Neurodevelopmental Outcomes in Infants Screened for Retinopathy of Prematurity

Extracorporeal membrane oxygenation (ECMO) is lifesaving for many critically ill children with congenital heart disease (CHD). However, limited information is available about their ensuing neurodevelopmental (ND) outcomes. We describe early ND outcomes in a cohort of children supported with ECMO for cardiac indications. Twenty-eight patients supported with ECMO at age < 36months underwent later ND testing at 12-42months of age using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). ND scores were compared with normative means and with ND outcomes of a matched cohort of 79 children with CHD undergoing cardiac surgery but not requiring ECMO support. Risk factors for worse ND outcomes were identified using multivariable linear regression models. Cardiac ECMO patients had ND scores at least one standard deviation below the normative mean in the gross motor (61%), language (43%), and cognitive (29%) domains of the Bayley-III. Cardiac ECMO patients had lower scores on the motor, language, and cognitive domains as compared to the matched non-ECMO group and clinically important (1/2 SD) differences in the motor domain persisted after controlling for primary caregiver education and number of cardiac catheterizations. Risk factors of worse ND outcomes among cardiac ECMO patients in more than one developmental domain included older age at first cannulation and more cardiac catheterization and cardiac surgical procedures prior to ND assessment. Overall, children supported on ECMO for cardiac indications have significant developmental delays and warrant close ND follow-up.

Previous data from our institution demonstrated a decline in mortality among infants born at 22 weeks' gestation from 1998 to 2008, alongside a reduction in neurodevelopmental impairment in infants born at 23 to 24 weeks' gestation. This study aimed to analyze temporal trends and identify clinical and perinatal factors associated with survival and neurodevelopmental outcomes in periviable infants (gestational age ≤25 weeks) born between 2009 and 2020.This retrospective cohort study was conducted at a single level III neonatal intensive care unit. Infants born at ≤25 weeks' gestation were grouped into two epochs: 2009 to 2014 and 2015 to 2020. Survival, major in-hospital morbidities, and neurodevelopmental outcomes at 2 years' corrected age were compared. Clinical practice changes during the study period were evaluated as potential contributors to variations in outcome.A total of 672 infants were included (Epoch 1 [E1]: n = 316; Epoch 2 [E2]: n = 356) during the study period. Survival rates were similar between epochs (E1 vs. E2; 76 vs. 78%; p = 0.42). However, rates of grade 2 or 3 bronchopulmonary dysplasia (41 vs. 57%; p < 0.01) and oxygen use at discharge (23 vs. 47%; p < 0.01) increased significantly in Epoch 2. The prevalence of severe neurodevelopmental impairment also rose substantially (19 vs. 38%; p < 0.01). Follow-up at 2 years declined markedly in Epoch 2 (75 vs. 40%; p < 0.01), limiting confidence in long-term outcome estimates. Notably, a shift in clinical practice toward higher oxygen saturation targets was associated with this increase in pulmonary and neurodevelopmental morbidity.Although survival rates for infants born at ≤25 weeks' gestation have stabilized, the concurrent rise in pulmonary and neurodevelopmental morbidities signals the need for improved care strategies, particularly oxygen management, and emphasizes the importance of long-term monitoring for this vulnerable population. · Survival rates at ≤25 weeks have plateaued at our single center over the past decade.. · Pulmonary morbidities have increased, likely influenced by evolving care practices.. · Neurodevelopmental outcomes are worsening, highlighting the need to improve intact survival..

