administer immunizations according to
chronological, not gestational, age.” When the infant is home and
stable for 2 weeks, diphtheria-tetanus-pertussis (DTP) and oral polio
vaccines can be started at full doses according to the usual sched-
ule. Occasionally, concern regarding the side effects of pertussis im-
munizations leads physicians to give a diphtheria-tetanus injection
and exclude the pertussis portion of the vaccine. The serious risks
of a child with BPD contracting pertussis must be carefully consid-
ered in making this decision. Current guidelines state that pertussis
immunization should be deferred in a I‘. . . neurological disorder
characterized by progressive developmental delay or changing neu-
rologic findings .” Further, “Prematurity per se does not in-
crease the risk of seizures following immunization. Similarly chil-
dren with developmental delay or cerebral palsy without other
evidence of a predisposition to seizures are not considered at an
increased risk of seizures following pertussis immunization.“70 The
reader is referred to The Red Book for further discussion regarding
pertussis immunization. Other routinely used vaccines, measles-
mumps-rubella (MMRI and Hemophilus inj?uenzae type b (HIB) are
given at the usual times.” Influenza vaccine should be administered
to infants with BPD at 6 months of age or older.7’ To protect infants
with chronic conditions such as BPD before this age, the family and
other caretakers should be immunized against influenza.7”
200 cur-r Probl Pediatr, April 1989

MEDICAL MANAGEMENT OF THE CHILD WITH
BRONCHOPULMONARY DYSPLASIA
NUTRITIONAL MANAGEMENT
Nutritional follow-up is an important component of the manage-
ment of the infant with BPD. The caloric requirements of these pa-
tients are increased”’ 45,46 and growth failure is common in BPD.44-46
Often up to 150 to 160 calories/kg/day are needed to achieve normal
growth.44 The reason for the increased caloric need has yet to be
folly elucidated. Although the patient with BPD works harder to
breathe, this only partially explains the excess caloric needs; other
currently unknown mechanisms play a role as we11.46 In addition to
the increased caloric requirements, feeding difficulties frequently
compromise the nutritional status and complicate management.
Neurologic abnormalities can interfere with sucking and swallowing
and lead to aspiration. Also, rumination7’ and gastroesophageal
reflux73 have been noted with increased frequency in children with
BPD.
Many children with BPD can thrive on ad lib schedules of stan-
dard 20 calorie/ounce formula, but a large number require more in-
tense nutritional management. In some cases, simply scheduling
feedings and specifying a minimum daily intake is sufficient. In oth-
ers, especially when caloric requirements are high or when fluid in-
take must be limited, increased caloric density is needed. Commer-
cially available 24 calories/ounce formula is frequently used, but even
this is not always sufficient. At times formula prepared with up to
30 calories/ounce is indicated. There are a variety of ways to achieve
this increased density. Stock 20 calorie/ounce formula (especially
low-sodium formula) can be concentrated by adding sufficiently less
than the recommended amount of water to the powdered or liquid
concentrate preparations, thus increasing caloric content to 24 cal-
ories/ounce. Additionally, Polycose and/or medium-chain triglycer-
ide (MCT) oil can be added to 24 calorie/ounce formula to further
increase caloric density (see accompanying Table).
Nutritional
Supplements
Polycose: powder, one
level teaspoon = 2
gm = 8 kcal; liquid,
2 kcaL’m1
MCT oil: 7.6 kc&ml
Availability, cost, and parental competence should be considered

when making decisions regarding choice of formula. High-dose vita-
min and mineral supplements are not recommended except where
specifically indicated (e.g., rickets or anemia).
When other feeding difliculties are present, increasing caloric den-
sity alone may not be sufficient to achieve acceptable growth. If
sucking or swallowing is ineffective or rumination is present, feed-
ings can be very prolonged and extremely frustrating. A patient, car-
ing, and consistent caretaker is helpful, but physical therapy consul-
tation may be needed for suggestions and guidance regarding
feeding techniques. The risk of aspiration must be kept in mind and
if this is significant, a gastrostomy tube may be indicated to bypass
the swallowing mechanism. A gastrostomy tube may also be helpful
for children who simply cannot take adequate volume by mouth due
to respiratory symptoms, fatigue with feedings, or who refuse to take
oral feedings. Continuous drip feeds via gastrostomy may be needed
if bolus feeds are not well tolerated. Finally, gastric fundoplication
may be indicated for the infant with severe gastroesophageal reflux
that contributes to growth failure or in whom aspiration results.73
CAZ3DIORESPZRATORY MANAGEMENT
Long-term studies of the comprehensive management of cardio-

