PURPOSE:Dexamethasone eye drops are being introduced off-label to prevent progression of severe retinopathy of prematurity (ROP). We evaluated ophthalmologic outcomes in early childhood after postnatal topical dexamethasone exposure in pre-term infants at a standardized follow-up examination. METHODS:This prospective cross-sectional follow-up study included preterm infants born between 2019 and 2022 in the Västra Götaland region, Sweden, who received topical dexamethasone off-label during ROP screening. As a follow-up, a single standardized ophthalmological examination assessed visual acuity, refractive error, ocular motility, intraocular pressure (IOP) and structural ocular abnormalities. RESULTS:Twenty-four infants (median gestational age 25.0 weeks, range 22.6-27.7 weeks; 58% male) were examined at a median age of 2.9 years (range 1.1-5.0 years). Dexamethasone eye drops were initiated mainly for severe ROP at a median postmenstrual age of 35.1 weeks (range 32.0-52.0 weeks) and given for a median duration of 28 days (range 4-136 days). Median IOP was 18.9 mmHg (range 9.0-22.3 mmHg), and no child showed clinical signs of glaucoma. One child had a unilateral peripheral lens opacity without visual significance. No other ocular structural abnormalities were detected. Strabismus was detected in 2 (8%) of the children, and 3 (12%) had refractive errors. CONCLUSION:Preliminary data from extremely preterm infants exposed to off-label topical dexamethasone during ROP screening showed no clinically significant ocular adverse effects at standardized early childhood follow-up. Rates of strabismus and refractive errors were lower than expected. Larger studies with longer follow-up are needed to further assess ocular and systemic safety.

AIM:Extremely preterm birth is associated with high morbidity and long-term support needs. This study estimated long-term medical and non-medical costs throughout childhood among children born before 24 weeks of gestation in Sweden. METHODS:This nationwide register-based study included 344 infants born before 24 weeks of gestation in Sweden between 2007 and 2018 who survived at least one year. Individual-level data from national health registers and social insurance records were linked to estimate costs of hospital care, outpatient care, prescribed drugs and parental support until the end of 2022. Costs were analysed from a societal perspective and expressed in 2022 Swedish kronor. RESULTS:The mean follow up time was 7.8 years. Average total costs per child were 1.68 million Swedish kronor in the first year of life, with medical care accounting for more than 80% of expenditures. Non-medical costs increased during childhood and exceeded medical costs from approximately four years of age. Neonatal morbidities, including bronchopulmonary dysplasia, treated retinopathy of prematurity, and severe intraventricular haemorrhage, were associated with sustained long-term costs. CONCLUSION:Birth before 24 weeks of gestation was linked to high long-term costs. Early costs were related to hospital care, while long-term costs increasingly reflected social and welfare support.

Retinopathy of prematurity (ROP) is a neurovascular retinal disease affecting extremely preterm infants (<28 weeks' gestational age), and links between early lipid metabolism and ROP are unclear. We investigated whether the lipid mediator sphingosine-1-phosphate (S1P) and its carrier apolipoprotein M (ApoM) are associated with ROP and parenteral nutrition in preterm infants. In this multicenter cohort, extremely preterm infants were grouped by ROP outcome: no ROP (n = 72) or any ROP (n = 105). Serum was collected at birth and longitudinally to postnatal day 100. S1P was quantified by LC-MS/MS and ApoM by proximity extension assay. Associations between first month mean parenteral fluid intake, S1P, ApoM, and ROP were analyzed using logistic regression; log-normal linear regression was applied to continuous outcomes, adjusting for gestational age and LCPUFA supplementation. Results showed that serum S1P and ApoM were positively correlated (r = 0.53, 95% confidence interval [CI] = 0.50-0.56). Higher first-month parenteral fluid intake was associated with lower S1P and ApoM (per 50 ml/kg/day increase, geometric mean ratio = 0.84, 95% CI = 0.79-0.88 for S1P; 0.97, 95% CI = 0.96-0.98 for ApoM; both P < 0.001). Higher mean S1P in the first month was associated with reduced odds of any ROP (per 0.1 μmol/l increase, adjusted odds ratio = 0.84; 95% CI = 0.71-0.99; P = 0.037). Mean ApoM was associated with ROP only in unadjusted analyses. In conclusion, low S1P and ApoM levels were linked to high parenteral fluid exposure and ROP development, suggesting that infants with high parenteral nutrition requirements may be particularly vulnerable to S1P-ApoM depletion, supporting this pathway as a potential therapeutic target.

