Transient activation of retinopathy of prematurity secondary to erythrocyte suspension transfusion.

Retinopathy of prematurity (ROP) is a serious retinal vascular disorder that needs prompt diagnosis, and treatment to prevent undesired visual outcomes. Due to its shorter period of disease progression, it is important to be hasty in treating ROP. Erythrocyte suspension (ES) aggravates the progression of ROP. However, this progression may be transient as in the present case reports. This case report aimed to present two cases that developed type 1 ROP after erythrocyte suspension transfusion. Clinical findings of the patients were resolved within a few days without any intervention. Premature infants receiving ES treatment can be observed for 24-48 hours, and the treatment can be planned after determining the persistence of the plus sign. Abbreviations: ES = Erythrocyte suspension, ROP = Retinopathy of prematurity, NICU = neonatal intensive care unit.

Postnatal weight gain and retinopathy of prematurity in preterm infants: a population-based retrospective cohort study.

OBJECTIVE: Infants who meet the screening guidelines for retinopathy of prematurity (ROP) based on birth weight and gestational age undergo serial ophthalmological examinations for its detection and treatment. However, <10% of patients require treatment, and less than half develop ROP. Poor postnatal weight gain has been reported to be a strong indicator of ROP development; however, the information regarding this is unclear. Therefore, this study aimed to determine the relationship between postnatal weight gain and ROP development in preterm infants. METHODS: The data of 675 preterm infants with gestational age ≤32 weeks, who were hospitalized in our neonatal intensive care unit, were obtained retrospectively from file records. The infants' demographic characteristics, clinical findings, and weekly weight gain (g/kg/day) during the first 8 weeks were recorded. The univariate was used to examine the risk factors for ROP followed by multivariate regression. RESULTS: The incidence of ROP in the infants included in the study was 41% (n = 278) and 13.3% (n = 37) of them required treatment. In the infants of the group that developed ROP, the mean birth weight and gestational age were significantly lower than those in the group that did not develop ROP (973 ± 288 and 1301 ± 349 g, p = 0.001 and 28.48 ± 1.95 and 30.08 ± 1.60 weeks, p = 0.001, respectively). As the gestational week and birth weight decreased, ROP development and the risk of ROP-requiring treatment increased. In the infants of the group that developed ROP, the mean weight gain in the postnatal third week was detected as significantly lower compared to those in the group that did not develop ROP (13.9 ± 8.2 and 15.4 ± 6.8 g, p = 0.034). On multiple logistic regression analysis, birth weight (<750 g) (odds ratio [OR], 8.67; 95% confidence interval [CI], 3.99-18.82, p = 0.001), blood transfusion (OR, 2.39; 95% CI, 1.34-4.24, p = 0.003), necrotizing enterocolitis (OR, 4.79; 95% CI, 1.05-26.85, p = 0.045), bronchopulmonary dysplasia (OR, 2.03; 95% CI, 1.22-3.36, p = 0.006), antenatal steroid therapy (OR, 1.60; 95% CI, 1.05-2.43, p = 0.028), surfactant administration (OR, 2.06; 95% CI, 1.32-3.2, p = 0.001) were independent risk factors for ROP development. CONCLUSION: Postnatal weight gain may not be an accurate predictor of ROP development after adjusting for confounding factors. However, the analysis of independent risk factors that influenced the development of ROP revealed a statistically significant effect in cases of low birth weight, blood transfusion, necrotizing enterocolitis, bronchopulmonary dysplasia, and antenatal steroid and surfactant therapies. These findings may help ophthalmologists and neonatologists to pay special attention to this patient group during ROP scanning.

Global Prevalence and Severity of Retinopathy of Prematurity over the Last Four Decades (1985-2021): A Systematic Review and Meta-Analysis.