respiratory complications of BPD are nonexistent. Treatment strate-
gies are based on clinical experience, short-term studies, studies in
similar diseases, and a knowledge of the pathology of BPD. In many
ways these patients have a striking similarity to patients with
asthma. In patients discharged from the hospital, the most common
clinical manifestations of BPD are a persistent oxygen requirement,
reactive airways, recurrent respiratory infections, and pulmonary
edema.’ In addition, obstruction of the large airways is emerging as
a more commonly recognized component of BPD.34’ 35
Oxygen
Oxygen therapy is essential in the infant with significant BPD. Ox-
ygen consumption and work of breathing is increased in BPD,“, 46
and this increased energy expenditure may interfere with growth.
Theoretically, supplemental oxygen will decrease the caloric expen-
diture for breathing and permit calories to be used for growth, and
in fact, improved weight gain has been demonstrated in BPD with
the use of supplemental oxygen’l Chronic hypoxia can result in pul-
monary hypertension. When the Pao, falls below 55 mm Hg in in-
fants with BPD, right ventricular function is compromised.74 Al-
though in some infants a degree of the pulmonary vascular lesion
causing pulmonary hypertension may be lixed and nonreversible,38
in general the elevated pulmonary artery pressure in BPD is respon-
sive to increased levels of inspired oxygen.38-40 High oxygen concen-
xl2 Curr Probl Pediatr, April 1989
nations are not necessary, as low-flow oxygen is adequate for most
of the beneficial response seen.3b40.
The goal of oxygen therapy is to maintain an acceptable Pao,-
currently thought to be 60 mm Hg or greater.’ Once an infant is on
a fraction of inspired oxygen of less than 40%, this can usually be
accomplished by use of a nasal cannula or nasal prongs with 100%
oxygen delivered at a flow rate of between l/s and 1 Wmin. The oxy-
gen requirement will vary with the infant’s activity.4’8 Oxygenation
should be assessed during feeding, quiet wakefulness, and sleep,
and the flow rate set to provide adequate oxygenation throughout
all of these physical states. In assessing and monitoring oxygenation,
it is clear that intermittent arterial punctures are not adequate in
the infant with BPD. Recently, pulse oximetry has proven to be ex-
tremely useful in determining oxygen needs. Values obtained by
pulse oximetry have good correlation with actual arterial oxygen
saturation66’ 67 and in BPD provide a more accurate reflection of ar-
terial oxygen status than transcutaneous PO, (TcPoJ measure-
ments.67 Saturation as measured by pulse oximetry should be main-
tained greater than 90%, which corresponds to a Pao, of greater than
60 mm Hg. Oxygenation status should be documented at all follow-
up visits as well as during any acute illness. Although high concen-
trations of oxygen initially may contribute to the development of
BPD,8 once the infant has improved to the point where only low-
flow oxygen is required, the risks of hypoxia may outweigh the risks
of continued oxygen administration. Therefore, it is important not to
wean or discontinue the use of oxygen too rapidly. We decrease ox-
ygen flow in increments of not more than 0.25 Umin flow rate at
intervals of not less than 2 weeks. It is critical to remember that
desaturation can occur during sleep and that adequate oxygenation
while awake does not ensure adequate oxygenation while sleeping.48
Once satisfactory oxygenation can be maintained while the child is
awake breathing room air, oxygen use can be discontinued during
waking hours. However, it may need to be maintained nocturnally
for a longer period of time. Ideally, measurement of oxygen satura-
tion during sleep should be performed prior to discontinuing noc-
turnal oxygen therapy. Despite the tendency to wean oxygen flow as
rapidly as possible in order to “prove” that the child is improving, it
is our own opinion that it would be a mistake in this setting to give
too little oxygen.
Many BPD follow-up programs routinely employ home cardiores-
piratory monitoring in children discharged on home oxygen.4 The
benefits of home cardiorespiratory monitoring in these children re-
main unproven. However, in view of the reported high incidence of
unexpected death, it is also our own practice to monitor children at
least until they have not required oxygen supplementation for one
month and are clinically well.

Bronchodilators
Bronchodilators play an important role in the management of BPD
patients. Rationale for the use of bronchodilators is derived from var-
ious sources. Pathologically, infants with BPD have smooth-muscle
hypertrophy in the tracheobronchial tree.24’36 Clinically, children
with BPD frequently have recurrent episodes of wheezing and have
a significant family history of asthma in first- and second-degree rel-
atives? Also, mothers of prematurely born infants have a high prev-
alence of reactive airways.75 Follow-up studies of older children who
have survived BPD show a high prevalence of bronchial hyperreac-
tivity as measured by a positive response to methacholine inhalation
challenge and improvements in expiratory flow rates following bron-
chodilator administration.31 More recently, physiologic studies have
demonstrated that this airway hyperreactivity can develop very early
in the infant who eventually develops BPD, even as early as 26 weeks
postconception3’
Kao et al.” examined the effects of inhaled isoproterenol on the
pulmonary mechanics of ten infants with BPD. Within 36 minutes
after receiving isoproterenol inhalation, mean airway resistance de-
creased 28% and specific airway conductance increased 53%. Orally
administered theophylline has also been shown to have favorable
effects on pulmonary mechanics in BPD.76 Consistent with the fore-
going information, we have been strongly impressed with the simi-
larity between BPD and asthma. There may be potentially beneficial
nonbronchodilator effects of bronchodilators in BPD. Inhaled beta-
adrenergic agonists enhance mucociliary clearance both in vitro77
and in viv~.~’ Theophylline has diuretic properties and increases
diaphragmatic contractility while decreasing diaphragmatic fatigue
in adults with airway disease.7g
The initial treatment of wheezing is usually a selective beta-, ad-
renergic agonist administered by inhalation. Inhaled bronchodila-
tors are currently the treatment of choice for acute exacerbations in
asthma.80’81 When administered by inhalation, response is superior
to or equal to that obtained when the same agents are given by
mouth or injection, even in the presence of severe small airways
obstruction.81’sZ The use of inhaled agents provides a more favorable
therapeutic/toxic ratio.” The most commonly noted side effects are
transient tachycardia and tremulousness.81J82 By restricting the
choice of bronchodilators to agents that are more beta-, receptor
specific, such as albuterol or terbutaline, toxicity can be further di-
minished (Table 5).
Inhaled bronchodilators are most often used on an as needed ba-
sis during intermittent, acute episodes of bronchospasm. However,
they can also be given on a regularly scheduled basis as a mainte-
nance medication in patients with frequent or persistent wheezing,
although for the purpose of preventing wheezing the use of an agent

TABLE 5.
Medications Used for Brunchopulmonary Dysplasia
=‘v3 Available Form Dosage
Albuterol nebulizer solution 0.5% (5 mg/ml) 0.05-0.15 mg/kg/dose every 2-6 hr

