Indomethacin for symptomatic patent ductus arteriosus in preterm infants
Bibliographic record
Abstract
BACKGROUND: Symptomatic patent ductus arteriosus (PDA) is associated with mortality and morbidity in preterm infants. In these infants, prophylactic use of indomethacin, a non-selective cyclooxygenase inhibitor, has demonstrated short-term clinical benefits. The effect of indomethacin in preterm infants with a symptomatic PDA remains unexplored. OBJECTIVES: To determine the effectiveness and safety of indomethacin (given by any route) compared to placebo or no treatment in reducing mortality and morbidity in preterm infants with a symptomatic PDA. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 7), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 31 July 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included RCTs and quasi-RCTs that compared indomethacin (any dose, any route) versus placebo or no treatment in preterm infants. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal, with separate evaluation of trial quality and data extraction by at least two review authors. We used the GRADE approach to assess the certainty of evidence for the following outcomes: failure of PDA closure within one week of administration of the first dose of indomethacin; bronchopulmonary dysplasia (BPD) at 28 days' postnatal age and at 36 weeks' postmenstrual age; proportion of infants requiring surgical ligation or transcatheter occlusion; all-cause neonatal mortality; necrotizing enterocolitis (NEC) (≥ Bell stage 2); and mucocutaneous or gastrointestinal bleeding. MAIN RESULTS: We included 14 RCTs (880 preterm infants). Four out of the 14 included studies were judged to have high risk of bias in one or more domains. Indomethacin administration was associated with a large reduction in failure of PDA closure within one week of administration of the first dose (risk ratio (RR) 0.30, 95% confidence interval (CI) 0.23 to 0.38; risk difference (RD) -0.52, 95% CI -0.58 to -0.45; 10 studies, 654 infants; high-certainty evidence). There may be little to no difference in the incidence of BPD (BPD defined as supplemental oxygen need at 28 days' postnatal age: RR 1.45, 95% CI 0.60 to 3.51; 1 study, 55 infants; low-certainty evidence; BPD defined as supplemental oxygen need at 36 weeks' postmenstrual age: RR 0.80, 95% CI 0.41 to 1.55; 1 study, 92 infants; low-certainty evidence) and probably little to no difference in mortality (RR 0.78, 95% CI 0.46 to 1.33; 8 studies, 314 infants; moderate-certainty evidence) with use of indomethacin for symptomatic PDA. No differences were demonstrated in the need for surgical PDA ligation (RR 0.66, 95% CI 0.33 to 1.29; 7 studies, 275 infants; moderate-certainty evidence), in NEC (RR 1.27, 95% CI 0.36 to 4.55; 2 studies, 147 infants; low-certainty evidence), or in mucocutaneous or gastrointestinal bleeding (RR 0.33, 95% CI 0.01 to 7.58; 2 studies, 119 infants; low-certainty evidence) with use of indomethacin compared to placebo or no treatment. Certainty of evidence for BPD, surgical PDA ligation, NEC, and mucocutaneous or gastrointestinal bleeding was downgraded for very serious or serious imprecision. AUTHORS' CONCLUSIONS: High-certainty evidence shows that indomethacin is effective in closing a symptomatic PDA compared to placebo or no treatment in preterm infants. Evidence is insufficient regarding effects of indomethacin on other clinically relevant outcomes and medication-related adverse effects.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.015 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".