Severe Retinopathy Of Prematurity Research Articles

Aflibercept to treat retinopathy of prematurity: need for more research.

Until recently, the standard care for retinopathy of prematurity (ROP) was destructive treatment of the peripheral avascular retina, most often using laser therapy. Now, intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have been included in recommendations for treatment-warranted ROP. The three anti-VEGF agents used to treat ROP are bevacizumab, ranibizumab, and aflibercept and clinical trials using, a variety of treatment strategies, have shown all three are efficacious and easy to administer. Intravitreal Bevacizumab is most used in the US, and ranibizumab has been approved for ROP use in Europe. In 2023, the FDA approved aflibercept for treatment of severe ROP. We summarize the clinical trial results and provide a side-by-side comparisons of the three drugs. Despite FDA approval of the use of aflibercept to treat ROP, there is a need for more research as the body of knowledge regarding this agent to treat ROP is limited.

Stage III Chorioamnionitis Is Associated with Reduced Risk of Severe Retinopathy of Prematurity

ObjectiveTo identify whether histologically confirmed chorioamnionitis (hCAM) is associated with development of retinopathy of prematurity (ROP). Study designWe retrospectively analyzed two different cohorts. Cohort 1 was the national database of newborns in Japan born at ≤1500g or <32 weeks’ gestation (January 2003 through April 2021, n=38,013). Cohort 2 was babies born at <1500g from a single institution in Tsuchiura, Japan, (April 2015 through March 2018, n=118). ResultsFor Cohort1, after adjusting for potential confounders, stage III CAM (n=5,554) was associated with lower odds of severe ROP (stage ≥3 or required peripheral retinal ablation) by 14% (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.78–0.94]. CAM of stage I (n=3,277) and II (N=4,319) was not associated with the risk of ROP. For Cohort 2, the odds of severe ROP were significantly reduced in moderate to severe hCAM groups (stage II, OR: 0.06, 95% CI: 0.05–0.82; stage III, OR: 0.10, 95% CI: 0.01-0.84). Neonates with funisitis, comorbidity of hCAM, and a finding of fetal inflammatory response had lower odds of severe ROP (OR: 0.11; 95% CI: 0.01–0.93). ConclusionsAfter adjusting for confounders, severe hCAM with fetal inflammatory response was associated with reduced risk of ROP.

Isolated retinal neovascularization in retinopathy of prematurity: clinical associations and prognostic implications

Isolated retinal neovascularization (IRNV) is a common finding in patients with stage 2 and 3 retinopathy of prematurity (ROP). This study aims to further classify the clinical course and significance of these lesions (previously described as "popcorn" based on clinical appearance) in patients with ROP as visualized with ultra-widefield optical coherence tomography (UWF-OCT). Single center, retrospective case series. Images were collected from 136 babies in the Oregon Health and Science University neonatal intensive care unit. A prototype UWF-OCT device captured en face scans (>140°), which were reviewed for the presence of IRNV along with standard zone, stage, and plus classification. In a cross-sectional analysis we compared demographics and the clinical course of eyes with and without IRNV. Longitudinally, we compared ROP severity using a clinician-assigned vascular severity score (VSS) and compared the risk of progression among eyes with and without IRNV using multivariable logistic regression (MLR). Differences in clinical demographics and disease progression between patients with and without IRNV. Of the 136 patients, 60 developed stage 2 or worse ROP during their disease course, 22 of whom had IRNV visualized on UWF-OCT (37%). On average, patients with IRNV had lower birth weights (BW) (660.1g vs 916.8g, p = 0.001), gestational age (GA) (24.9 vs 26.1 weeks, p = 0.01), and were more likely to present with ROP in zone I (63.4% vs 15.8%, p < 0.001). They were also more likely to progress to stage 3 (68.2% vs 13.2%, p < 0.001) and receive treatment (54.5% vs 15.8%, p = 0.002). Eyes with IRNV had a higher peak VSS (5.61 vs 3.73, p < 0.001) and averaged a higher VSS throughout their disease course. On MLR, IRNV was independently associated with progression to stage 3 (p = 0.02) and requiring treatment (p = 0.03), controlling for GA, BW, and initial zone 1 disease. In this single center study, we found that IRNV occurs in higher risk babies and was an independent risk factor for ROP progression and treatment. These findings may have implications for OCT-based ROP classifications in the future.

Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity

Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Complications of ROP treated at investigator discretion (no study treatment). Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. ClinicalTrials.gov Identifier: NCT04015180.

Nutritional interventions to prevent retinopathy of prematurity.

Very preterm infants are at high risk of growth failure. Poor weight gain is a prominent risk factor for retinopathy of prematurity (ROP) and optimizing nutrition could potentially promote growth and reduce ROP. Most infants at risk of ROP need parenteral nutrition initially and studies of enhanced parenteral provision of lipids and amino acids have suggested a beneficial effect on ROP. Higher amino acid intake was associated with lower incidence of hyperglycemia, a risk factor for ROP. For very preterm infants, providing unpasteurized fortified raw maternal breast milk appears to have a dose-dependent preventive effect on ROP. These infants become deficient in arachidonic acid (ArA)and docosahexaenoic acid(DHA) after birth when the maternal supply is lost. Earlier studies have investigated the impact of omega-3 fatty acids on ROP with mixed results. In a recent study, early enteral supplementation of ArA 100 mg/kg/d and DHA 50 mg/kg/d until term equivalent age reduced the incidence of severe ROP by 50%. IMPACT: Previous reviews of nutritional interventions to prevent morbidities in preterm infants have mainly addressed bronchopulmonary dysplasia, brain lesions and neurodevelopmental outcome. This review focusses on ROP. Neonatal enteral supplementation with arachidonic acid and docosahexaenoic acid, at levels similar to the fetal accretion rate, has been found to reduce severe ROP by 50% in randomized controlled trials.

Clinical and Growth Correlates of Retinopathy of Prematurity in Preterm Infants with Surgical Necrotizing Enterocolitis and Intestinal Perforation.

This study aimed to identify the clinical and growth parameters associated with retinopathy of prematurity (ROP) in infants with necrotizing enterocolitis (NEC) and spontaneous ileal perforation (SIP). We conducted a retrospective cohort study that compared clinical data before and after NEC/SIP onset in neonates, categorizing by any ROP and severe ROP (type 1/2) status. The analysis included 109 infants with surgical NEC/SIP. Sixty infants (60/109, 55%) were diagnosed with any ROP, 32/109 (29.3%) infants (22% type 1 and 7.3% type 2) with severe ROP. On univariate analysis, those with severe ROP (32/109, 39.5%) were of lower median gestational age (GA, 23.8 weeks [23.4, 24.6] vs. 27.3 [26.3, 29.0], p < 0.001), lower median birth weight (625 g [512, 710] vs. 935 [700, 1,180], p < 0.001) and experienced higher exposure to clinical chorioamnionitis (22.6 vs. 2.13%, p < 0.006), and later median onset of ROP diagnosis (63.0 days [47.0, 77.2] vs. 29.0 [19.0, 41.0], p < 0.001), received Penrose drain placement more commonly (19 [59.4%] vs. 16 [34.0%], p = 0.04), retained less residual small bowel (70.0 cm [63.1, 90.8] vs. 90.8 [72.0, 101], p = 0.007) following surgery, were exposed to higher FiO2 7 days after birth (p = 0.001), received ventilation longer and exposed to higher FiO2 at 2 weeks (p < 0.05) following NEC and developed acute kidney injury (AKI) more often (25 [86.2%] vs. 20 [46.5%], p = 0.002) than those without ROP. Those with severe ROP had lower length, weight for length, and head circumference z scores. In an adjusted Firth's logistic regression, GA (adjusted odds ratio [aOR] = 0.51, 95% confidence interval [CI]: [0.35, 0.76]) and diagnosis at later age (aOR = 1.08, 95% CI: [1.03, 1.13]) was shown to be significantly associated with any ROP. Infants who develop severe ROP following surgical NEC/SIP are likely to be younger, smaller, have been exposed to more O2, develop AKI, and grow poorly compared with those did not develop severe ROP. · Thirty percent of infants with NEC/SIP had severe ROP.. · Those with severe ROP had poor growth parameters before and after NEC/SIP.. · Risk factors based ROP prevention strategies are needed to have improved ophthalmic outcomes..

