Toddler Development-Third Edition Research Articles

Parent screening questionnaires to detect cognitive and language delay at 2 years in high-risk infants: an analysis from the Victorian Infant Collaborative Study 2016–2017 cohort

ObjectiveTo determine the accuracy of two developmental screening questionnaires to detect cognitive or language delay, defined using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), in children born...

Are sucking patterns and early spontaneous movements related to later developmental functioning outcomes? A cohort study.

Sucking patterns and early spontaneous movements have an important role in the determination of later developmental problems, but the relationship of the two together with long-term outcomes has not been investigated. The objectives of this study were to (i) examine the relationship between sucking patterns using the Neonatal Oral Motor Assessment Scale (NOMAS) and fidgety movements and other movement patterns using detailed General Movements Assessment (GMA), and (ii) investigate the relationship between these early assessment methods and developmental functioning outcomes at later ages. We analyzed the NOMAS from 34weeks' postmenstrual age up to 10weeks post-term and GMA between 9 and 20weeks post-term age, and the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) was applied for the developmental functioning outcomes to 62 infants (61%, 62/102) between 12 and 42months of age. Among 102 infants at-risk, 70 (69%) showed a normal sucking pattern, and 85 (83%) had fidgety movements. The median Motor Optimality Score-Revised (MOS-R), as determined by GMA, of all infants was 24. The NOMAS was related to the MOS-R and its subcategories (p < 0.05) in all infants at-risk. The NOMAS, MOS-R and its subcategories were also related to cognitive, language, and motor development at later ages according to Bayley-III (p < 0.05). Conclusion: This longitudinal study showed that the quality of sucking patterns, fidgety movements, and MOS-R were related to later developmental functioning, indicating that abnormal sucking patterns, aberrant fidgety movements, and lower MOS-R might predict developmental disorders. What is Known: • Sucking patterns and early spontaneous movements in which central pattern generators play an important role are related. • Sucking patterns and early spontaneous movements might be used separately to predict developmental outcomes. What is New: • Sucking patterns and early spontaneous movements, when used together, were related to later developmental functioning, including cognitive, language, and motor developmentin at-risk infants. • Predictive value of sucking patterns was lower for each developmental functioning outcome than early spontaneous movements.

Caregiver report of social-emotional functioning in infants and young children after inflicted traumatic brain injury

ABSTRACT Social-emotional difficulties are common sequelae of traumatic brain injury (TBI). Children who have experienced inflicted TBI (iTBI) may be at increased risk for social-emotional problems due to the risk factors associated with both early neurologic injury and with child maltreatment. We characterized the associations among injury severity, caregiver type (i.e., biological parents, non-kinship, kinship), and child social-emotional functioning in 41 infants and young children who had sustained iTBI and were seen in a large, regional children’s hospital. This study was a retrospective analysis, utilizing data collected from the medical record as part of routine clinical care. Social-emotional functioning was assessed with the Bayley Scales of Infant and Toddler Development-Third Edition. Children with more severe injuries were rated as having worse social-emotional functioning. Caregiver type was associated with child social-emotional scores, above and beyond injury and demographic predictors. Biological parents were more likely to report better social-emotional skills than non-kinship caregivers, with the pattern of results suggesting that rater bias plays a role in this difference. In order to ensure that children are accurately identified for supports, these relationships should be considered when interpreting caregiver report of social-emotional skills.

General Movements trajectories and outcome at 12 months in very preterm infants: An analysis of tendencies and pathological persistence