BACKGROUND: Retinopathy of prematurity (ROP) is a vasoproliferative disease of the retina that occurs in premature infants. The prevalence of ROP reported so far is inconsistent. AIM: To conduct a systematic review to describe the trend of ROP prevalence between 1985 and 2021, and to determine the influence of countries' economic conditions on ROP prevalence. METHODS: We searched PubMed, Embase, and Google Scholar for studies published between January 1985 and December 2021 using the following MeSH terms: "retinopathy of prematurity", "ROP", "incidence", and "prevalence". Two independent reviewers examined the articles to select studies that met the selection criteria and performed data extraction and study quality assessment. For the meta-analysis, the pooled prevalence was calculated using a random-effects model and R software. RESULTS: Of 5,250 titles and abstracts, 139 original studies met the inclusion criteria; a total of 121,618 premature infants were included in these studies. The pooled prevalence of ROP was 31.9% (95% confidence interval [CI] 29.0-34.8) and that of severe ROP was 7.5% (6.5-8.7). In general, no significant differences in prevalence were found over the four decades; however, we found a higher prevalence in premature infants ≤28 weeks of gestational age. In addition, the highest ROP prevalence was found in lower-middle-income countries with high mortality rates. In contrast, the highest severe ROP prevalence was found in high-income countries. CONCLUSION: ROP remains a common cause of morbidity in premature infants worldwide. Therefore, it seems necessary to maintain early identification strategies for patients at higher risk, particularly in low- and middle-income countries.

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

BACKGROUND: Retinopathy 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. METHODS: A 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. RESULTS: There 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. CONCLUSION: A 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.

Insights into Risk: Exploring Retinopathy of Prematurity and Short-term Comorbidities in Moderate-to-Late Preterm Infants.

BACKGROUND: Retinopathy of prematurity (ROP) and short-term comorbidity data moderate-to-late preterm (MLP) infants in Saudi Arabia are limited. AIM: The present study mainly aimed to identify ROP incidence and severity in MLP infants. The secondary objective was to explore whether moderate preterm infants are more prone to systemic short-term comorbidities compared to late preterm infants. MATERIALS AND METHODS: This retrospective study was conducted at King Abdulaziz University Hospital, a tertiary center in Jeddah, Saudi Arabia. Two-hundred and sixty-eight MLP infants born with gestational ages (GAs) of 32 to 36 + 6 weeks were included. Births were classified as moderate preterm (GA 32 to 33 + 6 weeks) and late preterm (GA 34 to 36 + 6 weeks) and the two groups were compared with an independent t-test. RESULTS: ROP incidence was 1.5%; all cases were stage 1 and involved zone II or III. No patient had type 1 ROP requiring treatment. The short-term comorbidity incidence was high (76.1%) and included hyperbilirubinemia (n = 206, 76.7%), respiratory distress syndrome (n = 178, 66.4%), hypoglycemia (n = 32, 11.9%,), and transient tachypnea of newborn (n = 25, 9.3%). Moderate preterm infants were more likely to have lower birth weight (P < 0.001), any-stage ROP (P = 0.032), respiratory distress syndrome (P = 0.031), intraventricular hemorrhage (P = 0.038), and hyperbilirubinemia (P < 0.001) compared to the late preterm infants. CONCLUSIONS: Any-stage ROP incidence among MLP infants was low, with no type 1 ROP cases requiring treatment. Short-term comorbidity incidence was relatively high among the moderate preterm infants. Despite the low non-type 1 ROP incidence at our center, MLP infants require proper surveillance of systemic short-term comorbidities.

Neonatal sepsis as a cause of retinopathy of prematurity: An etiological explanation.

Retinopathy of prematurity (ROP) is a complex neonatal disorder with multiple contributing factors. In this paper we have mounted the evidence in support of the proposal that neonatal sepsis meets all requirements for being a cause of ROP (not a condition, mechanism, or even innocent bystander) by means of initiating the early stages of the pathomechanism of ROP occurrence, systemic inflammation. We use the model of etiological explanation, which distinguishes between two overlapping processes in ROP causation. It can be shown that sepsis can initiate the early stages of the pathomechanism via systemic inflammation (causation process) and that systemic inflammation can contribute to growth factor aberrations and the retinal characteristics of ROP (disease process). The combined contribution of these factors with immaturity at birth (as intrinsic risk modifier) and prenatal inflammation (as extrinsic facilitator) seems to provide a cogent functional framework of ROP occurrence. Finally, we apply the Bradford Hill heuristics to the available evidence. Taken together, the above suggests that neonatal sepsis is a causal inducer of ROP.

