Search Results (232)

Objective: In addition to hyperoxia, inflammation and infection contribute to the pathogenesis of retinopathy of prematurity (ROP). However, the differential effects of specific bacterial pathogens on ROP development remain unclear. This study aimed to evaluate the association between sepsis due to Gram-positive and Gram-negative bacteria and the development and severity of ROP. Materials and Methods: Infants at risk for ROP, defined as those with birth weight ≤1500 g or gestational age ≤32 weeks, or those with birth weight >1500 g or gestational age >32 weeks who required cardiorespiratory support, were included in this retrospective study. Patients were categorised into no-ROP and any-stage ROP groups, as well as treatment-requiring and non-treatment-requiring ROP groups. The clinical characteristics, laboratory findings, and microbiological data were compared between the groups. Results: Among the 319 enrolled infants, 193 (60.6%) did not develop ROP, whereas 126 (39.4%) developed any-stage ROP. Clinical early-onset sepsis, clinical and proven late-onset sepsis, and increased frequency of late-onset sepsis episodes were significantly associated with any-stage and treatment-requiring ROP (p < 0.05). In multivariate analysis, both Gram-positive (OR 2.36, 95% CI 1.2–4.6, p = 0.012) and Gram-negative bacterial sepsis (OR 3.56, 95% CI 1.5–8.3, p = 0.004) were independently associated with any-stage ROP. In addition, Gram-positive bacterial sepsis (OR 4.4, 95% CI 1.1–16.9, p = 0.031) was independently associated with treatment-requiring ROP. Conclusions: Gram-positive bacterial sepsis was associated with both any-stage ROP and treatment-requiring ROP, whereas Gram-negative bacterial sepsis was associated with any-stage ROP only. These findings support the potential role of pathogen-specific inflammatory processes in ROP development and progression. Further prospective studies incorporating detailed inflammatory and oxygenation parameters are required to clarify these relationships. Full article

The management of retinopathy of prematurity (ROP) has evolved alongside advances in neonatal medicine, shaped by both scientific progress and medico-legal influences. ROP-related medical malpractice lawsuits provide a unique perspective on how standards of care are defined and evaluated. This review comprises two complementary components: a narrative medico-historical review of ROP management and a structured descriptive comparison of judicial cases identified in publicly accessible legal databases in Japan. The aim was to clarify how evolving clinical practice, dissemination of knowledge, and institutional capacity have influenced judicial interpretations of the standard of care. The findings indicate that standards of care in ROP management have been determined not solely by established evidence but by a broader assessment of contemporaneous professional knowledge and clinical practice. A marked shift in judicial outcomes after the mid-1970s corresponded to the widespread adoption of systematic screening and photocoagulation therapy. These results suggest that medico-legal evaluation reflects system-level maturity in neonatal care. In the current era of anti-vascular endothelial growth factor therapy, litigation is likely to focus less on specific interventions and more on the appropriateness of clinical decision-making, consideration of alternatives, and adequacy of informed consent procedures. This review provides a medico-historical framework for improving patient safety, risk management, and quality of care in neonatal practice. Full article

Background: Providing optimal parenteral nutrition to extremely preterm babies in the first week after birth is challenging, and different strategies may be associated with both short- and long-term outcomes. Methods: In a secondary cohort analysis of the ProVIDe trial, a multicentre, randomised, controlled trial in extremely-low-birthweight babies of increased amino acid intake in the first five days after birth, we explored the associations between parenteral amino acid and lipid intakes and blood spot amino acid concentrations, clinical outcomes and neurodevelopment. The cohort comprised 382 babies born in six New Zealand hospitals of whom 342 survived to 28 days. Nutritional intake data in the first week and newborn metabolic screening data on days 1, 5, 14, and 28 were retrieved, and 294 children were assessed for neurodevelopmental outcome at 2 years’ corrected age. Results: Blood spot amino acid concentrations were positively associated with amino acid intake (p < 0.005). Higher amino acid intakes were associated with increased odds (OR), 95% confidence intervals (CIs) of bronchopulmonary dysplasia (tyrosine: OR 2.2, CI 1.2–3.9; proline: OR 2.3, CI 1.3–4.0), patent ductus arteriosus and probable sepsis. No significant associations were found for necrotising enterocolitis. Higher lipid intakes were associated with lower odds of intraventricular haemorrhage (0.33 [0.16, 0.66]), bronchopulmonary dysplasia (0.31 [0.13, 0.73]) and retinopathy of prematurity (0.29 [0.12, 0.72]). Unlike short-term outcomes, neurodevelopment did not differ according to blood spot or intake quartile for any amino acid in week 1. Conclusions: Parenteral nutritional intakes in the first week after birth are associated with short-term outcomes. Further research is needed to optimise the composition of amino acid solutions. Trial Registration: ACTRN12612001084875, (accessed on 10 October 2012). Full article

