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Systemic corticosteroid regimens for prevention of bronchopulmonary dysplasia in preterm infants

Overview of attention for article published in Cochrane database of systematic reviews, March 2023
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (91st percentile)
  • Good Attention Score compared to outputs of the same age and source (71st percentile)

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Systemic corticosteroid regimens for prevention of bronchopulmonary dysplasia in preterm infants
Published in
Cochrane database of systematic reviews, March 2023
DOI 10.1002/14651858.cd010941.pub3
Pubmed ID

Wes Onland, Moniek van de Loo, Martin Offringa, Anton van Kaam


Systematic reviews showed that systemic postnatal corticosteroids reduce the risk of bronchopulmonary dysplasia (BPD) in preterm infants. However, corticosteroids have also been associated with an increased risk of neurodevelopmental impairment. It is unknown whether these beneficial and adverse effects are modulated by differences in corticosteroid treatment regimens related to type of steroid, timing of treatment initiation, duration, pulse versus continuous delivery, and cumulative dose. To assess the effects of different corticosteroid treatment regimens on mortality, pulmonary morbidity, and neurodevelopmental outcome in very low birth weight infants. We conducted searches in September 2022 of MEDLINE, the Cochrane Library, Embase, and two trial registries, without date, language or publication- type limits. Other search methods included checking the reference lists of included studies for randomized controlled trials (RCTs) and quasi-randomized trials. We included RCTs comparing two or more different treatment regimens of systemic postnatal corticosteroids in preterm infants at risk for BPD, as defined by the original trialists. The following comparisons of intervention were eligible: alternative corticosteroid (e.g. hydrocortisone) versus another corticosteroid (e.g. dexamethasone); lower (experimental arm) versus higher dosage (control arm); later (experimental arm) versus earlier (control arm) initiation of therapy; a pulse-dosage (experimental arm) versus continuous-dosage regimen (control arm); and individually-tailored regimens (experimental arm) based on the pulmonary response versus a standardized (predetermined administered to every infant) regimen (control arm). We excluded placebo-controlled and inhalation corticosteroid studies. Two authors independently assessed eligibility and risk of bias of trials, and extracted data on study design, participant characteristics and the relevant outcomes. We asked the original investigators to verify if data extraction was correct and, if possible, to provide any missing data. We assessed the following primary outcome: the composite outcome mortality or BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes were: the components of the composite outcome; in-hospital morbidities and pulmonary outcomes, and long-term neurodevelopmental sequelae. We analyzed data using Review Manager 5 and used the GRADE approach to assess the certainty of the evidence. We included 16 studies in this review; of these, 15 were included in the quantitative synthesis. Two trials investigated multiple regimens, and were therefore included in more than one comparison. Only RCTs investigating dexamethasone were identified. Eight studies enrolling a total of 306 participants investigated the cumulative dosage administered; these trials were categorized according to the cumulative dosage investigated, 'low' being < 2 mg/kg, 'moderate' being between 2 and 4 mg/kg, and 'high' > 4 mg/kg; three studies contrasted a high versus a moderate cumulative dose, and five studies a moderate versus a low cumulative dexamethasone dose. We graded the certainty of the evidence low to very low because of the small number of events, and the risk of selection, attrition and reporting bias. Overall analysis of the studies investigating a higher dose versus a lower dosage regimen showed no differences in the outcomes BPD, the composite outcome death or BPD at 36 weeks' PMA, or abnormal neurodevelopmental outcome in survivors assessed. Although there was no evidence of a subgroup difference for the higher versus lower dosage regimens comparisons (Chi2 = 2.91, df = 1 (P = 0.09), I2 = 65.7%), a larger effect was seen in the subgroup analysis of moderate-dosage regimens versus high-dosage regimens for the outcome cerebral palsy in survivors. In this subgroup analysis, there was an increased risk of cerebral palsy (RR 6.85, 95% CI 1.29 to 36.36; RD 0.23, 95% CI 0.08 to 0.37; P = 0.02; I² = 0%; NNTH 5, 95% CI 2.6 to 12.7; 2 studies, 74 infants). There was evidence of subgroup differences for higher versus lower dosage regimens comparisons for the combined outcomes death or cerebral palsy, and death and abnormal neurodevelopmental outcomes (Chi2 = 4.25, df = 1 (P = 0.04), I2 = 76.5%; and Chi2 = 7.11, df = 1 (P = 0.008), I2 = 85.9%, respectively). In the subgroup analysis comparing a high dosage regimen of dexamethasone versus a moderate cumulative-dosage regimen, there was an increased risk of death or cerebral palsy (RR 3.20, 95% CI 1.35 to 7.58; RD 0.25, 95% CI 0.09 to 0.41; P = 0.002; I² = 0%; NNTH 5, 95% CI 2.4 to 13.6; 2 studies, 84 infants; moderate-certainty evidence), and death or abnormal neurodevelopmental outcome (RR 3.41, 95% CI 1.44 to 8.07; RD 0.28, 95% CI 0.11 to 0.44; P = 0.0009; I² = 0%; NNTH 4, 95% CI 2.2 to 10.4; 2 studies, 84 infants; moderate-certainty evidence). There were no differences in outcomes between a moderate- and a low-dosage regimen. Five studies enrolling 797 infants investigated early initiation of dexamethasone therapy versus a moderately early or delayed initiation, and showed no significant differences in the overall analyses for the primary outcomes. The two RCTs investigating a continuous versus a pulse dexamethasone regimen showed an increased risk of the combined outcome death or BPD when using the pulse therapy. Finally, three trials investigating a standard regimen versus a participant-individualized course of dexamethasone showed no difference in the primary outcome and long-term neurodevelopmental outcomes. We assessed the GRADE certainty of evidence for all comparisons discussed above as moderate to very low, because the validity of all comparisons is hampered by unclear or high risk of bias, small samples of randomized infants, heterogeneity in study population and design, non-protocolized use of 'rescue' corticosteroids and lack of long-term neurodevelopmental data in most studies. The evidence is very uncertain about the effects of different corticosteroid regimens on the outcomes mortality, pulmonary morbidity, and long term neurodevelopmental impairment. Despite the fact that the studies investigating higher versus lower dosage regimens showed that higher-dosage regimens may reduce the incidence of death or neurodevelopmental impairment, we cannot conclude what the optimal type, dosage, or timing of initiation is for the prevention of BPD in preterm infants, based on current level of evidence. Further high quality trials would be needed to establish the optimal systemic postnatal corticosteroid dosage regimen.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 63 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 11%
Other 7 11%
Student > Bachelor 5 8%
Student > Ph. D. Student 5 8%
Researcher 4 6%
Other 9 14%
Unknown 26 41%
Readers by discipline Count As %
Medicine and Dentistry 21 33%
Unspecified 3 5%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Biochemistry, Genetics and Molecular Biology 2 3%
Arts and Humanities 1 2%
Other 4 6%
Unknown 30 48%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 22. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 May 2023.
All research outputs
of 24,710,887 outputs
Outputs from Cochrane database of systematic reviews
of 12,960 outputs
Outputs of similar age
of 411,811 outputs
Outputs of similar age from Cochrane database of systematic reviews
of 128 outputs
Altmetric has tracked 24,710,887 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,960 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 34.9. This one has gotten more attention than average, scoring higher than 71% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 411,811 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 91% of its contemporaries.
We're also able to compare this research output to 128 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.