Prevalence and pattern of retinopathy of prematurity at two national referral hospitals in Uganda: a cross-sectional study.

BACKGROUND: Retinopathy of prematurity (ROP) is a leading cause of blindness in children and an ROP epidemic is predicted this decade in sub-Saharan Africa. With the increasing survival rate of preterm babies in Uganda, and no data on ROP prevalence, there is a need to assess the burden of ROP to inform preventive strategies and targeted screening. METHODS: We conducted a two-center cross-sectional study of preterm (< 37 weeks gestational age) infants from the neonatal units of Kawempe National Referral Hospital (KNRH) and Mulago Specialised Women and Neonatal Hospital (MSWNH) from August 2022 to October 2022. An ophthalmologist examined all participants using an indirect ophthalmoscope with a + 20D convex lens and captured digital images using a Volk iNview™ Fundus Camera. The collected data were entered into Epidata 4.2 and exported to Stata 14.0 for analysis. RESULTS: 331 preterm infants enrolled in this study. The oxygen received was unblended. The mean gestational age was 30.4 ± 2.7 weeks, and the mean birth weight was 1597 ± 509 g. 18/101 (17.8%) were found to have any ROP amongst the preterm infants recruited from MSWNH, 1/230 (0.4%) from KNRH [95% CI] had any stage of ROP (i.e. stage 5). Of these, 8 (42.1%) had stage 2 ROP. Infants with a birth weight below 1500 g were 10 times more likely to have ROP than those among infants with a birth weight more than 1500 g [AOR: 10.07 (2.71-37.44)]. Infants who were not fed exclusively on breast milk had higher odds of having ROP than those exclusively fed on breast milk [AOR: 7.82(1.92-31.82)]. CONCLUSION: 6% of preterm infants born in two tertiary hospitals in Uganda were found to have ROP. Lack of exclusive feeding on breast milk and birth weight of less than 1500 g were strong predictors of ROP. The higher prevalence of ROP in MSWNH calls for cautious use of oxygen among preterms. We recommend targeted ROP screening for those at risk.

Oxygen saturation levels and retinopathy of prematurity in extremely preterm infants - a case control study.

PURPOSE: To investigate the association of risk factors, including oxygen exposure, for developing retinopathy of prematurity (ROP) in preterm infants at increased risk of ROP. METHODS: A case-control study was conducted where each infant born at < 28 weeks gestation with ROP was matched with another without ROP over five years (July 2015 - June 2020). Clinical information about the infants was collected from electronic medical records, including method of oxygen delivery, oxygen saturation (SpO2), fraction of inspired oxygen (FiO2) and mean airway pressure (MAP) measurements. MATLAB was used for a time-averaged analysis. Stata/SE 16.0 was used for statistical analysis. RESULTS: 123 ROP/non-ROP pairs were included in this study. The time-averaged SpO2 analysis showed non-ROP group spent more time in hyperoxia than the ROP group (p < 0.001). The non-ROP group had lower respiratory severity scores and analysis when FiO2 > 21% showed that were was no difference in SpO2 between the two groups when the infants were receiving oxygen support. Conditional logistic regressions showed neonatal surgery significantly increased the risk of ROP (OR = 1.4347, p = 0.010), while the influence of birthweight (odds ratio of 0.9965, p = 0.001) and oxygen exposure (OR = 0.9983, p = 0.012) on ROP outcome was found to be negligible as their odds ratios indicated no influence. CONCLUSIONS: At times when infants were receiving respiratory support (FiO2 > 21%) the SpO2 data indicated no difference in SpO2 between the ROP and non-ROP groups. Analysis of clinical variables found that neonatal surgery increased the odds of developing ROP.

Erythrocyte transfusions are associated with retinopathy of prematurity in extremely low gestational age newborns.

