Severe Retinopathy Of Prematurity Research Articles

Daily Oxygen Supplementation and Risk of Retinopathy of Prematurity

ABSTRACT Purpose Excessive oxygen supplementation increases risk of retinopathy of prematurity (ROP). While numerous oxygen parameters could be considered when predicting ROP (saturation targets, actual saturation, fraction of inspired oxygen, etc.), complicated measures are impractical as screening criteria. We sought to develop a simple, clinically useful measure of daily oxygen supplementation during ages 0–28 days to improve prediction of ROP Methods Secondary analysis of two Postnatal Growth and ROP (G-ROP) Study cohorts (G-ROP-1 and G-ROP-2) at 45 hospitals. Infants with a known ROP outcome and complete oxygen data were included. Associations between severe ROP and days on supplemental oxygen (FiO2 > 21%), during ages 0–28 days (DSO28) were assessed, controlling for birth weight (BW) and gestational age (GA). New screening criteria incorporating DSO were developed and compared to current guidelines. Results Among 8,949 studied infants, 459 (5.1%) developed type 1 ROP. DSO28 was associated with severe ROP (adjusted-OR 1.05 per day supplemental oxygen, 95%CI 1.03–1.07, p < .0001). The following criteria had 100% sensitivity for type 1 ROP and higher specificity than current guidelines: new BW/GA criteria with DSO (BW<901 g, GA<26 weeks, or DSO >3), 23.4% fewer infants examined; modified G-ROP criteria including DSO, 29.0% fewer infants; original G-ROP criteria, 31.8% fewer infants. Conclusion In high-level neonatal-care settings, incorporating DSO (a simple measure of oxygen supplementation) into screening criteria improves sensitivity and specificity for type 1 ROP over current BW-GA criteria, but does not perform as well as the validated G-ROP criteria.

Birth during on-call period: Impact of care organization on mortality and morbidity of very premature neonates.

ObjectivesThe evidence that risks of morbidity and mortality are higher when very premature newborns are born during the on-call period is inconsistent. This study aimed to assess the impact of this situation among other determinants of outcomes, particularly newborn characteristics and care organization.MethodsObservational study including all infants born < 30 weeks’ gestation in a French tertiary perinatal center between 2007 and 2020. On-call period corresponded to weekdays between 6:30 p.m. and 8:30 a.m., weekends, and public holidays. The primary endpoint was survival without severe morbidity, including grade 3–4 intraventricular hemorrhage (IVH), cystic periventricular leukomalacia, necrotizing enterocolitis, severe bronchopulmonary dysplasia (BPD), and severe retinopathy of prematurity. The relationship between admission and outcome was assessed by an adjusted odds ratio (aOR) on the propensity of being born during on-call period and expressed vs. weekday. Secondary analyses were carried out in extremely preterm newborns (<27 weeks’ gestation), in cases of early death (within 7 days), and before (2007–2013, 51.5% of the cohort) vs. after (2014–2020, 48.5% of the cohort) the implementation of a pediatrician-nurse team dedicated to newborn care in the delivery room.ResultsA total of 1,064 infants [27.9 (26.3; 28.9) weeks, 947 (760; 1,147) g] were included: 668 during the on-call period (63%) and 396 (37%) on weekdays. For infants born on weekdays, survival without severe morbidity was 54.5% and mortality 19.2%. During on-call, these rates were 57.3% [aOR 1.08 (0.84–1.40)] and 18.4% [aOR 0.93 (0.67–1.29)]. Comparable rates of survival without severe morbidity [aOR 1.42 (0.87–2.34)] or mortality [aOR 0.76 (0.47–1.22)] were observed in extremely preterm infants. The early death rate was 6.4% on weekdays vs. 8.2% during on-call [aOR 1.44 (0.84–2.48)]. Implementation of the dedicated team was associated with decreased rates of mortality [aOR 0.57 (0.38, 0.85)] and grade 3–4 IVH [aOR 0.48 (0.30, 0.75)], and an increased rate of severe BPD [aOR 2.16 (1.37, 3.41)], for infants born during on-call.ConclusionIn this cohort, most births of very premature neonates occurred during the on-call period. A team dedicated to newborn care in the delivery room may have a favorable effect on the outcome of infants born in this situation.

