Neuromotor Outcome Research Articles

The role of Thompson score of term newborns in predicting neuromotor outcome at 1 year of age

Background: The mortality rate is approximately 20% and the frequency of neurodevelopmental sequelae in surviving newborns is approximately 30% in perinatal asphyxia; hypoxic-ischemic encephalopathy (HIE) is brain dysfunction due to lack of oxygen and blood supply to the brain. Aims and Objectives: This study was conducted to predict the pattern of neuromotor outcome as early as 3 months using Hammersmith Infant Neurological Examination (HINE) in term hypoxic babies and its relation with the Thompson score (HIE score). Materials and Methods: One-hundred twenty four term newborns with hypoxic babies were admitted to the neonatal care unit from January 2021 to August 2021. Thompson scoring was done on admission and subsequently reviewed. Discharged babies were followed up at 3 months, 6 months, and 1 year of age. A neurological examination (HINE) was done in this high-risk follow-up clinic. Maximum Thompson score was correlated with neurological score at various months. The earliest predictability of neurological examination was done at 3 months and was correlated with the neurological examination done at 12 months. Results: The correlation between the Thompson score and the 3-month score is −0.65 indicating a strong negative association between the two measurements. The correlation between 3 months and 6 months and 1-year neurological scores was moderately associated with each other. Conclusion: The maximum Thompson score was significantly higher in the mortality group compared to the discharged group. Thompson score has a significant correlation with the 3, 6, and 12-month neurological scores examined by HINE. The 3-month neurological outcome has a very significant correlation with the 1-year outcome.

Neurological functional outcome of early versus delayed cranioplasty following decompressive craniectomy at a tertiary care centre

Cranioplasty performed after a decompressive craniectomy (DC) for traumatic brain injury (TBI), stroke, or aneurysmal bleed has a role of restoring cerebral protection and craniofacial cosmesis as well as improving neuromotor function. There has been no consensus with regards to the ideal timing of cranioplasty (CP) after DC. A retrospective cohort study was carried out at a tertiary care hospital on patients who had undergone early (less than or equal to 12 weeks) and late (greater than 12 weeks) cranioplasty using autologous cranial bone after DC. Functional independence measure (FIM) tools were used to compare neuromotor and cognitive function outcome between the two groups. Appropriate statistical tools were used to compare neuromotor and cognitive function improvement as well as complication rates between early and late cranioplasty. A total of 31 adult patients of cranioplasty (21 male and 10 female) were evaluated. Sixteen had undergone early and 15 late cranioplasty. Comparison for neuromotor and cognitive function using FIM tools revealed statistically significant neuromotor and cognitive advantages in the early cranioplasty group. Overall complication rates between the two groups varied but were statistically insignificant. Performing an early cranioplasty provides advantages of improvement of neuromotor and cognitive function through early restoration of cerebrospinal fluid and intracerebral haemo-dynamics. It further avoids the potential problems of developing the ‘Syndrome of the Trephined’ (otherwise known as sinking skin flap syndrome) and resorption of the autologous bone.

Neuro-modulatory impact of felodipine against experimentally-induced Parkinson's disease: Possible contribution of PINK1-Parkin mitophagy pathway

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, characterized by motor and psychological dysfunction. Palliative treatment and dopamine replenishment therapy are the only available therapeutic options. Calcium channel blockers (CCBs) have been reported to protect against several neurodegenerative disorders. The current study was designed to evaluate the neuroprotective impact of Felodipine (10 mg/kg, orally) as a CCB on motor and biochemical dysfunction associated with experimentally induced PD using rotenone (2.5 mg/kg, IP) and to investigate the underlying mechanisms. Rotenone induced deleterious neuromotor outcomes, typical of those associated with PD. The striatum revealed increased oxidative burden and NO levels with decreased antioxidant capacity. Nrf2 content significantly decreased with the accumulation of α-synuclein and tau proteins in both the substantia nigra and striatum. These observations significantly improved with felodipine treatment. Of note, felodipine increased dopamine levels in the substantia nigra and striatum as confirmed by the suppression of inflammation and the significant reduction in striatal NF-κB and TNF-α contents. Moreover, felodipine enhanced mitophagy, as confirmed by a significant increase in mitochondrial Parkin and suppression of LC3a/b and SQSTM1/p62. In conclusion, felodipine restored dopamine synthesis, attenuated oxidative stress, inflammation, and mitochondrial dysfunction, and improved the mitophagy process resulting in improved PD-associated motor impairment.

