Retinopathy of prematurity and cognitive development in enteral docosahexaenoic acid-supplemented preterm infants: a systematic review and meta-analysis

Introduction

Preterm birth remains a leading cause of neonatal mortality and long-term neurodevelopmental impairments, affecting approximately 15 million infants worldwide annually (1). Increased pre- and postnatal care has resulted in decreased mortality and morbidity. A considerable percentage of survivors experience different impairments. Among infants born before 27 weeks of gestation, Bell et al. reported that 12.8% developed severe retinopathy of prematurity (ROP), and among those evaluated at 2 years, 21.2% had severe neurodevelopmental impairment (2). Appropriate nutrition is a critical therapy for preterm infants. Early nutritional interventions in preterm infants greatly influence their growth patterns and risk of morbidity, including neurodevelopmental outcomes and ROP (3-6). Long-chain polyunsaturated fatty acids (LCPUFAs), particularly the omega-3 fatty acid docosahexaenoic acid (DHA), play a critical role in neural and retinal development during early infancy (7,8). Both the recent Food and Agriculture Organization (FAO)/World Health Organization (WHO) consultation report and the research by Kuratko et al. provide supporting evidence that DHA is associated with cognitive functions such as learning, memory, and behavior, suggesting that it may contribute positively to cognitive health (9). Preterm infants are born with significant DHA deficits due to interrupted placental transfer during the third trimester (10). However, the effectiveness of DHA supplementation in preterm infants remains controversial. Some studies have suggested benefits in the neurodevelopment of preterm infants given formula supplemented with DHA (11,12); in contrast, some have suggested a reverse association or no association between DHA and neurodevelopment (13,14).

As widely known, a better control of SpO₂-levels was associated with a decreased risk of ROP (15-17). However, current evidence regarding DHA supplementation for the prevention of ROP in preterm infants remains inconsistent, with potential variations in efficacy between enteral and parenteral lipid administration (18). To clarify these uncertainties, we performed a systematic review and meta-analysis to assess the effects of DHA on ROP incidence and neurodevelopmental outcomes. We present this article in accordance with the PRISMA reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0057/rc).

Methods

Protocol and guidance

This review was registered in PROSPERO (CRD42024562517).

Inclusion and exclusion criteria

We included randomized controlled trials (RCTs) that met the following criteria:

• Population: preterm infants (<37 weeks or birth weight <2,500 g).
• Intervention: enteral DHA supplementation (alone or in combination with other LCPUFAs).
• Comparison: placebo or standard care.
• Outcomes: cognitive development was evaluated using standardized Bayley Scales of Infant Development II (Bayley-II) at 6, 12, and 18 months postterm and/or ROP incidence (severe ROP is defined by the International Classification of ROP (ICROP) as either: (i) stage ≥3 disease, (ii) type 1 ROP (zone I any stage plus disease or zone II stages 2–3 plus disease), or (iii) cases requiring treatment with laser therapy, cryotherapy, or intravitreal anti-VEGF agents (19).
• Study design: individual or cluster RCTs.

Search strategy

Four electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials) were searched from database establishment and literature inclusion up to August 1, 2025. Gray literature sources were obtained from ClinicalTrials.gov and the WHO ICTRP. The search strategy was established using MeSH terms and keywords related to “DHA”, “preterm infants”, “ROP”, and “neurodevelopment”. There were no language or date restrictions. Table S1 presents the search strategy.

Data extraction and quality assessment

After removing duplicates, two independent researchers (X.M.X. and Y.G.) screened all titles and abstracts. They obtained full texts for further screening of eligible studies. Two independent researchers (H.S.M. and J.Y.W.) used a standard data extraction form to extract data from the included trials. Disagreements were resolved by consensus. When RCTs had more than two groups, we extracted data separately. The Cochrane RoB 2.0 tool was used to assess the risk of bias (ROB), and evidence quality was graded via GRADEpro GDT (20,21).