Very preterm infants (VPI) < 32 weeks are at increased risk of developmental disorders detectable using the Prechtl General Movements Assessment (GMA) and the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). The aim of this study was to investigate General Movements (GMs) trajectories from preterm to fidgety age including GMs tendencies and their association with cognitive and motor outcome. Retrospective analysis of VPI with GMA at preterm (35 ± 2 weeks postmenstrual age (PMA), T1) and fidgety age (12 ± 3 weeks corrected age CA), T2), and BSID-III (12 ± 3 months CA, T3) is performed. Data are analysed using Pearson χ2-test, Fisher-Freeman-Halton Exact test, and residual analyses. This study found significant associations between (a) GMs (T1) and (b) persistent pathological GMs (T1 + T2) with cognitive outcomes at 12 months (T3) considering the tendencies of GMs in addition to the global character (p = 0.007, p = 0.022, respectively), representing medium-sized effects. There were no significant associations between GMs or persistence of pathological GMs and gross and fine motor outcomes, regardless of GMs tendencies. Findings indicate that considering tendencies of GMs and the persistence of pathological GMs may be important in identifying children at risk of cognitive impairments early. This additional assessment parameter may have the potential for early identification of infants with milder motor and/or cognitive impairments. However, more research is needed using larger sample cohorts to generalise the results and to be able to recommend sequential GMA for clinical routine.

Association of Postnatal Growth Changes and Neurodevelopmental Outcomes in Preterm Neonates of

To examine associations between weight and head circumference (HC) changes and neurodevelopment in preterm infants. This retrospective cohort study of Canadian Neonatal Network and Canadian Neonatal Follow-Up Network sites included preterm infants born 2010-2018. Logistic regression and model diagnostics evaluated relationships between changes in z score and velocity of weight and HC from birth to discharge from a tertiary neonatal intensive care unit, discharge to 18-24months corrected age (CA), and birth to 18-24months CA and significant cognitive/motor impairment at 18-24months CA classified using a Bayley Scales of Infant and Toddler Development-Third Edition cognitive or motor composite score <70. In total, 4530 infants (53.0% male) with a mean (SD) gestational age of 26.3 (1.4) weeks and birth weight of 920 (227) g were included. Weight and HC changes were associated with lower odds of significant cognitive/motor impairment including an OR of 0.87 (95% CI: 0.83, 0.91; P< .001) for a 1-g/d increase in weight from discharge to 18-24months CA and 0.81 (95% CI: 0.75, 0.88; P< .001) for a 1-unit increase in HC z score from birth to 18-24months CA. Associations were not statistically significant in morbidity-free neonates. Weight and HC gains poorly discriminated between infants with and without significant cognitive/motor impairment (areas under the receiver operating characteristic curve of <0.64). No growth measure had a clinically useful balance of sensitivity and specificity. Weight and HC changes were associated with significant cognitive/motor impairment but had poor discriminatory capability. Neonatal morbidities may make a larger contribution than postnatal growth to neurodevelopment.

Prediction of cord blood leptin on infant’s neurodevelopment: A birth cohort in rural Yunnan, China

BackgroundLeptin, one of the peptide hormones secreted by adipocytes, plays a vital part in metabolism, but its role in early-life neurodevelopment remains poorly understood. MethodsWe performed leptin analysis on 323 cord blood samples collected from a birth cohort in Yunnan rural area, China, and assessed infants’ neurodevelopment at one year of age by the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Multiple linear regression and binary logistic regression models were used to explore the associations between cord blood leptin (CBL) concentrations and infants’ neurodevelopment and the ability of CBL to predict the probabilities of infants’ neurodevelopment delay. ResultsOverall, 323 infants were included in this study. The median concentration of CBL was 4.7 ng/ml. The proportion of 1-year-old infants identified as being neurodevelopmental delayed was 34.5%, and delays in cognitive, language, and motor domains were 11.1%, 26.6%, and 13.9%, respectively. Multiple linear regression analyses manifested that the CBL concentration (log10-transformed) was positively correlated with the cognitive, language, and motor composite scores in infants, respectively (β = 7.76, 95%CI: 3.81–11.71; β = 6.73, 95%CI: 3.41–10.06; and β = 6.88, 95%CI: 3.48–10.29, respectively). Binary logistic regression analysis showed that compared with the higher, lower CBL (< 4.7 ng/ml) yielded a 1.41-fold increase in the risk of language development delay (OR = 2.41，95%CI: 1.42–4.09), a 1.49-fold higher risk of motor development delay (OR = 2.49, 95%CI: 1.25–4.96), and a 1.71-fold higher risk of neurodevelopment delay (OR = 2.71, 95%CI: 1.64–4.48) among infants. The prediction models showed that the probabilities of development delay in infants’ language, motor, and neurodevelopment increased with the decline of CBL concentrations [rs = −0.63 (95% CI: −0.71, −0.56), rs = −0.46 (95% CI: −0.55, −0.38), rs = −0.55 (95% CI: −0.63, −0.46), respectively]. ConclusionThe decline of CBL was associated with the decrease in infants’ neurodevelopment scores at one year of age. CBL below 4.7 ng/ml may increase the risk of infants’ neurodevelopment delay. The probabilities of infants’ neurodevelopment delay increased with the decrease of CBL concentrations. CBL may be a predictor of the probability of children’s neurodevelopment delay.