Correlation between apelin and VEGF levels in retinopathy of prematurity: a matched case–control study

BackgroundAlthough several clinical studies have analysed the relationship between the levels of vascular endothelial growth factor (VEGF) and apelin-13 in venous blood and retinopathy of prematurity (ROP), no definitive conclusions have been reached. This study aimed to investigate the relationship between apelin-13 levels and VEGF levels and ROP.MethodsDifferences in plasma apelin-13 and VEGF levels were analysed in two groups of infants born with birth weight < 1500 g and gestational age < 32 weeks at Peking University People’ s Hospital. One group comprised infants diagnosed with ROP and the other group was a control group comprising infants without ROP.ResultsApelin-13 levels were significantly lower in the ROP group than in the control group, while VEGF levels showed the opposite result (both P < 0.001). Infants with severe ROP had lower apelin-13 levels and higher VEGF levels than with mild ROP (both P < 0.05).The receiver operating characteristic curve for apelin-13 level as the indicator of ROP showed that a cut-off value of 119.6 pg/mL yielded a sensitivity of 84.8% and a specificity of 63.6%, while for VEGF level, the cut-off value of 84.3 pg/mL exhibited a sensitivity of 84.8% and a specificity of 66.7%.ConclusionsPlasma apelin-13 and VEGF levels at 4–6 weeks of age may play a role in assisting the diagnosis of ROP.

Peripapillary Retinal Nerve Fiber Layer Thickness in Adults Born Extremely, Very, and Moderately Preterm With and Without Retinopathy of Prematurity: Results From the Gutenberg Prematurity Eye Study (GPES)

This study investigated whether prematurity and associated factors or prenatal growth restriction have long-term effects on the peripapillary retinal nerve fiber layer (pRNFL) in adulthood. Retrospective cohort study. The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. Selected individuals born term and preterm (age 18-52 years) were examined with spectral-domain optical coherence tomography (SD-OCT) in adulthood, and perinatal medical charts were reviewed. The pRNFL thickness was measured using SD-OCT. Univariate and multivariable linear regression analyses were conducted to investigate associations between pRNFL and gestational age (GA; categorical), birth weight percentile (categorical), retinopathy of prematurity (ROP) occurrence, and treatment and other perinatal parameters with adjustment for age, sex, and spherical equivalent. In total, 766 eyes of 406 preterm and full-term individuals were included (mean age 28.4 ± 8.6 years, 228 females). After adjustment for age, sex, and spherical equivalent, global pRNFL thinning was associated with moderate (GA=33-36 wk, β=-4.68, P < .001), very (GA=29-32 wk, β=-5.72, P < .001), and extreme (GA ≤ 28 wk, β=-8.69, P < .001) prematurity but not with low birth weight percentile (<25th percentile, P=.9) and ROP occurrence (P=.9) in multivariable analysis. ROP treatment was associated with increased pRNFL in the temporal sector (P=.002). Maternal smoking during pregnancy showed an association with pRNFL thinning (P=.07). Our data indicate that the more preterm individuals are born the more pRNFL thinning occurs, whereas prenatal growth restriction and postnatal occurrence of ROP show less effects on pRNFL thickness. Furthermore, individuals with severe ROP with treatment but not lower ROP stages without treatment showed an increased temporal pRNFL thickness.

Outcomes at discharge of preterm infants born

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.

Semi-automated measures of foveal development by handheld swept-source optical coherence tomography may correlate with retinopathy of prematurity severity

Handheld swept-source optical coherence tomography (SS-OCT) is a noncontact technique to image retinal layers; however, correlation between foveal maturity and retinopathy of prematurity (ROP) severity is not well described.

