Bronchopulmonary dysplasia (BPD) in neonates

Key messages

1. Bronchopulmonary dysplasia (BPD) is defined as oxygen dependency at 36 weeks corrected

gestational age.
2. Those neonates most severely affected by bronchopulmonary dysplasia are babies who are the
most premature.
3. Diuretics and corticosteroids are effective in achieving short-term improvement in the status of
ventilator dependant babies but the safety issues of steroid use are unresolved.
4. There is no consensus on how to wean oxygen in babies with BPD.

Over the past decade the clinical definition of bronchopulmonary dysplasia (BPD) has evolved from
describing oxygen dependency at 28 days of age to oxygen dependency at 36 weeks corrected
gestational age.

Terminology and definitions

The term bronchopulmonary dysplasia (BPD) is now used rather than chronic lung disease. The
definition is complicated. BPD here refers to a premature baby who has been in oxygen for > 28 days.

The National Institute for Health in the USA has further divided this definition into:

 Mild in supplemental oxygen at 28 days of age, but in air by 36 weeks corrected age.
 Moderate requiring <30% supplemental oxygen at 36 weeks corrected age.
 Severe in >30% supplemental oxygen and/or requiring positive pressure support, CPAP or
ventilation, at 36 weeks corrected age.

BPD is the single most important factor determining length of hospital stay in babies born at less than 29
weeks. The most severely affected babies are the most premature, particularly 23 - 26 week gestation
babies.

Risk factors for BPDRisk factors for bronchopulmonary dysplasia include:

1. prematurity
2. peripartum inflammation/infection associated with preterm labour and/or clinical or subclinical
chorioamnionitis
3. postnatal lung injury due to volutrauma, barotrauma,oxygen toxicity, hypocarbia or infection

Clinical features of BPD

Tertiary unit babies with BPD (actual or evolving) fall into three broad groups:

1. babies dependant on endotracheal mechanical ventilation (MV)

2. babies dependant of nasal CPAP
3. babies who are oxygen dependant, usually by nasal prongs
The most common clinical scenario is the 23 - 26 week gestation baby who, over a period of 4 - 10
weeks, progresses from MV, NCPAP through to requiring supplementary oxygen. These babies are
usually transferred to a Special care nursery (SCN) for ongoing care.

Although some of these babies spend many weeks on NCPAP it is common to see rapid improvement in
their respiratory stability once weaned from NCPAP.

Respiratory stability off NCPAP is the single most important criterion that determines suitability for
transfer to a SCN. It is important to understand the tertiary unit's experience with babies at these
gestations as it has a significant impact on decision making with respect to transfer to SCNs.

Issues include:

All tertiary units experience late deaths of extremely premature babies due to chronic lung disease.

When prolonged MV is needed there are often many weeks before one can reassure the family with
confidence that the baby is likely to survive. Once a baby is showing consistent growth associated with
an oxygen requirement less than 40% the recovery process is likely to be successful.

Some babies cope for many months on NCPAP in high (more than 40%) oxygen concentrations before
dying. Fortunately this group is rare.

These factors make the care of babies with BPD extremely demanding for babies and their families, as
well as for nursing, medical and ancillary staff.

Management of BPD in Neonatal intensive care units (NICU)

Respiratory support

Endotracheal ventilation is increasingly being replaced by NCPAP, for even the tiniest babies. Many are
being managed with NCPAP from birth. Results from a recent randomised controlled trial have shown
that 50% of babies 25-28 weeks gestation are able to manage without ever requiring intubation and
ventilation and that infants of this age who commence NCPAP from birth have no increased risk of death
or BPD and in fact are less likely to be in oxygen at 28 days of age.

For those who do require intubation and ventilation there is an intense focus on minimizing ventilator
associated lung injury from the moment a baby is placed on a ventilator. Synchronised modes of MV
with close monitoring of tidal volumes are key features of current practice. In addition there is a more
liberal approach to carbon dioxide control, allowing CO2 to rise into the 50s and 60s providing the pH
remains better than 7.25

Oxygen damages delicate lung tissue as well as the immature retina. Pulse oximetry targets are set
between 91 to 95%.

Babies who require endotracheal ventilation are aggressively weaned and extubated to NCPAP often
within 1-2 days of birth.
Drug therapy for established/evolving BPD

Corticosteroids

Dexamethasone is effective in achieving short-term improvement in the status of ventilator dependant

babies, as well as longer term reductions in BPD, however, there is now level evidence showing that
dexamethasone in the first week of life is associated with an increased risk of cerebral palsy in survivors.