Longitudinal changes of swallowing safety and efficiency in infants with spinal muscular atrophy who received disease modifying therapies.

Dysphagia is a common feature of the natural history of patients with spinal muscular atrophy (SMA). Literature regarding swallowing safety and efficiency is scarce in patients with SMA, particularlyin the era of newborn screening programs and disease-modifying therapies. To describe the longitudinal changes of swallowing safety and efficiency in children with SMA who received one or more disease modifying therapies METHODS: Case series of patients with SMA followed at the University of Florida from 1 May 2019 to 31 December 2022 who had two or more videofluoroscopy swallowing studies (VFSS), with the first being within 30 days of their first treatment. Data extracted from the electronic health record included: neuromotor outcomes, VFSS penetration aspiration scores (PAS), presence of abrnormal oral or pharyngeal residue, clinical history, and timing of disease-modifying therapies administration. Seven subjects were included (five male); three were diagnosed via newborn screen. Median age at diagnosis was 10 days (range: 4-250). Median age at initial VFSS was 29 days (range: 9-246), and age at the last VFSS was 26.1 months (range: 18.2-36.2). All subjects received onasemnogene-abeparvovec (OA); four received additional therapies. PAS at diagnosis was abnormal in four subjects. Six subjects required feeding modifications after VFSS results. Of these, three had silent aspiration (PAS 8) and three of them improved after treatment. Swallowing safety and efficiency can be impaired in patients with SMA despite early treatment. Larger, prospective studies are needed to define optimal timiing of longitudinal instrumental evaluations.

Application of the Hammersmith Infant Neurological Examination in the developmental follow-up of high-risk infants.

To investigate the independent influences affecting the global score of the Hammersmith Infant Neurological Examination (HINE) in the early life of high-risk infants and to provide evidence for early effective screening and for evaluating interventions. We conducted a prospective cohort study of 258 high-risk infants assessed by the HINE and Gesell Developmental Diagnosis Schedule at 3, 6, 9, and 12 months corrected age. A multiple linear regression model was developed to investigate independent influences on HINE global score at 3 months corrected age. The accuracy of the HINE global score was analysed by calculating the discriminant, concurrent, and predictive validities according to ages. There were nine independent influences affecting the HINE global score at 3 months corrected age in high-risk infants. The discriminant, concurrent, and predictive validities of the HINE for gross motor developmental delays at 12 months corrected age were all statistically significant (p < 0.05). Different neonatal clinical settings are related to the HINE global score of high-risk infants early in life. The HINE can be used for longitudinal monitoring of neurological development in the first year of life in a typical Chinese clinical setting and the findings at all four ages tested relate to neuromotor outcomes at 12 months corrected age.

Ab. No. 8 Neonatal Procedural Pain and Neuromotor Changes on Multisensory Stimulation and Soft Tissue Therapy Among Hospitalized Preterm Neonates: One-Group Pretest-Post-Test Trial

Introduction: Neonatal physiotherapy procedures including MSS and STT might be beneficial for reducing pain and improving neuromotor outcomes among hospitalized neonates. To determine the effects of MSS and STT on reducing procedural pain and improving neuromotor outcomes among hospitalized preterm neonates. Methods: MSS and STT were provided for 5 days of NICU stay. The Premature Infant Pain Profile-Revised (PIPP-R) and Neonatal Pain and Sedation Scale (N-PASS) were used for assessing procedural pain. For assessing neuromotor outcomes among preterm neonates, Infant Neurological International Battery (INFANIB) and Premie neuro scale were used. Wilcoxon signed-rank test was used for estimating the statistically significant difference. Effect Size (ES) within the group was calculated by using the formulae “Wilcoxon Signed-ranks test” for ES. Result: Both statistically significant differences (p&lt;0.05), and clinically important differences were noted in procedural pain (PIPP-R; 3.0, N-PASS; 3.0) and neuromotor outcomes (INFANIB; 3.0, Premie Neuro; 8.0) among hospitalized preterm neonates. Conclusion: MSS and STT given for 5 days of NICU stay reduces procedural pain, and improves neuromotor development among hospitalized preterm neonates. MSS and STT might be given as early intervention care regularly for reducing pain and promoting neuromotor development among hospitalized preterm neonates. However, further randomized controlled trial is needed to substantiate these findings.