BACKGROUND/AIMS:This study represents an external validation with model updating of the online DIGIROP-Prescreen and DIGIROP-Screen 2.0 prediction models, incorporating ≥14 days of parenteral nutrition as an additional predictor, to identify infants requiring treatment for retinopathy of prematurity (ROP) in a contemporary Swedish cohort, estimate potential cost savings and compare DIGIROP performance with other models. METHODS:Infants born in Sweden, 2021-2023 (n=1530) were evaluated. ROP and neonatal data were retrieved from Swedish quality registers. Sensitivity, specificity and the area under the receiver operating characteristic (AUC) curve were calculated. In the Västra Götaland Region cohort (n=245), the DIGIROP models were compared with WINROP and two Postnatal Growth and ROP (G-ROP) models. We estimated DIGIROP models' cost-saving. RESULTS:The mean gestational age was 27.7 (SD 2.2) weeks, birth weight 1029 (SD 317) g, 689 (45.0%) were girls and 85 (5.6%) infants received ROP treatment. For DIGIROP-Prescreen 2.0, the AUC was 0.89 (95% CI 0.86 to 0.92), sensitivity was 100% (95% CI 95.8% to 100%) and specificity 27.5% (95% CI 25.3% to 29.9%). For DIGIROP-Screen 2.0, the cumulative specificity increased from 27.7% to 67.8% between postnatal weeks 6-14, with a sensitivity of 100%. In total, ∼Int$750 000 could have been saved in screening costs in Sweden during 2021-2023 using DIGIROP models. DIGIROP-Screen at postnatal age 10 weeks had the same sensitivity but higher specificity than G-ROP. WINROP showed lower sensitivity but the highest specificity. CONCLUSION:DIGIROP 2.0 demonstrated high sensitivity and the most robust discrimination for treatment-requiring ROP in a contemporary Swedish cohort, compared with other models, with the potential to reduce unnecessary eye examinations and healthcare costs.

OBJECTIVE:Investigate whether enteral supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA), from birth to term-equivalent age (TEA), promotes brain maturation as a prespecified secondary outcome of a multicentre randomised controlled trial. PARTICIPANTS:206 infants born at 22-28 weeks gestational age (GA) were randomised into intervention or control groups from three university hospitals in Sweden. INTERVENTION:The intervention group received an oil with AA (100 mg/kg/d) and DHA (50 mg/kg/d) starting at birth until 40 weeks postmenstrual age (PMA) in addition to standard nutrition. Standard-of-care infants received standard nutrition according to national guidelines. MAIN OUTCOME AND MEASURES:MRI volumetrics were defined a priori as a secondary outcome of the trial and included total brain, white and cortical grey matter, central structures and cerebellum. Univariable and multivariable linear regression models were used for comparisons. RESULTS:MRI data in 117 infants had sufficient quality for inclusion (n=58 intervention). Birth weight, GA at birth, sex distribution, and PMA at MRI were similar in the groups. Infants receiving intervention had significantly larger white-matter volume at TEA, as compared with standard of care, in models adjusted for GA at birth, sex, study centre and PMA at MRI (β=6.8 cm3, 95% CI 0.7 to 12.9, p=0.028). The contribution of the intervention to white-matter volume corresponded to 10 days of prolonged gestation. CONCLUSION AND RELEVANCE:Our findings in this hypothesis-generating study suggest that AA+DHA promotes white matter growth, which may protect the developing brain in this vulnerable population. TRIAL REGISTRATION NUMBER:NCT03201588.