Safety of corticosteroids used later in the course of evolving BPD between 14 - 28 days is unresolved and
the Cochrane review of current evidence suggests reserving the use of late corticosteroids to infants
who cannot be weaned from mechanical ventilation, and minimising the dose and duration of
treatment.

In light of this evidence frequency of the use of steroids for BPD in NICUs has dramatically declined in
the past 5 years and a ‘low’ dose regimen ( 0.15 - 0.25mg/kg/day) weaned and ceased over a 7 - 10 day
period is recommended.

Typical clinical scenarios where steroids would be considered are a baby > 2 weeks of age who is unable
to be weaned from endotracheal MV.

There is no place for the use of steroids in the treatment of BPD outside a tertiary neonatal unit.

Early use of inhaled steroids is ineffective in preventing BPD, although there is some evidence they can
be used to assist extubation in ventilator dependant infants.

More work is needed in this area before this approach is taken.

Diuretics

Insufficient studies of suitable size reporting on important outcomes exist to strongly support the use of
diuretics for the treatment of BPD.

Diuretics are an effective short term therapy for ventilated babies.

There is no evidence for efficacy in non ventilated babies therefore diuretic therapy should be weaned
and ceased once babies are stable off mechanical ventilation.

Typical combinations include hydrochlorothiazide and spironolactone.

NaCl and KCl supplementation are commonly required.

Chronic frusemide administration is generally avoided, as it has been associated with the development
of nephrocalcinosis and hyperchloremic metabolic alkalosis.

There is no place for long term therapy with diuretics in SCN's.

Nutrition
Issues to note regarding nutrition:

Provision of adequate calories in a nutritionally appropriate form is critical. Infants with BPD utilise 20-
40% more kcal than infants without BPD.

Caloric requirements of babies with moderate to severe lung disease can be as high as 130 - 150
calories/kg/day.

Babies with BPD tolerate fluid overload poorly and are modestly fluid restricted (150 - 160mL/kg/day)
and fed fortified breast milk or low birthweight formula.

Growth is closely monitored and caloric intake titrated against growth.

Vitamin A supplementation reduces death and oxygen requirements at 36 weeks corrected gestational
age. Vitamin A is often given as Pentavite to all infants from day 5 until discharge.

Babies sufficiently stable to transfer to a SCN should not require a caloric density of > 24 cal/30mls.

Oxygen therapy

Oxygen is the one constant in the treatment of BPD but it has been poorly studied.

Once weaned from NCPAP oxygen is delivered by nasal prongs using low flow (<0.5L/min).

There is no consensus on how to wean oxygen in babies with BPD.

Weaning is dictated to some extent by the equipment available. Some tertiary units have only recently
moved from having flow meters with a lower limit of 0.25L/min/O2. Other units use flow meters that
allow weaning down to as low as 0.005mL/min/O2. Most believe that weaning should be slow, but what
this means varies from institution to institution.

Babies with BPD have a degree of pulmonary hypertension and are therefore likely to benefit from a
more generous oxygen administration regimen rather than from a restrictive policy. However, the
corrected gestational age and the state of vascularistion of the retina need to be taken into
consideration. Whilst there is some logic to this approach there is indirect evidence from randomized
controlled trials conducted for other reasons suggesting that a more liberal oxygen policy in these
babies can actually increase the pulmonary morbidity. RCT's are in progress to address this question.

Respiratory criteria for transfer to a SCN

These criteria should be met prior to transfer:

Absolute minimum of 7 days off respiratory support including NCPAP or "high flow"(1-2L/min) intra
nasal oxygen.

Maximum of 1 apnoea /bradycardia that required no or minimal stimulation for recovery.

Consistent, stable oxygen saturation on 0.5L/min intranasal oxygen, or 35% headbox oxygen.
Not receiving corticosteroids for BPD.

Preferably the baby should not be diuretic dependant for respiratory stability.

Consistent growth on 2-3 hourly bolus feeds with a caloric density no more than 24 cals/30mls.

There is a small number of babies with severe but non NCPAP dependant BPD who are transferred to
SCN units. These are a specific group of babies where the decision to transfer and the principles of
ongoing medical management require an individualised management plan worked out between
referring and receiving consultant medical staff, preferably in collaboration with a paediatric thoracic
consultant. The principles of care for such babies is beyond the scope of this content.

