Language outcomes at 18-24 months of preterm infants from US Spanish- and English-speaking homes.

AIM: To evaluate the association of Spanish compared to English primary household language on preterm (PT) infants' language outcomes in the United States and to examine associations with socio-economic factors. METHODS: This was a retrospective cohort of PT infants born <32 weeks gestation from Spanish-speaking (n = 95) and English-speaking homes (n = 1030) born 2005-2019. Language (primary outcome) and cognitive and motor skills (secondary outcomes) were measured using the BSID-III at 18-24 months corrected age. Group differences were evaluated using bivariate comparisons and logistic regression analyses. RESULTS: Mothers reporting Spanish-speaking homes had higher rates of public insurance and lower educational achievement. Group newborn characteristics were similar. Preterm infants from Spanish-speaking homes had significantly lower BSID-III language composite, cognitive composite, receptive and expressive scores compared to infants from English-speaking homes. Logistic regression modelling identified independent negative effects of Spanish-speaking household OR 3.26 (CI 1.89-5.62) and public insurance OR 2.31 (CI 1.71-3.12) with a protective benefit derived from breast milk OR 0.68 (CI 0.50-0.92) when adjusting for medical morbidities, socio-economic factors and gestational age. CONCLUSION: Public health policies and interventions in the United States should target language and cognitive outcomes of PT infants from Spanish-speaking homes.

Cerebral oxygenation immediately after birth and long-term outcome in preterm neonates-a retrospective analysis.

BACKGROUND: Prematurity is associated with increased risk for morbidity and mortality. Aim of this study was to evaluate whether cerebral oxygenation during fetal-to-neonatal transition period was associated with long-term outcome in very preterm neonates. METHODS: Preterm neonates ≤ 32 weeks of gestation and/or ≤ 1500 g with measurements of cerebral regional oxygen saturation (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) within the first 15 min after birth were analysed retrospectively. Arterial oxygen saturation (SpO2) and heart rate (HR) were measured with pulse oximetry. Long-term outcome was assessed at two years using "Bayley Scales of Infant Development" (BSID-II/III). Included preterm neonates were stratified into two groups: adverse outcome group (BSID-III ≤ 70 or testing not possible due to severe cognitive impairment or mortality) or favorable outcome group (BSID-III > 70). As the association between gestational age and long-term outcome is well known, correction for gestational age might disguise the potential association between crSO2 and neurodevelopmental impairment. Therefore, due to an explorative approach the two groups were compared without correction for gestational age. RESULTS: Forty-two preterm neonates were included: adverse outcome group n = 13; favorable outcome group n = 29. Median(IQR) gestational age and birth weight were 24.8 weeks (24.2-29.8) and 760 g (670-1054) in adverse outcome group and 30.6 weeks (28.1-32.0) (p = 0.009*) and 1250 g (972-1390) (p = 0.001*) in the favorable outcome group, respectively. crSO2 was lower (significant in 10 out of 14 min) and cFTOE higher in adverse outcome group. There were no difference in SpO2, HR and fraction of inspired oxygen (FiO2), except for FiO2 in minute 11, with higher FiO2 in the adverse outcome group. CONCLUSION: Preterm neonates with adverse outcome had beside lower gestational age also a lower crSO2 during immediate fetal-to-neonatal transition when compared to preterm neonates with age appropriate outcome. Lower gestational age in the adverse outcome group would suggest beside lower crSO2 also lower SpO2 and HR in this group, which were however similar in both groups.

Effects of prenatal exposure to pyrethroid pesticides on neurodevelopment of 1-year- old children: A birth cohort study in China.