Effects of prenatal and infant daily exposure to pyrethroid pesticides on the language development of 2-year-old toddlers: A prospective cohort study in rural Yunnan, China

BackgroundPrenatal and infant daily exposures to pyrethroid pesticides (PYRs), used in the elimination of harmful organisms in the family environment and agricultural activities, may have an impact on children's language development. ObjectivesTo determine the impacts of prenatal and infant PYRs exposure on 2-year-old toddlers’ language development. MethodsFrom January 2016 to December 2018, women in the third trimester of pregnancy, in Yunnan rural area, China, were recruited, and the development of their newborns was observed from birth till the age of two. We examined three PYRs metabolites: 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-2,2dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA) in urine samples collected from women in the third trimester of pregnancy and their infants of 6–8 months after birth, and assessed language development of 2-year-old toddlers by the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Generalized linear models were used to analyze the impacts of exposure to PYRs on 2-year-old toddlers’ language development. ResultsThe median concentrations of 3PBA, 4F3PBA and DBCA creatinine-adjusted were 0.21, 0.19, and 0.15 μg/g in pregnancy, and 0.25, 0.72, and <LOD μg/g in infancy, respectively. The average scores of Language Composite (LC), Receptive Communication (RC), and Expressive Communication (EC) in 2-year-old toddlers were 100.0 ± 16.5, 10.0 ± 3.1, and 10.0 ± 3.1, respectively. Multiple linear regression analyses manifested that the concentration of 4F3PBA in infancy was negatively correlated with toddlers’ RC scores [β = −0.43 (95 % CI: −0.85, −0.01), p = 0.046]; the total PYRs metabolites in infancy were negatively correlated with boys’ LC scores and RC scores [β = −1.14 (95 % CI: −2.25, −0.04, p = 0.042 and β = −0.23 (95 % CI: −0.44, −0.01), p = 0.039, respectively]. Generalized linear models showed that exposure versus non-exposure to PYRs with DBCA in infancy increased 4.58 times risk of language development delay (OR = 5.58, 95 % CI: 1.76–17.68, p = 0.004) and a 21 % risk of not passing expressive communication items (OR = 1.21, 95 % CI: 1.01–1.45, p = 0.040). The risk of not passing RC items increased 9 % with 4F3PBA increasing per 1 μg/g in infancy (OR = 1.09, 95 % CI: 1.02–1.15, p = 0.007). The probability of not passing RC items ascended with infant 4F3PBA (rs = 0.57, 95%CI: 0.48–0.67, p < 0.001). ConclusionWomen in the third trimester of pregnancy and their infants were widely exposed to low-dose PYRs. Infant daily exposure to PYRs may negatively impact toddlers’ language development, with the 6–8 months age bracket being a sensitive window. The probability of toddlers’ language development delay may be predicted by PYRs metabolites of infants aged 6–8 months.

Exposure to perfluoroalkyl substances and neurodevelopment in 2-year-old children: A prospective cohort study.