Retinopathy of Prematurity (ROP) affects preterm infants worldwide, involving abnormal development of retinal blood vessels associated with supplemental oxygen use in neonatal care. Although there have been strides in identifying at-risk infants, implementing early screening, updating disease criteria through the International Classification of Retinopathy of Prematurity (ICROP), and developing new therapies, ROP remains a leading cause of preventable blindness. As preterm birth survival rates rise, the incidence of ROP continues to increase and is projected to rise even in countries with abundant resources and well-established care programs. Improving ROP care requires global standardization of screening, diagnosis, and management to prevent missed diagnoses and minimize outcome variability. Intravitreal anti-vascular endothelial growth factor (VEGF) injections are changing the landscape of ROP management, but longitudinal research is needed to determine their long-term safety in preterm infants. Effective ROP management relies on teamwork across disciplines and open communication with parents. Given that parents are lifelong caregivers of a child who may be affected by ROP-related vision impairment, including them in the care team and encouraging psychosocial support is vital. Socioeconomic disparities and limited access to ROP-trained ophthalmologists exacerbate disease burden, underscoring the need for innovative solutions to improve access to care. This perspective emphasizes the importance of globally standardizing ROP prevention and care, noting that efforts are still incomplete, equitable access has not been realized, and the long-term role of anti-VEGF agents in ROP treatment remains unclear. Full article

Background/Objectives: To compare long-term refractive and anterior segment outcomes among preterm infants with retinopathy of prematurity (ROP) who underwent laser photocoagulation (LP), untreated preterm infants, and term-born controls. Methods: This study included 285 eyes of 144 patients aged 6–10 years, categorized into three groups: LP-treated type 1 ROP (Group 1), untreated preterms without type 1 ROP (Group 2), and full-term controls (Group 3). Data were collected, including birth weight (BW), gestational age (GA), ROP status, LP parameters (if required), as well as all ophthalmologic findings. Corneal tomography assessed keratometry, corneal thickness, corneal volume, anterior chamber metrics, and keratoconus indices. Optical biometry evaluated axial length (AL), keratometry, astigmatism (Ast), and anterior chamber depth (ACD). Cycloplegic autorefractometry measured spherical equivalent (SE), astigmatism (KAst), and keratometry. Results: Among 144 patients (63 female, 43.8%), the mean age was 8.7 ± 1.2 years, with a median GA of 34 weeks and BW of 2165 g. Significant differences were observed in corneal tomography parameters (Kh, Kv, Km, Kmax, astigmatism, and thickness metrics, p < 0.001), keratoconus indices (p < 0.001), optical biometry (AL, lens power, and ACD, p < 0.001), and cycloplegic autorefractometry (astigmatism and keratometry, p < 0.001) among the three groups. Refractive errors, including myopia and astigmatism, were most pronounced in laser-treated ROP cases (p < 0.036 and p < 0.001, respectively). Conclusions: Children with laser-treated ROP had steeper and thinner corneas, higher posterior astigmatism, and shallower ACD than preterm and term-born children. These findings likely reflect developmental anterior segment differences related to prematurity and treatment-requiring ROP, supporting careful long-term ophthalmologic follow-up. Full article