Statistical analysis

RevMan 5.3 and Stata 16 software were used for all statistical analyses. Continuous variables were analyzed with weighted mean differences (WMDs), and dichotomous variables were analyzed with risk ratio (RR), both reported with 95% confidence intervals (CIs). Statistical significance was defined as P<0.05. Heterogeneity was assessed through Q and I² tests: fixed-effect models were applied when I²<50% and P≥0.10, whereas random-effects models were used for I²≥50% or P<0.10. Sensitivity analyses were conducted using the leave-one-out method, which involved the sequential exclusion of each study. Funnel plots and Egger’s test were used to assess publication bias. We performed subgroup analyses to test the effects of different gestational ages (GAs) on the results.

Results

Study selection

Six electronic databases yielded 2,369 publications. After removing duplicates, 1,283 studies remained. After screening the titles and abstracts, 40 papers were retained for full-text review. Thirteen studies remained for the final systematic review and meta-analysis after 27 papers failed to meet the inclusion criteria (11,12,22-32). A flowchart of the literature search is shown in Figure 1.

Figure 1 PRISMA flow diagram of systematic literature selection process. DHA, docosahexaenoic acid; LCPUFA, long-chain polyunsaturated fatty acids; RCT, randomized controlled trial.

Study characteristics

The review included 13 RCTs involving a total of 3,150 patients, 12 RCTs with birth weights below 1,500 g and GAs under 32 weeks, except one study that focused on larger preterm infants. Four RCTs specifically examined the relationship between DHA and ROP. Among the included studies, six studies (10,19,22,25-27) administered DHA as a single intervention; the remaining studies included both DHA and arachidonic acid (AA), with varying doses of DHA used across investigations. Most interventions commenced at the first enteral feeding. The maximum duration of intervention was up to 12 months, particularly in ROP research. The characteristics of the included studies are detailed in Table 1.

ROB assessment and certainty of evidence (CoE)

The research conducted by Clandinin et al. (12) was categorized as “high risk” because of inadequate outcome data, indicating attrition bias. Khalesi et al. (30) failed to provide the randomization process or details in two areas. Fewtrell et al. (29) demonstrated a high ROB (ROB 2.0) due to >20% attrition and lack of a prospectively registered protocol. Cagliari et al. (31) and Woltil et al. (26) neglected allocation concealment and blinding in their papers. Therefore, this literature was categorized as “some concerns” in Figure 2. Table 2 presents an overview of the findings obtained via the GRADE technique, and the evidence quality of the primary outcome was low.

Figure 2 Risk of bias assessment of individual trials. Green: low risk; yellow: unclear risk; red: high risk.

Primary outcomes: Bayley Psychomotor Development Index (PDI) and Mental Development Index (MDI) scores at 6, 12, and 18 months postterm

According to nine of the 13 included studies, the neurodevelopment of the two groups at various postnatal ages did not differ significantly. No discernible impact of DHA supplementation was found in a meta-analysis of two studies (11,25) that evaluated Bayley Scales of Infant Development at 6 months (n=69) [MDI—mean difference (MD): −1.76, 95% CI: −14.20 to 10.68; P=0.78; I²=79%; PDI—MD: −1.36, 95% CI: −16.53 to −13.81; P=0.86; I²=83%]. Three studies (11,23,25) at 12 months (n=532) revealed no significant effect of DHA on neurodevelopment (MDI—MD: 1.54, 95% CI: −0.45 to 3.53; P=0.13; I²=50%; PDI—MD: 1.14, 95% CI: −3.93 to 6.21; P=0.66; I²=71%). Finally, four studies (12,26,28,29) at 18 months (n=535) indicated a slight benefit of DHA on neurodevelopment (MDI—MD: 2.7, 95% CI: 0.01 to 5.38; P=0.05; I²=0%; PDI—MD: 4.25, 95% CI: −1.24 to 9.75; P=0.13; I²=75%) (Figure 3A-3F). No significant small study effects were detected via Egger’s test.

Figure 3 Forest plots illustrating the impact of enteral DHA relative to the control on the Bayley MDI in preterm infants at 6 months postterm (A), 12 months postterm (B), and 18 months postterm (C) and the Bayley PDI at 6 months postterm (D), 12 months postterm (E), and 18 months postterm (F). Subgroup study on Bayley MDI in infants born at less than 30 weeks of GA (G). CI, confidence interval; CON, control; df, degree of freedom; DHA, docosahexaenoic acid; GA, gestational age; IV, inverse variance; M-H, Mantel-Haenszel; MDI, Mental Developmental Index; PDI, Psychomotor Developmental Index; SD, standard deviation.

