Project description:The immature retinas of preterm neonates are susceptible to insults that disrupt neurovascular growth, leading to retinopathy of prematurity. Suppression of growth factors due to hyperoxia and loss of the maternal-fetal interaction result in an arrest of retinal vascularisation (phase 1). Subsequently, the increasingly metabolically active, yet poorly vascularised, retina becomes hypoxic, stimulating growth factor-induced vasoproliferation (phase 2), which can cause retinal detachment. In very premature infants, controlled oxygen administration reduces but does not eliminate retinopathy of prematurity. Identification and control of factors that contribute to development of retinopathy of prematurity is essential to prevent progression to severe sight-threatening disease and to limit comorbidities with which the disease shares modifiable risk factors. Strategies to prevent retinopathy of prematurity will depend on optimisation of oxygen saturation, nutrition, and normalisation of concentrations of essential factors such as insulin-like growth factor 1 and ω-3 polyunsaturated fatty acids, as well as curbing of the effects of infection and inflammation to promote normal growth and limit suppression of neurovascular development.
Project description:ImportanceStudies report conflicting associations between preeclampsia and retinopathy of prematurity (ROP). This study provides explanations for the discrepancies to clarify the relationship between preeclampsia and ROP.ObjectiveTo evaluate the association of maternal preeclampsia and risk of ROP among infants in an unrestricted birth cohort and a restricted subcohort of preterm, very low birth weight (P-VLBW) infants.Design, setting, and participantsA retrospective review of 290 992 live births within the Intermountain Healthcare System in Utah from January 1, 2001, through December 31, 2010, was performed. Generalized estimating equations for logistic regressions with covariate adjustment were applied to relate ROP to preeclampsia among the full cohort and in a subcohort of P-VLBW infants born at younger than 31 weeks' gestation and weighing less than 1500 g.Main outcomes and measuresThe occurrence of ROP was related to maternal preeclampsia in the full cohort and in a subcohort of P-VLBW infants.ResultsIn the full cohort, 51% of the infants were male and the mean (SD) gestational age was 38.38 (1.87) weeks. In the P-VLBW cohort, 55% were male and the mean (SD) gestational age was 26.87 (2.40) weeks. In the full cohort, preeclampsia was associated with an increased risk of all ROP (adjusted odds ratio [aOR], 2.46; 95% CI, 2.17-2.79; P < .001), severe ROP (aOR, 5.21; 95% CI, 3.44-7.91; P < .001), infant death (aOR, 1.66; 95% CI, 1.16-2.38; P = .006), and giving birth to a P-VLBW infant (aOR, 7.74; 95% CI, 6.92-8.67; P < .001). In the P-VLBW subcohort, preeclampsia was inversely associated with the development of all ROP (aOR, 0.79; 95% CI, 0.68-0.92; P = .003), severe ROP (aOR, 0.62; 95% CI, 0.36-1.06; P = .08), and infant death (aOR, 0.19; 95% CI, 0.11-0.32; P < .001).Conclusions and relevancePreeclampsia was associated with an increased risk of developing ROP among an unrestricted cohort but with a reduced risk of ROP among a restricted subcohort of P-VLBW infants. Although the conflicting associations in the full and P-VLBW cohorts may reflect true differences, the association of a reduced risk of ROP among the P-VLBW subcohort also may reflect biases from restricting the cohort to prematurity, because prematurity is an outcome of preeclampsia.
Project description:Aggressive posterior retinopathy of prematurity (AP-ROP) is a severe form of ROP occurring in preterm infants that is characterized by rapid progression and prominent vascularity. We report the use of investigational bedside noninvasive optical coherence tomography angiography to visualize the slow and progressive perifoveal vascular formation in an infant with AP-ROP treated with bevacizumab. We also document extensive vascular shunts and morphological differences between arrested and growing retinal capillaries at the vascular wavefront.
Project description:BackgroundBlood loss and adult blood transfusions are common during the neonatal period in preterm infants. The objective of the study was to clarify if degree of loss of fetal haemoglobin (HbF) was associated with later retinopathy of prematurity (ROP).MethodsRetrospective observational cohort study. In total, 452 infants born <30 gestational weeks at a tertiary level neonatal intensive care unit in Sweden in 2009-2015 were included, 385 of whom had final ROP outcome. Mean fractions of HbF (%) during the first postnatal week were calculated from 11 861 arterial blood gas analyses. The relationship between fractions of HbF (%) and ROP was evaluated.ResultsThe mean (SD) gestational age (GA) at birth was 26.4 (1.8) weeks. In total, 104 (27 %) infants developed ROP. Higher fraction of HbF (%) was associated with a lower prevalence of ROP, OR by a 10% increase 0.83 (95% CI: 0.71 to 0.97; p=0.019), following adjustment for GA at birth, small for GA and sex. Infants with HbF (%) in the lowest quartile had OR of 22.0 (95% CI: 8.1 to 59.2; p<0.001) for ROP development compared with those in the highest quartile. The predictive ability (area under the curve) of HbF (%) in the full model during the first week was 0.849 for ROP.ConclusionsEarly low fraction of HbF is independently associated with abnormal retinal neurovascular development in the very preterm infant. The potential benefit of minimising blood loss on development of ROP will be investigated in a multicenter randomised trial (NCT04239690).