Importance:Identifying early proteomic profiles in infants who develop severe retinopathy of prematurity (ROP) may reveal targets for preventive interventions to reduce retinal vessel loss and the subsequent risk of severe ROP. Objective:To assess early longitudinal profiles of blood protein levels in preterm infants with or without severe ROP and the effect of arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation. Design, Setting, and Participants:This was an exploratory, post hoc analysis of serum proteome profiles in preterm infants in the double-masked Mega Donna Mega (MDM) randomized clinical trial using targeted Olink Proximity Extension Assay proteomics covering 538 analytes. The setting was 3 university hospitals in Sweden and included extremely preterm infants born before 28 weeks of gestational age (GA), from 2016 to 2019. Data were analyzed from January to March 2025. Exposures:All infants received standard nutrition; additionally, half received enteral lipid supplementation with AA/DHA (100/50 mg/kg per day) from birth to term equivalent age. Main Outcomes and Measures:Longitudinal protein profiles during the first month of life were examined using mixed models for repeated measures, adjusted for GA, study center, and AA/DHA supplementation, and tested for the interaction between severe ROP (stage ≥3 and/or treated) and postnatal age. Results:A total of 177 extremely preterm infants (mean [SD] GA, 25.6 [1.4] weeks; 100 male [56.5%]) were included, of whom 50 (28.2%) developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life associated with severe ROP, proteins related to immune response, apoptotic processes, blood coagulation, and lipid metabolism. The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; β = 0.68; 95% CI, 0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; β = 0.21; 95% CI, 0.13-0.29; Q <.001) during the first postnatal days. The increase in serum FGF-21 level in the first week of life was associated with lower GA, lower birth weight, low enteral energy intake, and more days receiving mechanical ventilation. No association was observed between AA/DHA supplementation and the proteome. Conclusions and Relevance:In this post hoc exploratory analysis of data from the MDM randomized clinical trial, a fast rise in FGF-21 levels, a metabolic stress-induced hormone, during the first postnatal days was strongly associated with the development of severe ROP in extremely preterm infants. These findings suggest that early interventions improving bioenergetic status may help prevent severe ROP. Trial Registration:ClinicalTrials.gov Identifier: NCT03201588.

Abstract Background A recent meta-analysis by Dang et al. [1] concluded that enteral supplementation with docosahexaenoic acid (DHA), with or without arachidonic acid (ARA) did not significantly affect retinopathy of prematurity (ROP) outcomes in preterm infants. Of four eligible trials that supplemented both DHA and ARA, only two contributed to each ROP outcome analyzed, and severe ROP was not assessed. Methods We replicated the eligibility criteria and search strategy of Dang et al ., restricted to trials that supplemented both DHA and ARA, and reanalyzed three ROP endpoints (any ROP, ROP requiring treatment, and severe ROP [stage 3 and/or treated]) using complete outcome records from all eligible trials. Crude risk ratios (RR) were pooled by Mantel-Haenszel fixed-effect meta-analysis. Gestational age-adjusted odds ratios (adjOR) were pooled on the log scale by inverse-variance random-effects meta-analysis with restricted maximum likelihood (REML) estimation of between-study variance and Hartung-Knapp confidence intervals. Results Five trials were included; one trial was identified in our replicated search but was excluded by Dang et al . without a stated rationale. The pooled estimate for any ROP was consistent with Dang et al . (RR 0.87 [95% CI 0.71–1.08]; adjOR 0.70 [0.46–1.08]). For ROP requiring treatment, the crude RR suggested a lower risk but did not reach statistical significance (RR 0.60 [0.35–1.04]), whereas the gestational age-adjusted estimate indicated lower odds (adjOR 0.47 [0.23–0.94]). For severe ROP, DHA+ARA supplementation produced a significant protective effect in both unadjusted and adjusted models (RR 0.56 [0.36–0.86]; adjOR 0.42 [0.19–0.96]). Conclusions When all eligible trials contribute to each endpoint and severe ROP is included as an outcome, enteral DHA+ARA supplementation reduces severe ROP and is associated with lower odds of ROP requiring treatment after adjustment for gestational age. These findings differ from the conclusions of Dang et al . and support reconsideration of DHA+ARA supplementation as a strategy to reduce sight-threatening ROP in preterm infants.

This secondary analysis of a randomized clinical trial examines what risk factors for retinopathy of prematurity are influenced by supplementation with arachidonic acid and docosahexaenoic acid and their interactions with severe retinopathy of prematurity.