Risk factor-based models to predict severe retinopathy of prematurity in preterm Thai infants.

To develop prediction models for severe retinopathy of prematurity (ROP) based on risk factors in preterm Thai infants to reduce unnecessary eye examinations in low-risk infants. This retrospective cohort study included preterm infants screened for ROP in a tertiary hospital in Bangkok, Thailand, between September 2009 and December 2020. A predictive score model and a risk factor-based algorithm were developed based on the risk factors identified by a multivariate logistic regression analysis. Validity scores, and corresponding 95% confidence intervals (CIs), were reported. The mean gestational age and birth weight (standard deviation) of 845 enrolled infants were 30.3 (2.6) weeks and 1264.9 (398.1) g, respectively. The prevalence of ROP was 26.2%. Independent risk factors across models included gestational age, birth weight, no antenatal steroid use, postnatal steroid use, duration of oxygen supplementation, and weight gain during the first 4 weeks of life. The predictive score had a sensitivity (95% CI) of 92.2% (83.0, 96.6), negative predictive value (NPV) of 99.2% (98.1, 99.6), and negative likelihood ratio (NLR) of 0.1. The risk factor-based algorithm revealed a sensitivity of 100% (94, 100), NPV of 100% (99, 100), and NLR of 0. Similar validity was observed when "any oxygen supplementation" replaced "duration of oxygen supplementation." Predictive score, unmodified, and modified algorithms reduced eye examinations by 71%, 43%, and 16%, respectively. Our risk factor-based algorithm offered an efficient approach to reducing unnecessary eye examinations while maintaining the safety of infants at risk of severe ROP. Prospective validation of the model is required.

Characteristics of red blood cell transfusion among very preterm infants in China.

National-level data on the incidence of red blood cell (RBC) transfusions and outcomes among very preterm infants (VPIs) are lacking in China. This study aims to describe the use and variation of RBC transfusion among VPIs in China. This cohort study was conducted among 70 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 2019 to 2020 across China. All VPIs admitted to the CHNN neonatal intensive care units (NICUs) were included. A total of 13,447 VPIs were enrolled, of whom 7026 (52.2%) received ≥1 RBC transfusions. The mean number of transfusions per infant was 2 (interquartile range [IQR] 1-4 times) and the median age at first transfusion was 15 days (IQR 3-27 days). The transfusion rate was higher in critically ill infants compared with non-critically ill infants (70.5% vs. 39.3%). The transfusion rate varied widely (13.5%-95.0%) between different NICUs. The prevalence of death, severe intra-ventricular haemorrhage, necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP), sepsis, bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP) and cystic periventricular leukomalacia (cPVL) was significantly higher in the transfused group. Among non-critically ill infants, RBC transfusion was independently associated with BPD, severe ROP and cPVL. Our study, providing the first baseline data on RBC transfusions among VPIs in China, shows an alarmingly high RBC transfusion rate with significant site variations. There is an urgent need for national guidelines on RBC transfusions for VPIs in China.

Timing and Substrate of Enteral Feeding as Risk Factors for Developing Retinopathy of Prematurity

Objective Enteral feeding has advantages over parenteral nutrition, so the objective is to evaluate the effects of timing and substrate of enteral feeding on the risk of developing retinopathy of prematurity (ROP). Study Design Retrospective cohort study of 7,483 premature infants undergoing ROP examinations at 29 North American and Canadian hospitals, 2006–2012 (The G-ROP Study). Multivariable regression evaluated associations between enteral feeding by week of life and any or severe ROP, adjusting for birth weight and gestational age. Results 3,224 (43.1%) had ROP and 931(12.4%) severe ROP. Compared to no enteral feeding, any enteral feeding was independently protective for ROP in all weeks 1–6; odds ratios 0.50–0.74 ( P &lt; .0001 to P &lt; .02) for any ROP and 0.43–0.59 ( P &lt; .02 to P = .0001) for SEVERE ROP. Conclusion In this cohort, any substrate of enteral feeding during each of the first SIX weeks of life was associated with lower odds of ROP and severe ROP.

Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18–24 months in very low birthweight infants?

BackgroundImmediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85–95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3–0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence.MethodsAn international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks’ gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months’ and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity).DiscussionThe use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18–24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice.Trial registrationThe trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

Critical period of oxygen supplementation and invasive ventilation: implications for severe retinopathy of prematurity

BackgroundSeveral studies have identified graded oxygen saturation targets to prevent retinopathy of prematurity (ROP), a serious complication in preterm infants. We aimed to analyze the critical period of oxygen supplementation and/or invasive ventilation associated with severe ROP.MethodsThis retrospective case-control study included neonates with a gestational age (GA) < 29 weeks. Participants were divided into two groups: treated retinopathy and untreated/no retinopathy. Time-weighted average FiO2 (TWAFiO2) and weekly invasive ventilation were compared between groups by postnatal age (PNA) and postmenstrual age (PMA). The association of treated retinopathy with TWAFiO2 and invasive ventilation was analyzed.ResultsData from 287 neonates were analyzed; 98 were treated for ROP and had lower GAs (25.5 vs. 27.4 weeks, p < 0.01) and lower birthweights (747.6 vs. 1014 g, p < 0.001) than those with untreated/no ROP. TWAFiO2 was higher from PMA 26–34 weeks, except for PMA 31 weeks in treated ROP, and higher in the first nine weeks of life in treated ROP. On multiple logistic regression, TWAFiO2 and invasive ventilation were associated with ROP treatment during the first seven weeks PNA. Invasive ventilation was associated with ROP treatment from PMA 26–31 weeks; no association was found for TWAFiO2 and PMA.ConclusionsAmount of oxygen supplementation and/or invasive ventilation during the first 7 weeks of life or up to 31 weeks PMA was associated with development of severe ROP. This period might be candidate timing for strict oxygen supplementation strategies in preterm infants, while concerns of mortality with low oxygen supplementation should be further explored.

Platelet count and platelet indices in early life of infant with retinopathy of prematurity

Background and objectives. Retinopathy of prematurity (ROP) is a complication of prematurity. Early detection of ROP is important because its management depends on prevention of severe ROP and its complications. Pro- and anti-angiogenic factors are involved in ROP pathogenesis. Platelet store and release these factors, but its role as predictor of ROP is still obscure. This study aimed to compare platelet count, mean platelet volume (MPV), platelet distribution width (PDW), and platelet mass index (PMI) value between two age groups in early life of infant diagnosed with ROP. Materials and methods. This study was retrospective study of medical record data of infants born at “dr. Soetomo” General Academic Hospital Surabaya during 2021-2023. The infants were divided into two groups, they who have complete blood count result (CBC) in 0-7 days old (group 1) and 8-28 days old (group 2). We evaluated platelet count, MPV, PDW, and PMI value from CBC data. These data were analyzed using suitable statistical test. Results. Total of 126 infants were involved in this study. It consisted of 62 infants in group 1 and 64 infants on group 2. Platelet count was significantly different between groups (230.460±102.040/μL vs 313.664±182.890/μL, p=0,002). Value of MPV, PDW, and PMI were also significantly higher in group 2 (p&lt;0.001). Frequency of thrombocytosis (&gt;500.000/μL), high MPV (&gt;10.05 fL), and high PMI (3640 fL/nL) were also significantly higher in group 2 (p&lt;0.05). Conclusions. Higher platelet count, MPV, PDW, and PMI value were observed in 8-28 days old infant with ROP. They also more likely to experienced thrombocytosis, high MPV, and high PMI value.

The scope of artificial intelligence in retinopathy of prematurity (ROP) management.