Pregnant women have been ubiquitously exposed to pyrethroid pesticides. Previous studies, mainly based on third trimester measurements of maternal urinary pyrethroid metabolites, have reported inconsistent findings in the effects of prenatal pyrethroid exposure on children's neurodevelopmental outcomes. The purpose of this study was to clarify if pyrethroid exposure during the entire three trimesters of pregnancy may be associated with deleterious effects on infant neurodevelopmental status, particularly at a high dosage of exposure. We measured maternal urinary concentrations of pyrethroid metabolites in all trimesters of pregnancy and assessed children's neurodevelopment at one year of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multiple linear regression models were used to estimate the effects of metabolites (3-PBA, 4 F-3-PBA, cis-DBCA) in each trimester on BSID-III composite scores. Logistic regression analyses were applied to predict developmental delay vs non-delayed status (cut-off composite score of below 80 for developmental delay) based on the maternal levels of pyrethroid metabolites. In the first, second and third trimesters of pregnancy, the detection rates of pyrethroid metabolites were 94.7%, 90.7%, and 89.0%; the 50th percentiles of exposure level were 0.24 µg/g, 0.24 µg/g and 0.21 µg/g for 3-PBA, 0.14 µg/g, 0.17 µg/g and 0.15 µg/g for 4 F-3PBA, 0.21 µg/g, 0.25 µg/g and 0.19 µg/g for cis-DBCA respectively. In the second trimester, 3-PBA was inversely associated with Cognition and Language scores [ß = -3.34 (95% CI = -6.11, -0.57) and ß = -2.90 (95% CI = -5.20, -0.61), respectively], and significantly increased the risk of Cognition and Language developmental delay [OR= 1.64 (95% CI = 1.03, 2.62) and OR = 1.52 (95% CI = 1.06, 2.19), respectively]; cis-DBCA was inversely associated with Adaptive Behavior scores [ß = -0.73 (95% CI = -1.27, -0.19)], and significantly increased the risk of Adaptive Behavior developmental delay [OR= 1.11 (95% CI = 1.02, 1.21)]. When the maternal levels of pyrethroid metabolites were stratified into the regression models according to the 90th percentile of exposure, in the first trimester, Cognition and Motor scores were inversely associated with higher cis-DBCA [ß = -7.19 (95% CI = -12.97, -1.41) and ß = -8.20 (95% CI = -13.35, -3.05), respectively], Language scores were inversely associated with higher 3-PBA [ß = -6.01 (95% CI = -10.96, -1.06)]; in the second trimester, Cognition scores were inversely associated with higher cis-DBCA [ß = -6.64 (95% CI = -12.51, -0.76)], Language scores were inversely associated with higher 3-PBA [ß = -5.17 (95% CI = -10.07, -0.27)] and cis-DBCA [ß = -5.40 (95% CI = -10.28, -0.52)]. We concluded that pyrethroid exposure in the first and second trimesters was associated with poorer infants neurodevelopmental outcomes at one year of age, and these effects were particularly pronounced at high levels of pyrethroid exposure.

Nutritional, Socioeconomic, and Delivery Characteristics Are Associated with Neurodevelopment in Tanzanian Children.

OBJECTIVES: To evaluate the hypothesis that various maternal, socioeconomic, delivery, and infant nutritional characteristics are associated with early childhood development in young Tanzanian children. STUDY DESIGN: We performed a prospective cohort study among 206 HIV-exposed, uninfected and 247 HIV-unexposed Tanzanian infants who had been enrolled in 2 separate micronutrient trials (NCT00197730 and NCT00421668). Trained nurses administered culturally modified Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III), to evaluate cognitive, motor, and language development at 15 months of age. This analysis explored predictors of BSID-III z-scores using multivariable linear regression. RESULTS: Among maternal determinants, we found that low maternal height predicted all BSID-III domains in HIV-unexposed children; low maternal education predicted lower cognitive (standardized mean difference, -0.41; 95% CI, -0.74 to -0.08) and lower gross motor scores (standardized mean difference, -0.32; 95% CI, -0.61 to -0.04) in HIV-exposed children. Among delivery characteristics, facility delivery predicted higher cognitive scores (standardized mean difference, 1.36; 95% CI, 0.26-2.46); and oxytocin administration predicted lower fine motor scores (standardized mean difference, -0.48; 95% CI, -0.87 to -0.09) in HIV-exposed children. Higher length-for-age z-scores at 6 weeks of age predicted better cognitive (standardized mean difference, 0.15; 95% CI, 0.01-0.29) and expressive language scores (standardized mean difference, 0.16; 95% CI, 0.02-0.29) at 15 months in HIV-exposed infants. CONCLUSIONS: This hypothesis-generating study found significant associations between nutritional status and health of the mother and child, and maternal educational attainment, with direct measures of early childhood development at 15 months of age. In addition, several aspects of delivery (facility birth and oxytocin administration) were associated with early childhood development. Future intervention trials should focus on modifiable maternal, infant, and obstetric factors to strengthen the evidence base concerning early childhood development. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00197730 and NCT00421668.