Background: The first 1000 days of life, from conception to 2 years of age, represent a critical window during which nutrition can exert long-lasting effects on neurodevelopment, immune maturation, and susceptibility to prematurity-related morbidity. Docosahexaenoic acid (DHA) is a key structural n-3 long-chain polyunsaturated fatty acid of the brain and retina, characterized by rapid fetal accretion during the third trimester. Methods: We conducted a narrative review of studies published from March 2015 up to December 2025, including randomized controlled trials, follow-up studies, and systematic reviews/meta-analyses about DHA supplementation during pregnancy, lactation, infancy and early childhood, and its role on development. Results: Across the first 1000 days, DHA supplementation improves biochemical DHA status, particularly in populations with low baseline levels (moderate to high level of evidence), while clinical outcomes remain heterogeneous. During pregnancy, some benefits in specific cognitive and behavioral domains have been demonstrated, whereas effects on global cognition and long-term behavior are frequently null (moderate evidence). Visual outcomes appear favorable, with improvements in visual acuity (moderate evidence). In preterm infants, enteral DHA—often combined with arachidonic acid (ARA)—is feasible and well tolerated. DHA may reduce inflammatory markers and necrotizing enterocolitis risk when in equilibrium with ARA (low to moderate evidence), while no evidence supports the link between DHA and reduced risk of bronchopulmonary dysplasia and retinopathy of prematurity (moderate evidence). Neurodevelopmental outcomes are mixed: neuroimaging studies suggest enhanced white matter maturation with DHA + ARA, whereas most trials show no clear benefit regarding standardized developmental scores (moderate evidence). Conclusions: DHA is biologically essential during the first 1000 days, but its clinical impact depends on timing, dose, baseline status, and prematurity-related context. The balance between DHA and ARA, rather than DHA supplementation alone, emerges as a key determinant of clinical efficacy, supporting a shift toward precision-based nutritional strategies in early life. Full article

Background/Objectives: We aimed to evaluate the association between diabetes mellitus (DM) during pregnancy and retinopathy of prematurity (ROP) in preterm infants younger than 32 gestational weeks or infants with low birthweight (<1500 g). Methods: We conducted a retrospective nested case–control study of all premature infants who were born alive and survived the post-delivery hospitalization period in Soroka Medical Center, with either gestational age younger than 32 weeks or birthweight less than 1500 g, during the years 2013–2021. The infants were divided into two groups according to ROP status. Multivariable Generalized Estimating Equations (GEE) were used to analyze the association between ROP and DM, adjusting for potential confounders, including maternal age, diabetes type (GDM vs. pre-gestational DM), gestational age, birthweight (<1250 g), duration of oxygen supplementation, antenatal corticosteroid courses, and birth plurality. Results: During the study period, there were 881 pairs of women and newborns who met the inclusion criteria. The ROP group included 345 infants (39.1%). Twenty-two (6.4%) of the mothers in the ROP group were diagnosed with DM during pregnancy compared with 52 of 536 (9.7%) in the control group (p = 0.082). ROP was associated with oxygen treatment (OR 1.05; 95% CI, 1.03–1.08; p < 0.001), birthweight < 1250 g (OR 2.70; 95% CI, 1.93–3.78; p < 0.001) and advanced maternal age (OR 1.04; 95% CI, 1.01–1.06; p = 0.006). Prenatal steroid treatment was identified as a significant protective factor against ROP (OR 0.73; 95% CI, 0.60–0.89; p = 0.002). No statistically significant association was observed between maternal DM and ROP (OR 0.62; 95% CI 0.34–1.13; p = 0.12). These findings should be interpreted cautiously given the retrospective design and the limited availability of glycemic control data. Conclusions: Maternal diabetes mellitus was not significantly associated with the risk of ROP in this cohort. Full article

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness characterized by disrupted physiologic vascularization followed by pathologic neovascularization, classically organized around the insulin-like growth factor-1 (IGF-1)–vascular endothelial growth factor (VEGF) axis in the retina. Increasing evidence suggests that early-life gut dysbiosis may act as an upstream modifier of this biphasic process. In this review, we synthesize human cohort studies, multi-omics analyses, and experimental animal models examining associations between the neonatal gut microbiome and ROP. Preterm infants who develop severe ROP demonstrate enrichment of facultative anaerobes and reduced acquisition of obligate anaerobes, alongside altered predicted metabolic capacity. Microbiome-derived metabolites, including short-chain fatty acids, bile acid derivatives, and lipid mediators, have been shown in experimental systems to influence systemic IGF-1 production, hypoxia-inducible factor-1α stabilization, and VEGF signaling. Rodent oxygen-induced retinopathy models offer a translation framework to assess the functional link between microbial perturbation and retinal angiogenic responses. Collectively, these findings support a conceptual microbiome–IGF-1–VEGF–retina axis in which early intestinal dysbiosis may modulate inflammatory tone, metabolic signaling, and retinal vascular development. Although current evidence remains largely associative, integrating microbiome profiling with mechanistic and longitudinal studies may clarify potential causal pathways and identify novel biomarkers or preventive strategies for severe ROP. Full article