Humans are widely exposed to per- and polyfluoroalkyl substances (PFAS). As fetal stage is a critical window for neurodevelopment, it is important to know if in utero exposure to PFAS affects fetal neurodevelopment. However, previous human studies are both limited and inconsistent. To investigate the relationship between PFAS exposure during early pregnancy and the neurodevelopmental status at 2years of age in a prospective cohort study. We measured 10 PFAS in maternal plasma samples collected prior to 16weeks of gestation in the Shanghai Birth Cohort Study between 2013 and 2016. Childhood neurodevelopment was assessed at 2years of age using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Associations with domain specific scores for individual PFAS were assessed by multiple linear regression and binary logistic regression when scores were dichotomized. Quantile-based g-computation was used to estimate the joint effects of PFAS mixture. A total of 2257 mother-child pairs who had both PFAS and BSID measurements were included in our analyses. The means and standard deviations of comprehensive scores were 115±22, 96±15 and 108±15 for cognition, language, and motor, respectively. In multiple linear regressions, we observed significant negative associations of perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA) with cognitive scores; PFNA, PFDeA, PFUnDA and perfluorohexanesulfonate (PFHxS) negatively with language scores; and PFNA and PFUnDA negatively with motor scores. Quantile-based g-computation showed that PFAS mixture was significantly associated with decreased cognitive and language scores, with an estimated β of -2.1 [95% confidence interval (CI): -3.5, -0.7)] and -2.0 (95% CI: -2.9, -1.0) per one quartile increase in PFAS mixture for cognitive and language domains, respectively. PFAS mixture was associated with increased odds of low cognition (adjusted odds ratio [OR]=1.3, 95% CI:1.0, 1.6) and language scores (OR=1.2, 95% CI: 1.1, 1.3). PFAS exposure during early pregnancy was significantly associated with the adverse neurodevelopmental status at 2years of age, which raises a serious public health concern.

MOTOR DEVELOPMENT OUTCOMES OF CHILDREN WHO HAVE UNDERGONE THERAPEUTIC HYPOTHERMIA: WITH PARENTS’ VIEWS

Objective: Neurodevelopmental follow-up of infants with hypoxic ischemic encephalopathy (HIE) and supporting their development have great importance for the later years of their life. The aim of this study was to evaluate motor development outcomes of children with HIE who have undergone therapeutic hypothermia (TH) in Turkey with an objective assessment and the point of view of the parents, and to compare these two assessment methods. Materials and Methods: Twenty two cases (11 girls, 11 boys) with HIE who have undergone TH were included. Sixteen (72.7%) of the cases were classified as Sarnat Stage-2, and six (27.3%) of the cases were classified as Sarnat Stage-3. Motor development of the cases were evaluated by the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Parents’views on their children’s development were examined with The Ages and Stages Questionnaire-2 (ASQ-2). Results: 68.2% (n=15) of the cases had normal motor development, 18.2% (n=4) had mild-moderate motor delay and 13.6% (n=3) had severe motor delay according to the Bayley-III motor scale results. When looking at the sub-areas of motor development, 68.2% (n=15) of the cases had normal gross motor development and 86.4% (n=19) of the cases had normal fine motor development. Additionally, 68.2% (n=15) of the cases demonstrated normal gross motor &amp; fine motor development according to ASQ-2 results. Conclusion: Although there are some parallels in the results of the objective assessments and parental views regarding gross motor development, they differ in terms of fine motor development. However, ASQ-2 can be helpful for follow-up of children with HIE in situations where access to a clinician is limited or difficult and also it can provide an opinion to parents about their children’s development.

Developmental Functioning Outcomes in Infants With Cystic Fibrosis: A 24- to 36-Month Follow-Up Study.

This study aimed to examine early motor repertoire using Prechtl General Movement Assessment (GMA) and later developmental functioning of infants with cystic fibrosis (CF). Early motor repetoire was evaluated using Prechtl GMA, and developmental functioning was assessed using Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) in infants with CF and their peers who were neurotypical, as the control group. Twelve infants with CF clinically stable and 12 infants who were neurotypical, with respective median post-term ages of 14 and 13weeks, were assessed using GMA. At 24 to 36months, the Bayley-III was applied to the CF group (median post-term age = 27.5months) and the control group (median post-term age = 27.0months). Fidgety movements were absent in 5 infants with CF, whereas all infants who were neurotypical had normal fidgety movements. The Motor Optimality Score was significantly lower in the CF group (median = 18.5) compared with the control group (median = 26). The CF group had significantly lower composite scores in the Bayley-III cognition, language, and motor domains compared with the control group. Cognitive, language, and motor development was delayed in infants with CF. Developmental functioning of infants with CF should be assessed as early as possible and monitored, and age-specific early intervention programs should be considered when necessary. Infants with CF may have motor, cognitive, and language developmental delays compared with peers who are neurotypical during early childhood, and hospitalization was negatively correlated with motor development at 24 to 36months of age. This study highlights the importance of early assessment of developmental functioning and age-specific, early intervention programs when necessary in infants with CF. It is important to assess developmental functioning as early as possible in infants with CF and to consider age-specific early intervention programs when necessary.