BackgroundcCMV infection is a major contributor to childhood neurologic and cognitive disabilities including sensorineural hearing loss (SNHL). Neonatal treatment with ganciclovir/valganciclovir improves hearing outcomes, but its impact on neurodevelopmental outcomes remains an important knowledge gap. We describe the neurodevelopmental outcomes of children with cCMV infection and evaluate the effect of neonatal antiviral therapy on outcomes. MethodsSince 2013, infants with cCMV infection referred to Nationwide Children’s Hospital’s NEO-ID Clinic have had a complete evaluation at diagnosis as well as follow-up neurodevelopmental assessments. Pertinent demographic, clinical, laboratory, radiographic, and follow-up data were obtained and managed using REDCap. Neurodevelopmental assessments were performed using Bayley Scales of Infant and Toddler Development (BSID) III/IV (cognitive, language, motor domains) at ~ 24 months of age. The Gross Motor Function Classification System was used to classify functional motor impairment. Neurodevelopmental outcomes were compared by receipt of antiviral therapy in early infancy. Results95 infants (mean ± SD; gestational age 35 ± 5 wk, birth weight 2121 ± 948 g; Table 1) with cCMV infection had follow-up neurodevelopmental assessments. 62% had central nervous system involvement, 37% had SNHL, 23% developed cerebral palsy (CP), and 6% were diagnosed with autism spectrum disorder. The majority had normal BSID scores (≥ 85) in cognitive and motor domains (65% and 54%, respectively) while 48% had normal scores in the language domain. 35% had severe impairment (< 70) in ≥ 1 domain (Table 2). 9 children had clinically inapparent cCMV infection; 2 (22%) had abnormalities on BSID testing (1, cognitive score: 80; 1, cognitive, language, and motor scores: 65, 68, 73, respectively). 11 (12%) children, including 6 who received antiviral therapy, had severe neurodevelopmental impairment, with CP and severe (< 70) BSID scores in both the cognitive and motor domains. Table 1. Demographic and Clinical Characteristics of 95 Children with Congenital CMV Infection by Receipt of Antiviral TreatmentTable 2. Neurodevelopmental Outcomes Based on Testing with the Bayley Scales of Infant and Toddler Development (BSID) III/IVConclusionA substantial proportion of children with cCMV infection had moderate (29%) or severe (33%) neurodevelopmental impairment, CP, or autism spectrum disorder, irrespective of antiviral treatment. Urgency exists for antenatal preventive strategies and vaccine development.DisclosuresAsuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member)

To investigate the 2-year outcomes of the natural history of retinopathy of prematurity (ROP) in Taiwan. A prospective study was conducted at two tertiary medical centers. Premature infants were screened and examined for ROP. The postmenstrual ages of developing each stage of ROP and the associated risk factors were recorded. A total of 698 infants were included. The incidences of ROP and treatment-requiring ROP in all patients with ROP were 29.7% and 37.2%. When only including patients with birth weight of 1,250 g or less, the incidences were 62.2% and 39.1%, respectively. In patients with ROP with birth weight over 1,250 g, 25% of them developed treatment-requiring ROP. The median postmenstrual ages for the development of Stage 1, Stage 2, and Type 1 ROP were 33.0, 34.0, and 34.7 weeks, respectively. Gestational age at birth and birth weight were the most important factors associated with treatment-requiring ROP (hazard ratios of 0.3 and 0.6). Our hospital-based study reveals an earlier postmenstrual age of developing ROP in this Asian population than in the Early Treatment for ROP study. Infants with birth weight over 1,250 g could still develop treatment-requiring ROP. Suboptimal oxygen control, different genetic dispositions among different races, inconsistencies in ROP diagnosis, and earlier screening might account for such a phenomenon.

Evaluation of three-year neurodevelopmental outcomes in infants prenatally exposed to substance use