Purpose: This study aimed to comprehensively map the structural impacts of ROP on all ocular structures, including and extending beyond the inner retina and the associated long-term sequelae that manifest into adulthood. Methods: This scoping review identified studies on animal oxygen-induced retinopathy and clinical retinopathy of prematurity using a multi-database search. Study selection and data extraction were performed independently by multiple reviewers using Covidence software. Results: ROP results in lasting ocular complications. Posterior segment findings include choroidal insufficiency, photoreceptor dysfunction, and retinal detachment. Anterior segment complications involve a higher incidence of angle-closure glaucoma, strabismus, and significant myopia. Conclusions: This scoping review was conducted and reported in accordance with the PRISMA-ScR guidelines, though it is limited by the exclusion of non-English studies. Lifelong ophthalmic monitoring is essential for ROP patients due to persistent anterior and posterior segment complications. This study also identifies key future research priorities, including elucidating mechanisms of foveal development and conducting longitudinal studies. Furthermore, as neonatal intensive care expands in low and middle-income regions, international collaboration is vital to guide screening and treatment and prevent a debilitating surge of ROP. Full article

Surgical necrotising enterocolitis (NEC) continues to carry significant morbidity and mortality in preterm and very-low-birth-weight infants. This review presents up-to-date evidence to guide the shift from medical to surgical treatment and to improve management during and after surgery. Need for surgery is best anticipated through dynamic clinical assessment, supported by laboratory markers of systemic inflammation or ischemia and targeted imaging, while pneumoperitoneum remains the sole absolute indication for immediate intervention. In infants without perforation, the timing of surgery remains challenging: delayed surgery after clinical deterioration worsens long-term outcomes, whereas very early surgery often reflects severe disease leading to greater bowel loss, highlighting the need for carefully timed intervention after brief stabilisation. Laparotomy remains the cornerstone of surgical management, with peritoneal drainage serving as a temporising option for the most unstable infants and laparoscopy emerging as a feasible adjunct. Long-term complications, including strictures, short bowel syndrome, neurodevelopmental impairment, bronchopulmonary dysplasia and severe retinopathy of prematurity highlight the need for better predictive tools, enhanced imaging of bowel viability, and rigorous nutritional support, while long-term quality-of-life outcomes remain insufficiently studied. Full article

Background: Neonatal hyperglycemia is a common metabolic complication in extremely preterm (EP) infants; however, early risk factors and associated outcomes remain incompletely defined. Objective: To evaluate the association between neonatal hyperglycemia in the first postnatal week and key neonatal morbidities including early neurodevelopmental risk in EP infants. Methods: We conducted a retrospective cohort study of EP infants born in 2018–2019 at the Women’s Wellness and Research Center. Neonatal hyperglycemia was defined as a blood glucose level > 8.3 mmol/L. Maternal factors, delivery room interventions, early physiological markers, neonatal morbidities, and follow-up outcomes were compared. Propensity score matching was applied to balance the baseline demographic and perinatal differences. Results: Among 225 EP infants, 131 (58.2%) developed neonatal hyperglycemia in the first week (mild, 21.4%; moderate, 42%; severe, 36.6%). Before matching, infants with neonatal hyperglycemia had lower gestational age and birth weight and required more delivery-room surfactant, and their mothers had lower rates of premature rupture of membranes. After matching, neonatal hyperglycemia was associated with higher rates of ventilator-associated pneumonia (1.45 vs. 0.37; IRR 6.2, 95% CI 1.4–27.6), longer duration of invasive ventilation (19.8 ± 25.3 vs. 8.9 ± 24.8 days; mean difference −10.9 days; p = 0.042), higher postnatal steroid exposure (18.2% vs. 5.5%; OR 4.6, 95% CI 1.6–14.4; p = 0.040), and severe retinopathy of prematurity (ROP) (21.6% vs. 6.4%; OR 4.0, 95% CI 1.0–15.5; p = 0.032). A trend toward moderate-to-severe bronchopulmonary dysplasia was observed (33.3% vs. 15.9%; p = 0.054). Mortality did not differ significantly between groups; however, among non-survivors, age at death was higher in the neonatal hyperglycemia group. Conclusions: In EP infants, early neonatal hyperglycemia is associated with higher respiratory morbidity and severe ROP even after propensity score matching. These findings support neonatal hyperglycemia as a clinically relevant early risk marker and justify further prospective and interventional studies. Full article