EARLY MALTREATMENT AND CURRENT QUALITY OF RELATIONAL CARE PREDICT SOCIOEMOTIONAL PROBLEMS AMONG INSTITUTIONALIZED INFANTS AND TODDLERS.

The present study is focused on child socioemotional problems 6 months after institutionalization, by considering the putative predictive role of child maltreatment, of developmental functioning at admission and the following months, and of the quality of institutional relational care. Fifty institutionalized infants and toddlers participated in this study. Child developmental functioning (i.e., cognitive, language, and motor development) was assessed at admission to the institution (Wave 0), and 3 (Wave 1) and 6 months (Wave 2) thereafter. The quality of institutional relational care-operationalized in terms of caregivers' sensitivity and cooperation-was measured at Wave 2. Caregivers reported on the presence of disturbed socioemotional behaviors at Wave 2. Child gestational age, birth weight, age, and stunted growth at admission to the institution served as covariates. Results revealed significant associations between socioemotional difficulties and lower levels of motor development at Waves 0 and 1, child maltreatment, and less sensitive caregiving. A logistic regression showed that child maltreatment and caregiver insensitivity were the only significant predictors of disturbed socioemotional functioning by the end of 6 months of institutionalization.

Impaired Neurodevelopment in Children with 5q-SMA - 2 Years After Newborn Screening.

OBJECTIVE: Numerous studies have consistently found that reduced SMN protein expression does not severely affect cognitive function in SMA patients. However, the average intelligence quotient of SMA patients has ranged above to below average in different studies. The cognitive development of SMA patients identified through newborn screening remains largely unknown. METHODS: 40 of 47 eligible SMA patients (23 females/17 males) from 39 families identified through newborn screening between January 2018 and December 2020 underwent developmental testing using Bayley III (BSID) after the 2 years of age. The mean age was 29.25 months (23-42 months). 17 patients had 2, 11 patients had 3 and 12 patients had ≥4 copies of SMN2. RESULTS: cognitive scale: mean 94.55 (SD 24.01); language scale: mean 86.09 (SD 26.41); motor scale: 81.28 (SD 28.07). Overall, the cognitive scales show that 14 children were below average, 20 children were average and 6 children were above average. 10/14 children with below average scores had 2 SMN2 copies. The post-hoc pairwise comparisons showed that the cognition main scale was significantly more sensitive to the number of SMN2 copies than the motor main scale of the BSID (MΔ= 10.27, p = 0.014). There is also evidence that cognition scored higher than the language main scale (MΔ= 7.11, p = 0.090). CONCLUSION: The impaired cognitive development of SMA children with 2 SMN2 copies, despite early initiation of therapy, underscores the critical role of the SMN protein in the early stages of brain development.

Cognitive function in SMA patients with 2 or 3 SMN2 copies treated with SMN-modifying or gene addition therapy during the first year of life.

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease, causing progressive muscle weakness due to loss of lower motoneurons. Since 2017, three therapies, two modifying gene transcription and one adding the defective gene, have been approved with comparable efficacy on motor outcome. Data on cognitive outcomes of treated SMA type 1 patients is limited. The aim of this study was to evaluate cognitive function in symptomatic and presymptomatic SMA type 1 patients with two or three SMN2 copies who received SMN-modifying or gene-addition therapy in the first year of life. METHODS: Cognitive testing was performed in 20 patients, including 19 symptomatic SMA type 1 patients with up to three SMN2 copies and 1 pre-symptomatically treated patient. Children were tested using Bayley Scales of Infant Development (BSID-III) at the age of 2 or 3 years or the Wechsler Preschool and Primary Scale of Intelligence (WPSII-IV) at the of age of 5 years. RESULTS: 11/20 patients showed subnormal cognitive development. Boys had significantly lower cognitive scores. Patients requiring assisted ventilation or feeding support were more likely to have cognitive deficits. Achieving more motor milestones was associated with a better cognitive outcome. CONCLUSION: Treated patients with SMA type 1 have heterogeneous cognitive function with 55 % of patients showing deficits. Risk factors for cognitive impairment in our cohort were male gender and need for assisted ventilation or feeding support. Therefore, cognitive assessment should be included in the standard of care to allow early identification of deficits and potential therapeutic interventions.