Background: Retinopathy of prematurity (ROP) is the most common cause of preventable blindness in preterm infants. First-line treatments include intravitreal bevacizumab (IVB) or laser photocoagulation (LPC). Objectives: The aim of the study was to evaluate neurodevelopmental safety of IVB compared to LPC for ROP. Methods: MEDLINE, Embase, and Cochrane library were searched up to September 2022. Studies were included with at least 12-month follow-up of primary outcomes such as severe neurodevelopmental impairment (sNDI), cerebral palsy (CP), and hearing impairment (HI). Secondary outcomes were moderate-to-severe neurodevelopmental impairment (msNDI), Bayley Scores of Infant Development (BSID-III), and visual impairment. Results: 1,231 patients from 11 comparative studies were included. Quality of evidence was rated low for all outcomes. IVB was associated with a higher risk for sNDI (risk ratio [RR] = 1.25, 95% confidence interval [CI]: [1.01, 1.53], p = 0.04); and CP (RR = 1.40, CI: [1.08, 1.81], p = 0.01) compared to LPC. There was no significant difference between IVB and LPC for msNDI (RR = 1.15, CI: [0.98, 1.35], p = 0.08) and HI (RR = 1.43, CI: [0.86, 2.39], p = 0.17). BSID-III percentile scores were similar between IVB and LPC, with weighted mean differences of 1.51 [CI = −1.25, 4.27], 2.43 [CI = −1.36, 6.22], and 1.97 [CI = −1.06, 5.01] for cognitive, language, and motor domains, respectively (p > 0.05). Conclusion: To our knowledge, this is the largest meta-analysis on neurodevelopmental outcomes and the first to rigorously examine IVB monotherapy in ROP treatment. Compared to LPC, there was a marginally increased risk for sNDI and CP with IVB but little or no difference in the risk of msNDI and HI. Further randomized studies are needed to strengthen these findings.

Optical coherence tomography (OCT) is an emerging adjunct imaging modality to evaluate retinopathy of prematurity (ROP). From an 11-year research database, we identify early OCT biomarkers that predict treatment-requiring ROP (TR-ROP). For preterm infants with acceptable OCT images at 32 ± 1weeks postmenstrual age (PMA), we extracted the following measures: total retina, inner retinal layer (IRL), and outer retinal layer (ORL) thicknesses at the fovea and the parafovea, inner nuclear layer (INL) and choroidal thickness, parafovea/fovea (P/F) ratio, and presence of macular edema. Using univariable and multivariable logistic regression models, we evaluated the association between retinal and choroidal OCT measurements at 32 ± 1weeks PMA and development of TR-ROP. Of 277 eyes (145 infants) with usable OCT images, 67 eyes had TR-ROP. Lower P/F ratio (P<0.0001), thicker foveal IRL (P=0.0001), and thinner choroid (P=0.03) were associated with TR-ROP in univariable analysis, but lost significance of association when adjusted for gestational age and race. Absence of macular edema was associated with TR-ROP when adjusted for gestational age and race (P=0.01). In 185 eyes without macular edema, P/F ratio was associated with TR-ROP in both univariable analysis (P<0.0001) and multivariable analysis (P=0.02) with adjustment for gestational age and race. Presence of macular edema at 32 ± 1weeks PMA in infants with lower gestational age may be protective against TR-ROP. In infants without macular edema, P/F ratio may be an early OCT biomarker for development of TR-ROP. Incorporation of early OCT biomarkers may be useful in prediction of TR-ROP.

The purpose of this study was to measure the accuracy of retinopathy of prematurity (ROP) diagnosis by retinal fellows. An atlas of 804 retinal images was captured from 248 eyes of 67 premature infants with a wide-angle camera (RetCam-II, Clarity Medical Systems, Pleasanton, CA). Images were uploaded to a study Web site, from which an expert pediatric retinal specialist and 7 retinal fellows independently provided a diagnosis (no ROP, mild ROP, type 2 ROP, or treatment-requiring ROP) for each eye. The sensitivity and specificity of each retinal fellow were calculated and subsequently compared with a reference standard of diagnosis by an expert pediatric retinal specialist. For detection of type 2 or worse ROP by fellows, mean (range) sensitivity was 0.751 (0.512-0.953), and specificity was 0.841 (0.707-0.976). For detection of treatment-requiring ROP, mean (range) sensitivity was 0.914 (0.667-1.000), and specificity was 0.871 (0.678-0.987). In general, fellows showed high accuracy for detecting ROP. However, 3 of 7 fellows achieved <80% sensitivity for diagnosis of type 2 or worse ROP, and 2 of 7 achieved <90% sensitivity for diagnosis of treatment-requiring ROP. This could lead to undermanagement and undertreatment of clinically significant disease and raises potential concerns about the quality of ROP screening examinations performed by less-experienced examiners.