Based on the interesting findings of the 18-month MDI, in Fewtrell et al.’s research (29), we only included data from studies with GAs below 30 weeks, which lowered the overall average GA. We then re-ran the meta-analysis. The DHA groups exhibited a statistically significant difference in the MDI at 18 months of age (MD: 3.07, 95% CI: 0.13–6.01; P=0.04; I²=0%) (Figure 3G). Egger’s test revealed no significant small study effects (P=0.31).

As shown in Figure 4, funnel plot analysis revealed no asymmetry.

Figure 4 Funnel plot of studies included in this meta-analysis. Bayley MDI at 6 months postterm (A), 12 months postterm (B), and 18 months postterm (C), and Bayley PDI at 6 months postterm (D), 12 months postterm (E), and 18 months postterm (F). Subgroup study on Bayley II in infants born at less than 30 weeks of GA (G), with any ROP (H) and severe ROP (I); funnel plot results of ROP for the primary outcomes of any ROP (J) and severe ROP (K). CI, confidence interval; IV, inverse variance; MD, mean difference; MDI, Mental Developmental Index; PDI, Psychomotor Developmental Index; ROP, retinopathy of prematurity; SE, standard error.

Secondary outcome: ROP

Incidence of ROP

In seven RCTs (12,22,27,28,30,31,33), ROP was measured as either a primary or secondary outcome. Compared with control or standard treatment, enteral DHA did not decrease the incidence of any ROP (RR: 0.86, 95% CI: 0.67–1.10; I²=47%) in preterm infants (Figure 5A). The regression-based Egger’s test for small-study effects (P=0.08) revealed no significant small-study effects. The absolute risk reduction for any ROP was 2.4% [number needed to treat (NNT): 43]. However, enteral DHA administration significantly reduced the incidence of severe ROP in preterm infants compared with standard feeding regimens [six trials (n=1,942 infants); RR: 0.66, 95% CI: 0.51–0.86; P=0.002; I²=39%] (Figure 5B). Egger’s test revealed no significant small study effects (P=0.07).

Figure 5 Enteral DHA vs. control in preterm infants: forest plots for (A) any ROP and (B) severe ROP. Meta-analysis of primary outcomes: (C) any ROP, (D) severe ROP. GA-stratified subgroup analysis: (E) any ROP. CI, confidence interval; df, degree of freedom; DHA, docosahexaenoic acid; GA, gestational age; M-H, Mantel-Haenszel; ROP, retinopathy of prematurity.

Incidence of ROP

Only RCTs (n=631) that used ROP as the main outcome measure were included in this analysis. Four RCTs (22,27,30,31) in which ROP was assessed as the main outcome were examined independently. Compared with the control, enteral DHA reduced the incidence of any ROP (RR: 0.78; 95% CI: 0.64–0.95; I²=18%) in preterm infants (Figure 5C). Similarly, in patients with severe ROP, a significant decrease was observed in the DHA group (RR: 0.35, 95% CI: 0.21–0.59; I²=0%) (Figure 5D).

Subgroup analysis of ROP incidence based on GA

Further stratified analysis was conducted to determine the GA. Two RCTs were grouped according to GA, but Collins et al. [2017] did not group those younger than 27 weeks (32). In Hellström et al. [2021] (22), they were grouped according to GA above 27 weeks and below 25 weeks, and the results revealed that with GA less than 25 weeks, DHA was the greatest contributor to a decrease in ROP. However, given the limited sample size in the subgroup analysis, it remains uncertain whether higher GA weakens the protective effect of ROP (Figure 5E). Additionally, the Egger’s test (any ROP, P=0.07; severe ROP, P=0.29) detected no significant small study effects.