Effect of gender on retinopathy of prematurity severity among multiple gestation infants

Previous studies suggest a “male disadvantage” among premature infants, perhaps due to genetic, hormonal, and/or immunological differences between genders which contribute to worse systemic outcomes. This association may extend to retinopathy of prematurity (ROP) severity. The purpose of this study is to explore whether gender affects ROP severity among mixed gender multiple gestation premature infants.

Evaluation of risk factors, treatment, and outcome of patients with retinopathy of prematurity at tertiary hospital

Retinopathy of prematurity (ROP) is a proliferative vitreoretinopathy affecting premature infants which a leading cause of childhood blindness worldwide. Screening is scheduled according to gestational age and birth weight to detect ROP development and to determine the appropriate timing of treatment. Screening also identified any risk factors for ROP development. Aim of this study is to evaluate risk factors, choice of treatment and outcome based on severity of ROP.

Refractive outcomes after primary bevacizumab followed by laser versus primary laser alone for retinopathy of prematurity

Children with severe retinopathy of prematurity (ROP) commonly develop myopia or high myopia. One proposed benefit of intravitreal bevacizumab (IVB) over laser is decreased myopia; however, many IVB eyes are later treated with laser. We sought to compare incidence of myopia and high myopia after primary IVB followed by laser photocoagulation (VEGF/LASER) to primary laser (LASER).

Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial

Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome. We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076. Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia. Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction. French Ministry of Health.

Changes Overtime in Perinatal Management and Outcomes of Extremely Preterm Infants in One Tertiary Care Romanian Center.

Background and Objectives: Extremely preterm infants were at increased risk of mortality and morbidity. The purpose of this study was to: (1) examine changes over time in perinatal management, mortality, and major neonatal morbidities among infants born at 250–286 weeks’ gestational age and cared for at one Romanian tertiary care unit and (2) compare the differences with available international data. Material and Methods: This study consisted of infants born at 250–286 weeks in one tertiary neonatal academic center in Romania during two 4-year periods (2007–2010 and 2015–2018). Major morbidities were defined as any of the following: severe intraventricular hemorrhage (IVH), severe retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD). Adjusted logistic regression models examined the association between the mortality and morbidity outcome and the study period. Results: The two cohorts differed with respect to antenatal antibiotics and rates of cesarean birth but had similar exposure to antenatal steroids and newborn referral to the tertiary care center. In logistic regression analyses, infants in the newer compared to the older cohort had a lower incidence of death (OR: 0.19; 95% CI: 0.11–0.35), a lower incidence of IVH (OR: 0.26; 95% CI: 0.15–0.46), and increased incidence of NEC (OR: 19.37; 95% CI: 2.41–155.11). Conclusions: Changes over time included higher use of antenatal antibiotics and cesarean delivery and no change in antenatal steroids administration. Overall mortality was lower in the newer cohort, especially for infants 250–266 weeks’ gestation, NEC was higher while BPD and ROP were not different.

Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity

Laser photocoagulation, which is the standard treatment for retinopathy of prematurity (ROP), can have adverse events. Studies of anti-vascular endothelial growth factor injections have suggested efficacy in the treatment of ROP, but few studies have directly compared them with laser treatments. To compare intravitreal aflibercept vs laser photocoagulation in infants with ROP requiring treatment. This noninferiority, phase 3, 24-week, randomized clinical trial was conducted in 27 countries (64 hospital sites) throughout Asia, Europe, and South America. Overall, 118 infants (gestational age ≤32 weeks at birth or birth weight ≤1500 g) with ROP severity (zone I stage 1+ [stage 1 plus increased disease activity], zone I stage 2+, zone I stage 3, zone I stage 3+, zone II stage 2+, or zone II stage 3+) requiring treatment or with aggressive posterior ROP in at least 1 eye were enrolled between September 25, 2019, and August 28, 2020 (the last visit occurred on February 12, 2021). Infants were randomized 2:1 to receive a 0.4-mg dose of intravitreal aflibercept (n = 75) or laser photocoagulation (n = 43) at baseline. Additional treatment was allowed as prespecified. The primary outcome was the proportion of infants without active ROP and unfavorable structural outcomes 24 weeks after starting treatment (assessed by investigators). The requirement for rescue treatment was considered treatment failure. Intravitreal aflibercept was deemed noninferior if the lower limit of the 1-sided 95% bayesian credible interval for the treatment difference was greater than -5%. Among 118 infants randomized, 113 were treated (mean gestational age, 26.3 [SD, 1.9] weeks; 53 [46.9%] were female; 16.8% had aggressive posterior ROP, 19.5% had zone I ROP, and 63.7% had zone II ROP) and 104 completed the study. Treatment (intravitreal aflibercept: n = 75; laser photocoagulation: n = 38) was mostly bilateral (92.9%), and 82.2% of eyes in the intravitreal aflibercept group received 1 injection per eye. Treatment success was 85.5% with intravitreal aflibercept vs 82.1% with laser photocoagulation (between-group difference, 3.4% [1-sided 95% credible interval, -8.0% to ∞]). Rescue treatment was required in 4.8% (95% CI, 1.9% to 9.6%) of eyes in the intravitreal aflibercept group vs 11.1% (95% CI, 4.9% to 20.7%) of eyes in the laser photocoagulation group. The serious adverse event rates were 13.3% (ocular) and 24.0% (systemic) in the intravitreal aflibercept group compared with 7.9% and 36.8%, respectively, in the laser photocoagulation group. Three deaths, which occurred 4 to 9 weeks after intravitreal aflibercept treatment, were considered unrelated to aflibercept by the investigators. Among infants with ROP, intravitreal aflibercept compared with laser photocoagulation did not meet criteria for noninferiority with respect to the primary outcome of the proportion of infants achieving treatment success at week 24. Further data would be required for more definitive conclusions regarding the comparative effects of intravitreal aflibercept and laser photocoagulation in this population. ClinicalTrials.gov Identifier: NCT04004208.

Association of platelet deficiency with severe retinopathy of prematurity: a review.

The aim of this review was to compile existing evidence on the role of platelets in the development of severe retinopathy of prematurity (ROP), highlight the strengths and weaknesses of the available studies and critically discuss the reported data. A comprehensive literature search was conducted on PubMed from January 2000 to January 2022, and the reference lists of the included studies were screened manually. There were 19 primary studies that fulfilled the eligibility criteria. Experimental research indicated lower platelet count in mice oxygen-induced retinopathy model compared with normoxia controls, while platelet transfusions suppressed neovascularisation. The latter finding was not consistently confirmed in clinical research, where a low platelet count, an increased number of thrombopenic episodes and of platelet transfusions have all been implicated in the development of ROP requiring treatment, either type I or aggressive posterior or both. However, existing studies exhibit significant clinical heterogeneity and present methodological limitations that imperil their reliability and validity. Platelet deficiency has been associated with severe ROP. However, critical thresholds of platelet parameters are still unrecognised. Future research is required to determine whether platelet parameters can be predictive biomarkers for ROP requiring treatment and at what thresholds.

Early and late onset sepsis and retinopathy of prematurity in a cohort of preterm infants