AIM: Retinopathy of prematurity (ROP) is a major morbidity in preterm infants causing visual impairment including blindness. Prevention and timely treatment are critical. We investigated the potential role of red blood cell (RBC) transfusions as risk factor for ROP development. METHODS: Retrospective cohort study of data from 68 tertiary level neonatal intensive care units in Germany. Preterm infants born at 22 + 0 to 28 + 6 weeks of gestation between January 2009 and December 2021 were enrolled. RESULTS: We included n = 12 565 infants. Prevalence of any ROP was 49.2% with most infants being diagnosed with stage 1 (21.5%) and 2 disease (17.2%). ROP stage 3 was present in 10.2%, stage 4 in 0.3%, and ROP requiring treatment in 6.6%. Infants with ROP had significantly more frequently a history of RBC transfusions. Adjusting for confounders, RBC transfusions were associated with increased odds of ROP (OR 1.4, p < 0.001), ROP progression (OR 2.1, p < 0.01) and ROP requiring treatment (OR 3.6, p < 0.001). Restrictive transfusion approaches correlated with decreased (OR 0.7, p < 0.001), liberal regimes with increased odds (OR 1.2, p = 0.001). CONCLUSION: The present study confirmed an association of RBC transfusions and ROP. Our findings emphasise the need for anaemia prevention and critical re-evaluation of transfusion practices in preterm infants.

Risk factors in the development of retinopathy of prematurity: A 10-year retrospective study.

OBJECTIVE: To evaluate Retinopathy of Prematurity (ROP) rate and risk factors in a large cohort of preterm newborns. METHODS: Single center retrospective study. All preterm inborn hospitalized at the Neonatal Intensive Care Unit of the Policlinico of Catania from January 1, 2009 till December 31, 2018, were included. ROP stage and location, treatments required, maternal and infant risk factors were evaluated. RESULTS: Medical records of 898 preterms were retrospectively examined (mean gestational age 32.9 ± 2.3 weeks). Of them 149 (16.6 %) developed bilateral ROP (92 stage 1, 44 stage 2 and 13 stage 3); 66 (7.3 %) received bilateral laser treatment. Six eyes of three patients affected by zone I ROP 1, with plus persistence 15 days after an optimal laser treatment, also received intravitreal ranibizumab injection. Risk factors for ROP development were gestational age (GA) (p < 0.001), birthweight (p < 0.001), assisted ventilation duration (p < 0.001), multiple birth (p = 0.003), erythropoietin (EPO) administration (p = 0.005) and persistence of tunica vasculosa lentis. The decision-tree analysis showed gestational age as the most significant predictive factor (P < 0.001); secondary predictive factors were EPO administration (p = 0.001) in newborns 29-31 weeks GA and birthweight lower than 2090 g (p < 0.001) in 32-34 weeks GA; in this latter group patent ductus arteriosus (PDA) was a tertiary predictive factor (p = 0.043). CONCLUSIONS: In our study ROP incidence was 16,6 %; 7.3 % of the patients required laser treatment. Besides well-known factors, such as GA and birthweight, other factors like duration of assisted ventilation, EPO, multiple births, PDA, tunica vasculosa lentis persistence should be considered to tailor ophthalmic evaluation and follow-up.

Retinopathy of Prematurity: The Role of Nutrition.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. ROP occurs in infants who are born very preterm. In ROP, retinal blood vessel development, which is prematurely arrested in preterm infants, is altered by perinatal exposures like oxygen and inflammation. Optimizing nutritional practices for preterm infants may mitigate the risk of ROP. In this article, we review the evidence that postnatal growth, hyperglycemia, polyunsaturated fatty acids, and breast milk provision may affect ROP risk. We also outline the current management strategies for ROP and describe the vision outcomes of children affected by ROP. [Pediatr Ann. 2023;52(8):e303-e308.].

Insulin-like growth factor-1 and retinopathy of prematurity: A systemic review and meta-analysis.

The prevalence of retinopathy of prematurity (ROP) is rapidly increasing worldwide. Many researchers have explored the relationship between insulin-like growth factor-1 (IGF-1) and ROP; however, the results are controversial. This meta-analysis evaluates the correlation between IGF-1 and ROP systematically. We searched for PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, SinoMed, ClinicalTrials.gov, and 3 Chinese databases up to June 2022. Then, the meta-regression and subgroup analysis were carried out. Twelve articles with 912 neonates were included in this meta-analysis. The results revealed that 4 of 7 covariates account for significant heterogeneity: location, measurement method of IGF-1 levels, collection time of blood sample, and the severity of ROP. The pooled analysis showed that low IGF-1 levels could serve as a risk factor associated with the development and severity of ROP. Serum IGF-1 monitoring in preterm infants after birth will be helpful in the diagnosis and treatment of ROP, and the reference value of IGF-1 should be standardized according to the measurement of IGF-1 and the region, as well as the postmenstrual age of prematurity.