as needed
Terbutaline injectable 0.1% (1 mg/mlI 0.1-0.3 mg/kg/dose every 2-6 hr as
solution (used as needed
nebulizer solutioni
* See text
Theophylline
Cromolyn sodium nebulizer 20 mg/Z ml ampule 20 mg 4 times daily
solution
Fumsemide 10 mEq/ml l-2 mg/kg/day divided every 8-12 hr
Potassium chloride 1 mEq/ml l-3 mEq/kg/dose every 8-12 hr
Chlorothiazide 50 mg/ml 20-30 mg/kg/day divided every 12 hr
Spimnolactone 2 mg/ml (prepared from l-3 mg/kg/day divided every 12 hr
25-mg tablets1
Prednisone 1 mg/ml l-2 mg/kg/day divided every 6-12 hr
‘Various liquids and bead-filled capsules available
such as cromolyn or theophylline may be superior.‘* Often, inhaled
bronchodilators are administered prior to chest percussion and pos-
tural drainage to improve mucus clearance.
In infants and young children, these drugs are administered by
compressed air or oxygen and jet nebulizer with either a face mask
or a mouthpiece held directly in front of the mouth and nose. The
recommended dose for albuterol is 0.05 to 0.15 mg/kg/dose diluted
to 3 ml with normal saline and given every two to six hours.83 In an
acute illness with wheezing, smaller but more frequent doses may
be preferable. In a study of acute asthma in children, low-dose (0.05
mgkg) albuterol administered every 20 minutes by nebulizer pro-
duced a greater improvement in pulmonary function than a larger
dose (0.15 mgkg) given every 60 minutes.84 Terbutaline is not cur-
rently available in nebulizer form in the United States, but the solu-
tion designed for subcutaneous injection can be given via nebulizer.
A dose roughly equipotent to that recommended for albuterol is 0.1
to 0.3 mg/kg.83
Although of potential benefit, the use of theophylline in BPD may
present special problems. Adverse effects include gastrointestinal ir-
ritation, sleep difficulty, behavior changes, and lowering of lower
esophageal sphincter pressures5 This latter effect may contribute to
gastroesophageal reflux. Also, although dosage recommendations ex-
ist, individual dose requirements vary and must be guided by deter-
minations of serum theophylline concentration. Monitoring levels
and observing for side effects of toxicity is not generally a problem
in the hospitalized patient, but can be difficult and a source of frus-
tration in the outpatient setting. For these reasons, we restrict the
use of theophylline to maintenance therapy in those patients where
wheezing is continuous or frequently recurring. When this continu-
ous therapy is indicated, the risk of adverse effects can be reduced
by beginning therapy at two thirds the average dose requirements
for age and increasing by 25% increments every 3 days to the mean
age-adjusted dosage.” For infants less than 1 year of age, the mean
dose in milligrams required to achieve therapeutic levels is 8 + 0.3
times age in weeks.87 In all cases the final dosage is guided by the
serum theophylline concentration. The use of slow release bead-
filled capsules allows for a convenient twice-daily dosing schedule,
but aqueous-based solutions given every 6 hours may be preferred
when administration of the beads is problematic or in small infants
where more exact-dose titration is necessary.
Recently, there has been a renewed interest in the use of anti-
cholinergic aerosols in patients with obstructive lung disease. These
agents can produce bronchodilation in asthmatics and in adults
with chronic obstructive pulmonary disease (COPD).” The efficacy
of this approach in patients with BPD is just beginning to be studied.
In five ventilator-dependent infants with chronic lung disease, Wilkie

et al.8’ found an increase in respiratory compliance and a decrease
in airway resistance following inhalation of ipratropium bromide.
Ipratropium bromide, like the prototypic anticholinergic atropine, is
an effective bronchodilator but, unlike atropine, is not well absorbed
from the respiratory tract and thus has fewer side effects.81’88 At the
present time, ipratropium is available only in metered-dose inhaler
form in the United States. Future studies will determine what the
role of this agent will be in the management of children with BPD.
Cromolyn Sodium
Cromolyn sodium is widely used in the treatment of childhood
asthma and has been shown to be effective in a majority of these
patients. As a result of the high frequency of reactive airways disease
in the setting of BPD, it is possible that this agent may be of benefit
in selected infants.31’ SoThe primary indication for cromolyn is per-
sistent or frequent symptoms that are not adequately controlled
with the “as needed” use of inhaled bronchodilators.” While cromo-
lyn reduces the frequency and severity of symptoms from reactive
airways, it has no intrinsic bronchodilator activity. Its primary mech-
anism of action appears to be inhibition of mediator release from
mast cells after immunologic or nonimmunologic stimulation.” For
the child with BPD, it is particularly noteworthy that cromolyn can
protect against nonimmunologic triggers such as exercise, cold air,
and sulfur dioxide. Few studies have specifically examined the role
of cromolyn in BPD. Stenmarksl studied 10 ventilator-dependent in-
fants with BPD. Following treatment with nebulized cromolyn (20
mg every 6 hours), 8 of the 10 demonstrated clinical improvement as
measured by decreased Fio,, wheezing, respiratory rate, and venti-
latory pressures.
As experience in BPD is limited, many recommendations for treat-
ment are extrapolated from experience in asthma (see Table 5).
When beginning cromolyn therapy, one must assure relatively good
airway patency to allow penetration into the lung. Obstruction
should be relieved initially with the concomitant administration of
bronchodilators and/or a short course of corticosteroids. If benefi-
cial, a progressive improvement may start in the first few days or
weeks. However, response may not be immediate, therefore a trial
should last at least 6 weeks before concluding failure.” The starting
dose is 20 mg four times per day regardless of age. If the symptoms
are well controlled after 6 or more weeks, the dose can be reduced
to 3 times per day and sometimes to twice daily. In many patients
it is helpful to combine a bronchodilator with cromolyn and deliver
them simultaneously via nebulizer. Cromolyn is perhaps the safest
drug for the management of reactive airways. Side effects are rare. In
a large study of asthmatics, only one of 97 children less than 12
years of age experienced an adverse reaction.”