Postoperative electroencephalographic seizures are associated with deficits in executive function and social behaviors at 4 years of age following cardiac surgery in infancy

Purpose To report the incidence of treatment-requiring retinopathy of prematurity (ROP) in Greece at a national level. Methods Multicenter prospective cohort study of infants that required treatment for ROP at any unit in Greece between June 1st, 2020, and May 31st, 2021. Twelve out of the 13 invited centers contributed their data. Collected parameters included infants’ demographics, ROP examination findings prior to treatment, and treatment characteristics. Results The overall incidence of treatment-requiring ROP (TR-ROP) was 3.8%, given the fact that 1133 live births of infants with GA <32 weeks and/or BW < 1501 g were reported during the study period. Median (range) gestational age and birth weight of treated infants were 26.9 (23.4–33.0) weeks and 850 (500–2370) g, respectively, and 55.8% were male. The most prevalent ROP severity among treated infants was type 1 ROP (70 eyes), followed by type 2 ROP (8 eyes) and aggressive ROP (6 eyes). Laser photocoagulation (69.8%) was the predominant treatment modality used vs intravitreal anti-VEGF injections (30.2%). The median postnatal age at initial treatment was 9.6 weeks (range 5.6–21.7). Re-treatment rate was 30.2% and was higher among infants treated with anti-VEGF (69.2%) vs laser (13.3%). Treatment failure was reported in one case (progression to stage 4B in one eye and stage 5 in the other), whereas ROP regressed in all other patients. Conclusion This is the first study to report TR-ROP incidence in Greece, treated infants’ characteristics at a national level, preferred practice patterns, failure rate and recurrence rate at 6 months from initial treatment.

Sleep disturbances impact over half of older children and teens with acquired brain injury (ABI) following critical care hospitalization but are underevaluated in infants and young children. Given the importance of sleep in brain development and healing after injury, we hypothesized sleep disturbances would be associated with worse neurodevelopmental outcomes in infants with ABI. We performed a retrospective cohort study of 68 children aged 2-32 months following critical care hospitalization for ABI. The Brief Infant Sleep Questionnaire assessed sleep disturbances. Bayley Scales of Infant and Toddler Development, third edition and Adaptive Behavior Assessment System, third edition assessed developmental and adaptive functioning outcomes, respectively. t tests compared sleep characteristics in infants with ABI to historical healthy controls. Spearman's correlation evaluated relationships among sleep and outcomes. Multiple linear regression investigated relationships controlling for demographic and ABI characteristics. Compared to healthy controls, children with ABI had shorter nighttime sleep duration (P = .01), longer daytime sleep duration (P < .001), and longer duration of nighttime awakenings (P < .001). Duration of night awakenings negatively correlated with Bayley Cognitive scores (Spearman's correlation = -.40). Night awakenings negatively correlated with worse Adaptive Behavior Assessment System, third edition General Adaptive Composite scores (Spearman's correlation = -.42). When controlling for demographic and ABI characteristics, ≥ 3 awakenings was significantly associated with worse Adaptive Behavior Assessment System, third edition General Adaptive Composite (β = -11.3; 95% confidence interval = -19.2, -3.5). Sleep disturbances are associated with poorer outcomes in infants and toddlers after ABI. Sleep is vital to recovery and a potentially modifiable target to improve outcomes. Klapp JM, Hall TA, Riley AR, Williams CN. Sleep disturbances in infants and young children following an acquired brain injury. J Clin Sleep Med. 2022;18(10):2387-2395.