Discussion

The present study demonstrates the influence of enteral DHA supplementation in preterm babies, illustrating that it primarily has a positive effect on retinal outcomes, rather than on neurodevelopmental indices. Overall, cognitive performance did not show a significant increase with DHA supplementation; however, one benefit was apparent among infants born at <30 weeks’ GA, suggesting a possible GA-dependent effect on early brain maturation. Furthermore, the DHA supplementation was accompanied by a protective effect against the severest case of ROP; the was cut reduced by approximately one-third. The benefit to the retina was strong among preterm infants, further demonstrating DHA’s involvement in retinal blood vessel growth and oxygen control. The evidence suggests that routine enteral DHA might not facilitate neurodevelopmental outcomes uniformly across preterm populations but might function as a preventive strategy against severe ROP in the most immature infants. Evidence regarding whether ROP is independently associated with worse neurodevelopmental outcomes is conflicting and there is controversy. While many studies observe a strong correlation between ROP and developmental delays, recent high-quality research suggests that this may be due to shared underlying risk factors—such as extremely low birth weight and GA—rather than the eye disease itself (34-36).

In 2009, Makrides et al. (37) reported that supplementation with DHA could improve the MDI scores for girls, and Shulkin et al. (38) reported that omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation improved the MDI in preterm infants. However, a 2015 Cochrane meta-analysis by Moon et al. (39) found no long-term advantages or detriments for preterm infants consuming LCPUFA-supplemented formula. However, a significant trend was observed for the 18-month MDI, particularly when the GA of the included samples was lower. Therefore, we hypothesized that GA is the key factor affecting DHA and neurological prognosis. In theory, Hortensius et al. (40) reported that higher serum DHA levels correlate with increased brain volume in extremely preterm infants, while Baack et al. (41) identified a direct relationship between DHA levels and GA (P<0.0001), with the most premature infants facing the highest risk of LCPUFA deficiency. Fewtrell et al. observed no developmental score differences in randomized nutritional intervention trials. However, Fewtrell et al. revealed a greater (nonsignificant) advantage in newborns younger than 30 weeks of gestation (MDI: 4.5 points, PDI: 5.8 points) (28). In 2022, Gould et al. found the administration of enteral DHA correlated with modestly elevated full scale intelligence quotient scores (95.4±17.3 versus 91.9±19.1) at the age of 5 years compared with control feeding (42). A RCT evaluating the 5-year follow-up of N3RO (N3RO trial) assessed the respiratory outcomes in 1,273 infants born <29 weeks’ gestation, comparing enteral DHA supplementation (60 mg/kg/day) with placebo to evaluate its impact on bronchopulmonary dysplasia. The results revealed that the mean IQ in the DHA group was 3.45 points higher (95% CI: 0.38–6.53 points) than that in the control group (43). Importantly, the infants’ GA was younger than 29 weeks, and the mean GA was 26.8±1 at birth. Based on the aforementioned results, the neuroprotective effect of DHA may become increasingly pronounced with decreasing GA. In summary, most studies solely indicated variations in mean scores, lacked a stratified evaluation of GA, necessitated consideration of confounders and effect modifiers, and suggested that effects on the proportion of infants below a specific cut-off may be more sensitive and clinically meaningful.

The results of previous studies on the association between DHA and ROP have been conflicting and not fully consistent with our findings. Hellström et al. [2021] (22) and Diggikar et al. [2022] (44) reported positive associations between DHA and severe ROP, but no associations between DHA and ROP. However, when we included only RCTs with ROP as the primary outcome in the meta-analysis, both ROP and severe ROP demonstrated statistical significance, possibly due to the exclusion of newly added studies. Compared with the review by Diggikar et al., two RCTs (32,45) were excluded because they did not report ROP as a primary outcome. Moreover, this study included two new RCTs (27,31). Four RCTs that examined ROP as the primary outcome were analyzed. Three of these studies reported positive results, whereas one reported no association between DHA supplementation and ROP (26). However, we believe that the data presented in this article may be questionable. Notably, extremely preterm infants (<28 weeks) receiving DHA had a significantly lower incidence of ROP (6.25%, 3/48) compared to controls (75%, 21/28), a 12-fold difference. It appears that DHA is effective; however, the incidence was up to 75% (21/28) in the DHA group for infants >28 weeks, which exceeds typical epidemiological patterns for this GA subgroup and requires further investigation. Moreover, meta-stratification based on GA further revealed that a younger GA is correlated with a more pronounced protective effect of DHA. Therefore, earlier intervention times and higher DHA doses, as well as younger mean GAs, were observed in trials that focused primarily on ROP. Given the complex pathophysiology associated with DHA, its effects are likely more significant than those reported in trials where ROP was considered a secondary outcome.