Diuretics
Diuretic therapy for BPD is based on a number of observations.
Impaired pulmonary fluid dynamics with delayed lymphatic drain-
age and pulmonary interstitial edema are known factors in the
pathophysiology of BPD.8’ ls The presence of pulmonary edema leads
to poor pulmonary compliance. This requires the infant with BPD to
generate high negative intrathoracic pressures that may in turn con-
tribute to further pulmonary edema.8’20,21 In some instances, ele-
vated levels of endogenous antidiuretic hormone may play a role as
we11.s3 Finally, the caloric needs of the infant with BPD may neces-
sitate a high fluid intake, which in turn predisposes to pulmonary
edema in this situation.
A number of investigations have documented improvement in res-
piratory mechanics following administration of diuretics to infants
with BPD. In ten ventilated infants, Kao et aLg4 found increased com-
pliance and increased airway conductance following a single intra-
venous dose of furosemide (1 mg/kg). Within 1 hour after administra-
tion of the drug, airway resistance fell 36%, airway conductance
increased 84%, and dynamic pulmonary compliance increased 54%.
With longer-term use of orally administered diuretics (chlorothiazide
and spironolactone), similar improvements in respiratory function
have been demonstrated?
Although undoubtedly useful in the management of BPD, the pro-
longed use of diuretics has potential detrimental effects. Electrolyte
imbalances dre possible and alterations in calcium and phosphorus
homeostasis may adversely affect bone growth.8 Nephrocalcinosis is
a well-described complication of the hypercalciuria induced by
long-term furosemide therapy.s6 Also, diuretic-induced metabolic al-
kalosis may produce undesirable compensatory hypoventilation and
hypercarbia.s7
The two most frequently employed diuretic regimens are furose-
mide with potassium supplementation and the combination of
chlorothiazide with the potassium-sparing diuretic spironolac-
tone. The latter combination given twice daily has fewer side ef-
fects and is preferable for outpatient use. Spironolactone for oral
use is available only in tablet form, but the tablets can be easily
crushed and placed in solution (2 mg/ml) (see Table 5). Most
pharmacies are very willing to prepare the drug in this manner.
Some patients will need to have their dosage adjusted with
growth in order to prevent fluid retention and respiratory deteri-
oration. Others can be slowly weaned from diuretics by main-
taining a constant dose while they outgrow the medication. The
frequency of administration can then be decreased to once daily
and finally discontinued entirely. Serum electrolytes should be
checked periodically in all infants receiving diuretics.
208 Cut-r Probl Pediatr, April 1989
Corticosteroids
Steroid therapy in infants with BPD who are not ventilator-depen-
dent has never been prospectively examined. The use of these
agents in this setting is based on data and experience in children
with asthma and on studies involving ventilator-dependent children
with BPD. Two studies reported on the administration of dexameth-
asone to infants with BPD while ventilator-dependent. Mammel and
colleaguess8 noted improvement in respirator settings and oxygen
requirement in six infants treated in a double-blind, cross-over, ran-
domized study. However, infection was reported to be a significant
complication. Avery et al.” also demonstrated short-term improve-
ment in pulmonary compliance and weaning from the ventilator
with dexamethasone. In contrast to the previous study, increased
infection was not seen in those patients treated with steroids.
As noted, the efficacy of steroids in BPD infants who have been
weaned from ventilators and discharged from the hospital has not
been studied. It is well known, though, that these patients frequently
have evidence of airway hyperreactivity.8’30’31 Those with broncho-
spasm appear to respond to steroids in a manner similar to children
with asthma. In asthmatic patients, steroids are often employed dur-
ing acute exacerbations, particularly those associated with viral res-
piratory infections. Intervention with corticosteroids in these situ-
ations in asthmatics has been shown to hasten resolution of
symptomsl”’ lo1 and decrease the incidence of hospitalization.“’ In
a smaller number of patients, alternate-day administration may be
needed to control severe persistent bronchospasm.
The use of inhaled corticosteroid aerosols is an attractive concept
in BPD. Inhaled steroids are effective in both steroid-dependent”’
and nonsteroid-dependent asthmaticslo with few systemic effects.
Of perhaps greater interest, however, is the reduction in nonspecific
bronchial hyperreactivity observed after regular use of these aero-
sols.104 Unfortunately, inhaled steroids have not been investigated in
BPD and nebulizer forms of these drugs are not available in the
United States.
Chest Physiotherapy
Impaired clearance of respiratory mucus is not an uncommon
problem in BPD. Injury to the tracheobronchial tree from intubation,
positive-pressure ventilation, suctioning, and oxygen toxicity result
in a loss of cilia and ciliary dysfunction.‘05 Also, large airway abnor-
malities such as tracheobronchomalacia,34’35 subglottic stenosis,1o6
and tracheomegalylo7 are being increasingly recognized in survivors
of BPD and may contribute to retention of pulmonary secretions. In
infants who have difficulty clearing secretions, percussion and pos-
tural drainage may be beneficial. With acute illnesses and increased
mucus production more frequent percussion and drainage are often
needed. Because of the stress of the procedure, additional oxygen
may be required during and immediately after the treatment.
Respiratory Infections
Acute respiratory infections present a special challenge in the care
of the infant with BPD. These children have an increased incidence
of lower respiratory tract infections in the first 1 or 2 years of life,14’15
and are at increased risk of respiratory failure with respiratory ill-
nesses. Many of these infections are severe enough to warrant hos-
pitaIization4 14,I5 There have been no prospective studies to identify
respiratory pathogens that may specifically affect infants with BPD.
It is assumed that the BPD infant is susceptible to the usual pediat-
ric respiratory infections, the majority of which are of viral etiology.
In normal children clinically inapparent lower respiratory abnor-
malities (decreased expiratory flow rates) have been documented
spirometrically during viral upper respiratory infections.l” The large
expiratory reserve of the normal child prevents this lower respiratory
obstruction from becoming overtly symptomatic. In contrast, infants
with BPD have evidence of significant airway obstruction and thus
limited expiratory reserve even in the absence of acute infectionz7
This limited reserve places them at high risk for severe respiratory
distress during what otherwise might be a mild viral “cold.” Addi-
tionally, viral infections can precipitate bronchospasm in those pa-
tients with heightened airway reactivity,‘3 further compromising air-
way patency. Other observations further illustrate the potential
dangers of acute infection. Transient respiratory ciliary dysfunction
occurs in normal children during viral upper respiratory infec-
tions .log In the infant with BPD, this decreased ciliary function along
with increased respiratory mucus production and decreased airway
caliber can overload an already compromised mucociliary clearance
mechanism and lead to further obstruction, mucus plugging, and
atelectasis. This may be a particular problem in the infant with
tracheobronchomalacia or other large airway lesion that interferes
with the normal flow of mucus from the lungs. Lastly, one report
has shown increased plasma levels of antidiuretic hormone in BPD
during episodes of acute respiratory distress, which could promote
fluid retention and pulmonary edema.l”
The most important aspect of the management of acute respira-
tory illnesses is attention to warning signs and early intervention for
complications. Parents should be instructed to seek advice promptly
whenever respiratory symptoms increase or infection seems likely. A
seemingly minor infection can progress rapidly to respiratory failure.
With any increase in respiratory symptoms the infant should be ex-
amined, preferably by a physician familiar with the child’s baseline
vital signs, degree of respiratory effort, and auscultatory findings. Ox-
210 Curr Probl Pediafr, April 1989
ygen status should be assessed by pulse oximetty and the oxygen
flow rate increased if indicated. If moderate-to-severe distress is
present, a blood gas for pH and Pco, is obtained and compared to
previous values. A chest X-ray may be helpful. Although it may not
be of value in differentiating viral from bacterial etiology, it can aid
in gauging the severity of the episode. The most common acute
changes seen are hyperexpansion and/or atelectasis as a result of
airway edema, mucus plugging, and bronchospasm. Other studies
to consider are a blood count, serum electrolytes, serum or urine
bacterial antigens, and collection of nasal secretions for rapid detec-
tion of respiratory syncytial virus.
Several aspects of the management of these infants deserve com-
ment. Currently, there are no data to suggest that antibiotics should
be used prophylactically during viral respiratory infections. The de-
cision to institute antibacterial treatment must be determined on a
case-by-case basis.1’1 As discussed earlier, beginning or increasing
the frequency of chest physiotherapy is important when clearance
of respiratory secretions is problematic. The chest film may demon-
strate atelectasis and efforts can then be concentrated to a particular
lung or lobe. Diuretics are useful when pulmonary edema is sus-
pected. Although the physical examination is helpful, the decision
to use diuretics during infection is often based on knowledge of the
infant’s past history and response to these agents during previous
respiratory infections. Whenever diuretics are used on an acute ba-
sis, very close attention must be given to fluid balance. Frequently,
increased respiratory symptoms compromise fluid intake. Over-vig-
orous diuresis can result in significant dehydration and electrolyte
disturbances.
Vigorous treatment with bronchodilators should be started at the
onset of symptoms in all BPD infants with a history of reactive air-
ways and previous response to bronchodilators. Bronchodilators
should also be tried in all other infants who are not responding ad-
equately to other treatments, especially if symptoms are progressing
or severe. In asthma, early intervention with oral corticosteroids dur-
ing acute exacerbations can decrease morbidity, hasten resolution,
and decrease the need for hospitalization.“’ In one study of asth-
matic children, the institution of steroid therapy (prednisone, 1 mg/
kg/day) at the onset of symptoms suggestive of a viral respiratory
infection resulted in a 90% reduction in hospitalization rate. It re-
mains to be proven whether this approach is helpful in children
with airway hyperreactivity in the setting of BPD, but corticosteroids
should be considered when distress associated with a viral infection
is worsening or severe.
Despite vigorous and appropriate outpatient treatment, hospital-
ization may be needed. The decision for hospital admission is based
on a knowledge of the infant’s past history and respiratory reserve,

