Dataset Information

Neurodevelopmental Outcomes in Infants with Retinopathy of Prematurity and Bevacizumab Treatment.

ABSTRACT:

Purpose

The current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB) for the treatment of retinopathy of prematurity (ROP) up to the age of 2 years.

Methods

The study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment. Main Outcome Measures were neurodevelopmental outcomes of the patients after treatment were assessed by Bayley Scales for Infant Development.

Results

Sixty-one patients who finished the neurodevelopmental survey were included. No detrimental effects on neurodevelopment were found in IVB group compared with the patients who received laser treatment only. The patients in the IVB + laser group had a higher incidence of significant mental (p = 0.028) and psychomotor (p = 0.002) impairment at 24 months than the patients in the laser group. The odds ratio of having severe psychomotor defects in the IVB + laser group was 5.3 compared with the laser group (p = 0.041). The causal source for the differences that were detected remained unknown due to lack of randomization in the study and accompanying bias in patient selection.

Conclusions

Two years after laser and/or intravitreal injections of bevacizumab for infants with retinopathy of prematurity, no difference on neurodevelopment for those who received only bevacizumab versus only laser treatment were found. Those infants who required rescue therapy with laser or bevacizumab injection after initial, unsuccessful treatment showed some detrimental, neurodevelopmental effects.

SUBMITTER: Lien R

PROVIDER: S-EPMC4729687 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Neurodevelopmental Outcomes in Infants with Retinopathy of Prematurity and Bevacizumab Treatment.

Lien Reyin R Yu Mu-Hsien MH Hsu Kuang-Hung KH Liao Pei-Ju PJ Chen Yen-Po YP Lai Chi-Chun CC Wu Wei-Chi WC

PloS one 20160127 1

<h4>Purpose</h4>The current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB) for the treatment of retinopathy of prematurity (ROP) up to the age of 2 years.<h4>Methods</h4>The study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment. Main Outcome Measures were ...[more]

PMID: 26815000

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Project description:Among extremely preterm infants, we evaluated whether bevacizumab therapy compared with surgery for retinopathy of prematurity (ROP) is associated with adverse outcomes in early childhood. This study was a retrospective analysis of prospectively collected data on preterm (22-26 + 6/7 weeks' gestational age) infants admitted to the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers who received bevacizumab or surgery exclusively for ROP. The primary outcome was death or severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age (Bayley Scales of Infant and Toddler Development, Third Edition cognitive or motor composite score <70, Gross Motor Functional Classification Scale level ≥2, bilateral blindness or hearing impairment). The cohort (N = 405; 214 [53%] boys; median [interquartile range] gestational age: 24.6 [23.9-25.3] weeks) included 181 (45%) infants who received bevacizumab and 224 (55%) who underwent ROP surgery. Infants treated with bevacizumab had a lower median (interquartile range) birth weight (640 [541-709] vs 660 [572.5-750] g; P = .02) and longer durations of conventional ventilation (35 [21-58] vs 33 [18-49] days; P = .04) and supplemental oxygen (112 [94-120] vs 105 [84.5-120] days; P = .01). Death or severe NDI (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.94 to 2.14) and severe NDI (aOR 1.14; 95% CI 0.76 to 1.70) did not differ between groups. Odds of death (aOR 2.54 [95% CI 1.42 to 4.55]; P = .002), a cognitive score <85 (aOR 1.78 [95% CI 1.09 to 2.91]; P = .02), and a Gross Motor Functional Classification Scale level ≥2 (aOR 1.73 [95% CI 1.04 to 2.88]; P = .04) were significantly higher with bevacizumab therapy. In this multicenter cohort of preterm infants, ROP treatment modality was not associated with differences in death or NDI, but the bevacizumab group had higher mortality and poor cognitive outcomes in early childhood. These data reveal the need for a rigorous appraisal of ROP therapy.

Project description:ImportanceCirculating levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) are important in the course of brain injury in adults, but longitudinal postnatal circulating levels in preterm infants have not been investigated.ObjectivesTo examine postnatal longitudinal serum levels of NfL and GFAP in preterm infants during the first 15 weeks of life and to explore possible associations between these biomarkers, neonatal morbidities, and neurodevelopmental outcomes at 2 years.Design, setting, and participantsThis cohort study used data from 3 clinical studies, including 221 infants born before 32 weeks gestational age (GA) from 1999 to 2015; neurodevelopmental outcomes were evaluated in 120 infants. Data were collected at tertiary-level neonatal intensive care units in Gothenburg, Lund, and Uppsala, Sweden. Data analysis was conducted from January to October 2020.ExposurePreterm birth.Main outcomes and measuresSerum NfL and GFAP levels, retinopathy of prematurity (ROP), intraventricular hemorrhage, and Bayley Scales of Infant Development II and III at 2 years of age, analyzed by multivariate logistic regression measured by odds ratio (OR), and receiver operating characteristic curve (ROC) analysis. Area under the curve (AUC) was also measured.ResultsThe 221 included infants (108 [48.9%] girls) had a mean (SD) GA at birth of 26.5 (2.1) weeks and a mean (SD) birth weight of 896 (301) grams. NfL levels increased after birth, remaining high during the first 4 weeks of life before declining to continuously low levels by postnatal age 12 weeks (median [range] NfL level at birth: 58.8 [11.5-1371.3] ng/L; 1 wk: 83.5 [14.1-952.2] ng/L; 4 wk: 24.4 [7.0-306.0] ng/L; 12 wk: 9.1 [3.7-57.0] ng/L). In a binary logistic regression model adjusted for GA at birth, birth weight SD score, Apgar status at 5 minutes, and mode of delivery, the NfL AUC at weeks 2 to 4 was independently associated with any ROP (OR, 4.79; 95% CI, 2.17-10.56; P < .001). In an exploratory analysis adjusted for GA at birth and sex, NfL AUC at weeks 2 to 4 was independently associated with unfavorable neurodevelopmental outcomes at 2 years corrected age (OR per 10-unit NfL increase, 1.07; 95% CI, 1.02-1.13; P = .01). Longitudinal GFAP levels were not significantly associated with neonatal morbidity or neurodevelopmental outcome.Conclusions and relevanceIn this study, high NfL levels during the first weeks of life were associated with ROP and poor neurodevelopmental outcomes at 2 years of age. Associations between NfL and later neurovascular development in infants born prematurely should be investigated further.