Limitations and weaknesses

The major weakness of this systematic review is the lack of well-designed RCTs on this issue, as well as different types of interventions and contextual characteristics, such as dosing regimens, therapy durations, formulations, and timings of LCPUFA initiation. Another limitation is the small subgroup sizes and the possible presence of false positives due to repeated stratifications. Although all studies used the BSID-II at the same corrected age, variations in administration and blinding may have introduced inherent methodological heterogeneity. Therefore, our findings should be interpreted with caution. Additionally, it is important to note that the assessment of publication bias using funnel plots and Egger’s test may be unreliable in this analysis due to the limited number of included studies (k<10), as the statistical power of these methods is substantially reduced. Given this constraint, the findings regarding publication bias remain inconclusive, and future research with a larger number of high-quality studies is warranted to further clarify this issue.

Finally, due to the limited number of studies, we were unable to perform subgroup analyses based on whether DHA was supplemented alone or in combination with other LCPUFAs such as AA. Given the potential role of AA in neurodevelopment, this question warrants further investigation.

In future trials, large sample sizes with subgroup analyses, such as analyses of maternal factors, sex, and genetics, are recommended. The optimal dose for DHA supplementation should be determined, and the outcomes should be assessed using well-designed and valid measures.

Conclusions

In conclusion, this systematic review and meta-analysis revealed that enteral DHA supplementation in preterm infants does not exert a significant effect on cognitive outcomes at 6, 12, or 18 months postterm. However, it demonstrated a significant reduction in the risk of severe ROP; in infants born before 30 weeks, the intervention improved MDI scores by 3.07 points (P=0.04). Despite the methodological limitations (moderate heterogeneity, small subgroup samples), these results highlight the importance of GA as a critical determinant of DHA efficacy. Neonatal care may require GA-stratified approaches to optimize DHA supplementation. Further research should focus on long-term outcomes and mechanisms in extremely preterm infants.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0057/rc

