Refractive outcome in preterm newborns with ROP after propranolol treatment. A retrospective observational cohort study

Background: Recent explorative studies suggest that propranolol reduces retinopathy of prematurity (ROP) progression, but the short-term effects of propranolol treatment at 1 year of corrected age have not been extensively evaluated. Methods: A multi-center retrospective observational cohort study was conducted to assess the physical development and the refractive outcome of infants with prior ROP treated with propranolol. Forty-nine infants treated with propranolol were compared with an equal number of patients who did not receive any propranolol therapy and represent the control group, with comparable anthropometrical characteristics and stages of ROP. Results: The weight, length, and head circumference at 1 year of corrected age were similar between infants who had been treated, or not, with propranolol, without any statistically significant differences. Refractive evaluation at 1 year showed spherical equivalent values decreasing with the progression of ROP toward more severe stages of the disease, together with an increasing number of infants with severe myopia. On the contrary, no differences were observed between infants who had been treated with propranolol and those who had not. Conclusion: This study confirms that the progression of ROP induces an increase of refractive errors and suggests that propranolol itself does not affect the refractive outcome. Therefore, if the efficacy of propranolol in counteracting ROP progression is confirmed by further clinical trials, the conclusion will be that propranolol might indirectly improve the visual outcome, reducing the progression of ROP

Propranolol 0.2% eye micro-drops for retinopathy of prematurity : a prospective phase IIb study

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. Propranolol 0.1% eye micro-drops administered to newborns with stage 2 ROP are well-tolerated, but not sufficiently effective. Methods: A multi-center open-label trial was conducted to assess the safety and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1 ROP. The progression of the disease was evaluated with serial ophthalmologic examinations. Hemodynamic, respiratory, biochemical parameters, and propranolol plasma levels were monitored. Demographic and perinatal characteristics, co-morbidities and co-intervention incidences, together with ROP progression, were compared with a historical control group in the same centers participating in the trial. Results: Ninety-eight newborns were enrolled and compared with the historical control group. Populations were not perfectly homogeneous (as demonstrated by the differences in the Apgar score and the different incidence rate in surfactant administration and oxygen exposure). The progression to ROP stage 2 or 3 plus was significantly lower than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI 0.297- 0.916). No adverse effects related to propranolol were observed and the mean propranolol plasma level was significantly lower than the safety cutoff of 20 ng/mL. Unexpectedly, three newborns treated with oral propranolol before the appearance of ROP, showed a ROP that was unresponsive to propranolol eye micro-drops and required laser photocoagulation treatment. Conclusion: Propranolol 0.2% eye micro-drops were well-tolerated and appeared to reduce the ROP progression expected on the basis of a comparison with a historical control group. Propranolol administered too early appears to favor a more aggressive ROP, suggesting that a \u3b2-adrenoreceptor blockade is only useful during the proliferative phase. Further randomized placebo-controlled trials are required to confirm the current results

Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial

Background: Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). Methods: A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23–32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. Discussion: Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. Trial registration: ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014–005472-2

Born into an isolating world: family-centred care for babies born to mothers with COVID-19Research in context

Summary: Background: The benefits of facilitating breastmilk feeding and close contact between mother and neonate (family-centred care; FCC) in the perinatal period are well-established. The aim of this study was to determine how the delivery of FCC practices were impacted for neonates born to mothers with perinatal SARS-CoV-2 infection during the COVID-19 pandemic. Methods: Neonates born to mothers with confirmed SARS-CoV-2 infection during pregnancy were identified from the ‘EsPnIC Covid paEdiatric NeonaTal REgistry’ (EPICENTRE) multinational cohort between 10 March 2020 and 20 October 2021. The EPICENTRE cohort collected prospective data on FCC practices. Rooming-in and breastmilk feeding practice were the main outcomes, and factors influencing each were determined. Other outcomes included mother-baby physical contact prior to separation and the pattern of FCC components relative to time and local site guidelines. Findings: 692 mother-baby dyads (13 sites, 10 countries) were analysed. 27 (5%) neonates were positive for SARS-CoV-2 (14 (52%) asymptomatic). Most sites had policies that encouraged FCC during perinatal SARS-CoV-2 infection for most of the reporting period. 311 (46%) neonates roomed-in with their mother during the admission. Rooming-in increased over time from 23% in March–June 2020 to 74% in January–March 2021 (boreal season). 330 (93%) of the 369 separated neonates had no FCC physical contact with their mother prior, and 319 (86%) were asymptomatic. Maternal breastmilk was used for feeding in 354 (53%) neonates, increasing from 23% to 70% between March–June 2020 and January–March 2021. FCC was most impacted when mothers had symptomatic COVID-19 at birth. Interpretation: This is the largest report of global FCC practice during the COVID-19 pandemic to date. The COVID-19 pandemic may have impacted FCC despite low perinatal transmission rates. Fortunately, clinicians appear to have adapted to allow more FCC delivery as the COVID-19 pandemic progressed. Funding: The National Health and Medical Research Council (Australia): Grant ID 2008212 (DGT), Royal Children’s Hospital Foundation: Grant ID 2019–1155 (EJP), Victorian Government Operational Infrastructure Support Program