Background: Aflibercept is one of the anti-VEGF drugs used, among others, for the treatment of retinopathy of prematurity, alongside the widely used bevacizuab and ranibizumab. It is a recombinant fusion protein composed of the human VEGFR-1 and VEGFR-2 domains combined with the Fc part of human IgG, called VEGF-TRAP. The paper describes a group of premature infants treated with aflibercept due to retinopathy of prematurity at the Regional Specialized Children’s Hospital in Olsztyn, Poland, in the years 2017–2019. Methods: Eleven children (22 eyes) with extremely low birth weight and type 1 ROP and A-ROP qualified for treatment. The birth weight of the children was 460–940 g (average 677 g). Children were treated between 32 and 38 weeks of postconceptional age (on average in 33.3 week). We administered 1 mg (0.025 mL) of aflibercept intravitreal to each eye under local anesthesia. Results: In all cases, the retinopathy regressed. Between 2 and 7 weeks after treatment, the disease reactivated in five children (45%) in the form of ROP type 2, and these children underwent retinal laser photocoagulation. One child had a complication in the form of a cataract in one eye, while the remaining children had no complications after the injection and laser therapy. In all children, there was complete regression of ROP, and retinal vascularization was observed up to the end of zone III or up to the border of laser therapy. A child with cataract underwent lensectomy. All children are under the care of our center, and were examined ophthalmologically and strabologically; the results of these tests will be presented in a separate study. Conclusions: Aflibercept differs from other anti-VEGF drugs in its point of action and pharmacodynamics of action. In the literature, its effectiveness is estimated at over 80%, but there are also studies in which the reactivation of ROP after treatment reaches over 40%. In this study, the treated children were characterized by extremely low birth weight and, as a result, numerous complications related to prematurity occurred, such as bronchopulmonary dysplasia, sepsis, anemia, heart defects, and others. Many of them were in the intensive care unit. These factors may influence ROP reactivation and complications. The description compares studies in which aflibercept was administered at the same dose—1 mg. Currently, large studies (e.g., Firefleye and Butterfleye) describe the effects of a new aflibercept therapy at a dose of 0.4 mg. Studies on aflibercept obviously require further observations, so all reports, even from small groups, are important. Full article

Objective: To compare respiratory outcomes between infants undergoing retinopathy of prematurity (ROP) laser treatment with or without elective intubation. Study Design: This retrospective cohort study analyzed preterm infants treated by the same pediatric ophthalmologist at two tertiary hospitals between January 2010 and March 2023, Hospital 1 (No-endotracheal tube or ETT intubation) and Hospital 2 (ETT intubation). Infants intubated for unrelated reasons or treated with only anti-vascular endothelial growth factor (VEGF) injections were excluded. Data collected included demographics, comorbidities, ROP stage, and respiratory outcomes. Results: Among 91 infants (61 No-ETT, 30 ETT), the No-ETT group had significantly lower birth weight and had more Black infants. The mean duration of mechanical ventilation post-surgery was significantly shorter in the No-ETT than in the ETT cohort (0 vs. 1 days, p = 0.005), and the total respiratory support (both invasive and non-invasive) after surgery was significantly longer in the No-ETT than in the ETT cohort (108 vs. 4.5 days, p < 0.001). No statistically significant differences were observed between groups in terms of length of hospital stay after surgery. The two cohorts demonstrated similar clinical trajectories with respect to overall length of hospital stay, day of life at which laser surgery was performed, and multiple comorbidities. Over 90% of No-ETT infants tolerated the procedure without requiring elective intubation, with emergent intubation only occurring 9.8% of the time. Conclusions: Elective intubation during ROP surgery was associated with a longer length of post-surgery mechanical ventilation without clear improvements in short-term outcomes. Similar rates of multiple comorbidities, hospital length of stay, and timing of laser surgery suggest there is no associated clinical advantage to routine elective intubation. Routine elective intubation may be unnecessary for most infants during ROP laser surgery. Full article