Oxygen-Induced Retinopathy in the Rat: An Animal Model to Study the Proliferative Retinal Vascular Pathology.

Diabetic retinopathy (DR) is one of the leading causes of vision loss worldwide. There are numerous animal models available for developing new ocular therapeutics and drug screening and to investigate the pathological processes involved in DR. Among those animal models, the oxygen-induced retinopathy (OIR) model, though originally developed as a model for retinopathy of prematurity, has also been used to investigate angiogenesis in proliferative DR with the phenomenon of ischemic avascular zones and pre-retinal neovascularization it demonstrated. Briefly, neonatal rodents are exposed to hyperoxia to induce vaso-obliteration. Upon removal from hyperoxia, hypoxia develops in the retina that eventually results in neovascularization. The OIR model is mostly used in small rodents such as mice and rats. Here, we describe a detailed experimental protocol of rat OIR model and the subsequent assessment of abnormal vasculature. By illustrating the vasculoprotective and anti-angiogenic activities of the treatment, OIR model might advance to a new platform for investigating novel ocular therapeutic strategies for DR.

Increased risk of retinopathy of prematurity since increased O2 saturation targets: A multi-centre study.

BACKGROUND/AIMS: Retinopathy of prematurity (ROP) is a leading cause of visual impairment in premature neonates. The BOOST II, SUPPORT and COT trials recommended increasing O2 saturation targets for pre-term neonates to reduce mortality; however, this is a risk factor for ROP. We aimed to determine whether these targets increased prevalence of ROP among pre-term neonates and higher risk groups. METHODS: Retrospective cohort study conducted using data from the Australian and New Zealand Neonatal Network. 17 298 neonate cohort born 2012-2018 at <32 weeks' GA and/or <1500 g BW was analysed. Adjusted odds ratios (aORs) were calculated for post-2015 risk of: any ROP; ROP ≥ Stage 2; and treated ROP. Sub-analysis stratified at <28 GA, < 26 weeks' GA, <1500 g BW and <1000 g BW was performed. RESULTS: Risk of any ROP increased in the post-2015 group (aOR = 1.23, 95% confidence interval (CI) = 1.14-1.32), <28 weeks' GA (aOR = 1.31, 95% CI = 1.17-1.46), <26 weeks (aOR = 1.57, 95% CI = 1.28-1.91), <1500 g (aOR = 1.24, 95% CI = 1.14-1.34) and <1000 g (aOR = 1.34, 95% CI = 1.20-1.50). ROP ≥ Stage 2 increased at <28 weeks (aOR = 1.30, 95% CI = 1.16-1.46), <26 weeks (aOR = 1.57, 95% CI = 1.28-1.91), <1500 g (aOR = 1.18, 95% CI = 1.08-1.30), and <1000 g (aOR = 1.26, 95% CI = 1.13-1.42). CONCLUSION: O2 therapy guidelines since 2015 have resulted in decreased mortality but increased risk of ROP. Individualised NICU adjustments of ROP screening/follow-up methods are necessary to address the clinical burden.

Retinopathy of Prematurity and Glucose-6-Phosphate Dehydrogenase Activity: A Case-Control Study.