Artificial Intelligence (AI) is a revolutionary technology that has the potential to develop into a widely implemented system that could reduce the dependence on qualified professionals/experts for screening the large at-risk population, especially in the Indian scenario. Deep learning involves learning without being explicitly told what to focus on and utilizes several layers of artificial neural networks (ANNs) to create a robust algorithm that is capable of high-complexity tasks. Convolutional neural networks (CNNs) are a subset of ANNs that are particularly useful for image processing as well as cognitive tasks. Training of these algorithms involves inputting raw human-labeled data, which are then processed through the algorithm's multiple layers and allow CNN to develop their own learning of image features. AI systems must be validated using different population datasets since the performance of the AI system would vary according to the population. Indian datasets have been used in AI-based risk model that could predict whether an infant would develop treatment-requiring retinopathy of prematurity (ROP). AI also served as an epidemiological tool by objectively showing that a higher ROP severity was in Neonatal intensive care units (NICUs) that did not have the resources to monitor and titrate oxygen. There are rising concerns about the medicolegal aspect of AI implementation as well as discussion on the possibilities of catastrophic life-threatening diseases like retinoblastoma and lipemia retinalis being missed by AI. Computer-based systems have the advantage over humans in not being susceptible to biases or fatigue. This is especially relevant in a country like India with an increased rate of ROP and a preexisting strained doctor-to-preterm child ratio. Many AI algorithms can perform in a way comparable to or exceeding human experts, and this opens possibilities for future large-scale prospective studies.

Continuous oxygen saturation and risk of retinopathy of prematurity in a Japanese cohort

Background/aimsWe assessed the associations between retinopathy of prematurity (ROP) and continuous measurements of oxygen saturation (SpO2), and developed a risk prediction model for severe ROP using birth data and SpO2...

Association of Oxygen Therapy Concentration and Duration with Retinopathy of Prematurity Incidence at Naresuan University Hospital

Objective: This study aimed to evaluate the association between the concentration and duration of oxygen therapy and the development and severity of retinopathy of prematurity (ROP). Additionally, it sought to examine the incidence of ROP at Naresuan University Hospital. Materials and Methods: A retrospective observational cohort study was conducted, utilizing data from the medical records of infants admitted to the Neonatal Intensive Care Unit at Naresuan University Hospital, Phitsanulok, Thailand, from January 1, 2016, to December 31, 2022. The duration of various oxygen therapies was recorded in hours, and the concentration of oxygen administered per hour was calculated as the average fraction of inspired oxygen for each infant. These data were subsequently analyzed using STATA version 11.0. Results: Out of 100 eligible infants, 27 (27%) were diagnosed with ROP at different severity levels: 17 infants (62.96%) with ROP stage 1, 9 infants (33.33%) with stage 2, and 1 infant (3.70%) with stage 3. There were no cases of Stage 4 or 5 ROP. The adjusted risk ratio revealed that infants receiving an average FiO2 of 0.3 or higher had a 1.64 times greater risk of developing ROP [95%CI 1.03-2.62], (P-value=0.038). Further analysis using mean difference regression showed a significant correlation between the duration of oxygen therapy and the severity of ROP. Conclusion: This study suggests that regulating oxygen therapy to not exceed an FiO2 of 0.3 and administering it strictly as needed may mitigate the risk of developing ROP and its severe manifestations.

Comparing reactivation and retreatment for three doses of bevacizumab in type 1 retinopathy of prematurity

To determine timing and rates of reactivation and retreatment of type 1 retinopathy of prematurity (ROP) after treatment with either 0.125 mg, 0.250 mg, or 0.500 mg of intravitreal bevacizumab (IVB). Retrospective data, including demographic information, past medical history, and ROP characteristics were analyzed for babies with type 1 ROP treated with IVB at Riley Hospital for Children for the perioed 2014-2021. A total of 84 patients met inclusion criteria: 29 patients received 0.125 mg of IVB; 39, 0.250 mg; and 16, 0.500 mg. Of the 84, 67 (80%) had additional laser treatment because of late reactivation (n = 52) or persistent avascular retina (PAR) (n = 15). Subsequent laser treatment was more common with lower doses: 0.125 mg (n = 27 [93%]); 0.250 mg (n = 31 [80%]); 0.500 mg (n = 9 [57%]) (P = 0.012). There was no difference between groups with regard to reason for subsequent laser treatment (reactivation vs PAR). The 0.125 mg group required retreatment because of reactivation 3.8 weeks sooner than the other dosing groups (P = 0.047). The outcomes comparing three doses of IVB for severe ROP showed a difference in the timing of secondary treatment, with the lower dosing group requiring laser for reactivation earlier.