This study investigates the impact of antenatal and postnatal infection or inflammation on the onset and progression of Retinopathy of Prematurity (ROP). We retrospectively collected clinical and demographic data of preterm infants with birth weight ≤ 1500 g or gestational age < 30 weeks admitted to the neonatal intensive care unit of Verona from 2015 to 2019. Uni- and multivariable analysis was performed to evaluate the potential effect of selected variables on the occurrence of any stage ROP and its progression to severe ROP, defined as ROP requiring treatment. Two hundred and eighty neonates were enrolled and 60 of them developed ROP (21.4%). Oxygen need for 28 days and late-onset sepsis (LOS) increased the risk of any grade ROP after adjusting for birth weight and gestational age (OR 6.35, 95% CI 2.14–18.85 and OR 2.49, 95% CI 1.04–5.94, respectively). Days of mechanical ventilation and of non-invasive ventilation increased the risk of progression to severe ROP after adjusting for birth weight and gestational age (OR 1.08, CI 1.02–1.14 and OR 1.06, CI 1.01–1.11, respectively). Exposure to infection with production of inflammatory mediators may contribute to increase the risk of ROP occurrence in very preterm neonates.

The association between amniotic fluid-derived inflammatory mediators and the risk of retinopathy of prematurity.

Prenatal and perinatal infections and inflammation appear to associated with the development of retinopathy of prematurity (ROP). In this study, we evaluated whether inflammatory mediators in amniotic fluid (AF) retrieved during cesarean delivery influence the development of ROP in very low birth weight (VLBW) infants.This retrospective study included 16 and 32 VLBW infants who did and did not develop any stage of ROP, respectively. Each infant with ROP was matched with 2 infants without ROP based on days of ventilation care, gestational age, and birth weight. AF was obtained during cesarean delivery, and the levels of intra-amniotic inflammatory mediators such as interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, matrix metalloproteinase (MMP)-2, MMP-8, MMP-9, and tumor necrosis factor (TNF)-α were measured using a Human Magnetic Luminex assay (R&D Systems, Minneapolis, MN). The differences in the levels of inflammatory mediators according to the presence or absence of ROP were compared.In patients who developed ROP, the level of MMP-2 in the AF was significantly increased (P = .011), whereas the levels of IL-10 and TNF-α were significantly decreased (P = .028 and .046, respectively) compared with those in infants who did not develop ROP. The levels of the other mediators were not significantly different between the 2 groups. Multivariate regression analysis showed that MMP-2 was a risk factor for the development of ROP (odds ratio, 2.445; 95% confidence interval, 1.170-5.106; P = .017).The concentration of MMP-2 in AF is an independent factor in the development of ROP. Further studies are needed to determine whether the levels of inflammatory mediators in AF affect the ROP severity.

Outcomes of Preterm Infants Who Experienced Unplanned Extubation.

Unplanned extubation (UE) is associated with adverse outcomes. The aim of the study was to compare the clinical outcomes in preterm infants who experienced at least one UE to those who did not experience any UE. The matched cohort study compared ventilated preterm infants < 32 weeks who experienced UE to those who did not experience any UE. The main outcomes were duration of mechanical ventilation after matching, duration of hospital stay, retinopathy of prematurity (ROP) requiring intervention, and bronchopulmonary dysplasia (BPD). Forty-seven infants were included in each group. The groups were matched for mechanical ventilation duration before UE, birth gestation, and birthweight. The duration of mechanical ventilation after matching (adjusted odds ratio [aOR] 14.8 [11.2-18.4], P = <.001), the total length of stay in the hospital (aOR 16.4 [3.7-29.2], P = .01), and severe ROP (aOR 6.7 [1.7-27.0], P = .007) were significantly higher in infants who experienced UE. After adjusting for mechanical ventilation duration, UE was not associated with ROP or BPD. However, infants who spent longer time on mechanical ventilation had higher odds of developing ROP (aOR 1.1 [1.0-1.2], P = .004) and BPD (aOR 1.5 [1.1-2.1], P = .01). Sensitivity analysis including infants who had UE and managed on noninvasive respiratory support showed significant association between UE and the outcomes of duration of mechanical ventilation, hospital length of stay, ROP, and BPD. Infants who experienced UE had higher odds of spending longer time on mechanical ventilation and spent significantly more days in the hospital.

Impact of maternal age on neonatal outcomes among very preterm infants admitted to Chinese neonatal intensive care units: a multi-center cohort study.