The Rate of Retinal Vessel Dilation in Severe Retinopathy of Prematurity Requiring Treatment

ContextDebate exists regarding predictive value of brain MRI for long-term neurodevelopmental outcome (NDO) in infants with severe unconjugated hyperbilirubinemia (above exchange transfusion levels). ObjectiveTo investigate whether MRI findings among (pre-)term infants with severe unconjugated hyperbilirubinemia can predict NDO at ≥ 12 months and determine optimal timing for MRI. Data sourcesPubMed and Embase. Last update: June 14, 2024. Study selectionStudies in which (pre-)term infants with severe unconjugated hyperbilirubinemia who underwent an MRI before 24 months and had a reported NDO at ≥ 12 months were included. Data extractionPatient characteristics, MRI and NDO details were extracted. ResultsThe search yielded 732 studies, of which 22 were included. Individual patient information was obtained for 120 infants (MRI-timing: early (≤6 weeks) n = 75, late (>6 weeks) n = 19, unknown n = 26). Positive predictive value (PPV) of abnormal MRI in the total group for impaired NDO was high (77.5 %). The PPV of late compared to early MRI was much higher, 92.3 % versus 71.7 %. Negative predictive value of normal MRI for normal NDO in the total group was low (29.0 %) and again higher in late compared to early MRI, 50.0 % versus 27.3 %. LimitationsQuantitative synthesis of results was impossible due to large heterogeneity in study designs. Furthermore, selection bias towards patients with impaired outcome might have influenced our results. ConclusionsBrain MRI can serve as prognostic tool for NDO in infants with severe unconjugated hyperbilirubinemia, both in early and late stages, but each timing has inherent constraints. Further prospective studies are necessary.

Background: The COVID-19 pandemic and subsequent social distancing measures have disrupted various aspects of child development, with particular concern for infants in neonatal intensive care units (NICUs), where heightened vulnerabilities and limited external stimuli may exacerbate neurodevelopmental risks. Objective: The objective of this study was to examine the impact of the COVID-19 pandemic on neurodevelopmental outcomes in infants admitted to NICUs at birth, comparing neurodevelopmental indicators from before and during the pandemic period. Materials and Methods: A retrospected matched cohort study was conducted on infants admitted to NICUs at birth during the COVID-19 pandemic, with neurodevelopmental evaluations carried out at 6 and 12 months of age. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III, 2006). Results: From September 2020 to December 2021, a total of 114 infants were consecutively enrolled in the study, with a matched control group selected. Analyses revealed no significant differences in Bayley-III scores between infants in the pandemic group and those in the control group. Conclusion: Short-term neurodevelopmental outcomes for NICU infants were unexpectedly unaffected by the additional stress of pandemic-related restrictions.

Periventricular hemorrhagic infarction (PVHI) is a major contributing factor to poor neurodevelopmental outcomes in preterm infants. We hypothesized that surviving infants with unilateral PVHI would have more favorable outcomes than those with bilateral PVHI. This was a multicenter, retrospective study of infants who were admitted to 3 NICUs in North Carolina from 1998 to 2004. The clinical course and late neuroimaging studies and neurodevelopmental outcomes of 69 infants who weighed <1500 g and had confirmed PVHI on early cranial ultrasonography were reviewed. A predictive model for Bayley Scales of Infant Development, Second Edition, Mental Developmental Index (MDI) <70 was constructed by using radiologic and clinical variables. Infants with unilateral PVHI had higher median MDI (82 vs 49) and Psychomotor Developmental Index (53 vs 49) than infants with bilateral PVHI. Infants with unilateral PVHI were less likely to have severe cerebral palsy (adjusted odds ratio: 0.15 [95% confidence interval (CI): 0.05-0.45]) than infants with bilateral PVHI. Infants who had unilateral PVHI and developed periventricular leukomalacia and retinopathy of prematurity that required surgery had an increased probability of having MDI <70 compared with those without these complications (probability of MDI <70: 89% [95% CI: 0.64-1.00] vs 11% [95% CI: 0.01-0.28]). Infants with unilateral PVHI had better motor and cognitive outcomes than infants with bilateral PVHI. By combining laterality of PVHI, periventricular leukomalacia, and retinopathy of prematurity it is possible to estimate the probability of having an MDI <70, which will assist clinicians when counseling families.