Normalization of similarity-based individual brain networks from gray matter MRI and its association with neurodevelopment in infants with intrauterine growth restriction.

Obtaining individual biomarkers for the prediction of altered neurological outcome is a challenge of modern medicine and neuroscience. Connectomics based on magnetic resonance imaging (MRI) stands as a good candidate to exhaustively extract information from MRI by integrating the information obtained in a few network features that can be used as individual biomarkers of neurological outcome. However, this approach typically requires the use of diffusion and/or functional MRI to extract individual brain networks, which require high acquisition times and present an extreme sensitivity to motion artifacts, critical problems when scanning fetuses and infants. Extraction of individual networks based on morphological similarity from gray matter is a new approach that benefits from the power of graph theory analysis to describe gray matter morphology as a large-scale morphological network from a typical clinical anatomic acquisition such as T1-weighted MRI. In the present paper we propose a methodology to normalize these large-scale morphological networks to a brain network with standardized size based on a parcellation scheme. The proposed methodology was applied to reconstruct individual brain networks of 63 one-year-old infants, 41 infants with intrauterine growth restriction (IUGR) and 22 controls, showing altered network features in the IUGR group, and their association with neurodevelopmental outcome at two years of age by means of ordinal regression analysis of the network features obtained with Bayley Scale for Infant and Toddler Development, third edition. Although it must be more widely assessed, this methodology stands as a good candidate for the development of biomarkers for altered neurodevelopment in the pediatric population.

Association between feeding difficulties and language delay in preterm infants using Bayley Scales of Infant Development-Third Edition.

OBJECTIVE: To evaluate the relationship between abnormal feeding patterns and language performance on the Bayley Scales of Infant Development-Third Edition at 18-22 months adjusted age among a cohort of extremely premature infants. STUDY DESIGN: This is a descriptive analysis of 1477 preterm infants born ≤ 26 weeks gestation or enrolled in a clinical trial between January 1, 2006 and March 18, 2008 at a National Institute of Child Health and Human Development Neonatal Research Network center who completed the 18-month neurodevelopmental follow-up assessment. At 18-22 months adjusted age, a comprehensive neurodevelopmental evaluation was performed by certified examiners including the Receptive and Expressive Language Subscales of the Bayley Scales of Infant Development-Third Edition and a standardized adjusted age feeding behaviors and nutritional intake. Data were analyzed using bivariate and multilevel linear and logistic regression modeling. RESULTS: Abnormal feeding behaviors were reported in 193 (13%) of these infants at 18-22 months adjusted age. Abnormal feeding patterns, days of mechanical ventilation, hearing impairment, and Gross Motor Functional Classification System level ≥ 2 each independently predicted lower composite language scores. CONCLUSIONS: At 18 months adjusted age, premature infants with a history of feeding difficulties are more likely to have language delay. Neuromotor impairment and days of mechanical ventilation are both important risk factors associated with these outcomes.

Clinical, biochemical, and neuroimaging findings predict long-term neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection.

OBJECTIVE: To evaluate clinical, biochemical, and neuroimaging findings as predictors of neurodevelopmental outcome in patients with symptomatic congenital cytomegalovirus (CMV). STUDY DESIGN: The study cohort comprised 26 patients with symptomatic congenital CMV born between 1993 and 2009 in a single center. Absolute and weight deficit-adjusted head circumference were considered. Cerebrospinal fluid (CSF) investigations included standard cytochemical analysis, determination of beta2-microglobulin (ß2-m), neuron-specific enolase, and CMV DNA detection. Neuroimaging was classified according to a validated scoring system comprising calcifications, ventriculomegaly, and atrophy, with findings graded from 0 to 3. Systematic long-term neurodevelopmental assessment included motor function, cognition, behavior, hearing, vision, and epilepsy. Sequelae were graded as mild/absent, moderate, or severe; adverse outcome was defined as death or moderate to severe disability. RESULTS: Three children died. The mean age at follow-up of the survivors was 8.7 ± 5.3 years (range, 19 months to 18.0 years). Neonatal findings showing a significant association with adverse outcome were relative microcephaly, CSF ß2-m concentrations, and grade 2-3 neuroimaging abnormalities (P < .05). Receiver operator characteristic curve analysis indicated that the most accurate single factor for predicting unfavorable outcome was CSF ß2-m >7.9 mg/L (area under the curve, 0.84 ± 0.08; sensitivity, 69%; specificity, 100%). The combination of CSF ß2-m >7.9 mg/L and moderate-severe neuroimaging alterations improved predictive ability (area under the curve, 0.92 ± 0.06; sensitivity, 87%; specificity, 100%). CONCLUSION: Adjusted head circumference, CSF ß2-m level, and neuroimaging studies have prognostic significance for neurodevelopmental outcome in newborns with congenital CMV. A combination of early findings improves the predictive value.

