Culture-negative sepsis (CNNS) constitutes a significant proportion of neonates admitted to the NICU. However, the outcomes and factors influencing antimicrobial therapy in this group remain understudied. We prospectively enrolled preterm neonates (<34weeks' gestation) with clinical features of sepsis, with or without sepsis screen positive results. Primary outcome was a composite of death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity requiring treatment, Intraventricular haemorrhage ≥ 2 and periventricular leukomalacia. Details of antimicrobial therapy were also collected. Over an 18-month period, 172 neonates were enrolled. 104 had CNNS and 68 had culture-positive sepsis (CPNS). Primary outcome was observed in 19 (18.3%) neonates with CNNS and 25 (36.8%) with CPNS, with an adjusted odds ratio (aOR) of 0.50 (95% CI: 0.22-1.12, p = 0.095). Except for BPD, which was significantly lower in CNNS (aOR: 0.10; 95% CI: 0.02-0.52, p = 0.006), there was no statistically significant difference in other outcomes between groups. Multidrug-resistant organisms comprised 67.6% of the gram-negative bacterial isolates. Median (IQR) cumulative duration of antibiotic therapy was 5 (3-7) days in CNNS and 20.5 (15-24.3) days in CPNS. Prolonged cumulative antibiotic use was observed in 50 (48%) CNNS neonates (>5days) and 50 (73.5%) CPNS neonates (>14days). In CNNS group, 38 (36.5%) received second-line antibiotics, and 6 (5.7%) received third-line antibiotics. In preterm neonates, composite outcome of mortality and major morbidities did not differ significantly between those with CNNS and CPNS. However, a considerable proportion of CNNS neonates received a prolonged course of higher antibiotics. Thus, there is a need for strategies to improve clinical outcomes and strengthen adherence to antibiotic stewardship principles.

Retinopathy of prematurity (ROP) is an eye disease that affects premature infants. Early diagnosis is important to prevent vision loss and enable timely intervention. The work aims to develop a deep learning based automated ROP detection and classification pipeline from a large retinal image dataset. A dataset of 400 GB containing retinal fundus images was obtained from Narayana Nethralaya, Bengaluru, India. Both blood vessel and ridge feature segmentation were performed using a U-Net model. Gabor enhanced retinal images were used for ridge segmentation, while original retinal images were used for blood vessel segmentation as original images preserve critical vascular features. The segmented ridge and blood vessel masks were superimposed on sigmoid-enhanced retinal images and used as input to a ResNet50 classifier. The aim of this pipeline was to preserve the most prevalent disease features to facilitate in the stage wise classification of ROP. The pipeline achieves an accuracy of 98.40% in detecting ROP and 92.80% in staging ROP. This method improves image-based ROP screening by effectively identifying critical disease features. The results of this automated pipeline demonstrate its potential in supporting an early detection of ROP with high accuracy and efficiency. The integration of deep learning models such as U-Net and ResNet50 during the screening process helps support clinical decision making and advances neonatal ophthalmology practice.

Evaluating the G-ROP criteria sensitivity for type 1 ROP in a North American cohort.

<scp>EBNEO</scp> Commentary: Cord Blood Red Cell Transfusions and Severe Retinopathy of Prematurity in Preterm Neonates

Twin pregnancies contribute disproportionately to neonatal morbidity and mortality, primarily due to preterm birth and very low birth weight (VLBW). While studies have yielded conflicting findings on VLBW twins versus singletons, limited research exists in Ireland. This study examines whether survival, neonatal characteristics, and outcomes differ between VLBW twins and singletons in a national cohort. A secondary analysis was conducted using anonymised data from the National Perinatal Epidemiology Centre (NPEC) VLBW audit. The study included all liveborn VLBW infants (401-1500g and/or 22 + 0 to 29 + 6weeks' gestation) from singleton and twin pregnancies in Ireland between 2014 and 2022. Maternal and neonatal characteristics were compared using descriptive statistics. Chi-square and t-tests assessed group differences. Poisson regression computed crude and adjusted relative risks (RR). Of 4766 infants, 29% (n = 1380) were twins and 71% (n = 3386) singletons. Twins were born at higher gestational age (28.38 vs 27.9weeks, p < 0.001) and had higher birth weight (1087.76g vs 1059.66g, p = 0.006). Mortality was lower in twins (15.6% vs 18.9%, p = 0.014), but not after adjustment. Adjusted analyses showed higher risk in twins for delivery room death (RR 1.45, p = 0.013) and severe retinopathy of prematurity (RR 1.47, p = 0.047). Although VLBW twins appeared to have better crude outcomes than singletons, adjusted analyses showed broadly comparable survival and morbidity, with specific vulnerabilities. These findings reinforce that twins remain a high-risk population requiring intensive surveillance and proactive management. They also highlight the importance of structured models of care and support the need for updated national guidelines in Ireland to optimise outcomes for both groups.