Active versus restrictive ligation strategy for patent ductus arteriosus – A retrospective two-center study of extremely preterm infants born between 22 + 0 and 25 + 6 weeks of gestational age

BackgroundPatent ductus arteriosus (PDA) in premature infants is associated with adverse clinical outcomes. Mode and timing of treatment are still controversial. Data are limited in the most extremely premature infants <26 weeks of gestational age (GA), where clinical problems are most significant and patients are most vulnerable. AimsTo investigate whether different approaches to surgical closure of PDA in two large Swedish centers has an impact on clinical outcomes including mortality in extremely preterm infants born <26 weeks GA. Study designRetrospective, two-center, cohort study. SubjectsInfants born at 22+0–25+6 weeks GA between 2010 and 2016 at Uppsala University Children's Hospital (UUCH; n = 228) and Queen Silvia Children's Hospital Gothenburg (QSCHG; n = 220). Main outcome measuresSurvival, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP). ResultsSurgical closure of PDA was more common and performed earlier at QSCHG (50 % vs 16 %; median age 11 vs 44 days; p < 0.01). Survival was similar in both centres. There was a higher incidence of severe BPD and longer duration of mechanical ventilation at UUCH (p < 0.01). There was a higher incidence of ROP, IVH and sepsis at QSCH (p < 0.05, p < 0.01 and p < 0.01). A sub-group analysis matching all surgically treated infants at QSCHG with infants at UUCH with the same GA showed similar results as the total cohort. ConclusionEarlier and higher rate of surgical PDA closure in this cohort of extremely preterms born <26 weeks GA did not impact mortality but was associated with lower rates of severe BPD and higher rates of severe ROP.

The impact of blood lactic acid levels on retinopathy of prematurity morbidity

BackgroundRetinopathy of prematurity (ROP) is a common disease in premature infants. In recent years, most researchers have used lactic acid as poor prognosis marker in premature infants. This study aims to explore investigate the impact of blood lactic acid levels on ROP.MethodsA retrospective case-control study was conducted, and infants with severe ROP born with birth weight (BW) ≤ 1500 g and gestational age (GA) ≤ 32 weeks were enrolled from November 2016 to November 2021. Infants without any stage ROP were included as controls and were matched with ROP infants (1:2) by GA and BW. All selected preterm infants were tested for heel terminal trace blood gas analysis within two weeks of life. Changes in blood lactic acid levels in the two groups were compared and analyzed by using multivariate logistic regression analysis. Sensitivity and specificity were analyzed by receiver operating characteristic (ROC) curve.ResultsThere were 79 infants in ROP group, and 158 infants in control group. The levels of blood lactic acid were significantly higher in the ROP group on days 1, 3, 5, and 7 compared with control group (all p < 0.05). The blood lactic acid levels on day 5 was an independent risk factor for ROP (p = 0.017). The area under the curve (AUC), sensitivity and specificity were highest on day 5 (AUC 0.716, sensitivity 77.2% and specificity 62.0%, respectively, p < 0.001), and higher on days 1, 3, and 7.ConclusionA high blood lactic acid level in the first seven days of life may be associated with increases ROP occurrence in very preterm infants, and suggest blood lactic acid level may impact the occurrence of ROP.

Comparative analysis of risk factors for retinopathy of prematurity in single and multiple birth neonates