Histological characteristics of the fetal inflammatory response associated with neurodevelopmental impairment and death in extremely preterm infants.

OBJECTIVE: To test the hypothesis that increasing severity of the fetal inflammatory response (FIR) would have a dose-dependent relationship with severe neurodevelopmental impairment or death in extremely preterm infants. STUDY DESIGN: We report 347 infants of 23-28 weeks gestational age admitted to a tertiary neonatal intensive care unit between 2006 and 2008. The primary outcome was death or neurodevelopmental impairment at the 18- to 22-month follow-up. Exposure status was defined by increasing stage of funisitis (stage 1, phlebitis; stage 2, arteritis with or without phlebitis; stage 3, subacute necrotizing funisitis) and severity of chorionic plate vasculitis (inflammation with or without thrombosis). RESULTS: A FIR was detected in 110 placentas (32%). The rate of severe neurodevelopmental impairment/death was higher in infants with subacute necrotizing funisitis compared with infants without placental/umbilical cord inflammation (60% vs 35%; P < .05). Among infants with stage 1 or 2 funisitis, the presence of any chorionic vasculitis was associated with a higher rate of severe neurodevelopmental impairment/death (47% vs 23%; P < .05). After adjustment for confounding factors, only subacute necrotizing funisitis (risk ratio, 1.87; 95% CI, 1.04-3.35; P = .04) and chorionic plate vasculitis with thrombosis (risk ratio, 2.21; 95% CI, 1.10-4.46; P = .03) were associated with severe neurodevelopmental impairment/death. CONCLUSION: Severe FIR, characterized by subacute necrotizing funisitis and severe chorionic plate vasculitis with thrombosis, is associated with severe neurodevelopmental impairment/death in preterm infants.

Reach Out and Read Literacy Program for Infants in Neonatal Intensive Care Unit: A Pre-Post Experimental Study.

The elevated prevalence of linguistic delay in youngsters emphasizes the necessity to focus on strategies to improve language development, hence aimed to evaluate the effectiveness of Reach Out and Read (ROR) intervention on language development for infants admitted to neonatal intensive care unit (NICU) at a tertiary care hospital, in Belagavi, India. Eighteen infants admitted 7 or more days in NICU and had APGAR scores of more than 6 at the first and fifth minute after birth were recruited. Reach Out and Read was done for 6 months. At recruitment, corrected age 3 and 5 months' general movement assessment (GMA) and at corrected age, 6 months' Bayley Scale of Infant Development III (BSID III) language subtest was recorded. Wilcoxon matched paired test showed significant improvement (P = .0277; P = .0431) in GMA over time. Six-month parent delivered ROR intervention confirms its effectiveness in promoting general movement developmental trajectories of infants admitted to NICU.

Clinical course and long-term follow-up of a preterm infant with non-fatal respiratory distress syndrome due to heterozygous ABCA3 gene mutation: A case report and review of literature.