Prenatal pyrethroid pesticides exposure and neurodevelopment of 2-year-old children: a birth cohort study

Objective: To investigate the influence and critical windows of prenatal exposure to pyrethroid pesticides (PYRs) on neurodevelopment of 2-year-old children. Methods: The subjects of this study were derived from the Xuanwei Birth Cohort. A total of 482 pregnant women who participated in the rural district of Xuanwei birth cohort from January 2016 to December 2018 were included. Maternal urinary concentrations of PYRs metabolites during 8-12 gestational weeks, 20-23 gestational weeks and 32-35 gestational weeks were measured with ultra high performance liquid chromatography system coupled with a tandem mass spectrometry detector. Child neurodevelopment was evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition at 2 years of age. Multivariate linear regression models and binary logistic regression models were used to assess the association between PYRs exposure during pregnancy and children's neurodevelopment. Results: A total of 360 mother-child pairs had complete data on maternal urinary PYRs metabolites detection and children's neurodevelopment assessment. The detection rate of any one PYRs metabolites during the first, second and third trimester were 93.6% (337/360), 90.8% (327/360) and 94.2% (339/360), respectively. The neurodevelopmental scores of Cognitive, Language, Motor, Social-Emotional, and Adaptive Behavior of 2-year-old children were (102.3±18.9), (100.2±16.3), (102.0±20.3), (107.8±23.3) and (85.8±18.6) points, respectively. After controlling for confounding factors, 4-fluoro-3-phenoxybenzoic acid (4F3PBA, one of PYRs metabolites) exposure in the first trimester reduced Motor (β=-5.02, 95%CI: -9.08, -0.97) and Adaptive Behavior (β=-4.12, 95%CI:-7.92, -0.32) scores of 2-year-old children, and increased risk of developmental delay of adaptive behavior (OR=2.07, 95%CI:1.13-3.82). Conclusion: PYRs exposure during the first trimester of pregnancy may affect neurodevelopment of 2-year-old children, and the first trimester may be the critical window.

Missed Opportunities and the Impact of the Pandemic.

Benjamin is a 9-month-old, former 36-week gestation infant who presented to the high-risk infant follow-up clinic with parental concern for developmental regression. His mother reported that Benjamin seemed to be developing typically, but over the past 2 months, he has lost the ability to visually track objects, is not as engaged with her as he once was, and now only rarely makes babbling sounds. His mother also reported episodes of intermittent "bursts" of stiffening of his extremities and brief staring spells. Benjamin's mother described him as a "good, quiet baby." She commented that he used to laugh and cry more frequently but has recently been "very peaceful and calm." Benjamin's mother recently relayed her concerns for developmental regression to his pediatrician during an audio-only telehealth visit. Benjamin was referred to a pediatric neurologist, and the consultation visit is pending.His mother is a 28-year-old single parent whose pregnancy was complicated by pre-eclampsia, gestational diabetes, and anxiety. Benjamin required admission to the neonatal intensive care unit because of initial feeding difficulties. After 1 week, Benjamin was discharged to home and was referred for early intervention services. Owing to the pandemic, there were delays with initiating intervention, but bimonthly virtual interaction with a representative from the infant development program was eventually provided.Benjamin's mother expressed significant concerns regarding the potential of exposing him to a pandemic-related illness because of bringing her son to in-person medical visits. In fact, because of her concerns, she attended only virtual well-child pediatric visits over the past 6 months. A thorough social history revealed that she is a former dance studio instructor. The studio closed and she lost her primary source of income because of the pandemic. As a result, she decided to not send Benjamin to child care and maintained isolation from extended family members.On physical examination, pertinent findings included poor truncal tone, lack of orientation toward sounds, and limited eye contact. The Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) was administered, and the results indicated severe delays across all developmental areas, consistent with a diagnosis of global developmental delay.Benjamin's clinical presentation to the HRIF clinic and a history of developmental regression and intermittent body movements raised concerns for infantile spasms. He was transferred to the emergency department for evaluation and consideration for admission to the neurology service. An electroencephalogram confirmed epileptiform abnormalities consistent with infantile spasms, and he was immediately started on treatment.Impacts of the pandemic on the medical care of vulnerable/at-risk pediatric patients have included delayed receipt of early intervention services, parental fear regarding potential exposure to pandemic-related illness while seeking preventative care, increased use of virtual visit platforms for medical care and developmental intervention services, etc. What factors should be considered when providing support for these vulnerable/at-risk patients?

