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Postnatal corticosteroids and bronchopulmonary dysplasia: balancing pulmonary and neurologic effects to enable
Nehal A Parikh1,2,3, Shipra Jain1,2,3
1The Perinatal Institute.
Insights
Early, medium-dose dexamethasone in very preterm infants at high risk for bronchopulmonary dysplasia (BPD) reduces BPD/death. This treatment may also decrease neurodevelopmental impairments, supporting its use over late, low-dose strategies.
Area of Science:
- Neonatal medicine
- Pediatric pulmonology
- Pharmacology
Background:
- Bronchopulmonary dysplasia (BPD) is a significant risk factor for neurodevelopmental impairments (NDI) and mortality in very preterm infants.
- BPD incidence is increasing in Western countries, necessitating effective prevention and treatment strategies.
- Postnatal corticosteroid (PNC) therapy, particularly dexamethasone, is used to manage BPD but requires careful risk-benefit assessment.
Purpose of the Study:
- To review evidence on long-term effects of BPD and PNC treatment in very preterm infants (<32 weeks' gestation).
- To guide evidence-based risk-stratification for BPD and individualized treatment decisions.
- To optimize the timing and dosage of PNC for managing BPD and its associated outcomes.
Main Methods:
- Systematic review and meta-regression analysis of existing clinical trials and data on dexamethasone and other PNCs.
- Evaluation of BPD/death rates and neurodevelopmental outcomes in relation to corticosteroid treatment regimens.
- Analysis of how baseline BPD risk modifies the effects of dexamethasone treatment.
Main Results:
- Medium (2-4 mg/kg) or high (4-8 mg/kg) dose dexamethasone initiated after one week of age reduces BPD/death and may not negatively impact survival without NDI.
- Dexamethasone's efficacy is risk-dependent: beneficial in infants with >50-70% BPD risk, but potentially harmful with <30% risk.
- Moderately early (days 8-14) medium-dose dexamethasone offers the greatest reduction in BPD/death; high-dose courses are also effective, while low-dose or other steroids are less so.
Conclusions:
- Medium-dose systemic dexamethasone, initiated between days 8-14, is recommended for ventilator-dependent infants at high risk (>50-70%) of BPD.
- This regimen reduces BPD risk and may also reduce NDI risk, with benefits on BPD reduction potentially outweighing direct NDI toxicity.
- Transitioning from late, low-dose dexamethasone to moderately early, medium-dose therapy is advised to decrease high BPD rates in very preterm infants.
Purpose Of Review:
To summarize existing evidence about the long-term effects of bronchopulmonary dysplasia (BPD) and postnatal corticosteroid (PNC) treatment to enable evidence-based risk-stratification and individualized decision-making in very preterm (<32 weeks' gestation) infants.
Recent Findings:
BPD remains a top risk factor for neurodevelopmental impairments (NDI) or death and BPD rates are rising in Western nations. Conversely, clinical trials and meta-regression data suggest medium (2-4 mg/kg cumulative dose) or high dose (4-8 mg/kg) dexamethasone use after a week of age reduces BPD/death and may improve or at worst have no effect on survival without NDI, as compared to placebo. Data from a validated meta-regression of all dexamethasone RCTs suggest dexamethasone effects are modified by the baseline risk of BPD: in infants with >50-70% risk of BPD, dexamethasone improved survival free of cerebral palsy, but had an opposite effect when BPD risk was <30%. A recent network meta-analysis of all PNC RCTs identified: moderately early-initiated (days 8-14), medium dose dexamethasone provided the largest reduction in BPD/death; high dose courses between 8 and 27 days were also highly effective; low dose dexamethasone, hydrocortisone, and inhaled or intratracheal steroids are ineffective or exhibit low potency in reducing BPD/death.
Summary:
Current evidence supports the use of medium dose systemic dexamethasone - preferably between days 8 and 14 in ventilator-dependent infants at >50-70% risk of developing BPD. While more NDI follow-up data are needed, this regimen is proven to reduce BPD risk and may also reduce NDI risk, considering PNC effects on BPD reduction appear stronger than any direct NDI toxicity. Practical suggestions are provided to enable transition from the current prevalent use of late initiated (>3-4 weeks of age), low dose dexamethasone to moderately early, medium dose dexamethasone to reduce the ongoing high rates of BPD in very preterm infants.
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