OBJECTIVE: To determine whether red blood cell glucose-6-phosphate dehydrogenase (G6PD) activity is associated with retinopathy of prematurity (ROP). METHODS: This case-control study was conducted in a Level-3 neonatal unit. Subjects were inborn boys with birth weight <2000 g. "Cases" were consecutive subjects with ROP of any severity. "Controls" were consecutive unrelated subjects without ROP. Recipients of blood or exchange transfusions were excluded. Sixty cases (out of 98 screened) and 60 controls (out of 93 screened) were enrolled. G6PD activity (quantitative assay) as the candidate risk factor was evaluated. RESULTS: Sixty cases with 60 controls [mean (SD) gestation 28.80 (2.2) and 30.60 (2.2) wk respectively] were compared. "Cases" had a higher median (1st, 3rd quartile) G6PD activity compared to "controls" [7.39 (4.7, 11.5) vs. 6.28 (4.2, 8.8) U/g Hb, p = 0.084]. G6PD activity was highest among ROP requiring treatment [8.68 (4.7, 12.3)] followed by ROP not requiring treatment [6.91 (4.4, 11.0)], followed by controls (plinear trend = 0.06). Gestation, birth weight, duration of oxygen, breastmilk feeding, and clinical sepsis were other variables associated with ROP on univariable analysis. On multivariable logistic regression, G6PD activity [Adjusted OR 1.14 (1.03, 1.25), p = 0.01] and gestation [Adjusted OR 0.74 (0.56, 0.97), p = 0.03] independently predicted ROP. C-statistic of the model was 0.76 (95% CI 0.67, 0.85). CONCLUSIONS: Higher G6PD activity was independently associated with ROP after adjusting for confounders. Each 1 U/g Hb increase in G6PD increased the odds of ROP by 14%. Severer forms of ROP were associated with higher levels of G6PD activity.

Increased Risk of Retinopathy of Prematurity in Donors with Twin-to-Twin Transfusion Syndrome: A Cohort Study.

INTRODUCTION: The purpose of this study was to evaluate the within-pair difference in retinopathy of prematurity (ROP) between donors and recipients with twin-to-twin transfusion syndrome (TTTS) and to identify risk factors for ROP development. METHODS: This retrospective cohort study included 147 TTTS twin pairs managed between 2002 and 2022 and eligible for ROP screening. Primary outcomes were any stage ROP and severe ROP. Secondary outcomes were hemoglobin at birth, red blood cell transfusions, mechanical ventilation days, postnatal steroids, and neonatal morbidity. Donor status was defined as having polyhydramnios pre-laser. RESULTS: Rates of any stage ROP (23% vs. 14%) and severe ROP (8% vs. 3%) were significantly higher in donors compared to recipients. Donors received a higher number of blood transfusions (1 [±1.9] versus 0.7 [±1.5]). Five factors were univariately associated with any stage ROP: donor status (odds ratio [OR] 1.9; 95% CI 1.3-2.9), lower gestational age (GA) at birth (OR 1.7; 95% CI 1.4-2.1), small for GA (OR 2.1; 95% CI 1.3-3.5), mechanical ventilation days (OR 1.1; 95% CI 1.1-1.2), and blood transfusions in phase 1 (OR 2.3; 95% CI 1.2-4.3). Three factors were independently associated with any stage ROP: donor status (OR 1.8; 95% CI 1.1-2.9), lower GA at birth (OR 1.6; 95% CI 1.2-2.1), and mechanical ventilation days (OR 1.1, 95% CI 1.0-1.1). Donor status was univariately associated with severe ROP (OR 2.3, 95% CI 1.1-5.0). CONCLUSION: Any stage ROP and severe ROP are detected twice as frequently in donors compared to recipients. Increased awareness for ROP is needed in donors, especially those with lower GA at birth and longer duration of mechanical ventilation.

Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Gut Microbiome and Retinopathy of Prematurity.

Retinopathy of prematurity (ROP), a leading cause of childhood blindness worldwide, is strongly associated with gestational age and weight at birth. Yet, many extremely preterm infants never develop ROP or develop only mild ROP with spontaneous regression. In addition, a myriad of other factors play a role in the retinal pathology, one of which may include the early gut microbiome. The complications associated with early gestational age include dysbiosis of the dynamic neonatal gut microbiome, as evidenced by the development of often concomitant conditions, such as necrotizing enterocolitis. Given this, alongside growing evidence for a gut-retina axis, there is an increasing interest in how the early intestinal environment may play a role in the pathophysiology of ROP. Potential mechanisms include dysregulation of vascular endothelial growth factor and insulin-like growth factor 1. Furthermore, the gut microbiome may be impacted by other known risk factors for ROP, such as intermittent hypoxia and sepsis treated with antibiotics. This mini-review summarizes the literature supporting these proposed avenues, establishing a foundation to guide future studies.