Early initial video-electro-encephalography combined with variant location predict prognosis of KCNQ2-related disorder

BackgroundThe clinical features of KCNQ2-related disorders range from benign familial neonatal seizures 1 to early infantile epileptic encephalopathy 7. The genotype-phenotypic association is difficult to establish.ObjectiveTo explore potential factors in neonatal period that can predict the prognosis of neonates with KCNQ2-related disorder.MethodsInfants with KCNQ2-related disorder were retrospectively enrolled in our study in Children’s Hospital of Fudan University in China from Jan 2015 to Mar 2020. All infants were older than age of 12 months at time of follow-up, and assessed by Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III) or Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV), then divided into three groups based on scores of BSID-III or WPPSI-IV: normal group, mild impairment group, encephalopathy group. We collected demographic variables, clinical characteristics, neuroimaging data. Considered variables include gender, gestational age, birth weight, age of the initial seizures, early interictal VEEG, variant location, delivery type. Variables predicting prognosis were identified using multivariate ordinal logistic regression analysis.ResultsA total of 52 infants were selected in this study. Early interictal video-electro-encephalography (VEEG) (β = 2.77, 1.20 to 4.34, P = 0.001), and variant location (β = 2.77, 0.03 to 5.5, P = 0.048) were independent risk factors for prognosis. The worse the early interictal VEEG, the worse the prognosis. Patients with variants located in the pore-lining domain or S4 segment are more likely to have a poor prognosis.ConclusionsThe integration of early initial VEEG and variant location can predict prognosis. An individual whose KCNQ2 variant located in voltage sensor, the pore domain, with worse early initial VEEG background, often had an adverse outcome.