BACKGROUND:Supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) to extremely preterm infants reduces the risk of severe retinopathy of prematurity (ROP). The main aim of this study was to explore the involvement of AA:DHA supplementation in the developing gut microbiome, and its possible contribution to the ROP-protective effect. Secondly, additional covariates for microbiome maturation were evaluated. METHODS:Longitudinal gut microbiome profiles and bacterial gene pathways were characterised using shot-gun metagenomics in 75 extremely preterm infants who participated in a randomized clinical trial on AA:DHA supplementation. Serum protein levels quantified using proximity extension assays were merged with the microbiome data. RESULTS:AA:DHA supplementation was linked to an increase in relative abundance of Citrobacter koseri and associated with changes in proteins and metabolic pathways. Occurrence of severe ROP was associated with microbiome alpha diversity (Shannon and Evenness) and beta diversity (Bray-Curtis). Additionally, study centre and gestational age at birth impacted the microbiome composition. CONCLUSION:We conclude that AA:DHA supplementation impacts the microbiome. However, the current study could not determine the causality between the supplementation, microbiome and ROP-decrease. Nonetheless, these findings highlight the complex interplay between external interventions, including nutritional supplements, and the gut microbiome development in extremely preterm infants. IMPACT:Longitudinal gut microbiome profiles, bacterial gene pathways and serum protein expressions were determined using shotgun metagenomics and proximity extension assays in 75 extremely preterm infants included in a multicentre randomized clinical trial investigating enteral fatty acid supplementation. Dynamic shifts in microbiome and pathway composition were seen from birth to 34 weeks gestational age. Arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation was linked to an increase in relative abundance of Citrobacter koseri and associated with changes in proteins and metabolic pathways. However, the causality between the supplementation, microbiome, and ROP-decrease could not be determined.

Importance:Current treatment for type 1 retinopathy of prematurity (ROP), including laser photocoagulation and intravitreal anti-vascular endothelial growth factor therapy, is invasive but necessary to prevent blindness. Experimental evidence and limited clinical experience suggest that topical steroids may reduce disease progression and the need for invasive treatment. Objective:To evaluate whether dexamethasone eye drops reduce the proportion of preterm infants with prethreshold ROP progressing to treatment-requiring type 1 ROP. Design, Setting, and Participants:The DROPROP trial was a double-masked randomized clinical trial at 6 university hospitals and 8 county hospitals in Sweden. It evaluated infants born before 30 weeks' gestational age (GA), from 2022 to 2025, with severe ROP. Data analysis was performed from November 2025 to January 2026. Exposures:Infants were randomized to receive dexamethasone eye drops (1 mg/mL) or placebo (saline). One eye drop was administered every day or every other day for up to 12 weeks. Main Outcomes and Measures:The primary outcome was progression to type 1 ROP requiring invasive treatment. Logistic regression adjusted for GA and site was used for the primary analysis. Intention-to-treat analysis was performed. Adverse events were monitored as safety outcomes. Results:Among 100 infants, the mean (SD) GA at birth was 25.1 (1.4) weeks, 42 (42.0%) were female, and the mean (SD) birth weight was 712.9 (202.1) g. In the intention-to-treat population, type 1 ROP occurred in 10 of 50 infants (20.0%) in the dexamethasone group and 19 of 50 infants (38.0%) in the placebo group (adjusted odds ratio, 0.44; 95% CI, 0.17-1.12; P = .08), corresponding to a relative risk reduction of 47%. In the per-protocol population, type 1 ROP occurred in 9 of 48 infants (18.8%) in the dexamethasone group vs 19 of 49 infants (38.8%) in the placebo group (adjusted odds ratio, 0.40; 95% CI 0.15-1.05). No clinically significant differences in adverse events were observed between groups. Conclusions and Relevance:Timely administration of topical dexamethasone numerically reduced the risk of prethreshold ROP progressing to treatment-requiring type 1 ROP. Although the analysis did not reach statistical significance, these findings suggest that topical dexamethasone may be a safe, noninvasive strategy to reduce the need for invasive treatment. Trial Registration:euclinicaltrials.eu Identifier: 2023-505318-97-00.