Background/Objectives: Premature births below 32 weeks of gestation generally require respiratory oxygen support, leading to a relatively hyperoxic environment compared to in utero conditions. Transient hyperoxia exposure has been linked to an elevated risk of chronic lung disease and retinopathy of prematurity; however, its effects on skeletal muscles remain elusive. This study aimed to investigate the effects of hyperoxic exposure in rats as a model of premature infants receiving supplemental oxygen (30–60% O2 for several weeks). We hypothesized that rats exposed to postnatal hyperoxia would exhibit muscle fiber atrophy and alterations in fiber type. Methods: We used a rat model in which newborns were exposed to 80% oxygen from birth until postnatal day 12. We assessed the gastrocnemius muscles of rat legs at 12 weeks. Results: Rats exposed to hyperoxia showed substantially increased protein expression of Atrogin-1, along with elevated levels of adipophilin, myogenic differentiation factor 1, and myogenin. No significant changes were observed in the expression of slow or fast myosin heavy chain proteins. However, myofiber size in the gastrocnemius muscle was reduced in the hyperoxia-exposed group compared to the control group. Conclusions: Thus, transient hyperoxia exposure during early life can impede skeletal muscle development, potentially extending into adulthood.

To investigate whether postnatal haemoglobin oxygen affinity (P50), derived from serial arterial blood gases, is associated with the risk of retinopathy of prematurity (ROP) in preterm infants, as a potential physiologic marker. Retrospective cohort study. This study included 232 preterm infants born < 32 weeks gestation. Haemoglobin P50 and lactate values were calculated daily during the first week of life. The primary outcome was the development of any ROP; treatment-requiring (Type 1) ROP was a secondary endpoint. Associations were analysed using logistic regression and ROC analysis. Infants who developed ROP had significantly higher Day 7 P50 values (mean 26.9 ± 1.8 mmHg) than those without ROP (26.1 ± 1.7 mmHg; p = 0.003). A Day 7 P50 > 26.4 mmHg was independently associated with ROP (OR 2.5; 95% CI 1.3-4.9), though predictive performance was modest (AUC 0.60). Lactate levels showed no association with ROP. P50 was not predictive of Type 1 ROP. Increased postnatal P50 may be modestly associated with ROP development, reflecting impaired oxygen delivery during early retinal vascularization. While not suitable for screening, P50 may serve as a physiologic marker warranting further mechanistic investigation.

To develop prediction models for retinopathy of prematurity (ROP) recurrence after initial intravitreal injection of ranibizumab (IVR) or laser photocoagulation (LP). This multicenter retrospective cohort study included infants with aggressive posterior ROP (AP-ROP) and type-I ROP. Recurrence was defined as the reappearance of vascular dilation, tortuosity, or new/recurrent neo-vascularization in either eye of infants. The recurrence rates within 6months after initial treatment were compared. Machine learning (i.e., extreme gradient boost, categorical boost, adaptive boost, and random forest) and multivariable logistic regression were performed to identify risk factors and establish individualized prediction models for ROP recurrence. Area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were used to evaluate the performance of the prediction models. A total of 440 infants were included, with a mean gestational age (standard deviation [SD]) of 28.2 (2.4) weeks and birth weight (SD) of 1.1 (0.4) kg. ROP recurrence occurred in 62 of 344 (18.0%) infants after IVR treatment, while 7 of 96 (7.3%) infants after LP treatment required additional treatment (P < 0.05). Neonatal pneumonia, respiratory distress, septicemia, 5-min Apgar scoring, AP-ROP, and maternal uterine infection were significantly associated with the risk of ROP recurrence (all P < 0.05). The Categorical Boost model achieved the best overall performance. The mean AUC, accuracy, sensitivity, and specificity were 0.96 (95% confidence interval [CI] 0.93-0.99), 85.9% (95% CI 80.3-91.5%), 94.7% (95% CI 89.6-99.8%), and 77.0% (95% CI 67.4-86.6%) on the validation dataset, and 0.94 (95% CI 0.89-1.00), 84.1% (95% CI 77.1-93.2%), 95.5% (95% CI 89.8-100%), and 72.7% (95% CI 59.6-85.5%) on the testing dataset, respectively. This study presents a simple, rapid, and reliable predictive strategy for early identifying infants at high risk of ROP recurrence after initial treatment, which is potentially useful in improving the success rate of retreatment and reducing blindness resulting from ROP.