BackgroundThe percentage of advanced maternal age (aged over 35 years) mothers has been rising across the world, the evidence of maternal age on neonatal outcomes from low- and middle-income countries is scarce. Our objective was to evaluate the effect of maternal age on mortality and major morbidity among very preterm infants admitted to Chinese neonatal intensive care units.MethodsData from a retrospective multi-center cohort of all complete care very preterm infants admitted to 57 neonatal intensive care units that participated in the Chinese Neonatal Network from January 1st to December 31st, 2019 were analyzed. Neonatal outcomes including mortality or any major morbidity, defined as necrotizing enterocolitis stage 2 or 3, moderate & severe bronchopulmonary dysplasia, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. A multiple logistic regression model was constructed to analyze the independent association between maternal age and neonatal outcome.ResultsAmong 7,698 eligible newborns, 80.5% of very preterm infants were born to mothers between the ages of 21 and 35 years, with 18.0% born to mothers >35 years and 1.5% born to mothers <21 years. Higher rates of maternal hypertension, maternal diabetes, cesarean deliveries, antenatal steroid usage were noted as maternal age increased. The proportion of prenatal care, cesarean section, antenatal steroid usage and inborn for very preterm infants born to mothers <21 years was lower than those of mothers of other ages. Compared to the ages of 21–35 years group, the odds of severe intraventricular hemorrhage (adjusted odd ratio: 2.00, 95% CI: 1.08–3.71) was significantly higher in the ages of 15–20 years group. Increasing maternal age was associated with higher rates of small for gestational age and lower birth weight of very preterm infants, but no correlation between advanced maternal age and very preterm infants mortality or major morbidity.ConclusionsAmong very preterm infants, increasing maternal age was associated with higher rates of small for gestational age but not neonatal mortality or major morbidity. Young maternal age may increase the risk of severe intraventricular hemorrhage of very preterm infants.

Intravitreal Bevacizumab Is Associated With Prolonged Ventilatory Support in Preterm Infants With Bronchopulmonary Dysplasia

Intravitreal bevacizumab (IVB), an anti-vascular endothelial growth factor (VEGF) antibody, is a widely adopted treatment for retinopathy of prematurity (ROP). Although animal studies have demonstrated that IVB inhibits alveologenesis in neonatal rat lung, the clinical influence of IVB on respiratory outcomes has not been studied. Does IVB affect the respiratory outcome in preterm infants with bronchopulmonary dysplasia? We retrospectively assessed very low birth weight (VLBW) preterm infants admitted to our neonatal ICU between January 2016 and June 2021. Furthermore, we evaluated the short-term respiratory outcomes after IVB therapy in VLBW preterm infants requiring ventilatory support at 36weeks' postmenstrual age (PMA). One hundred seventy-four VLBW preterm infants with bronchopulmonary dysplasia were recruited. Eighty-eight infants showed ROP onset before being ventilator free, and 78 infants received a diagnosis of the most severe ROP before being ventilator free. Among them, 32 received a diagnosis with type 1 ROP and received IVB treatment. After adjusting for gestational age, birth body weight, and baseline respiratory status, we discovered that IVB is associated significantly with prolonged ventilatory support and a lower likelihood of becoming ventilator free (hazard ratio, 0.53; P= .03). IVB may have a short-term respiratory adverse effect in patients requiring ventilatory support at 36weeks' PMA. Therefore, long-term follow-up for respiratory outcomes may be considered in VLBW infants who receive IVB treatment.

