Enteral High-Dose Docosahexaenoic Acid and Neurodevelopment in Extremely Preterm Infants: A Systematic Review and Meta-analysis
Bibliographic record
Abstract
<h2>Abstract</h2><h3>Background</h3> Enteral high-dose docosahexaenoic acid (DHA) may be required for neurodevelopment, including cognition, of extremely preterm infants. High-level summative evidence is lacking. <h3>Objective</h3> To examine associations between enteral high-dose DHA during the neonatal period and neurodevelopment in infants born ≤ 29 weeks' gestation. <h3>Methods</h3> 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. <h3>Results</h3> 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<sup>2</sup> = 0%) or 5-7 years' CA (2 RCTs, 852 children, MD 2.22, 95% CI -0.14, 4.57; P=0.06; I<sup>2</sup> = 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. <h3>Conclusions</h3> 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. <h3>Registration</h3> 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 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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.001 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".