BACKGROUND: Adenosine triphosphate-binding cassette transporter A3 (ABCA3) mutations are recognized as a congenital cause of surfactant deficiency. Clinical presentations of such mutations are largely variable. There are many mutations of the ABCA3 gene, of which, p.E292V is the most common. Despite being the most common ABCA3 gene mutation, there is limited literature on extra pulmonary and long-term outcomes of the affected infants. CASE: We present the case of a Caucasian male infant born at 32 weeks gestation that developed severe respiratory distress shortly after birth, and review published case reports and case series of infants affected with this gene mutation. He was found to have a heterozygous missense mutation p.E292V of ABCA3 resulting in a chronic lung disease. He required multiple courses of systemic and inhalational steroids. He developed supraventricular tachycardia (SVT), feeding problems and hypotonia during his prolonged hospital stay. He demonstrated mild neurodevelopmental delays on follow up at 18 months of age. The chronic lung disease improved over the first 2 years of life. He continued to have feeding difficulties and supraventricular tachycardia at nearly 2 years of age. CONCLUSION: The infant's SVT may be associated with this ABCA3 variant. Further long-term follow-up studies are needed to better characterize extrapulmonary manifestations of this ABCA3 mutation.

Neonatal stroke: Clinical characteristics and neurodevelopmental outcomes.

BACKGROUND: Neonatal stroke can potentially result in significant neurological sequelae in affected infants. Studies on neurodevelopmental outcomes and the need for rehabilitation therapies in the first two years are limited. We aimed to describe the clinical characteristics, diagnostic evaluation, and neurodevelopmental outcomes of a cohort of infants with neonatal stroke. METHODS: A retrospective cohort study of infants with neonatal stroke, from 2011 to 2020. Maternal and infant characteristics were described. Placental pathology, echocardiogram results, and prothrombotic evaluations were reported. The neurodevelopmental outcomes using Bayley scale of infant development (BSID III), rates of epilepsy and cerebral palsy, and the need for rehabilitation therapies at two years were described. RESULTS: During the study period, 55 infants had neonatal stroke. Majority (93%) were term or late preterm infants. Maternal chorioamnionitis and perinatal HIE were diagnosed in about a third of the infants. Most (66%) of the infants presented with seizures. On brain MRI, the lesions were unilateral in 76% and arterial in origin in 86% of the infants. Meconium exposure (42%), intrauterine inflammation/infection (37%) and fetal vascular malperfusion (16%) were seen on placental histopathology. At two-year BSID III assessment, median (min, max) composite cognitive, language, and motor scores were 100 (55-145), 97 (47-124), and 100 (46-141), respectively. Among this cohort, epilepsy (27%), cerebral palsy (16%) and the need for rehabilitation therapies (physical -24%, occupational -18%, speech -21%) were reported at two years. CONCLUSION: Neonatal stroke presented commonly in term or late preterm infants with seizures. It was unilateral and arterial in origin in most infants. Maternal chorioamnionitis and perinatal HIE were the most commonly associated conditions at birth. About one-fifth of the infants had mild or severe developmental delays at two years. Epilepsy, cerebral palsy, and need for rehabilitation therapies were noted in a significant proportion of infants at two years.

Relationship between parental report of language skills and children's performance among 3-year-olds: Implications for screening language among preschoolers.

AIM: The study compared parental ratings of children's language abilities at 3-years of age with observations of children's language performance by Speech Language Pathologists (SLPs). METHOD: Children (n=85) around 3-years of age were recruited from a child development clinic. Detailed speech and language assessments were completed during a one-hour semi-structured clinician-child interactive session. Language assessment was carried out using a criterion-referenced checklist and the language sections of the Bayley Scale for Infant Development- 3rd Edition (BSID-III). All parents rated their children's language skills using seven statements related to reception and expression domains of language on a 7-point rating scale. The language status of the child (typical language vs delay) determined by the parental report was matched with the language status as per the child's performance during the SLP assessment. RESULTS AND DISCUSSION: Mean parental ratings of children assessed as having language delay by an SLP were significantly lower than children with typical language. Total parental rating score correlated highly with overall language scores on BSID-III; the highest correlation was observed for ratings of statements related to expressive language skills focusing on formation of sentences. Parental report of below normal performance on any one of the seven statements demonstrated acceptable sensitivity (0.95) and a high negative predictive value (0.98) with the child's performance as the gold standard. CONCLUSION: Parental ratings of language skills correlated with child's performance at 3-years of age with a higher agreement for identifying children with delays. Parental reports can be useful to red-flag children for further assessment and continued monitoring of language development in busy developmental clinics and preschools, especially in the context of low-resource settings.

The Predictive Value of Language Scales: Bayley Scales of Infant and Toddler Development Third Edition in Correlation With Korean Sequenced Language Scale for Infant.