Project description:ImportanceIntravitreous bevacizumab (0.25 mg to 0.625 mg) is commonly used to treat type 1 retinopathy of prematurity (ROP), but there are concerns about systemic toxicity, particularly the risk of neurodevelopmental delay. A much lower dose may be effective for ROP while reducing systemic risk. Previously, after testing doses of 0.25 mg to 0.031 mg, doses as low as 0.031 mg were found to be effective in small cohorts of infants.ObjectiveTo find the lowest dose of intravitreous bevacizumab effective for severe ROP.Design, setting, and participantsBetween April 2017 and May 2019, 59 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, dose de-escalation study. In cohorts of 10 to 14 infants, 1 eye per infant received 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreous bevacizumab. Diluted bevacizumab was prepared by individual research pharmacies and delivered using 300-µL syringes with 5/16-inch, 30-guage fixed needles. Analysis began July 2019.InterventionsBevacizumab intravitreous injections at 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg.Main outcomes and measuresSuccess was defined as improvement by 4 days postinjection and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks.ResultsFifty-five of 59 enrolled infants had 4-week outcomes completed; the mean (SD) birth weight was 664 (258) g, and the mean (SD) gestational age was 24.8 (1.6) weeks. A successful 4-week outcome was achieved for 13 of 13 eyes (100%) receiving 0.016 mg, 9 of 9 eyes (100%) receiving 0.008 mg, 9 of 10 eyes (90%) receiving 0.004 mg, but only 17 of 23 eyes (74%) receiving 0.002 mg.Conclusions and relevanceThese data suggest that 0.004 mg may be the lowest dose of bevacizumab effective for ROP. Further investigation is warranted to confirm effectiveness of very low-dose intravitreous bevacizumab and its effect on plasma vascular endothelial growth factor levels and peripheral retinal vascularization.

Project description:Purpose: To evaluate the relationship between retinopathy of prematurity (ROP) severity and neurodevelopmental outcomes in premature neonates at 0-36 months corrected age. Methods: A retrospective chart review was performed on 228 neonates screened for ROP at the UCLA Mattel Children's Hospital between 2011 and 2018. Demographic information, clinical outcomes, ROP severity (no ROP, type 1 ROP, type 2 ROP), and Bayley-III neurodevelopmental scores were collected. Infants were grouped into corrected age cohorts (0-12, 12-24, and 24-36 months) to assess neurodevelopmental outcomes with increasing age. Within each age cohort, ANOVA and Chi-Square testing were used to detect differences in birth characteristics and neurodevelopmental scores between infants with type 1 ROP, type 2 ROP, or no ROP. Univariable analyses assessed the relationship between ROP severity and neurodevelopmental outcomes within each age cohort. A multivariable analysis was then performed to determine if ROP severity remained significantly associated with worse neurodevelopmental scores after controlling for birth weight (BW), intraventricular hemorrhage grade (IVH), health insurance type, male sex, and age at Bayley testing. Results: Without controlling for factors associated with prematurity, neonates with type 1 ROP had poorer cognition (p = 0.001) and motor (p = 0.006) scores at ages 0-12 months and poorer cognition (p = 0.01), language (p = 0.04) and motor (p = 0.04) scores at ages 12-24 months than infants without ROP, but no significant differences were detected at ages 24-36 months. After adjusting for BW, IVH, insurance type, male sex, and age at Bayley testing, ROP severity was no longer associated with worse neurodevelopmental scores in any domain. Conclusion: This study emphasizes that poorer neurodevelopmental outcomes in preterm neonates are most likely related to lower birthweight, associated co-morbidities of prematurity, and socioeconomic factors such as health insurance, not severity of ROP itself.

Project description:BackgroundRetinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity.MethodsWe conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks' postmenstrual age.ResultsWe enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks' postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P=0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P=0.003) but not for zone II disease (P=0.27).ConclusionsIntravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. (Funded by Research to Prevent Blindness and others; ClinicalTrials.gov number, NCT00622726.).

Dataset Information

Neurodevelopmental Outcomes in Infants with Retinopathy of Prematurity and Bevacizumab Treatment.

Purpose

Methods

Results

Conclusions

Publications

Neurodevelopmental Outcomes in Infants with Retinopathy of Prematurity and Bevacizumab Treatment.

Similar Datasets

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