Interventions to Reduce Severe Brain Injury Risk in Preterm Neonates
Bibliographic record
Abstract
Importance: Interventions to reduce severe brain injury risk are the prime focus in neonatal clinical trials. Objective: To evaluate multiple perinatal interventions across clinical settings for reducing the risk of severe intraventricular hemorrhage (sIVH) and cystic periventricular leukomalacia (cPVL) in preterm neonates. Data Sources: MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched from inception until September 8, 2022, using prespecified search terms and no language restrictions. Study Selection: Randomized clinical trials (RCTs) that evaluated perinatal interventions, chosen a priori, and reported 1 or more outcomes (sIVH, cPVL, and severe brain injury) were included. Data Extraction and Synthesis: Two co-authors independently extracted the data, assessed the quality of the trials, and evaluated the certainty of the evidence using the Cochrane GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Fixed-effects pairwise meta-analysis was used for data synthesis. Main Outcomes and Measures: The 3 prespecified outcomes were sIVH, cPVL, and severe brain injury. Results: A total of 221 RCTs that assessed 44 perinatal interventions (6 antenatal, 6 delivery room, and 32 neonatal) were included. Meta-analysis showed with moderate certainty that antenatal corticosteroids were associated with small reduction in sIVH risk (risk ratio [RR], 0.54 [95% CI, 0.35-0.82]; absolute risk difference [ARD], -1% [95% CI, -2% to 0%]; number needed to treat [NNT], 80 [95% CI, 48-232]), whereas indomethacin prophylaxis was associated with moderate reduction in sIVH risk (RR, 0.64 [95% CI, 0.52-0.79]; ARD, -5% [95% CI, -8% to -3%]; NNT, 20 [95% CI, 13-39]). Similarly, the meta-analysis showed with low certainty that volume-targeted ventilation was associated with large reduction in risk of sIVH (RR, 0.51 [95% CI, 0.36-0.72]; ARD, -9% [95% CI, -13% to -5%]; NNT, 11 [95% CI, 7-23]). Additionally, early erythropoiesis-stimulating agents (RR, 0.68 [95% CI, 0.57-0.83]; ARD, -3% [95% CI, -4% to -1%]; NNT, 34 [95% CI, 22-67]) and prophylactic ethamsylate (RR, 0.68 [95% CI, 0.48-0.97]; ARD, -4% [95% CI, -7% to 0%]; NNT, 26 [95% CI, 13-372]) were associated with moderate reduction in sIVH risk (low certainty). The meta-analysis also showed with low certainty that compared with delayed cord clamping, umbilical cord milking was associated with a moderate increase in sIVH risk (RR, 1.82 [95% CI, 1.03-3.21]; ARD, 3% [95% CI, 0%-6%]; NNT, -30 [95% CI, -368 to -16]). Conclusions and Relevance: Results of this study suggest that a few interventions, including antenatal corticosteroids and indomethacin prophylaxis, were associated with reduction in sIVH risk (moderate certainty), and volume-targeted ventilation, early erythropoiesis-stimulating agents, and prophylactic ethamsylate were associated with reduction in sIVH risk (low certainty) in preterm neonates. However, clinicians should carefully consider all of the critical factors that may affect applicability in these interventions, including certainty of the evidence, before applying them to clinical practice.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.019 | 0.097 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.006 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".