OBJECTIVE: To compare the relationship of the Bayley Scales of Infant and Toddler Development 3rd Edition (K-BSID-III) language score and the Sequenced Language Scale for Infant (SELSI) score and evaluate the sensitivity and specificity of K-BSID-III language score and optimal cutoff value with receiver operator characteristic (ROC) curve analysis in infants and toddlers with delayed language development. METHODS: A total of 104 children with suspected language developmental delay were included in this retrospective study. Subjects were tested using the K-BSID-III and SELSI and subdivided into several groups according to the severity of language scores. ROC curve analysis was performed to assess K-BSID-III for delayed language development. RESULTS: Receptive and expressive language subscales of the K-BSID-III showed markedly significant correlation with the SELSI scores (p<0.001). ROC analysis showed an area under the curve of 0.877 (p<0.001) in SELSI receptive score and 0.935 (p<0.001) in SELSI expressive score. The optimal cutoff value where sensitivity of 85% and specificity of 81% were achieved with the K-BSID-III receptive score was 1.50 (between average and low average) in the SELSI receptive score. The optimal cutoff value where sensitivity of 96% and specificity of 82% were achieved with the K-BSID-III expressive score was also 1.50 in the SELSI expressive score. CONCLUSION: In this study, the correlations between K-BSID-III and SELSI language scores were statistically significant. However, the interpretation should be considered carefully in low average group due to tendency of underestimation of delayed language development.

Natural history of cognitive development in neuronopathic mucopolysaccharidosis type II (Hunter syndrome): Contribution of genotype to cognitive developmental course.

The natural history of cognitive growth in the neuronopathic form of Mucopolysaccharidosis type II (MPS II) is not well defined especially their patterns of development and decline. The ability to predict the developmental course of the neurologically impaired patient is necessary to assess treatment outcomes aimed at the brain. Thirteen intravenous enzyme replacement therapy-treated Japanese patients with neuronopathic MPSII who had mutation analysis were followed on one standard measure of cognitive development over time. Six children in Group MS had missense mutations and 7 children in Group NT had null type mutations such as deletions, recombination with the pseudogene, and nonsense mutations. The patients as a whole demonstrated cognitive growth until about 36-42 months of age, followed by a plateau in development. The mean age equivalent score at age 3 was similar to that at age 6. While the decline was slow for the entire group, the patients in Group NT showed a more rapid decline than those in Group MS. Two patients with deletions showed decline to a very low level by age 5. The long plateau in cognitive development in patents with MPS II was substantiated and was consistent with other studies. This is the first demonstration that different mutation types within the neuronopathic MPS II patients are associated with different rates of decline. We also were able to identify the chronological age before which a trial would need to start in order to maintain cognitive growth and a ceiling beyond which a relatively normal outcome would not be likely.

Integrative medicine rehabilitation for children with cerebral palsy: a study protocol for a multicenter pragmatic randomized controlled trial.

BACKGROUND: Traditional Korean medicine (TKM) has been employed for the treatment of children with cerebral palsy in Korea; however, the addition of TKM to usual rehabilitation (UR) treatment is hindered by insufficient evidence of clinical improvement with TKM in patients with cerebral palsy. In this study, we will evaluate the effectiveness and safety of integrative medicine rehabilitation (IMR) for cerebral palsy through a randomized controlled clinical study. METHODS: Eighty children (2-6 years old) diagnosed with cerebral palsy will be recruited and randomly divided into groups A and B. Patients in group A will receive IMR with UR, while those in group B will receive only UR during weeks 1-12 of the study. IMR includes acupuncture treatment (head and limb acupuncture) three times a week and the administration of herbal medicine (Yukgunza-tang and Yukmijihwang-tang extracts) twice a day in parallel with UR. Evaluations will be conducted at the beginning of the study and at 12 and 24 weeks (follow-up). The primary outcome is the Gross Motor Function Measure-88 score, and the secondary outcomes are the scores for the Goal Attainment Scale, Korean Bayley Scales of Infant Development III, and the Pediatric Quality of Life Inventory, and adverse events. DISCUSSION: This will be the first pragmatic randomized controlled trial to evaluate the efficacy and safety of IMR in children with cerebral palsy in Korea. The results will help to demonstrate if IMR is an effective therapeutic approach for cerebral palsy. TRIAL REGISTRATION: Ministry of Food and Drug Safety 31361 ( http://www.mfds.go.kr ). Registered on 29 June 2017. Clinical Research Information Service KCT0002620 ( https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=9819 ). Registered on 29 December 2017.