Asymmetric Retinopathy of Prematurity in Setting of Cutaneous Capillary Hemangioma.

Retinopathy of prematurity (ROP), an oxygen-induced retinopathy (OIR), triggers a series of vascular lesions and inflammatory responses and results in visual impairment or even blindness. Triptolide (TP) possesses many pharmacological properties, including immunosuppressive and anti-tumour effects. However, the effects of TP on ROP and its underlying mechanisms remain unclear. To investigate whether TP could inhibit the progression of OIR and to elucidate its underlying mechanisms. The 7-day-old mice (P7) were kept in a 75% hyperoxia incubator for 5 days to induce an OIR model, followed by TP treatment for 5 days. Biomedical analysis and histopathological examinations of harvested retinas were conducted to explore the effect of TP. Furthermore, the impact of TP on retinal neovascularisation and microglial activation was validated using human umbilical vein endothelial cells (HUVECs) and human microglial clone 3 cells (HMC3s). TP treatment could significantly alleviate retinal pathological neovascularisation by inhibiting microglial activation. It downregulated the elevated levels of inflammatory cytokines (inducible nitric oxide synthase, tumour necrosis factor-α, Cox2 and interleukin (IL)-1β) and angiogenesis-related factors (hypoxia-inducible factor-1α, matrix metalloproteinase-2 and vascular endothelial growth factor-A) in OIR retinas and hypoxic HMC3s. HUVECs' migration, proliferation and tube-forming capacities were also markedly suppressed under TP treatment. Further analysis suggested that TP exerted its anti-angiogenic effect in a way similar to NF-κB inhibitor (BAY117082). TP alleviates pathological neovascularisation in OIR, potentially through the inhibition of inflammation mediated by NF-κB pathway.

Infographic: early treatment with laser photocoagulation for retinopathy of prematurity (ETROP Study).

BackgroundThe predominant risk factors and outcomes of ROP in neonates with more than 34 weeks of gestation are not well described in low- and middle-income countries despite higher incidence of ROP in these neonates.ObjectivesTo determine the incidence and risk factors of ROP in neonates between 34 weeks and 38 weeks 6 days.Material and MethodsWe conducted a prospective observational study in a tertiary care paediatric hospital from January 2020 to June 2021. Neonates with gestational age between 34 and 38 weeks 6 days were included. Standardized screening protocols were adapted, with data on demographic characteristics, risk factors, ROP findings, and treatment collected systematically.ResultsAmong 267 neonates, 224 underwent ROP screening. Fifteen (6.7%) neonates had any ROP, with 6 (2.6%) having Type I ROP requiring treatment. Among the cohort, higher proportions of late preterm neonates had ROP 12 (8.5%) compared to early term neonates 3 (3.6%) and amongst the neonates who required treatment, 6 (2.6%) all were late preterm neonates. Significant risk factors for ROP development included being small for gestational age [12 (80%) versus 58 (28%), p < 0.01], postnatal weight gain [Mean Difference: 9.8 gm/kg/day; 95% CI, 6.7 - 13.0, p < 0.001] and associated comorbidities such as respiratory support [15 (100%) versus 128 (61%), p < 0.01], shock [13 (86.7%) versus 118 (56.5%), p < 0.01] and sepsis [3 (20% vs 22 (10%); p < 0.01].ConclusionsOur study supports extending ROP screening to neonates ≥34 weeks with growth restriction or comorbidities, particularly in low- and middle-income settings.

To evaluate the effectiveness of deep learning (DL) algorithms in diagnosing Retinopathy of Prematurity (ROP) cases that requires treatment using fundus images submitted to the ROP clinic as part of a telemedicine consultation system. This retrospective cross-sectional study analysed 1700 RetCam fundus images from 141 preterm infants screened for ROP at Khatam-Al-Anbia Eye Hospital. The images underwent preprocessing using Contrast Limited Adaptive Histogram Equalisation (CLAHE), Automated Multiscale Retinex (AMSR), and a machine learning-based optimisation approach (ML). Various convolutional neural network (CNN) models such as MobileNet, ResNet-18, ResNet-50, and DenseNet-121, were evaluated for their diagnostic performance utilising accuracy, sensitivity, specificity, and F1-score metrics. Among the models tested, MobileNet with CLAHE preprocessing achieved the highest accuracy (91.39%) and sensitivity (94.90%), establishing it as the most effective model for ROP detection. DenseNet-121 with CLAHE preprocessing showcased high sensitivity (94.26%) but slightly lower accuracy (90.98%). Additionally, ResNet-50 with AMSR preprocessing also demonstrated high accuracy (90.58%) and sensitivity (91.44%). These findings underscore the feasibility of DL models for real-time ROP screening in telemedicine environments. MobileNet with CLAHE preprocessing exhibited the highest diagnostic performance in identifying treatment-requiring ROP, positioning it as a promising tool for AI-assisted screening. Further validation in varied clinical settings is necessary to confirm its real-world applicability.