Importance Current treatment for type 1 retinopathy of prematurity (ROP), including laser photocoagulation and intravitreal anti–vascular endothelial growth factor therapy, is invasive but necessary to prevent blindness. Experimental evidence and limited clinical experience suggest that topical steroids may reduce disease progression and the need for invasive treatment. Objective To evaluate whether dexamethasone eye drops reduce the proportion of preterm infants with prethreshold ROP progressing to treatment-requiring type 1 ROP. Design, Setting, and Participants The DROPROP trial was a double-masked randomized clinical trial at 6 university hospitals and 8 county hospitals in Sweden. It evaluated infants born before 30 weeks’ gestational age (GA), from 2022 to 2025, with severe ROP. Data analysis was performed from November 2025 to January 2026. Exposures Infants were randomized to receive dexamethasone eye drops (1 mg/mL) or placebo (saline). One eye drop was administered every day or every other day for up to 12 weeks. Main Outcomes and Measures The primary outcome was progression to type 1 ROP requiring invasive treatment. Logistic regression adjusted for GA and site was used for the primary analysis. Intention-to-treat analysis was performed. Adverse events were monitored as safety outcomes. Results Among 100 infants, the mean (SD) GA at birth was 25.1 (1.4) weeks, 42 (42.0%) were female, and the mean (SD) birth weight was 712.9 (202.1) g. In the intention-to-treat population, type 1 ROP occurred in 10 of 50 infants (20.0%) in the dexamethasone group and 19 of 50 infants (38.0%) in the placebo group (adjusted odds ratio, 0.44; 95% CI, 0.17-1.12; P = .08), corresponding to a relative risk reduction of 47%. In the per-protocol population, type 1 ROP occurred in 9 of 48 infants (18.8%) in the dexamethasone group vs 19 of 49 infants (38.8%) in the placebo group (adjusted odds ratio, 0.40; 95% CI 0.15-1.05). No clinically significant differences in adverse events were observed between groups. Conclusions and Relevance Timely administration of topical dexamethasone numerically reduced the risk of prethreshold ROP progressing to treatment-requiring type 1 ROP. Although the analysis did not reach statistical significance, these findings suggest that topical dexamethasone may be a safe, noninvasive strategy to reduce the need for invasive treatment. Trial Registration euclinicaltrials.eu Identifier: 2023-505318-97-00

Objective Sweden has a long-standing tradition of actively managing infants born extremely preterm at 22–23 weeks’ gestational age. This study analyses screening and treatment pathways for retinopathy of prematurity (ROP) in these infants, assessing costs and health outcomes to develop a model of direct healthcare costs.Method and analysis The cohort included all 399 infants born at 22–23 weeks in Sweden (2007–2018) who underwent ROP screening, recorded in the national ROP registry SWEDROP. A health economic model estimated costs based on three primary pathways: (1) no sight-saving treatment, (2) laser as initial treatment and (3) anti-vascular endothelial growth factor (anti-VEGF) as initial treatment. Pathways 2 and 3 were further divided into single and multiple treatments. Costs were calculated using screening frequency, treatment and neonatal care expenses. Register data were verified against medical records. An expanded model incorporated gestational age and comorbidities.Results In the basic model, 36% received laser (16 screenings on average; 32% required retreatment), while 7% received anti-VEGF injections (25 screenings; 69% required retreatment). The cost of screening and treating an infant with laser was Int$ 18 590, compared with Int$ 20 792 for anti-VEGF. The expanded models showed similar screening and treatment frequencies.Conclusion Despite similar overall costs, the higher screening burden in the anti-VEGF group (25 vs 16 screenings) raises concerns regarding cost-effectiveness and potential health impacts. Main limitations include the use of cost data from a single hospital, potential selection bias between treatment groups and limited precision in small subgroups. These findings lay the groundwork for future research on long-term health and cost outcomes in this vulnerable population.