AimTo conduct a comparative analysis of risk factors for retinopathy of prematurity (ROP) in single- and multiple-born neonates.MethodsIn a retrospective evaluation of 521 premature neonates, encompassing singletons, twins, and triplets born at or before 34 weeks of gestational age with a birthweight of less than 2000 g and who completed the ROP screening program, between 2020 and 2023, in outpatient referral ROP screening clinic affiliated by Shiraz University of Medical Sciences, were included. Neonates with the eligibility criteria were enrolled in the screening program from 28 days old age and followed up to discharge or treatment based on national ROP screening guideline. Data on ROP severity, outcome, treatment modality, and risk factors, including gestational age (GA), birth weight (BW), sex, duration of neonatal intensive care unit (NICU) admission, oxygen supplementation, mechanical ventilation, blood transfusion, method of delivery, and maternal and neonatal comorbidities, were extracted and compared between premature neonates from singleton and multiple births.Results The analysis of the ROP severity distribution revealed 238 neonates (45.7%) with low-risk (type 2 prethreshold ROP or less severe) ROP and 16 (3.1%) with high-risk (type I prethreshold ROP or more severe) ROP who underwent treatment. According to the comparative analysis of risk factors in neonates with ROP requiring treatment, multiple birth neonates exhibited significantly greater GA (27.50 ± 3.27 vs. 30.00 ± 2.00 vs. 31.14 ± 0.38 weeks, p = 0.032 for singletons, twins and triplets, respectively); greater BW (861.67 ± 274.62 vs. 1233.33 ± 347.75 vs. 1537.14 ± 208.86 g, p = 0.002); and shorter duration of NICU admission (60.17 ± 21.36 vs. 34.00 ± 12.17 vs. 12.00 ± 6.32 days, p = 0.001) and oxygen supplementation (47.33 ± 16.57 vs. 36.00 ± 8.49 vs. 4.60 ± 2.41 days, p = 0.001). There was no significant difference between single-born neonates and multiple-born neonates regarding the prevalence of other risk factors. Multiple-born neonates with no ROP and low risk ROP showed significantly lower GA and BW compared to singletons (p < 0.001).ConclusionMultiple gestation neonates may develop high-risk ROP requiring treatment at a greater gestational age and birth weight and at a lower duration of oxygen supplementation and NICU admission compared to the single birth neonates. This pattern prompts a reevaluation of screening criteria, suggesting a potential need to consider multiple birth neonates with lower traditional risk factors in screening programs. This pattern should be further evaluated in larger populations of multiple born premature neonates.

A retrospective cohort study on mortality, morbidity, and care practices for 1750 very low birth weight infants, 2016-2021.

Very low birth weight (VLBW) infants are the key populations in neonatology, wherein morbidity and mortality remain major challenges. A retrospective cohort study conducted aiming to analyze the clinical characteristics of VLBW in our hospital between January 2016 and December 2021. Neonates with a birth weight of <1500g were included. Mortality, care practices, and major morbidities were analyzed, and compared with that of previous 7years (2009-2015). Of the total 1750 VLBW, 1386 infants born with birth weight between 1000-1499 g and 364 were below 1000 g, 42.9% (751/1750) required delivery room resuscitation, 53.9% (943/1750) received non-invasive ventilation only, 38.2% (669/1750) received invasive ventilation; 1517 VLBW infants received complete treatment. Among them, 60.1% (912/1517) of neonates had neonatal respiratory distress syndrome (NRDS), 28.7% (436/1517) had bronchopulmonary dysplasia (BPD), 22.0% (334/1517) had apnea, 11.1% (169/1517) had culture-confirmed sepsis, 8.4% (128/1517) had pulmonary hemorrhage, 7.6% (116/1517) had severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL), 5.7% (87/1517) had necrotizing enterocolitis (NEC), 2.0% (31/1517) had severe retinopathy of prematurity. The total and in-hospital mortality rates were 9.7% (169/1750) and 3.0% (45/1517), respectively. The top three diagnoses of death among those who had received complete treatment were sepsis, NRDS, and NEC. In 2009-2015, 1146 VLBW were enrolled and 895 infants received complete treatment. The incidences of apnea, IVH, and IVH stage ≥3/PVL, were higher in 2009-2015 compared with those in 2016-2021, while the incidences of NRDS and BPD were characterized by significant increases in 2016-2021. The total and in-hospital mortality rates were 16.7% (191/1146) and 5.6% (50/895) respectively in 2009-2015. Among VLBW infants born in 2016-2021, the total and in-hospital mortality rates were lower than those of neonates born in 2009-2015. Incidences of NRDS and BPD increased in 2016-2021, which affected the survival rates and long-term prognosis of VLBW.