Background/Objectives: The retina is enriched in polyunsaturated fatty acids (PUFAs) which are indispensable for normal vision, and recent clinical studies have shown that dietary supplementation of ω-6-and ω-3-polyunsaturated fatty acids (PUFAs) can provide a protective role against retinopathy of prematurity (ROP). Our study aims to understand the mechanisms by which altering ω-6-and ω-3-polyunsaturated fatty acids (PUFAs) in the eye can protect against pathologic retinal neovascularization (NV). Methods: We interrogated the effects of endogenous ω-3-PUFA enrichment using transgenic fat-1 mice which convert ω-6-PUFAs to ω-3-PUFAs in the oxygen-induced retinopathy (OIR) murine model. In the OIR model, mice are exposed to 75% oxygen from postnatal day 7 (P7) to P12, then returned to room air (RA). We used a combination of immunofluorescence, bulk retinal RNA sequencing, and lipid mediator profiling by UHPLC-MS/MS in P17 mouse retinas to identify mechanisms underlying the protective effect against NV seen in fat-1 mice exposed to OIR. Results:Fat-1 OIR mice were protected against the development of retinopathy, demonstrating 15.1% less vaso-obliteration (75.5% relative reduction) after OIR and a 6.1% reduction in neovascularization (71.8% relative reduction) at P17 (p < 0.0001 for both). We found a dampened transcriptional response to OIR in the retina of fat-1 mice as compared to WT mouse retinas (198 vs. 782 genes, adjusted p-value < 0.01). Pathway analyses confirmed these findings, with significant OIR-induced transcriptional shifts in angiogenesis (adjusted p-value < 10⁻²⁷), inflammation (adjusted p-value < 10⁻²⁵), and microglial activation pathways (adjusted p-value < 10⁻⁹) in WT mouse retina that were not observed in fat-1 mice. Enrichment scores obtained through the integration of our bulk transcriptomics data with cell-resolved retina data indicate that the protective phenotype observed in fat-1 mice could be associated with intrinsic differences in microglia cell subtypes between WT and fat-1 mice. In situ, WT OIR mice demonstrated an increase in Iba1+ microglia compared to WT RA mice, whereas fat-1 OIR mice showed no difference when compared to fat-1 RA mice. Three ARA-derived oxylipins, 12-hydroxyeicosatetraenoic acid (12-HETE), prostaglandin D2 (PGD2), and thromboxane B2 (TXB2) demonstrated a pattern of upregulation in WT OIR compared to WT RA, but no upregulation in fat-1 OIR mice compared to fat-1 RA. Two EPA-derived specialized pro-resolving mediators and two LA-derived oxylipins were also differentially expressed. Conclusions: These findings show that a lower ω-6:ω-3 protects against neovascularization and is associated with attenuation of hyperoxia-induced microglial recruitment and activation, as well as inflammation and angiogenic signaling. Full article

Background: ROP Check^® monitoring and documentation software from 28 American hospitals collected clinical data from 2010 to 2024 representing infants from a wide range of races and ethnicities. Methods: De-identified data compared gender to treatment status, race, birthweight (BW), gestational age (GA) and gestational age at first treatment. Results: From 7070 total patients, with 5060 having timely or early initial exams based on American Academy of Pediatrics (AAP) guidelines, 386 had treatment for ROP. Males constituted 54.3% of treated infants and 54.4% of all infants. There was no gender difference in gestational age or age at treatment, but males had greater birthweights (685 to 610 g). There were more females treated under 600 g. There were race-related birthweight differences in infants treated for ROP. Conclusion: There are more males screened and treated for ROP, but treatment rates are similar for both genders. Male preponderance reverses for infants with birthweight less than 600 g. Race has an influence on treated ROP. Full article