As the survival rate of preterm infants continues to rise worldwide, more infants are at risk of developing sight-threatening retinopathy of prematurity (ROP). Destructive retinal laser treatment and intravitreal injections of anti-vascular endothelial growth factor (VEGF), factor, which have potential systemic side effects, are necessary to prevent blindness in severe cases of ROP. Off-label use in clinical settings suggests that dexamethasone eye drops, 1 mg/ml, may prevent the progression of ROP to severe disease (Type 1 ROP) requiring treatment. Our current study aims to assess the efficacy and safety of timely administered dexamethasone eye drops to reduce the need for laser or anti-VEGF ROP treatment in preterm infants. In a randomized prospective interventional, multi-centre, double-blinded trial, we plan to include 100 infants with severe ROP born before gestational age 30 weeks in Sweden. Infants will be randomized to intervention with dexamethasone eye drops (1 mg/ml) (n = 50) or placebo, saline (n = 50) until either ROP is resolved or severe ROP (Type 1 ROP) development occurs, fulfilling ROP treatment criteria. Eye drops will be administered one drop per day or every other day, depending on the severity of ROP, with a maximum duration of 12 weeks. The primary objective is to evaluate whether dexamethasone intervention reduces the proportion of infants developing Type 1 ROP compared to infants receiving a placebo. Adverse events and potential side effects will be recorded, such as high intraocular pressure and growth restriction. Levels of cortisol in saliva and glucose in urine will be measured repeatedly. Secondary outcomes will include the timing of ROP progression, the recurrence rate after ROP treatment and retinal morphology. An ophthalmological follow-up will be initiated at 2 and 5.5 years of age, evaluating visual acuity, refractive errors, strabismus, retinal morphology and ophthalmological complications. All outcomes in the study will be compared between the infants receiving dexamethasone intervention and those receiving placebo. Timely administration of dexamethasone eye drops may prevent severe ROP from progressing to Type 1 ROP, which requires treatment. This study aims to assess the efficacy and safety of dexamethasone intervention to support its clinical use and national guidelines. EudraCT, 2020–004933-19, registered in January 2021 and CTIS, 2023–505318-97–00, registered in August 2023. Not applicable.

Extremely preterm infants are at risk of immune-mediated complications such as infections and inflammatory conditions like bronchopulmonary dysplasia and necrotizing enterocolitis. Preterm infants are immunologically distinct from term infants at birth, but subsequently undergo adaptive postnatal changes resulting in immunological convergence during their first 3 months. Here, we performed a systems-level analysis of immune development in 72 preterm infants born as early as 22 weeks to investigate factors associated with variation. We find similar immune trajectories during early postnatal immune development but occurring more slowly in infants born at 22-24 weeks. Immune development showed a greater resemblance to that of term-born children in preterm infants fed mother's own milk compared to donor milk. This developmental normalization was manifested by NK cell development and was not explained by differences in microbial colonization between feeding groups, possibly suggesting direct effects of bioactive milk molecules on developing immune cells in extremely preterm infants.

PURPOSE:The Extremely Preterm Infants in Sweden Study (EXPRESS) followed a national cohort of extremely preterm born (EPT, i.e. <27 weeks) children until 12 years of age. This study aimed to investigate the longitudinal development of visual acuity (VA) in children born EPT, explore the predictive value of early visual assessments, and evaluate risk factors for visual impairment at the age of 12 years. METHODS:All 462 children born EPT in Sweden during April 2004-March 2007, and surviving to age 6.5 years, and full-term born matched controls were invited to participate in the 12-year follow-up. VA was assessed at 12 years and the results were compared with values at 2.5 and 6.5 years. RESULTS:At age 12, 332 (72%) EPT survivors and 189 controls were examined. The mean VA in the EPT group was lower than in the control group (1.15, 95%CI [1.12-1.19] vs. 1.33, 95% CI [1.29-1.37]). Fifteen (4.5%) EPT had visual impairment. The examination at age 2.5 failed to identify most of them, while the examination at 6.5 could predict the final visual outcome at 12. Risk factors for visual impairment were low gestational age, moderate and severe intraventricular haemorrhage, treatment-requiring retinopathy of prematurity, cerebral palsy, and cognitive disability. CONCLUSION:In this national cohort, the VA outcome at age 12 was lower in children born EPT than full-term controls. As eye examination at 2.5 years did not reliably identify visual impairment, clinical risk factors should be considered in the screening of children born EPT to early identify the visually impaired.