Specialized Manual Therapy Techniques Can Improve Neuromotor Outcome in Patients with Foot-Drop Syndrome

Introduction: Functional rehabilitation of foot-drop syndrome due to lumbar disc herniation it is a problem that concerns many researchers. Study objective was to investigate if specialized manual therapy techniques and functional electrical stimulation alone and combined can influence the overall neuromotor outcome. Methods: 90 subjects were randomized to 3 groups, 30 subjects allocated to control group (CG) which received physical therapy, 30 subjects in functional electrical stimulation group (FES) and 30 subjects in combined FES with manual therapy techniques (FES-MT). All groups received a number of 20 sessions. We evaluated nerve conduction study, dynamometry, goniometry, functional ankle disability index (FADI), Oswestry Disability Index (ODI) and Numeric Rating Scale (NRS). Results: For Compound muscle action potential we have found significant modifications when comparing FES-MT vs CG (p&lt;0.011). For dynamometry we registered as follows: FES-MT vs CG (0.0001), FES-MT vs FES (p&lt;0.003). ODI and FADI scores were more significant in FES-MT and FES compare with CG. Conclusions: Manual therapy techniques utilized for increasing the excitability of neuromuscular spindle can increase the overall functionality of the tibialis muscle in case of foot drop syndrome. The combination between FES and MT showed better functional results than physical therapeutic exercises and FES alone.

Neonatal Physiotherapy Interventions in Reducing Acute Procedural Pain and Improving Neuromotor Development in a Preterm Neonate

Background: Repeated painful procedures are very common in neonatal intensive care unit (NICU). A combination of multisensory stimulation (MSS) and soft tissue therapy (STT) potentiates each other's analgesic effects and helps in reducing procedural pain. Case Description: Thirty-six weeks and 2 days old preterm neonate was undergoing venipuncture at right forearm for diagnostic purpose when admitted in NICU because of prematurity. MSS and STT were provided once in a day for 30 minutes, total for 5 days for pain relief and improvement in neuromotor outcomes. Outcomes: Pain intensity was assessed with Preterm Infant Pain Profile-Revised (PIPP-R) and Neonatal Pain, Agitation and Sedation Scale (N-PASS). The neuromotor outcomes were also assessed with Infant Neurological International Battery (INFANIB) and Premie-Neuro Scale. All the measurements were taken at baseline and after 5 days of intervention. The pain scores, PIPP-R and N-PASS, were measured at 30 seconds, 60 seconds, 90 seconds, and 120 seconds before the intervention. The PIPP-R: 7, 7, 10, and 6, and N-PASS scores before the intervention were: 2, 9, 4, and 5, respectively. After 5 days of intervention, the pain scores were PIPP-R: 3, 9, 3, and 3, and N-PASS: 3, 3, 4, and 4, respectively. The neuromotor tests, INFANIB and Premie-Neuro, were measured at baseline and postintervention. The scores were INFANIB: 58 and 60, respectively, and Premie-Neuro: 90 and 92, respectively. Discussion/Conclusion: Neonatal physiotherapist may give importance to procedural pain management in NICU settings to promote good clinical practice along with other physiotherapy interventions. Along with pain scores, neuromotor scores were improved after the 5th day of intervention in the preterm neonate. MSS and STT might help in reducing procedural pain and improving neuromotor outcomes after 5 days of intervention among preterm neonates.