To evaluate the long-term structural and functional ocular outcomes in school-aged children with ROP treated by laser photocoagulation, and to compare them with those of term-born controls. This retrospective cohort study included premature children treated with laser photocoagulation for type 1 ROP, leading to regression without progression to advanced stages, and followed up to school age at a single tertiary center. Age- and sex-matched term-born controls were selected. Retinal and choroidal structures were assessed using SS-OCT, and retinal vascular tortuosity was quantified based on fundus photographs obtained during follow-ups conducted between ages 6 and 14 years. Overall, 23 treated ROP children (45 eyes) and 50 term-born controls (100 eyes) were included. Mean age at examination was 8.83 ± 2.53 years for the ROP group and 9.54 ± 1.79 years for controls. Spherical equivalent did not differ significantly between groups (ROP vs. control; -2.05 ± 3.12 vs. -1.55 ± 1.31, p = 0.307) but treated ROP children had significantly lower vision (ROP vs. control; logMAR 0.16 ± 0.13 vs. 0.08 ± 0.12, p < 0.001). Retinal vascular tortuosity was significantly higher in the ROP group (1.163 ± 0.091 vs. 1.073 ± 0.036, p < 0.001), and SS-OCT measurements revealed statistically significant retinal thickening at central foveal and parafoveal regions. No significant choroidal thinning or differences in choroidal vascularity index was observed (p = 0.918 and p = 0.827, respectively). A negative association was observed between gestational age and central foveal thickness (p = 0.048) and between birth weight and retinal vascular tortuosity (p = 0.001). Central foveal thickness negatively correlated with gestational age and tortuosity with BW. Lower vision was significantly associated with increased retinal vascular tortuosity but not with OCT-derived retinal or choroidal metrics. School-aged children treated with laser photocoagulation for ROP showed increased retinal vascular tortuosity and thickness in the central foveal to parafoveal regions, while choroidal thickness and vascularity remained unchanged in the central 1500μm zone on SS-OCT device. These findings suggest localized retinal changes with preserved choroidal integrity.

To determine rates of active approach, mortality, and morbidity for periviable infants at level 3 maternity hospital between 2013 and2022. Single center retrospective cohort study including mothers and their liveborn infants at gestational age from 22+0 weeks to 24+6 weeks during a ten-year period. Clinical data regarding pregnancy, delivery, neonatal mortality, and morbidity were collected from the Vermont Oxford Network (VON) database. 185 liveborn infants with gestational age (GA) from 22+0 to 24+6 weeks were included. A high proportion of the most immature infants were not treated actively (92 % infants born at 22weeks of GA died in delivery room). Survival rates according to GA were 4 % (22weeks), 40.7 % (23weeks), and 65.1 % (24weeks). Of the infants admitted to the neonatal intensive care unit (n=142), 25.3 % had severe intraventricular hemorrhage (grade III or IV) or periventricular leukomalacia, 13.4 % underwent abdominal surgery (due to necrotizing enterocolitis), and 17.6 % required laser treatment for retinopathy of prematurity. Supplemental oxygen at 36weeks postmenstrual age was required by 40.8 % infants. At our center, which cares for more than 90 % of periviable newborns born in Slovenia, we achieved comparable survival and morbidity outcomes for actively approached liveborn periviable infants compared to those from developed countries reported in the literature. In the future, we aim to implement active antenatal care for pregnant women and infants born after completed 22weeks of gestation and monitor the long-term outcomes of all infants born at the limit of viability.

Association of Childhood Neighborhood Opportunity With Retinopathy of Prematurity.

Retinopathy of Prematurity and Risk of Structural Brain Abnormalities on Magnetic Resonance Imaging at Term Among Infants Born at Less Than or Equal to 32 Weeks of Gestation.

Placental Transcriptomic Analysis in Retinopathy of Prematurity Reactivation After Anti-VEGF Treatment.

Retinal Blood Flow Decreases after Treatment with Bevacizumab for Retinopathy of Prematurity.

Ocular Biometry in Preterm Newborns in the Neonatal Intensive Care Unit Environment of a Referral Hospital.