PURPOSE:To estimate the effect of dexamethasone eye drops on the risk of progression from type 2 retinopathy of prematurity (ROP) to ROP requiring traditional treatments. DESIGN:Register-based cohort study. PARTICIPANTS:Preterm infants born before 30 weeks' gestation from 2015-2018 (control years) and from 2020-2021 (intervention years) registered in the Swedish Quality Register for ROP at 4 Swedish sites were included. In 1 of these sites, the intervention site, topical dexamethasone was introduced during the later period when type 2 ROP was diagnosed. METHODS:The frequency of traditional ROP treatments (laser ablation or intravitreal injection of anti-VEGF) was compared between the 2 periods at sites that had and had not introduced topical dexamethasone during the later period. Analyses were conducted both on infants with severe ROP and on all included infants. The difference-in-differences statistical method was used. MAIN OUTCOME MEASURES:The proportion of infants that required traditional ROP treatment in each group and the interaction odds ratio, adjusted for potential confounding factors. RESULTS:At the intervention site, the incidence of traditional ROP treatment fell from 23/32 (72%) to 4/32 infants (13%; P < 0.001) with severe ROP and from 23/409 (5.6%) to 4/217 screened infants (1.8%; P = 0.03). For the 3 control sites, the equivalent numbers were from 82/175 (47%) to 32/57 infants (56%; P = 0.22) and from 82/950 (8.6%) to 32/441 infants (7.3%; P = 0.38). The difference-in-differences analyses resulted in an adjusted interaction odds ratio of 0.05 (95% confidence interval, 0.01-0.22; P < 0.001) for infants with severe ROP, suggesting a markedly larger decline in occurrence of traditional ROP treatments at the intervention site. CONCLUSIONS:In this population of infants with severe ROP, the introduction of dexamethasone eye drops was associated with a significant reduction in the proportion of infants requiring traditional ROP treatments. A timely administration of low-dose dexamethasone eye drops may serve as a simple, cost-effective, and noninvasive intervention to reduce one of the leading causes of severe visual impairment worldwide. Further studies are needed to confirm our findings. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of pain and sedation management for screening or treatment of retinopathy of prematurity in preterm infants compared to placebo, no intervention, or other interventions.

Retinopathy of prematurity (ROP) with early vessel loss (Phase I) followed by uncontrolled vessel growth (Phase II) causes visual impairment in premature infants. Although supplementation with omega-3 (n-3) docosahexaenoic acid (DHA) alone shows mixed results in preventing ROP, supplementation with both n-3 DHA and n-6 arachidonic acid (ARA) in early postnatal life reduces severe ROP by 50 % (Mega Donna Mega study). In the Mega Donna Mega study, 146 (72.6 %) of 201 included infants had at least one hyperglycemic episode during the first 14 days of life, which is a strong ROP risk factor. We therefore evaluated the protective effects and mechanisms of combined dietary n-3 DHA and n-6 ARA in a neonatal mouse model of hyperglycemia-induced suppression of retinal vascular development (Phase I ROP). At postnatal day (P) 10, retinal vessel growth was improved in pups from mothers on diets enriched with 1 % DHA + 2 % ARA vs. 3 % DHA. Lipid changes in pup plasma and RPE complex (retinal pigment epithelium with choroid and sclera) were in accordance with maternal diets' DHA and ARA levels, indicating that milk lipids reflected maternal diets. Proteomic retinal analysis revealed increased abundances of proteins related to mitochondrial respiration and glucose metabolism with the combined diet. Inhibition of mitochondrial ATP synthase negated the protective effects of the combined diet. In conclusion, combined DHA+ARA oral maternal supplementation protects against hyperglycemia-induced retinopathy in mouse neonates (Phase I ROP model) through enhanced retinal metabolism, suggesting the potential of balanced lipid supplementation for ROP prevention.

ABSTRACT Aim The Extremely Preterm Infant Target Optimise and Prevent (EPITOP) study aimed to develop an ethical and practical approach to biobanking salvaged residual blood samples from extremely preterm infants (< 28 weeks gestational age, GA) for biomarker research while minimising clinical risks and addressing ethical concerns. Methods Initiated in collaboration with Sahlgrenska University Hospital and Biobank Väst, Region Västra Götaland, Sweden, residual blood samples were collected from infants admitted to the neonatal intensive care unit (NICU) from March 2020 to March 2024. Samples were ethically salvaged and biobanked following parental consent and in compliance with Sweden's Biobank Act. Results Among 215 eligible infants (mean (GA) 25.4 weeks), 122 consents enabled the collection of 4238 residual samples, of which 92.5% were from blood gas analyses. Sample collection was highest during the first weeks of life, with a median of 35 samples per infant. A higher number of morbidities and lower GA were both associated with an increase in sample numbers. Plasma and whole blood aliquots were prepared and stored for future biomarker studies. Conclusion The EPITOP study demonstrates the feasibility of ethically biobanking salvaged residual blood samples from extremely preterm infants. This approach minimises clinical risks while supporting biomarker discovery, providing a scalable model for neonatal research.