the severity or rate of progression of the acute illness, and the par-
ents’ capabilities. Once hospitalized, the treatments outlined above
are continued, though perhaps more intensively. If respiratory syn-
cytial virus infection is documented, ribavirin should be consid-
ered.ll’ Following a respiratory infection, it may be weeks before re-
covery is complete and respiratory symptoms and oxygen
requirements decrease to previous levels.l13 The case history that fol-
lows illustrates several of these principles.
Case History
This patient began life as the 2.99-kg product of a 35-week gesta-
tion. The pregnancy had been uneventful until the day of the pa-
tient’s birth, when the mother developed heavy vaginal bleeding and
delivery was accomplished by emergency cesarean section. The in-
fant had Apgar scores of 0 and 7 at 1 and 5 minutes, respectively.
His early neonatal course was significant for RDS; he required me-
chanical ventilation with high concentrations of supplemental oxy-
gen for 2 weeks and for the gradual evolution of BPD. He was dis-
charged home at 6 weeks of age on l/s L/minute O2 by nasal cannula,
twice-daily chiorothiazide and spironolactone, and 24 calorie/ounce
formula.
The infant initially did well following discharge. He was success-
fully weaned from supplemental oxygen over several weeks. His
chest findings were further improving and he was beginning to ex-
hibit catch-mp growth. However, during his first winter home, at the
age of 6 months, he was seen at our follow-up clinic with a 2-day
history of fever, cough, fussiness, and decreased oral intake. Vital
signs revealed the following: respiratory rate, 100 breaths per minute,
heart rate, 130 beats per minute, temperature, 38” C. His examination
was remarkable for intercostal and subcostal retractions, diffuse in-
spiratory crackles, and a prolonged expiratory phase with wheezing.
His chest radiograph (Fig 2) showed hyperinflation and patchy areas
of consolidation in both lungs. Although he was not cyanotic, pulse
oximetry revealed significant hypoxemia on room air and he re-
quired reinstitution of supplemental oxygen in order to maintain ac-
ceptable pulse oximetry saturation values. Respiratory syncytial virus
infection was confirmed by a positive immunofluorescence test to
respiratory syncytial virus antigen in nasal secretions.
The infant was admitted and treated with intravenous hydration,
nebulized albuterol, and supplemental oxygen. His improvement on
this treatment during the first 48 hours was marginal. He continued
to require increasing amounts of oxygen and have respiratory rates
close to 100 breaths per minute. Treatment with ribavirin was begun
on the third hospital day. There was only marginal improvement
during the subsequent 5 days. Serial chest radiographs (see Fig 2)
showed migrating atelectasis and continued hyperinflation.

