Later, it was proposed to use the need for supplemental oxygen at 36 weeks postmenstrual age (PMA) as the diagnostic criterion especially in preterm very low birth weight (VLBW) infants
Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics 1988
NIH DEFINITION < 32 weeks > 32 weeks Time point of assessment 36 weeks PMA or discharge* > 28 days but < 56 days postnatal age or discharge* Treatment with oxygen > 21% for at least 28 days > 21% for at least 28 days Mild Breathing room air at 36 weeks PMA or discharge Breathing room air at 56 days postnatal age or discharge* Moderate Need for <30% oxygen at 36 weeks PMA or discharge Need* for <30% oxygen at 56 days postnatal age or discharge Severe Need for > 30% oxygen and/or positive pressure (IMV/CPAP) at 36 weeks PMA or discharge Need for > 30% oxygen and/or positive pressure (IMV/CPAP) at 56 days postnatal age or discharge
The major risk factors include
infection( u urealyticum)
patent ductus arteriosus (PDA)
Excessive early intravenous fluid administration
genetic predisposition ( inadequate activity of antioxidant enzymes sod, catalase, glutathione peroxidase and ceruloplasmin --- predisposes to o2 toxicity)
Familial airway hyperreactivity
Increased inositol clearance
The most important factor in the pathogenesis of CLD is prematurity
Exposure of immature lungs to high O2 concentrations and positive pressure ventilation results in oxidative stress and ventilator induced lung injury (barotrauma/volutruma)
Intrauterine infection (chorioamnionitis)
Inflammatory cytokines(IL-1,IL6 and TNF alfa)
Lung injury and arrest of lung growth
U urealyticum is most commonly implicated
Several large clinical studies have found a strong correlation between the presence of BPD and the development of late-onset sepsis, usually with organisms such as staphylococcus epidermidis
The most immediate and frequent cause of BPD is the lung injury imposed by mechanical ventilatory support.
positive-pressure mechanical ventilation
Injury to endothelium
increased permaebility of serum protiens
Inhibition of surfactant
Increased surface tension, unequal areation, collapse of alveoli
Increased pressure to distend saccules->lung injury, PIP ,pneumothorax.
Studies have shown that overdistension of the lung (not increased pressure) is responsible for lung injury in the surfactant-deficient lung
volutrauma and not barotrauma is the primary determinant of VILI.
NIPPV is a method of augmenting NCPAP by delivering ventilator breaths via the nasal prongs.
Improves the tidal and minute volumes and decrease the inspiratory effort required by neonates as compared to nCPAP
The Cochrane review that included three RCTs found a trend towards reduction in rates of chronic lung disease.
Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database of Systematic Reviews
Patient-triggered ventilation (PTV):
Patient triggered modes (SIMV, assist-control, and pressure support ventilation) improve the infant-ventilator asynchrony.
The Cochrane review concluded that though PTV is associated with shorter duration of ventilation, it does not reduce the incidence of BPD.
Synchronized mechanicalventilation for respiratory support in newborn infants. Cochrane Database of SystematicReviews2008
High-frequency ventilation (HFV):
Animal studies indicate that HFV could lead to less lung injury when compared to conventional ventilation
A recent meta-analysis that included 17 RCTs of conventional versus high frequency ventilation found no significant difference in the incidence of BPD
Ventilation strategies and outcome in Randomised Trials of High Frequency Ventilation Arch Dis Child. 2005
Volume targeted ventilation
The Cochrane review that included four RCTs found significant reduction in the duration of ventilation and pneumothorax rates but only a borderline reduction in the incidence of BPD.
Volume-targeted versus pressure-limited ventilation in the neonate. Cochrane Database of Systematic Reviews 2005
PERMISSIVE HYPERCAPNIA :
Hypocapnia that occurs during assisted ventilation is an independent risk factor for BPD
Co2 targets of 45-55 mm hg are now recommended in order to reduce the days of ventilation.
Permissive hypoxemia: A ccepting lower oxygen saturation values is associated with decreased incidences of CLD and ROP
BOOST-trial and STOP-ROP trial indicate that maintaining higher oxygen saturation (>95%) is associated with increased need for oxygen at 36 weeks PMA and greater use of postnatal steroids and diuretics in premature infants (when compared to maintaining lower oxygen saturation of 89-94%).
Spo2 b/w 85-93% ---- < 32 wks
The systematic review of studies on fluid restriction has not found any significant reduction in the incidence of BPD
The amount of fluid restriction in VLBW infants is not definitely known.
Fluid restriction for treatment of preterm babies with chronic lung disease. (Protocol) Cochrane Database of Systematic Reviews 2005;
Aggressive parenteral nutrition and early enteral feeding decreases the incidence of BPD in VLBW infants
( The role of nutrition in the prevention and management of bronchopulmonary dysplasia. Semin Perinatol 2006 )
Enteral feeding is often delayed in these infants due to gastrointestinal immaturity, parenteral nutrition with proteins and lipids should be initiated as soon as possible after birth.
Metabolic rate and energy expenditure are elevated in BPD
Infants developing BPD require 20 to 40% more calories than their age-matched healthy controls .
caloric requirement varies from 120 to 150 Kcal/kg/day
More calories– lipids( mct oil)> carbohydrates, lowers respiratory quotient and decreases co2 production.
When enteral feeding is started --- give only EBM.
Addition of HMF will also increase the calories and make up the deficiencies of protiens and minerals.
Mct oil and glucose polymers can also be added.