Reaching skills of infants born very preterm predict neurodevelopment at 2.5 years.

The purpose was to investigate associations between quality of reaching for moving objects at 8 months corrected age and neurodevelopment at 2.5 years in children born very preterm (gestational age (GA), 24-31 weeks). Thirtysix infants were assessed while reaching for moving objects. The movements were recorded by a 3D motion capture system. Reaching parameters included aiming, relative length of the reach, number of movement units, proportion of bimanual coupled reaches and number of hits. Neurodevelopment was assessed at 2.5 years by the Bayley Scales of Infant Development III. There were strong associations between infant reaching kinematics and neurodevelopment of cognition and language but the patterns differed: in children born extremely preterm (GA < 28 weeks), planning and control of reaching was strongly related to outcome, while in children born very preterm (GA 28-31 weeks) number of hits and bimanual strategies were of greater relevance. In conclusion, for extremely preterm infants, basic problems on how motion information is incorporated with action planning prevail, while in very preterm infants the coordination of bimanual reaches is more at the focus. We conclude that the results reflect GA related differences in neural vulnerability and that early motor coordination deficits have a cascading effect on neurodevelopment.

Shunting outcomes in posthemorrhagic hydrocephalus: results of a Hydrocephalus Clinical Research Network prospective cohort study.

OBJECTIVE Previous Hydrocephalus Clinical Research Network (HCRN) retrospective studies have shown a 15% difference in rates of conversion to permanent shunts with the use of ventriculosubgaleal shunts (VSGSs) versus ventricular reservoirs (VRs) as temporization procedures in the treatment of hydrocephalus due to high-grade intraventricular hemorrhage (IVH) of prematurity. Further research in the same study line revealed a strong influence of center-specific decision-making on shunt outcomes. The primary goal of this prospective study was to standardize decision-making across centers to determine true procedural superiority, if any, of VSGS versus VR as a temporization procedure in high-grade IVH of prematurity. METHODS The HCRN conducted a prospective cohort study across 6 centers with an approximate 1.5- to 3-year accrual period (depending on center) followed by 6 months of follow-up. Infants with premature birth, who weighed less than 1500 g, had Grade 3 or 4 IVH of prematurity, and had more than 72 hours of life expectancy were included in the study. Based on a priori consensus, decisions were standardized regarding the timing of initial surgical treatment, upfront shunt versus temporization procedure (VR or VSGS), and when to convert a VR or VSGS to a permanent shunt. Physical examination assessment and surgical technique were also standardized. The primary outcome was the proportion of infants who underwent conversion to a permanent shunt. The major secondary outcomes of interest included infection and other complication rates. RESULTS One hundred forty-five premature infants were enrolled and met criteria for analysis. Using the standardized decision rubrics, 28 infants never reached the threshold for treatment, 11 initially received permanent shunts, 4 were initially treated with endoscopic third ventriculostomy (ETV), and 102 underwent a temporization procedure (36 with VSGSs and 66 with VRs). The 2 temporization cohorts were similar in terms of sex, race, IVH grade, head (orbitofrontal) circumference, and ventricular size at temporization. There were statistically significant differences noted between groups in gestational age, birth weight, and bilaterality of clot burden that were controlled for in post hoc analysis. By Kaplan-Meier analysis, the 180-day rates of conversion to permanent shunts were 63.5% for VSGS and 74.0% for VR (p = 0.36, log-rank test). The infection rate for VSGS was 14% (5/36) and for VR was 17% (11/66; p = 0.71). The overall compliance rate with the standardized decision rubrics was noted to be 90% for all surgeons. CONCLUSIONS A standardized protocol was instituted across all centers of the HCRN. Compliance was high. Choice of temporization techniques in premature infants with IVH does not appear to influence rates of conversion to permanent ventricular CSF diversion. Once management decisions and surgical techniques are standardized across HCRN sites, thus minimizing center effect, the observed difference in conversion rates between VSGSs and VRs is mitigated.