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0057/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0057/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Ohuma EO, Moller AB, Bradley E, et al. National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis. Lancet 2023;402:1261-71. [Crossref] [PubMed]
2. Bell EF, Hintz SR, Hansen NI, et al. Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018. JAMA 2022;327:248-63. [Crossref] [PubMed]
3. Toppe F, Rasche T, Weiss C, et al. Relationship between early nutrition and deep gray matter and lateral ventricular volumes of preterm infants at term-equivalent age. World J Pediatr 2023;19:460-8. [Crossref] [PubMed]
4. Thoene M, Anderson-Berry A. Early Enteral Feeding in Preterm Infants: A Narrative Review of the Nutritional, Metabolic, and Developmental Benefits. Nutrients 2021;13:2289. [Crossref] [PubMed]
5. Stephens BE, Walden RV, Gargus RA, et al. First-week protein and energy intakes are associated with 18-month developmental outcomes in extremely low birth weight infants. Pediatrics 2009;123:1337-43. [Crossref] [PubMed]
6. Stoltz Sjöström E, Lundgren P, Öhlund I, et al. Low energy intake during the first 4 weeks of life increases the risk for severe retinopathy of prematurity in extremely preterm infants. Arch Dis Child Fetal Neonatal Ed 2016;101:F108-13. [Crossref] [PubMed]
7. Zárate R, El Jaber-Vazdekis N, Tejera N, et al. Significance of long chain polyunsaturated fatty acids in human health. Clin Transl Med 2017;6:25. [Crossref] [PubMed]
8. Crawford MA, Horn LA, Brenna T, et al. The Quantum Brain: The Untold Story of Docosahexaenoic Acid's Role in Brain Evolution, Biophysics, and Cognition. Int J Mol Sci 2025;26:11542. [Crossref] [PubMed]
9. Kuratko CN, Barrett EC, Nelson EB, et al. The relationship of docosahexaenoic acid (DHA) with learning and behavior in healthy children: a review. Nutrients 2013;5:2777-810. [Crossref] [PubMed]
10. Innis SM. Essential fatty acid transfer and fetal development. Placenta 2005;26 Suppl A:S70-5.
11. Fang PC, Kuo HK, Huang CB, et al. The effect of supplementation of docosahexaenoic acid and arachidonic acid on visual acuity and neurodevelopment in larger preterm infants. Chang Gung Med J 2005;28:708-15.
12. Clandinin MT, Van Aerde JE, Merkel KL, et al. Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. J Pediatr 2005;146:461-8. [Crossref] [PubMed]
13. Almaas AN, Tamnes CK, Nakstad B, et al. Long-chain polyunsaturated fatty acids and cognition in VLBW infants at 8 years: an RCT. Pediatrics 2015;135:972-80. [Crossref] [PubMed]
14. Keim SA, Boone KM, Klebanoff MA, et al. Effect of Docosahexaenoic Acid Supplementation vs Placebo on Developmental Outcomes of Toddlers Born Preterm: A Randomized Clinical Trial. JAMA Pediatr 2018;172:1126-1134. [Crossref] [PubMed]
15. Sola A. Monitoring SpO(2): The Basics of Retinopathy of Prematurity (Back to Basics) and Targeting Oxygen Saturation. Crit Care Nurs Clin North Am 2024;36:69-98. [Crossref] [PubMed]
16. Chow LC, Wright KW, Sola A, et al. Can changes in clinical practice decrease the incidence of severe retinopathy of prematurity in very low birth weight infants? Pediatrics 2003;111:339-45. [Crossref] [PubMed]
17. Sola A, Golombek SG, Montes Bueno MT, et al. Safe oxygen saturation targeting and monitoring in preterm infants: can we avoid hypoxia and hyperoxia? Acta Paediatr 2014;103:1009-18. [Crossref] [PubMed]
18. Nilsson AK, Löfqvist C, Najm S, et al. Influence of Human Milk and Parenteral Lipid Emulsions on Serum Fatty Acid Profiles in Extremely Preterm Infants. JPEN J Parenter Enteral Nutr 2019;43:152-61. [Crossref] [PubMed]
19. Chiang MF, Quinn GE, Fielder AR, et al. International Classification of Retinopathy of Prematurity, Third Edition. Ophthalmology 2021;128:e51-68.
20. Front Matter. Cochrane Handbook for Systematic Reviews of Interventions. 2019:i-xxviii.
21. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-6. [Crossref] [PubMed]
22. Hellström A, Nilsson AK, Wackernagel D, et al. Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial. JAMA Pediatr 2021;175:359-67. [Crossref] [PubMed]
23. O'Connor DL, Hall R, Adamkin D, et al. Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Pediatrics 2001;108:359-71. [Crossref] [PubMed]