Neurodevelopmental outcome in children with congenital cytomegalovirus infection: A prospective multicenter cohort study

BackgroundCongenital cytomegalovirus infection (cCMV) is the most common congenital infection worldwide and is a major cause of neurodevelopmental impairment in children. At this point there are insufficient data on neurodevelopmental outcome of children with cCMV, both symptomatic and asymptomatic. AimThis study aimed to describe the neurodevelopmental outcome in a large prospective cohort of children with cCMV. MethodsAll children with cCMV, included in the Flemish cCMV register, were eligible for this study. Data on neurodevelopmental outcome was available in 753 children. Data on neuromotor, cognitive, behavioral, audiological and ophthalmological outcome were analyzed. ResultsNeurodevelopmental outcome was normal in 530/753 (70,4 %) at any age of last follow-up. Mild, moderate and severe neurodevelopmental impairment was found in 128/753 (16,9 %), 56/753 (7,4 %) and 39/753 (5,2 %), respectively. Adverse outcome is found both in the symptomatic and asymptomatic children (53,5 % versus 17,8 %). Autism spectrum disorder (ASD) was diagnosed more often than in the general population in Flanders (2,5 % versus 0,7 %). Speech and language impairment was found in 2 %, even in absence of hearing loss. ConclusionBoth symptomatic and asymptomatic cCMV children are at risk of sequelae, with higher risk in case of first trimester infection. During follow-up of this population, special attention should be given to the audiological follow-up, the presence of hypotonia at young age, the possible higher risk of ASD and the risk of speech and language impairment even in absence of hearing loss. Our results emphasize the need for multidisciplinary neurodevelopmental follow-up of all cCMV infected children.

Prechtl’s General Movements performed at writhing age may help target MRI use in the NICU (P9-9.012)

<h3>Objective:</h3> We aimed to determine if Prechtl’s general movement assessment (GMA) could help target the use of magnetic resonance imaging (MRI) in the neonatal intensive care unit (NICU) to detect infants with neuroimaging abnormalities not detected by cranial ultrasound (CUS) alone. <h3>Background:</h3> Prechtl’s GMA is a bedside evaluation performed to identify infants at high-risk for neurological and motor disorders such as cerebral palsy (CP). Cramped synchronized (CS) GMA at writhing age has been associated with poor neuromotor outcomes. However, no clinical practice guideline exists to recommend routine use of term-equivalent MRI in infants with CS GMAs. <h3>Design/Methods:</h3> We retrospectively reviewed neuroimaging reports from pediatric neuroradiologists of all infants who had CS GMA between 36 and 44 weeks post-menstrual age at two level III and three level IV NICUs. All three sites used standard protocols for preterm neuroimaging with at least one CUS in the first week after birth and another near 30 weeks corrected gestational age. If an MRI was obtained (due to clinical suspicion for intracranial abnormality, abnormal CUS findings, or CS GMA) the reason for performing the MRI was recorded. <h3>Results:</h3> 144 infants had CS GMA, and of these, only 19 did not receive neuroimaging. Initial neuroimaging demonstrated abnormal (mild and severe) findings in 64.5% and clinically significant in 45.6%. When MRI was performed secondarily, agreement between the two types of imaging occurred most of the time. A higher level of insult was present in 20.7% of those receiving a secondary MRI. The frequency of clinically significant abnormal findings on final determination was 48.8%. In 14 cases, secondary MRI was performed in response to GMA CS pattern only; in this case, MRI was abnormal in 11 (76.8%) cases. <h3>Conclusions:</h3> These results suggest that infants with CS GMA at writhing age may represent a population with a high-likelihood of clinically significant abnormal neuroimaging findings. <b>Disclosure:</b> Dr. Chirigos has nothing to disclose. Dr. Burton has nothing to disclose. Dr. Maitre has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Thrive Neuromedical. Dr. Maitre has stock in Thrive Neuromedical. Dr. Ostrander has nothing to disclose.

Long-term neurodevelopmental follow-up of children exposed to pravastatin in utero

