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Systematic review and meta-analysis of early postnatal dexamethasone for prevention of chronic lung disease
Insights
Dexamethasone treatment for very low birthweight infants can reduce chronic lung disease (CLD) risk. However, potential side effects like hypertension and hyperglycemia necessitate caution, especially regarding long-term neurodevelopmental outcomes.
Area of Science:
- Neonatal Medicine
- Pediatric Pulmonology
- Pharmacology
Background:
- Chronic lung disease (CLD) is a significant complication in very low birthweight infants.
- Early dexamethasone treatment is explored as a potential intervention to prevent CLD.
- Concerns exist regarding the safety and long-term effects of early dexamethasone administration.
Purpose of the Study:
- To systematically review evidence on the efficacy of early dexamethasone (within 14 days of birth) in preventing CLD in very low birthweight infants.
- To assess the occurrence of clinically significant side effects associated with this treatment.
- To evaluate the impact of treatment timing (within 36 hours vs. 7-14 days) and surfactant use on outcomes.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials.
- Searches included electronic databases, scientific meeting proceedings, and personal files.
- Calculations included event rate ratios (ERR), event rate differences (ERD), numbers needed to treat (NNT), and numbers needed to harm (NNH).
Main Results:
- Dexamethasone treatment significantly reduced the risk of CLD at 28 days and 36 weeks postmenstrual age.
- In infants treated between 7-14 days of age, mortality was significantly reduced (ERR 0.35, NNT 8).
- Adverse effects included increased risks of hypertension, hyperglycemia, and delayed birthweight regain.
Conclusions:
- Early dexamethasone treatment (within 14 days) effectively reduces CLD in very low birthweight infants.
- Treatment initiated between 7-14 days showed a significant reduction in mortality.
- Routine use requires caution due to potential side effects and limited data on long-term neurodevelopmental outcomes.
Aim:
To review systematically the evidence to determine whether dexamethasone treatment of very low birthweight infants begun within 14 days of age prevents chronic lung disease (CLD) without clinically significant side effects.
Methods:
Randomised controlled trials of dexamethasone started within this time frame were identified through a search of electronic databases, proceedings of scientific meetings, and personal files. Meta-analyses using event rate ratio (ERR), event rate difference (ERD), and if significant, numbers needed to treat (NNT) for benefits and numbers needed to harm (NNH) for adverse effects were calculated. Weighted mean difference were used for continuous variables. Three prespecified subgroup analyses were performed for; (i) dexamethasone begun within 36 hours (hours) of birth; (ii) dexamethasone initiated between 7-14 days of age; or (iii) if surfactant treatment was used.
Results:
Ten studies were included in the review; six where dexamethasone was initiated within 36 hours of age, four studies for dexamethasone started between 7 and 14 days and six studies using surfactant. Mortality ERR and NNT with 95% confidence intervals for dexamethasone initiated at 7-14 days of age were 0.35 (0.16, 0.74) and 8 (4, 30). ERRs and NNTs for CLD at 28 days and 36 weeks of postmenstrual age were 0.71 (0.61, 0.84), 8 (5, 17), and 0.57 (0.44, 0.76), 10 (6, 23) in the overall analyses. When dexamethasone was started at 7 to 14 days of age ERR and NNT for CLD at 36 weeks were 0.63 (0.47, 0.85) and 3 (2, 9). Clinically significant side effects included increased risk of hypertension, hyperglycaemia, and increased time to regain birthweight.
Conclusions:
These meta-analyses show a significant reduction in risk of CLD at 28 days and 36 weeks of postmenstrual age. In the subgroup where dexamethasone was started between 7 and 14 days of age mortality was significantly reduced. Caution is warranted in the routine use of dexamethasone because of lack of data on long term neurodevelopmental outcomes.