24. Hewawasam E, Collins CT, Muhlhausler BS, et al. DHA supplementation in infants born preterm and the effect on attention at 18 months' corrected age: follow-up of a subset of the N3RO randomised controlled trial. Br J Nutr 2021;125:420-31. [Crossref] [PubMed]
25. van Wezel-Meijler G, van der Knaap MS, Huisman J, et al. Dietary supplementation of long-chain polyunsaturated fatty acids in preterm infants: effects on cerebral maturation. Acta Paediatr 2002;91:942-50. [Crossref] [PubMed]
26. Woltil HA, van Beusekom CM, Okken-Beukens M, et al. Development of low-birthweight infants at 19 months of age correlates with early intake and status of long-chain polyunsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids 1999;61:235-41. [Crossref] [PubMed]
27. Bernabe-García M, Villegas-Silva R, Villavicencio-Torres A, et al. Enteral Docosahexaenoic Acid and Retinopathy of Prematurity: A Randomized Clinical Trial. JPEN J Parenter Enteral Nutr 2019;43:874-82. [Crossref] [PubMed]
28. Fewtrell MS, Morley R, Abbott RA, et al. Double-blind, randomized trial of long-chain polyunsaturated fatty acid supplementation in formula fed to preterm infants. Pediatrics 2002;110:73-82. [Crossref] [PubMed]
29. Fewtrell MS, Abbott RA, Kennedy K, et al. Randomized, double-blind trial of long-chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants. J Pediatr 2004;144:471-9. [Crossref] [PubMed]
30. Khalesi N, Bordbar A, Khosravi N, et al. The Efficacy of Omega-3 Supplement on Prevention of Retinopathy of Prematurity in Premature Infants: A Randomized Double-blinded Controlled trial. Curr Pharm Des 2018;24:1845-8. [Crossref] [PubMed]
31. Cagliari PZ, Hoeller VRF, Kanzler ÉLR, et al. Oral DHA supplementation and retinopathy of prematurity: the Joinville DHA Clinical Trial. Br J Nutr 2024;132:341-350. [Crossref] [PubMed]
32. Collins CT, Makrides M, McPhee AJ, et al. Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants. N Engl J Med 2017;376:1245-55. [Crossref] [PubMed]
33. Wendel K, Aas MF, Gunnarsdottir G, et al. Effect of arachidonic and docosahexaenoic acid supplementation on respiratory outcomes and neonatal morbidities in preterm infants. Clin Nutr 2023;42:22-8. [Crossref] [PubMed]
34. Al-Moujahed A, Azad A, Vail D, et al. Retinopathy of prematurity and neurodevelopmental outcomes in premature infants. Eye (Lond) 2021;35:1014-6. [Crossref] [PubMed]
35. Karmouta R, Strawbridge JC, Langston S, et al. Neurodevelopmental Outcomes in Infants Screened for Retinopathy of Prematurity. JAMA Ophthalmol 2023;141:1125-32. [Crossref] [PubMed]
36. Choi YJ, Hong EH, Shin YU, et al. Severe Retinopathy of Prematurity Associated With Neurodevelopmental Disorder in Children. Front Pediatr 2022;10:816409. [Crossref] [PubMed]
37. Makrides M, Gibson RA, McPhee AJ, et al. Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. JAMA 2009;301:175-82. [Crossref] [PubMed]
38. Shulkin M, Pimpin L, Bellinger D, et al. n-3 Fatty Acid Supplementation in Mothers, Preterm Infants, and Term Infants and Childhood Psychomotor and Visual Development: A Systematic Review and Meta-Analysis. J Nutr 2018;148:409-18. [Crossref] [PubMed]
39. Moon K, Rao SC, Schulzke SM, et al. Longchain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Syst Rev 2016;12:CD000375. [Crossref] [PubMed]
40. Hortensius LM, Hellström W, Sävman K, et al. Serum docosahexaenoic acid levels are associated with brain volumes in extremely preterm born infants. Pediatr Res 2021;90:1177-85. [Crossref] [PubMed]
41. Baack ML, Puumala SE, Messier SE, et al. What is the relationship between gestational age and docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels? Prostaglandins Leukot Essent Fatty Acids 2015;100:5-11. [Crossref] [PubMed]
42. Gould JF, Makrides M, Gibson RA, et al. Neonatal Docosahexaenoic Acid in Preterm Infants and Intelligence at 5 Years. N Engl J Med 2022;387:1579-88. [Crossref] [PubMed]
43. Sullivan TR, Gould JF, Bednarz JM, et al. Mediation Analysis to Untangle Opposing Associations of High-Dose Docosahexaenoic Acid With IQ and Bronchopulmonary Dysplasia in Children Born Preterm. JAMA Netw Open 2023;6:e2317870. [Crossref] [PubMed]
44. Diggikar S, Aradhya AS, Swamy RS, et al. Effect of Enteral Long-Chain Polyunsaturated Fatty Acids on Retinopathy of Prematurity: A Systematic Review and Meta-Analysis. Neonatology 2022;119:547-57. [Crossref] [PubMed]
45. Carlson SE, Werkman SH. A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until two months. Lipids 1996;31:85-90. [Crossref] [PubMed]