Preeclampsia, especially before term, increases the risk of child neurodevelopmental adverse outcomes. Biological plausibility, preclinical studies, and pilot clinical trials conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Obstetric-Fetal Pharmacology Research Centers Network support the safety and use of pravastatin to prevent preeclampsia. This study aimed to determine the effect of antenatal pravastatin treatment in high-risk pregnant individuals on their child's health, growth, and neurodevelopment. This was an ancillary follow-up cohort study of children born to mothers who participated in the Obstetric-Fetal Pharmacology Research Centers Network pilot trials of pravastatin vs placebo in individuals at high risk of preeclampsia (ClinicalTrials.gov; identifier NCT01717586). After obtaining written informed consent (and assent as appropriate), the parent was instructed to complete the Child Behavior Checklist. To assess the child's motor, cognitive, and developmental outcomes, a certified and blinded study psychologist completed child motor, cognitive, emotional, and behavioral assessments using validated tools. Given the small number of individuals in the studies, the 10- and 20-mg pravastatin groups were combined into 1 group, and the results of the pravastatin group were compared with that of the placebo group. Of 40 children born to mothers in the original trial, 30 (15 exposed in utero to pravastatin and 15 to placebo) were enrolled in this follow-up study. The time of follow-up, which was 4.7 years (interquartile range, 2.5-6.9), was not different between children in the pravastatin group and children in the placebo group. There was no difference in the child's body mass index percentiles per sex and corrected age, the rates of extremes of body mass index percentiles, or the report of any other medical or developmental complications between the 2 groups. No child born in the pravastatin group had any limitation in motor assessment compared with 2 children (13.3%) who walked with difficulty and 4 children (26.7%) who had reduced manual abilities in the placebo group. Moreover, children born to mothers who received pravastatin had a higher general mean conceptual ability score (98.2±16.7 vs 89.7±11.0; P=.13) and a lower frequency (15.4% vs 35.7%; P=.38) of having a score of <85 (ie, 1 standard deviation lower than the mean) compared with those in the placebo group. Finally, there was no difference in the parents' report on the Child Behavior Checklist between the 2 groups. This study reported on the long-term neuromotor, cognitive, and behavioral outcomes among children exposed to pravastatin in utero during the second and third trimesters of pregnancy. Although the data were limited by the original trial's sample size, no identifiable long-term neurodevelopmental safety signal was evident with the use of pravastatin during pregnancy. This favorable neonatal risk-benefit analysis justifies continued research using pravastatin in clinical trials.

Day II: Friday, March 24, 2023; 9.00 AM Plumeria 3: Physiotherapy in Pediatric/ Neonatal conditions: AB No: 75 Sit Down and Play Intervention on Neuromotor Outcome and Parenting Behavior in Preterm Low Birth Weight Infants- Randomized Controlled Trial

Day II: Friday, March 24, 2023; 9.00 AM Plumeria 3: Physiotherapy in Pediatric/ Neonatal conditions: AB No: 75 Sit Down and Play Intervention on Neuromotor Outcome and Parenting Behavior in Preterm Low Birth Weight Infants- Randomized Controlled Trial

Transcranial Doppler in hypoxic-ischemic encephalopathy babies as a prognostic marker in the short-term outcome

Background: Birth asphyxia is a lack of blood flow or gas exchange to or from the fetus in the period immediately before, during, or after the birth process. Birth asphyxia can result in profound systemic and neurologic sequelae due to decreased blood flow and/or oxygen to the developing fetus or infant. Birth asphyxia is one of the most common causes of neonatal mortality and morbidity globally. Aims and Objectives: The aims of this study were to assess the importance of cranial Doppler as investigation tool for the early prognostic marker of babies with hypoxic-ischemic encephalopathy (HIE) in short term. Materials and Methods: This prospective study was carried out in a tertiary care teaching hospital. The present study includes 50 newborns, out of which 30 newborns admitted with birth asphyxia were considered as a case, while 20 healthy term newborns were taken as control. Transcranial Doppler of middle cerebral artery (MCA) was done on day 1 of life. They were followed up at discharge for neuromotor outcome by Hammersmith Neonatal neurological examination (HNNE). The outcome was correlated with, Doppler findings of MCA. P&lt;0.05 was taken significant. Results: Abnormality detected by transcranial Doppler within 24 h of life in neonates with birth asphyxia was significantly associated with poor neuromotor outcome when compared to healthy term neonates. HNNE score in HIE babies was lesser than healthy term neonates on discharge. Conclusion: Cranial Doppler within 24 h of birth in term HIE babies has very high sensitivity in predicting short-term outcome in babies with HIE, such as Low HNNE score.