FIG 2.
Serial chest radiographs of infant described in second case presentation. A, admission
chest x-ray showing hyperinflation, a right lower lobe consolidation, and scattered left-
sided areas of consolidation. B, chest radiograph 72 hours after admission: continued
hyperinflation, resolution of the previous areas of consolidation. C, film several weeks after
discharge showing reduction in degree of hyperinflation and persistent streak in right up-
per lobe.
Over the next 6 days, there was a very gradual improvement in the
infant’s pulmonary status, as reflected by improvement of his chest
examination and decrease in his respiratory rate to less than 40
breaths per minute. However, his requirement for oxygen therapy
did not decrease but remained at 0.75 Wmin by nasal cannula. His
affect improved and he began to take oral feedings again. He was
discharged home and did well, but for the initial 6 weeks following
discharge required both supplemental oxygen and frequent treat-
ment with nebulized albuterol. Neither of these had been required
in the month prior to his RSV illness. Following this 6-week period

his requirement for low-flow oxygen and bronchodilators gradually
remitted. He is currently 14 months old, is growing well, and has
had serial neurodevelopmental assessments that indicate normal
development.
LONG-TERM OUTCOME OF INFANTS WITH

BRONCHOPULMONARY DYSPLASZA
NE URODEVELOPMENTAL OUTCOME
As more premature infants survive their initial hospital stays, con-
cerns are raised about long-term neurologic and intellectual out-
come in these children. The concerns are shared by parents, physi-
cians, nurses, and society as a whole. The hazards of premature
birth and neonatal intensive care are well known: oxygen toxicity to
eyes and lungs, exposure to ototoxic drugs, vulnerability of the pre-
mature neonatal brain to intracranial hemorrhage and asphyxia,
respirator-induced lung injury, and prolonged periods of inadequate
extrauterine nutrition are frequently found despite the best efforts
to care for these children.
Infants with BPD constitute a special high-risk subgroup within
the population of premature infants. They have often had a difficult
perinatal course requiring prolonged mechanical ventilation, oxygen
therapy, and various pharmacologic interventions, and have been ex-
posed to most or all of the risk factors. Neurodevelopmental deficits
have been reported to occur with increased frequency in these chil-
dren by some investigators?7,55 In order to better predict the devel-
opmental prognosis for an infant with BPD, it would be important
to know whether the reported abnormalities are due to the chronic
respiratory illness itself, or to any perinatal or neonatal events. The
perinatal factors that most jeopardize future development are intra-
cranial hemorrhage, periventricular leukomalacia, asphyxia, inade-
quate nutrition, and sensory deficits.“4’115 Sensory deficits are both
an outcome themselves and a contributor to overall neurodevelop-
mental outcome.
Social and environmental factors have been shown to have a
strong influence on subsequent cognitive development in high-risk
children. Known environmental risks for developmental delay are
low socioeconomic status, single teenage motherhood, and parental
substance abuse.116’“7 While specific neurological handicaps such as
cerebral palsy and mental retardation are thought to be related to
biologic brain injury,“’ it is more difficult to sort out the cause of
less severe deficits such as delayed motor skills, delayed cognitive
development, and learning disorders. Sensory deficits may cause
poor performance on standard tests despite normal cognition. An
additional problem in evaluating development in infants with BPD is

that some of the deficits seen in the first and second year are tran-
sient and may be related to the chronic illness.1’g Accelerated prog-
ress may be seen as the respiratory illness resolves and general
health improves. On the other hand, some intellectual deficits do
not appear until school age, and early studies may not predict more
subtle problems such as perceptual-motor deficits that may atfect
learning and academic performance.120
Many of the early reports on the outcome of children with BPD
did not allow for confounding factors, and the reported incidence of
neurodevelopmental handicaps was high among infants with
BPD ? 55 Vohr et al. published a study in 1982 that attempted to
match study groups for multiple adverse perinatal events.l’l Twenty-
one infants with BPD were compared with two separate control
groups: eight infants who had required oxygen therapy beyond 21
days but did not develop BPD and 21 infants who had mild respira-
tory disease requiring oxygen for less than 5 days. The infants were
studied at 12 and 24 months of age. Eighteen of 21 (86%) infants in
the group with mild respiratory disease were normal. Infants with
prolonged oxygen requirement but no BPD had significant abnor-
malities at 12 months (Bayley scores) but were improved at 24
months. In contrast, among the 21 infants with BPD tested at 12
months, 11 (52%) were abnormal and 5 (24%) were suspect, More-
over, the situation for infants with BPD did not improve between 12
and 24 months. Vohr and colleagues concluded that the develop-
ment of BPD in and of itself accounted for a significant portion of
subsequent neurodevelopmental abnormalities in very-low-birth-
weight (VLBW) infants. In contrast, Markestad and Fitzhardingel’
studied 20 infants with BPD at 2 years of age. Five of their 20 infants
(25% 1 had neurodevelopmental delay. However, these infants had ex-
perienced a significantly more severe perinatal course, had a longer
period of oxygen therapy, and a longer duration of hospitalization.
Markestad and Fitzhardinge concluded that adverse perinatal events
were a stronger determinant of outcome than the presence or ab-
sence of BPD.
More recent studies have used matched controls from a cohort
without BPD and have attempted to control other neonatal condi-
tions. Meisels et al.“’ compared 17 infants with BPD to a control
group of 20 infants with RDS who were matched for sex, parity, fam-
ily configuration, and socioeconomic status. Subjects who had intra-
ventricular hemorrhage more than grade 2, hydrocephalus, sensory
disorders, metabolic disorders, hyperbilirubinemia greater than 15
mgdl, or intrauterine growth failure were excluded from the study.
The infants were tested at 12 or 18 months using the Bayley Mental
and Psychomotor Developmental scales, the Uzgiris-Hunt Scales,
and the Receptive-Expressive Emergent Language Scales. The infants
with BPD scored in the low average to delayed range, while the in-

fants with RDS scored in the normal range. Regression analyses
showed that the type of respiratory disorder (BPD vs. RDS) ac-
counted for most of the variance in cognitive outcomes. Same and
Singhall studied 179 infants with BPD and compared them with a
group of 112 controls matched only for birthweight and year of birth
but with multiple differences in perinatal events between the two
groups. The children were followed up with serial neurodevelop-
mental assessments until age 8 years. Neurological handicaps oc-
curred at about the same rate, 10% in the two groups. Developmen-
tal testing scores were slightly lower in the BPD group, but not
significantly so. No significant effect of BPD on neurodevelopmental
outcome was seen. In conclusion, there is some evidence that in-
fants with BPD are at increased risk for developmental delay inde-
pendent of other perinatal and neonatal events, but long-term con-
trolled follow-up studies of larger groups are needed to confirm this
and to determine the magnitude of the risk. Opinion on this issue
remains divided. The importance of serial long-term evaluation of
this group cannot be overemphasized.
GROWTH
Infants with BPD are often discharged from the hospital with sev-
eral features of malnutrition. The weight and length are frequently
below the 5th percentile. There may be clinical signs of rickets and
muscle tone may be poor. Linear growth delay may persist for sev-
eral years. Vohr et al.lz3 reported that lo-year-old children with BPD
were about 10% (137 cm vs. 151 cm) shorter than full-term controls
matched for age. Low-birthweight (LBW) children in the same cohort
without BPD also showed similar growth delay (139 cm). Other in-
vestigators have reported similar growth delays.‘4147’ lz2 Weight is
usually affected the most and head circumference the least, often
remaining in the normal range. When poor head growth is seen it is
strongly related to poor developmental outcome.*” In our own pop-
ulation, linear growth was often more severely affected than weight
in infants with severe pulmonary disease (ventilation longer than 6
months) and with clinical evidence of rickets.54
SCHOOL PERFORMANCE
While profound developmental disabilities and deficits can be rec-