Effect of Enteral Long-Chain Polyunsaturated Fatty Acids on Retinopathy of Prematurity: A Systematic Review and Meta-Analysis

Background: Long-chain polyunsaturated fatty acids (LCPUFA) are critical for the maturation of the brain and retina. Retinopathy of prematurity (ROP) is a preventable cause of blindness in preterm infants. LCPUFA have anti-inflammatory, antioxidant, and antiangiogenesis effects. Supplementation of enteral LCPUFA might mitigate the incidence of ROP in these infants. Available limited randomized studies showed promising results. We aimed to assess the effect of enteral supplementation of LCPUFA on ROP in preterm infants. Methods: We followed PRISMA guidelines and searched MEDLINE, Cumulative Index of Nursing and Allied Health Literature, Embase, and Cochrane Registry from 1990 to 2021 for the studies that examined the effects of enteral LCPUFA and ROP in preterm infants. We included the studies that satisfied the predefined inclusion criteria. RevMan 5.3 software derived the forest plot of pooled relative risk. We assessed the quality of all the included studies using GRADE recommendations. Results: Nine studies were eligible for the meta-analysis involving 2,482 infants. Of the nine RCTs, six studies provided LCPUFA (DHA/AA) as a separate intervention in different concentrations, and three studies provided formula milk enriched with LCPUFA. In addition, five studies recruited infants below 32 weeks of gestational age. Supplementation of LCPUFA did not reduce the incidence of severe ROP (RR 0.71, 95% CI: 0.50–1.01, 5 studies, 1,822 infants) with very low CoE or any ROP (RR 0.95, 95% CI: 0.73–1.12, 6 studies, 1,177 infants) with very low CoE or ROP requiring treatment (RR 0.92, 95% CI: 0.62–1.38, 4 studies, 1,395 infants) with very low CoE. Regarding safety outcomes, enteral LCPUFA did not increase the risk of necrotizing enterocolitis or mortality. Discussion/Conclusion: Supplementation of enteral LCPUFA to preterm infants did not reduce ROP incidence; however, there was a trend toward benefit in mitigating severe form of ROP. More well-designed, large, randomized controlled studies are warranted.

Development and Validation of a Deep Learning Model to Predict the Occurrence and Severity of Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is the leading cause of childhood blindness worldwide. Prediction of ROP before onset holds great promise for reducing the risk of blindness. To develop and validate a deep learning (DL) system to predict the occurrence and severity of ROP before 45 weeks' postmenstrual age. This retrospective prognostic study included 7033 retinal photographs of 725 infants in the training set and 763 retinal photographs of 90 infants in the external validation set, along with 46 characteristics for each infant. All images of both eyes from the same infant taken at the first screening were labeled according to the final diagnosis made between the first screening and 45 weeks' postmenstrual age. The DL system was developed using retinal photographs from the first ROP screening and clinical characteristics before or at the first screening in infants born between June 3, 2017, and August 28, 2019. Two models were specifically designed for predictions of the occurrence (occurrence network [OC-Net]) and severity (severity network [SE-Net]) of ROP. Five-fold cross-validation was applied for internal validation. Area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity to evaluate the performance in ROP prediction. This study included 815 infants (450 [55.2%] boys) with mean birth weight of 1.91 kg (95% CI, 1.87-1.95 kg) and mean gestational age of 33.1 weeks (95% CI, 32.9-33.3 weeks). In internal validation, mean AUC, accuracy, sensitivity, and specificity were 0.90 (95% CI, 0.88-0.92), 52.8% (95% CI, 49.2%-56.4%), 100% (95% CI, 97.4%-100%), and 37.8% (95% CI, 33.7%-42.1%), respectively, for OC-Net to predict ROP occurrence and 0.87 (95% CI, 0.82-0.91), 68.0% (95% CI, 61.2%-74.8%), 100% (95% CI, 93.2%-100%), and 46.6% (95% CI, 37.3%-56.0%), respectively, for SE-Net to predict severe ROP. In external validation, the AUC, accuracy, sensitivity, and specificity were 0.94, 33.3%, 100%, and 7.5%, respectively, for OC-Net, and 0.88, 56.0%, 100%, and 35.3%, respectively, for SE-Net. In this study, the DL system achieved promising accuracy in ROP prediction. This DL system is potentially useful in identifying infants with high risk of developing ROP.