Early Electroencephalogram as Predictor of Neuromotor Outcome in a Term Newborn with Hypoxic Ischaemia Encephalopathy- A Prospective Cohort Study

Introduction: Birth asphyxia is the leading cause of neonatal morbidity and mortality globally. Early prediction of neuromotor problems in babies with Hypoxic Ischaemic Encephalopathy (HIE) allows parental counseling regarding treatment continuation, better utilisation of limited resources and prompt referral for early intervention services to so that the best possible outcomes can be achieved. Aim: To investigate the role of early Electroencephalogram (EEG) background activity in prediction of cerebral palsy, epilepsy and developmental delay in term newborn with HIE and also to check the association of EEG background activity with Hammersmith Neonatal Neurological Examination (HNNE), Hammersmith Infant Neurological Examination (HINE) score and various short-term and long-term outcome. Materials and Methods: This prospective clinical study was conducted in Neonatal Intensive Care Unit (NICU) of Department of Paediatrics, Shyam Shah Medical college and associated Gandhi Memorial Hospital, Rewa (MP) during April 2019 to June 2020. Total 81 term neonates with HIE underwent conventional EEG within six hours of birth using International 10-20 system, (modified for neonate) for electrode placement. At the time of discharge HNNE was performed. On follow-up (6 to 12 months), cerebral palsy was evaluated using HINE and modified Ashworth score, Developmental delay by Development Assessment Scale for Indian Infant (DASII) scale and for epilepsy by clinical history and EEG background activity. Association between EEG background activity, HNNE, HINE score and various short-term and long-term outcome was calculated using Chi-square test and Fisher’s-exact test. Results: In present study, out of 81 cases, 58 (71.6%) cases were male and 23 (28.4%) cases were female with mean Gestational Age (GA) of 39 weeks. A total of 57 neonates were discharged successfully after stay of mean duration 13.8 days in NICU. All neonates with normal/mildly abnormal EEG background activity had 100% survival rates whereas only 68.2% (15) and 37% (10) could be discharged from moderately abnormal and severely abnormal EEG background activity group. Out of discharged patients none with severely abnormal background had optimal HNNE whereas 75% (24) of mildly abnormal EEG had optimal HNNE score. Mean HNNE and HINE score was significantly lower in newborns with severely abnormal EEG (mean score 20.8) as compared to normal EEG group (mean score 30.3). Severely abnormal EEG at birth had significant association with cerebral palsy (p-value&lt;0.0001), epilepsy (p-value= 0.003) and developmental delay (p-value&lt;0.001) as compared to moderately and mildly abnormal EEG background activity in newborns with HIE. Conclusion: EEG within six hours of birth in term neonate with HIE has very high sensitivity and Negative Predictive Value (NPV) in predicting short-term outcome as death, poor neurological outcome and long-terms outcome as cerebral palsy, epilepsy and developmental delay.

General Movement Assessment in Babies Born Preterm: Motor Optimality Score–Revised (MOS-R), Trajectory, and Neurodevelopmental Outcomes at 1 Year

To assess the association between the General Movement Assessment (GMA) findings, including Motor Optimality Scores-Revised (MOS-R) at 16weeks, and neuromotor outcome assessed by the Amiel-Tison Neurological Assessment at 9months of corrected age and the Developmental Assessment Scales for Indian Infants (DASII) at 1year of corrected age in preterm ≤32weeks. Serial GMA videos of infants born preterm ≤32weeks were recorded on day 7, 35weeks of postmenstrual age, 40weeks of postmenstrual age, and 16weeks of corrected age. The association between GMA findings, including MOS-R scores and GM trajectory between 35 to 40weeks and the Amiel-Tison Neurological Assessment and DASII scores, was assessed by Spearman correlation, Fisher exact tests, and ordinal regression. Moderate correlations were observed between MOS-R and the DASII motor DQ (Spearman r=0.70, P<.001) and between MOS-R and DASII Mental DQ (r=0.65, P<.001). The GMA trajectory at 35-40weeks was associated with DASII motor DQ (Fisher exact, P=.002), and also with the Amiel-Tison Neurological Assessment at 9months of corrected age (P<.01 by the Fisher exact test). On analysis by performing ordinal regression of predictive values of the general movements (GM)at 7days of age, GM at 35weeks, GM at 40weeks, GM at 16weeks, and MOS-R at 16weeks, MOS-R alone was a statistically significant predictor of motor DQ at 1year of age (OR -0.59; 95% CI -0.97 to -0.22; Wald statistics, P<.02). Consistent with findings in high-income countries, GMA including MOS-R scores performed in Indian infants born preterm during the neonatal period and early infancy is associated with neurodevelopmental outcomes in the first year of life. GMA can help initiate focused early intervention in low- and middle-income settings, where resources may be limited.