Prophylactic surfactant therapy in infants born before 30 weeks of gestation has not been shown to reduce the incidence of BPD. However, surfactant treatment for established RDS ( ‘rescue therapy’) in infants born at or after 30 weeks of gestation is associated with significant reduction in the incidence of BPD
American Academy of Pediatrics Committee on Fetus and Newborn.Surfactant-replacement therapy for respiratory distress in the preterm and term neonate. Pediatrics 2008;
Role of vit A
Vitamin A ---integrity of respiratory tract epithelial cells.
Very preterm infants are relatively deficient in vitamin A which has been shown to associated with CLD.
large dose of intramuscular vitamin A (5000 units three times a week for 4 weeks from birth) decreases the incidence of CLD.
(Cochrane Database Syst Rev 2007)
All ELBW infants with respiratory distress requiring supplemental oxygen or mechanical ventilation at 24 hours of age should recieve vit A
Vit E – antoxidant, no role in prevention of bpd
Role of superoxide dismutase :
sod antioxidant --eliminates the free radicles
Preterms – deficient in antioxidant enzymes and sucesptible to oxidant injury.
A RCT enrolled around 300 infants proved the safe nature of the drug CuZnSOD,
But did not find any difference in the primary outcome of BPD at 36 weeks PMA.
SOD treated infants-- fewer episodes of respiratory illness at I year of age.
Cochrane review on this subject conclude that “The use of superoxide dismutase to prevent chronic lung disease of prematurity is not recommended”
caffeine – reduced incidence of BPD .
In a multicenter trial , infants < 1,250 g who received caffeine had lower BPD rates than infants who did not receive it.
Duration of ventilaton, need for CPAP, and supplemental oxygen were reduced by caffeine administration.
( Adjunctive therapies in chronic lung disease:examining the evidence. Semin Fetal Neonatal Med 2008)
Another large RCT that used caffeine for these indications in infants with birth weights of 500-1250g has shown a significant decrease in the incidence of BPD.
Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnoea of prematurity. N Engl J Med 2006
The authors attributed this rather unexpected finding to reduced duration of mechanical ventilation in the caffeine treated group
Indomethacin / Ibuprofen therapy for PDA:
Patent ductus arteriosus is one of the major risk factors for BPD.
prevention or treatment of PDA should ideally reduce its risk.
However, prophylactic use of indomethacin in very low birth weight infants has failed to show any reduction in the incidence of BPD despite a significant reduction in the incidence of PDA
(Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001)
Similar results are obtained with ibufrofen.
Treatment of symptomatic PDA could possibly reduce the incidence of BPD .
Recommendations for the postnatal use of indomethacin: an analysis of four
separate treatment strategies. J Pediatr. 1996
ROLE OF STEROIDS
inflammation ----pathogenesis of BPD
Early : During the first 96 hrs after birth
Moderately early :Between postnatal days 7 and 14.
Delayed :After 3 weeks of age
Most commonly used steroid is :dexamethasone
AMERICAN ACADEMY OF PEDIATRICS Committee on Fetus and Newborn
Systemic Early Postnatal Corticosteroid Therapy <96 Hours
preterm, respiratory distress syndrome, and required mechanical ventilation with oxygen at the time of enrollment
Corticosteroids (dexamethasone)intravenously within 96 hours after birth.
The most commonly used dosages were 0.5 mg/kg of body weight per day for 3 days, followed by a tapering course
The combined outcome of death or CLD at 28 days PNA or at 36 weeks’PMA was significantly decreased by early corticosteroid treatment
Weaning from mechanical ventilation was more successful in infants treated with dexamethasone.
incidences of hypertension, hyperglycemia, insulin therapy for hyperglycemia, gastrointestinal bleeding or perforation, and hypertrophic obstructive cardiomyopathy were increased by early corticosteroid treatment.
Borderline increased risk of PVL in steroid group
Moderately Early Postnatal Corticosteroid Therapy (7–14 Days PNA)
The combined outcome of death or CLD was decreased at 28 days’ PNA and at 36 weeks’ PMA.
There was increase in incidence of hyperglycemia, gastrointestinal bleeding, hypertrophic obstructive cardiomyopathy, and infection.
AMERICAN ACADEMY OF PEDIATRICS Committee on Fetus and Newborn
Indication: clinical/radiographic features of pulmonary edema in an infant with evolving or established BPD Pharmacological strategies in the prevention and management of bronchopulmonary dysplasia. Semin Perinatol 2006
Dose: 0.5-1 mg/kg, stop after 24- 48 hours if no improvement in clinical condition.
no effects on mortality or the incidence of BPD
Mast cell stabilizers
decrease neutrophil migration and activation ----minimizes inflammation in the lungs
Dose: 10-20 mg 6-8 hr , nebulization.
2 trials– no benefit in prevention and treatment.
Cromolyn sodium for the prevention of chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2001
Systemic to pulmonary shunting
Metabolic imbalance– sec to diuretics
Infection-- urealasma and mycoplasma----rx with erythromycin
Viral infections and fungal infections are also common
Cns dysfunction: a neurologic syndrome presenting with EPS signs has been described
Spo2 maintained > 92-94%
No significant period of desaturation during feeding or sleep
Good weight gain
Stable respiratory status
In addition to standard immunization , infants with CLD should receive penumocoocal, influenza and palivizumab
AAP RECOMMENDATIONS FOR PALIVIZUMAB
Administer monthly beginning in early november for 5 months
Dose: 15mg/kg IM
MORTALITY: 10-20% in first year of life (infection)
Morbidity: increased risk of reactive airway disease , bronchiolitis and pneumonia
Rehospitalization rate is twice that of matched controls in first 2 yr of life
Growth failure: delayed growth in 1/3 to 2/3 of these infants at 2 years.