Project description:Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturbance is a significant and underexplored risk factor in the disease pathogenesis. Hyperglycemia and dyslipidemia correlate with the retinal neurovascular dysfunction in infants born prematurely. Nutritional and hormonal supplementation relieve metabolic stress and improve retinal maturation. Here we focus on the mechanisms through which metabolism is involved in preterm-birth-related retinal disorder from clinical and experimental investigations. We will review and discuss potential therapeutic targets through the restoration of metabolic responses to prevent disease development and progression.
Project description:ImportanceBinocular indirect ophthalmoscopy (BIO) examination for retinopathy of prematurity (ROP) is a well-known cause of repeated preterm infant stress.ObjectiveTo compare stress during investigational optical coherence tomography (OCT) imaging to that during BIO for ROP.Design, setting, and participantsThis cross-sectional study examined infants at the bedside in the intensive care nursery. Consecutive preterm infants enrolled in Study of Eye Imaging in Preterm Infants (BabySTEPS) who had any research OCT imaging as part of the study. Patients were recruited from June to November 2019, and analysis began April 2020.Main outcomes and measuresInfant stress was measured using modified components of a neonatal pain assessment tool before (baseline) and during OCT imaging and BIO examination of each eye.ResultsFor 71 eye examinations of 16 infants (mean [SD] gestational age, 27 [3] weeks; birth weight, 869 [277] g), change from baseline to each eye examination was lower during OCT imaging than during BIO and the difference between OCT imaging and BIO at each eye examination was significant for the following: infant cry score (first eye examination: mean [SD], 0.03 [0.3] vs 1.68 [1.2]; -1.65 [95% CI, -1.91 to -1.39]; second eye examination: mean [SD], 0.1 [0.3] vs 1.97 [1.2]; -1.87 [95% CI, -2.19 to -1.54]), facial expression (first eye: 3 [4%] vs 59 [83%]; -79% [95% CI, -87% to -72%]; second eye: 4 [6%] vs 61 [88%]; -83% [95% CI, -89% to -76%]), and heart rate (first eye: mean [SD], -7 [16] vs 13 [18]; -20 [95% CI, -26 to -14]); second eye: mean [SD], -3 [18] vs 20 [20] beats per minute; -23 [95% CI, -29 to -18]) (P < .001 for all). Change in respiratory rate and oxygen saturation did not differ between OCT imaging and BIO.Conclusions and relevanceWhile the role of OCT alone or in combination with BIO is currently unknown for ROP, these findings suggest that investigational OCT imaging of ROP is less stressful than BIO examination by a trained ophthalmologist.
Project description:At preterm birth, the retina is incompletely vascularized. Retinopathy of prematurity (ROP) is initiated by the postnatal suppression of physiological retinal vascular development that would normally occur in utero. As the neural retina slowly matures, increasing metabolic demand including in the peripheral avascular retina, leads to signals for compensatory but pathological neovascularization. Currently, only late neovascular ROP is treated. ROP could be prevented by promoting normal vascular growth. Early perinatal metabolic dysregulation is a strong but understudied risk factor for ROP and other long-term sequelae of preterm birth. We will discuss the metabolic and oxygen needs of retina, current treatments, and potential interventions to promote normal vessel growth including control of postnatal hyperglycemia, dyslipidemia and hyperoxia-induced retinal metabolic alterations. Early supplementation of missing nutrients and growth factors and control of supplemental oxygen promotes physiological retinal development. We will discuss the current knowledge gap in retinal metabolism after preterm birth.
Project description:PurposeTo delineate racial differences in the incidence and time course of ROP in a large cohort of premature infants.MethodsThe secondary analysis of data from the two Postnatal Growth and ROP Studies (G-ROP-1 and G-ROP-2) that were collected in 41 hospitals in North America from 2006 to 2017. According to self-reported maternal race, premature infants were classified into 3 groups: White (N = 5580), Black (N = 3252), and Asian (N = 353). Incidence, severity, and time course of ROP; plus disease; and postnatal weight gain rate were compared among racial groups.ResultsBlack infants had significantly smaller BW (mean 1035 vs. 1131 vs.1144 grams, P < .001) and lower GA (28.2 vs. 28.6, vs. 29.1 weeks, P < .001) than White and Asian infants. However, Black infants had lower incidences of severe ROP (11.1% vs. 12.4% vs. 11.9%), ROP (42.1% vs. 43.2% vs. 30.6%), and plus disease (3.6% vs. 6.3%, vs. 5.9%) than White and Asian infants (BW and GA adjusted risk ratio for Black vs. White 0.69 for severe ROP, 0.83 for ROP, 0.44 for plus disease, all P < .0001). Mean daily-weight-gain on days of life 11-20 and 21-30 were similar across groups (P > .05), but lower in Black and Asian infants on days 31-40 (P < .001). There were no differences in the timing of severe ROP and ROP across racial groups.ConclusionsDespite relatively lower GA, BW, and daily-weight-gain, Black preterm infants had lower incidences of ROP and plus disease than White preterm infants. The mechanisms for these differences require further investigation.