ognized early, assessment of school performance and identification
of less severe handicaps requires a long period of follow-up. A subtle
sensory deficit may not be discovered until school age, when it in-
terferes with learning. Neonatal intensive care as we know it today
has been practiced for less than 20 years, so long-term follow-up
studies of survivors have just started to appear in the literature. Here
216 Curr Probl Pecfiatr, April 1989
again, there is a diversity of opinions and reported results. Most re-
cent studies group all LBW infants together, including infants with
BPD. Lloyd et alIz studied the intellectual outcome of 45 LBW En-
glish children born in the late 1970s without major handicap, and
compared them with a control group matched for sex, race, age, and
social class. The LBW infants had lower IQs and were more likely to
be performing poorly or below average at school. The children most
likely to have low IQ scores and school problems were those who
had experienced a severe neonatal illness.
Sell et al.lz6 found school problems, defined as repetition of a
grade or special help in school, in 48.8% of 74 neonatal intensive
care unit graduates. In reporting a distinctly different outcome, Ei-
lers et al.lz7 compared 33 long-term very low birth weight (VLBW)
survivors with peers and school-age siblings. Ninety percent were
found to be comparable to classmates by teachers and test scores,
although 47% of these were receiving some remedial help. Only 9%
required special classes because of handicap. Data regarding the
outcome of 11 children with BPD compared to LBW and full-term
controls have been presented in abstract form.123 Reading evaluation
using the Wide Range Achievement Test showed much poorer per-
formance of the BPD children compared with both control groups.
Sauve and Singhail found that speech assessment, which included
expressive and receptive language as well as articulation and voice
quality, was more frequently abnormal in S-year-old children with
BPD than in controls matched for age and birthweight. Hunt and
colleaguesl” recently published a follow-up of VLBW infants at 8 and
11 years of age. Eighty-two percent had IQ in the normal range above
85, but 45% of these had unusual test score patterns suggesting spe-
cific intellectual problems, mostly language and visual-motor disa-
bility. Severity of disability was related to the parental educational
level.
In summary, most of the published studies show increased school
problems in LBW and BPD infants. These problems seem to be due
to a learning disability rather than a cognitive deficit, and should be
amenable to early diagnosis and proper intervention. We are await-
ing the publication of further data.
BEHAVIOBAL. DIFFICULTIES
Infants with BPD can be considered to be at risk for behavioral

disturbances: lack of early parent-infant bonding, prolonged hospi-
talization, abnormal parental behavior towards a chronically ill child,
and the presence of sensory or CNS deficits may all contribute to
this risk. Early in the child’s neonatal course, parents often do not
bond normally to their child, in part because of the trauma of the
early delivery and illness and in part because of the fear that the

child will not survive. Prolonged hospitalization in itself has a pro-
found effect on both parents and infant. Parents report feelings of
grief, anger, fear, and guilt when a premature infant is born and sub-
mitted to all the interventions in an intensive care nursery.12s The
infant learns to associate touch, handling, and interaction with pain.
This may be associated with the subsequent development of “tactile
defensiveness” and/or oral aversion. These in turn may later lead to
feeding difficulties, difficulties in calming, and “lack of cuddliness.”
These behavioral aberrations all have a potentially negative impact
on the parent-infant relationship.130
When the BPD infant is discharged from the hospital, the parents
have to cope with additional stresses that affect how they deal with
the infant. In addition to being at increased risk for abuse and ne-
glect, the children are also at risk for overprotection and “the vul-
nerable child syndrome.“13* Parents may be so concerned about the
risk of infection that they may avoid any social contact.12g This im-
paired socialization may contribute to later behavioral difficulties.
Sensory deficits and sequelae of perinatal brain injury are associ-
ated with higher risk of behavioral difficulties and emotional distur-
bances in children.‘15’ 1x, 13’ It is important to recognize the deficits
early and provide the proper intervention in order to minimize sub-
sequent problems. Early intervention programs, family support
groups, and multispecialty clinics have all been shown to have a
beneficial effect on outcome in handicapped children.‘zs”33
There are Very few studies in the literature that deal specifically
with behavioral problems in children with BPD. Most studies con-
sider LBW infants as a group, and have found a significant increase
in the incidence of emotional disturbances in the LBW infants com-
pared with matched school-age children. Vohrlz3 used a child behav-
ior checklist to assess her cohort of lo- to I.&year-olds. Children
with BPD had atypical behavior characteristics that were signifi-
cantly different from both LBW and full-term controls. Again, we are
awaiting the presentation of further data and analysis to shed addi-
tional light on this area.
PULMONARY OUTCOME
The long-term pulmonary outcome in children with BPD is uncer-

tain at the present time, although some general lessons can be
learned by a review of publications. There are several problems with
the literature that is available at present. Long-term outcome infor-
mation by its nature is far removed in time from the neonatal period.
Whether the results obtained with methods of care that were ap-
plied to the survivors from, for example, 10 years ago will be gener-
alizable to those obtained with contemporary care is a matter of
218 Curr Probl pediatr, April 1989