Effect of Early High-Dose Recombinant Human Erythropoietin on Behavior and Quality of Life in Children Aged 5 Years Born Very Preterm

In light of the promising neuroprotective properties of recombinant human erythropoietin (RHEpo), the Swiss EPO Neuroprotection Trial was started to investigate its effect on neurodevelopment in very preterm infants. The results of the primary and secondary outcome analysis did not show any effect of RHEpo on cognitive performance, neuromotor outcomes, or somatic growth of the study participants at ages 2 or 5 years. To investigate whether early high-dose RHEpo improves behavioral outcomes and health-related quality of life (HRQoL) at age 5 years. This was a prespecified secondary analysis of the double-blind, placebo-controlled, multicenter Swiss EPO Neuroprotection randomized clinical trial, which was conducted at 5 level-III perinatal centers in Switzerland. Infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were recruited between 2005 and 2012 and followed-up until age 5 years (last follow-up in 2018). Data were analyzed from January 6 to December 31, 2021. Infants were assigned to receive either RHEpo (3000 IU/kg) or placebo (saline, 0.9%) intravenously 3 times within the first 42 hours after birth. The prespecified parent-reported measures of behavioral outcomes and health-related quality of life (HRQoL) of their children at the age of 5 years were assessed by two standardized questionnaires: the Strengths and Difficulties Questionnaire (behavioral outcomes) and the KIDSCREEN-27 (HRQoL). Among 448 randomized infants, 228 infants were assigned to the RHEpo group and 220 infants were assigned to the placebo group. Questionnaire data were available for 317 children (71%) at a mean (SD) age of 5.8 (0.4) years (mean [SD] gestational age at birth, 29.3 [1.6] weeks; mean [SD] birth weight 1220 [340] grams; 128 [40%] female infants). At the age 5 years follow-up, the mean (SD) total difficulties score in the RHEpo group (8.41 [5.60] points) was similar to that of the placebo group (7.76 [4.81]) (P = .37). There were no statistically significant differences between the groups in any other outcome measures. This secondary analysis of a randomized clinical trial showed no evidence for an effect of early high-dose RHEpo administration on behavioral outcomes or HRQoL in children born very preterm at early school age. ClinicalTrials.gov Identifier: NCT00413946.

Neurovisual profile in children affected by Angelman syndrome

BackgroundAngelman syndrome (AS) is a rare neurogenetic disorder caused by altered expression of the maternal copy of the UBE3A gene. Together with motor, cognitive, and speech impairment, ophthalmological findings including strabismus, and ocular fundus hypopigmentation characterize the clinical phenotype. The aim of this study was to detail the neurovisual profile of children affected by AS and to explore any possible genotype-phenotype correlations. MethodsThirty-seven children (23 females, mean age 102.8 ± 54.4 months, age range 22 to 251 months) with molecular confirmed diagnosis of AS were enrolled in the study. All underwent a comprehensive video-recorded neurovisual evaluation including the assessment of ophthalmological aspects, oculomotor functions, and basic visual abilities. ResultsAll children had visual impairments mainly characterized by refractive errors, ocular fundus changes, strabismus, discontinuous/jerky smooth pursuit and altered saccadic movements, and/or reduced visual acuity. Comparing the neurovisual profiles between the deletion and non-deletion genetic subgroups, we found a significant statistical correlation between genotype and ocular fundus hypopigmentation (p = 0.03), discontinuous smooth pursuit (p < 0.05), and contrast sensitivity abnormalities (p < 0.01) being more frequent in the deletion subgroup. ConclusionsSubjects affected by AS present a wide spectrum of neurovisual impairments that lead to a clinical profile consistent with cerebral visual impairment (CVI). Moreover, subjects with a chromosome deletion show a more severe visual phenotype with respect to ocular fundus changes, smooth pursuit movements, and contrast sensitivity. Early detection of these impaired visual functions may help promote the introduction of neurovisual habilitative programs which can improve children’s visual, neuromotor, and cognitive outcomes.