Management in the SCN

The transition from a tertiary hospital nursery to a SCN is a difficult time for parents as they adjust to
different staff and practices. Both tertiary and level 2 staff should be proactive in anticipating and
addressing these issues. If the referring neonatologist believes a particular approach should be
considered for a particular baby, this should be discussed with the receiving paediatrician directly so
that a consistent message goes to the parents.

It is common in Victoria for SCN's to have oxygen flow meters that do not permit accurate delivery of
intranasal oxygen below 0.25L/min. Parents must be educated about this in advance so they do not see
the increased FiO2 dose as ‘wrong’ or ‘bad’ therapy or as an indication their baby has deteriorated.
Clearly Victoria needs to work towards a consistent approach to equipment such as oxygen flow meters
as the current system is illogical and confusing.

It is strongly recommended that these babies be nursed in the SCN rather than the Paediatric ward even
if post term corrected age. This should reduce the risk of developing nosocomial infection particularly
respiratory viral infections.

Nutrition

Issues to be aware of regarding nutrition for neonates with bronchopulmonary dysplasia in the SCN:

Aim to achieve an intake of 120cal/kg/day

Breast milk fortifier or a low birthweight formula can be continued until at least term without adverse
effects if caloric supplementation is required, and is recommended until at least 3kg.

For babies on tube feeds, oral feeds should be cautiously introduced eg initially one oral feed/day then 2
etc as the baby copes with the previous increment.

Oxygen

Aim to move to intermittent oximetry rather than continuous once it is clear the baby is not having
apnoea or bradycardia.
Saturation goals to be used are 91-95%.

During feeding and certain parts of sleep are the times where a baby's oxygen demand is higher.
Therefore if one is looking to see if a baby will manage in less oxygen saturations should be monitored
over several feed periods or for several hours during sleep.

For babies in headbox oxygen do not wean oxygen by more than 1% in a 24 hour period even if the
saturations are 100%.

For babies on low flow intranasal oxygen do not wean by more than 10mls/24 hours.

If the lowest accurate flow deliverable is 0.25L/min then the only option is to periodically ( twice/week)
turn off the oxygen and carefully monitor the saturations.

Blood gas monitoring is not required in stable babies.

The indications for blood transfusion in a growing stable baby with a mild oxygen requirement have
been the subject of a recent trail. The authors demonstrate that there is no benefit in maintaining higher
haemoglobin levels.

For babies receiving supplemental oxygen the authors showed no benefit to transfusion if the Hb was
above 85g/L on a capillary sample (or 77g/L on venous sampling). This conservative approach would be
especially supported if there is a good reticulocyte count.

Ceasing oxygen

There is no consensus on how to wean oxygen in babies with BPD:

A prolonged period (8-12 hours) of saturation monitoring should be undertaken that captures extended
periods of sleep and several feeds.

Babies with BPD should not be discharged until at least 72 hours after ceasing oxygen.

Home oxygen

Criteria for home oxygen general

Ensure appropriate social/home environment including reasonable access to medical care.

Baby is on 4 hourly or demand oral feeding regimen.

Baby is normothermic in an open cot.

Growth is satisfactory.

All babies discharged from tertiary units on home oxygen must have specific paediatric thoracic
specialist follow up. It is strongly recommended that paediatricians manage babies on home oxygen in
collaboration with a paediatric thoracic physician.
Criteria for home oxygen - respiratory

Baby must pass an ‘air test. The oxygen is turned off, the nasal prongs removed and the baby monitored
over 30 minutes.

If saturations are maintained >86% for 30 minutes the test should be repeated in 48 hours. If a second
test is satisfactory the baby is eligible for discharge on home oxygen on respiratory grounds. In other
words the baby has demonstrated a reasonable level of respiratory reserve.

Follow up

Issues to note:

These babies require long term follow up throughout childhood.

There is an increased pulmonary morbidity in the first 2 years of life. Parents should be counselled about
this morbidity and ways to minimise it.

Influenza vaccine is recommended for infants with ongoing cardiac, respiratory or neurological illnesses
at 6 months of age. Recommendations are 2 doses, 4 weeks apart.

Influenza vaccine is not officially recommended for these babies.

RSV prophylaxis is not routinely recommended, the American Academy of Pediatrics recommends use of
RSV prophlaxis for infants <2yrs, with BPD requiring treatment within the last 6 months, who are
discharged home prior to the RSV season. The Department of Health in the UK recommends its use in
children <2yrs with BPD on home oxygen or who have had prolonged use of oxygen.