speculation. There is information to suggest that certain respiratory
infections in infancy, such as RSV bronchiolitis, can alter long-term
pulmonary function.134 Such events, unrelated to neonatal events,
can influence results of studies of lung function in older children. A
similar situation exists for the development of asthma beyond the
neonatal period. Lastly, formal pulmonary function testing is difficult
to perform in children.135
The previously mentioned difficulties notwithstanding, several ab-
normalities of pulmonary mechanics have been consistently identi-
fied in infants with BPD beyond the time of hospital discharge.‘35
These include decreased compliance and increased resistance to
airflow. Also, there is significant maldistribution of ventilation result-
ing in many areas with low ratios of ventilation to perfusion. This
latter finding explains the large increase in Pao, or oxygen saturation
that can occur with seemingly small increases in Fio,. Finally, in
infancy chest radiographs generally continue to show hyperinflation,
despite the fact that formal pulmonary function testing has not con-
sistently shown increased lung volumes.135
Studies of older children with BPD are rare. The most frequently
referred to is that of Smyth and co-workers.31 Despite the frequent
reference to this work, only nine children were studied; the mean
age was 8 years. In these nine children pulmonary abnormalities
were common. Spirometric testing revealed the presence of obstruc-
tive airways disease, which reversed with bronchodilator therapy in
all nine. Six of eight children had methacholine challenge tests con-
sistent with bronchial hyperreactivity. Eight children had chest
roentgenograms that continued to show regional hyperinflation al-
though all were improving over time. Blood gas tensions were ab-
normal in most of the children. Many children in this study had
persistent respiratory symptoms.
The study by Smyth and colleagues stands in contrast to the
report of Harrod et al.,” who followed 15 children and reported that
13 of these had no respiratory symptoms after the first year of life.
They were of the opinion that children with BPD convalesced with
the passage of time and acquired normal lung function. Johnson
and co-workers studied 16 children and found four to have episodes
of wheezing with response to bronchodilators, consistent with the
diagnosis of asthma.13”
Those studies that reported normal lung function have not in-
volved formal pulmonary function testing nor have they performed
the methacholine challenge test. Moreover, any evidence of reactive
airways disease has been tacitly assumed to be due to asthma and
unrelated to perinatal events. The study of Smyth et al. clearly dem-
onstrates persistent pulmonary abnormalities and links reactive air-
ways disease to BPD.31
SUMMARY
In this review we have attempted to introduce bronchopulmonary

dysplasia as a new chronic lung disease of infancy and childhood.
The major risk factors for this illness are preterm birth and the res-
piratory distress syndrome. The precise etiology of BPD is not un-
derstood but trauma from mechanical ventilation and toxicity from
exposure to supplemental oxygen are thought to be important. Prob-
lems in diagnosis and diagnostic criteria have been discussed as
have the details of the unfavorable pulmonary mechanics. We have
mentioned some of our own practices in regard to a large and suc-
cessful home oxygen therapy program. Suggestions have been made
for establishing readiness for discharge and for follow-up of these
children. Medical management of these patients presently suffers
from a lack of prospective and controlled studies. Medical care
draws heavily from experience with pediatric asthma. What is
known about the long-term outcome of these children has been re-
viewed with an attempt to highlight controversies between pub-
lished reports and underscore the need for further investigation. The
greatest future success in this area would be the prevention of pre-
mature birth. Prior to this, we must await the completion of future
controlled and prospective studies.
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Bronchopulmonary Dysplasia: A Review For The Pediatrician: AND Incidence

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Bronchopulmonary Dysplasia: A Review For The Pediatrician: AND Incidence

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BRONCHOPULMONARY DYSPLASIA: A

REVIEW FOR THE PEDIATRICIAN

Bronchopulmonary dysplasia (BPD), or chronic lung disease of in-

EPIDEMIOLOGIC, ETIOLOGIC, AND DIAGNOSTIC ASPECTS

Curr Probl Pediatr, April 1989 177

178 Curr Probl Pediatr, April 1989

PATHOLOGY AND PATHOPHYSIOLOGY

Fortunately, only a minority of children with BPD come to post-

Curr Probl Pediatr, April 1989 179

The Small Conducting Airways

180 Cum Probl Pediatr, April 1989

The Large Conducting Airways

The Pulmonary Vasculature

Cardiac abnormalities are seen frequently in children with bron-

Cum Probl Pediatr, April 1989 181

Patients with bronchopulmonary dysplasia have a requirement for

1.92 Curr Probl Pediatr, April 1989

It is at present uncertain whether the neurologic and developmen-

Curr Probl Pediatr, April 1989 163

184 Cur-r Probl Pediatr, April 1989

Curr Probl Pediatr, April 1989

ASPECTS OF BPD AT DARTMOUTH-HITCHCOCK MEDICAL

Infants with BPD are at a significantly higher risk of dying in in-

Cur-r Probl Pediatr, April 1989 187

HOME OXYGEN THERAPY

188 Curr Probl Pediatr, April 1989

DISCHARGE PLANNING AND NURSE COORDINATOR

Curr Probl Pediatr, April 1989 189

190 Curr Probl Pediatr, April 1989

Parental Attitude and Preparedness

Cur-r Probl Pediatr, April 1989 191

Community-Based Support Services

DaiIy Care Routine

192 Cur-r Probl Pediatr, April 1989

Diagnosis and prognosis of BPD

appropriate use of equipment, (3) rationale for the various therapeu-

Zdentiflcation and Assessment of OFygen Equipment Vendor

ZChr/day call response system

Cur-r Probl Pediatr, April 1989 193

Baseline Medical Data

Arranging Medical Follow-Up

194 Curr Probl Pediatr, April 1989

THE ROLE OF THE NURSE COORDINATOR

SUPPORT SERVICES FREQUENTLY REQUIRED

Curr Probl Pediatr, April 1989 196

Professional Home Nursing Services

Early Intervention and Developmental Care

Parent Support Groups

196 Curr Probl Pediatr, April 1989

Curr Probl Pediatr, April 1989 197

Carbon Dio;uide Tension

198 Cur-r Probl Pediatr, April 1989

FOLLOW-UP BY PRIMARY CARE PROVIDERS

Curr Probl Pediafr, April 1989 199

immunizations when discharged to home and proper vaccination

200 cur-r Probl Pediatr, April 1989

Availability, cost, and parental competence should be considered

Long-term studies of the comprehensive management of cardio-

Cum Probl Pediatr, April 1989 203