Heart Rate and Pulse Oximetry Dynamics in the First Week after Birth in Neonatal Intensive Care Unit Patients and the Risk of Cerebral Palsy.

Infants in the neonatal intensive care unit (NICU) are at high risk of adverse neuromotor outcomes. Atypical patterns of heart rate (HR) and pulse oximetry (SpO2) may serve as biomarkers for risk assessment for cerebral palsy (CP). The purpose of this study was to determine whether atypical HR and SpO2 patterns in NICU patients add to clinical variables predicting later diagnosis of CP. This was a retrospective study including patients admitted to a level IV NICU from 2009 to 2017 with archived cardiorespiratory data in the first 7 days from birth to follow-up at >2 years of age. The mean, standard deviation (SD), skewness, kurtosis and cross-correlation of HR and SpO2 were calculated. Three predictive models were developed using least absolute shrinkage and selection operator regression (clinical, cardiorespiratory and combined model), and their performance for predicting CP was evaluated. Seventy infants with CP and 1,733 controls met inclusion criteria for a 3.8% population prevalence. Area under the receiver operating characteristic curve for CP prediction was 0.7524 for the clinical model, 0.7419 for the vital sign model, and 0.7725 for the combined model. Variables included in the combined model were lower maternal age, outborn delivery, lower 5-minute Apgar's score, lower SD of HR, and more negative skewness of HR. In this study including NICU patients of all gestational ages, HR but not SpO2 patterns added to clinical variables to predict the eventual diagnosis of CP. Identification of risk of CP within the first few days of life could result in improved therapy resource allocation and risk stratification in clinical trials of new therapeutics. · SD and skewness of HR have some added predictive value of later diagnosis of CP.. · SpO2 measures do not add to CP prediction.. · Combining clinical variables with early HR measures may improve the prediction of later CP..

Early feeding behaviours of extremely preterm infants predict neurodevelopmental outcomes

BackgroundInfants born extremely preterm are at high risk for early feeding difficulties, as well as poor neurodevelopmental outcomes in childhood. Feeding, a complex motor skill, may be predictive of later neuromotor outcomes. AimsTo determine the relationship between feeding behaviours of extremely preterm-born infants (<28 weeks gestational age) at 4-months corrected age (CA) and neurodevelopmental outcomes at 4–5 years. Study designRetrospective cohort design with prospectively collected data. SubjectsInfants born extremely preterm from September 1999 – October 2013 [n = 412, mean gestational age 25.4 (1.3) weeks; mean birth weight 771 (168) grams]. Oral feeding was assessed at 4-months CA by an experienced occupational therapist; infants were classified as either having poor suck-swallow (‘feeding difficulties’) or no feeding difficulties. Outcome measuresMotor outcomes were assessed at 4–5 years using the Movement Assessment Battery for Children (MABC). Children were categorized as: (1) typical motor development (TMD; n = 214); (2) Developmental Coordination Disorder (DCD; n = 116); or (3) major neurodevelopmental disorder (MND; n = 82). ResultsFeeding behaviour at 4-months CA predicted DCD (OR = 2.95, CI 1.13–7.68) and MND (OR = 3.67, CI 1.35–9.96) after controlling for confounders. Infants with feeding difficulties were more likely to be diagnosed with DCD (40 % of poor feeders) or MND (36 %) at 4–5 years, compared to infants without feeding issues. ConclusionsEarly feeding behaviours significantly predicted motor outcomes at 4–5 years. Infants born extremely preterm with early feeding difficulties should be identified as at high risk for poor motor outcomes later in childhood and screened for early diagnosis and intervention.

Neonatal research outcomes: the ethical imperative to change attitudes

As neonatal intensive care has advanced, long-term outcomes are a crucial marker of clinical care. Surviving preterm infants are described as having normal, moderate, or severe neurodevelopmental impairment, based on a composite measure of neuromotor, cognitive, neurosensory, and language outcomes. These measures have been established by health-care providers but questioned by parents of preterm infants who have articulated a preference for outcomes that are functional and relevant.1 As the discussion of how to measure outcomes unfolds, there is an ethical imperative to reconsider how long-term neonatal outcomes are presented.