Enteral High-Dose Docosahexaenoic Acid and Neurodevelopment in Extremely Preterm Infants: A Systematic Review and Meta-analysis
Bibliographic record
Abstract
Background Enteral high-dose docosahexaenoic acid (DHA) may be required for neurodevelopment, including cognition, of extremely preterm infants. High-level summative evidence is lacking. Objective To examine associations between enteral high-dose DHA during the neonatal period and neurodevelopment in infants born ≤ 29 weeks' gestation. Methods CINAHL, Cochrane Library, Embase, Medline, Scopus, Web of Science were searched (inceptions to 4/11/2024). Eligible randomised controlled trials (RCTs) in infants born ≤ 29 weeks, assessing direct enteral administration ≥ 40 mg/kg/day DHA, or breast milk/formula with DHA ≥ 0.60% total fatty acids, reporting neurodevelopmental outcomes. Two reviewers independently screened articles, extracted data and assessed quality using Cochrane Handbook guidance. Data were pooled using fixed or random-effect meta-analyses. Primary outcome was global cognitive scores from a standardised test. Results We screened 1978 articles and included 3 high-quality RCTs (2028 infants born ≤ 29 weeks). Enteral high-dose DHA was not associated with overall differences in global cognition scores at 18-36 months' corrected age (CA) (3 RCTs, 638 children, MD 0.67, 95% CI -1.80, 3.15; P=0.59; I 2 = 0%) or 5-7 years' CA (2 RCTs, 852 children, MD 2.22, 95% CI -0.14, 4.57; P=0.06; I 2 = 33%); however, benefit was observed in the largest RCT with a direct enteral emulsion (656 children, 5 years' CA, MD 3.45, 95% CI 0.38, 6.52; P=0.03). Associations with most secondary outcomes were not seen; however high-dose DHA was associated with reduced mild motor (3 RCTs, 18-36 months' CA) and cognitive (2 RCTs, 5-7 years' CA) impairment. No negative impacts were observed. Conclusions Enteral high-dose DHA in extremely preterm infants was not associated with differences in global cognition scores on meta-analysis; however, higher scores were observed with use of a direct emulsion. Results support contemporary recommendations. Registration PROSPERO, CRD42022382744, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382744
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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 | 0.010 | 0.026 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.016 | 0.025 |
| Bibliometrics | 0.006 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".