Association of inotrope use with neurodevelopmental outcomes in infants

Objective The primary objective was to compare neurodevelopmental (ND) outcomes at 18–24 months in preterm infants <29 weeks gestational age (GA) who received versus those who did not receive inotropes in the first week of life. The secondary objective was to assess ND outcomes according to the duration of inotropic support in the first week of life (≤3 or >3 days). Study design Retrospective population-based cohort study of preterm infants <29 weeks GA admitted to participating neonatal intensive care units (NICUs) of the Canadian Neonatal Network (CNN) from January 2010 to September 2011 with follow-up data available at 18–24 months. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Long-term outcomes were categorized as neurodevelopmental impairment (NDI) and significant neurodevelopmental impairment (sNDI), and effect modification due to other neonatal morbidities including receipt of antenatal steroids, GA, small for gestational age (SGA) status, sex, score for neonatal acute physiology (SNAP-II) >20, postnatal steroids, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) grade ≥3/periventricular leukomalacia (PVL), early- and late-onset sepsis, retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC) was assessed. Maternal and infant demographic characteristics and short- and long-term outcomes were compared using Pearson’s Chi-square test for categorical variables and Student’s t-test or the Wilcoxon rank test for continuous variables. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated using multivariable regression analysis. Results Of the 491 (18.7%) eligible preterm infants who received inotropes during the first week of life, 314 (64%) survived to NICU discharge and 245 (78%) had ND outcome data available. A total of 1775 eligible preterm infants did not receive inotropes in the first week of life; 1647 (92.7%) survived to NICU discharge and 1149 (70%) had ND outcome data. Maternal and infant characteristics associated with infants receiving inotropes included: younger maternal age, clinical chorioamnionitis, no antenatal steroids, outborn, lower GA, BW and Apgar scores at both one and five minutes; and higher SNAP-II scores (p < .05). Infants who received inotropes in the first week of life were more likely to be require postnatal steroids, had higher rates of BPD, IVH grade ≥3/PVL, early- and late-onset sepsis, ROP, NEC and mortality (p < .05). Infants who received inotropes in the first week of life also had higher rates of sensorineural or mixed hearing loss with an AOR (95% CI) of 1.99 (1.13, 3.49). After adjusting for confounding variables, there was no difference in the risk of NDI or sNDI between infants who did and did not receive inotropes in the first week of life. Of the infants with neurodevelopmental outcome data available, 186 received inotropes for ≤3 days and 59 for >3 days. After adjusting for confounding variables there was no difference in the risk of NDI or sNDI. Infants who received inotropes for >3 days were more likely to have lower BSID-III cognitive [AOR 2.43 95% CI (1.03, 5.76)] and motor scores <85 [AOR 2.38 95% CI (1.07, 5.30)] respectively. Conclusions In this large, population-based cohort, infants who received inotropes in the first week of life were at increased risk for sensorineural or mixed hearing loss. There was no difference in NDI or sNDI after adjusting for confounding variables. A longer duration of inotrope use in the first week of life was associated with lower BSID-III cognitive and motor scores, but no difference in overall NDI or sNDI.

Cognitive, motor, and visual development in healthy children in the first 42 months of life.

The Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) is a tool for measuring the developmental status of children, including cognitive and motor functioning, in the first three years of life. This study aims to evaluate the correlation between grating visual acuity and visual functionality in healthy children using the Bayley-III. Binocular grating visual acuity was measured using Teller Acuity Cards followed by the Bayley-III in healthy children aged 1-42 months. Visual acuity (logMAR) and Bayley-III scores for both cognitive and motor (gross and fine) skills were compared. Forty children (20 boys) aged 1.2-42.1 months were tested. Their mean visual acuity was 0.39 ± 0.27 logMAR, which was within the normal age limits for all children. There was a strong and significant negative correlation between visual acuity and age (r=-0.83, p<0.001). The mean cognitive raw data score was 49.92 ± 18.93 points, with a strong and significant positive correlation between cognitive score and age (r=0.81, p<0.001). The mean gross motor score was 41.72 ± 16.23 points, with a strong and significant positive correlation between gross motor score and age (r=0.75, p<0.001). The mean fine motor score was 39.75 ± 14.63 points, with a strong and significant positive correlation between fine motor score and age (r=0.77, p<0.001). Multiple linear regression demonstrated that older age and better visual acuity were significantly associated with higher Bayley-III scores. This study found a high correlation between grating visual acuity measured using Teller Acuity Cards and cognitive and motor scores measured using the Bayley-III in healthy children, demonstrating that the Bayley-III might be a useful tool for assessing the repercussions of visual impairment on the cognitive and motor development of young children.

Early visuospatial attention and processing and related neurodevelopmental outcome at 2 years in children born very preterm.

The ability to perceive and process visuospatial information is a condition for broader neurodevelopment. We examined the association of early visuospatial attention and processing with later neurodevelopmental outcome in very preterm infants. Visuospatial attention and processing was assessed in 209 children (<30 weeks gestation) using an easy applicable eye tracking-based paradigm at 1 and 2 years. Average reaction times to fixation (RTF) on specific visual stimuli were calculated, representing time needed for overall attention (Cartoon stimuli) and processing (Motion and Form stimuli). Associations between RTFs and various measures of development at 2 years including cognitive and motor development (Bayley Scales of Infant and Toddler Development-Third edition; Bayley-III), language (Lexi test) and behavior (Child Behavior Checklist) were examined. At 1 year, 100 ms slower Cartoon and Motion RTFs were associated with lower cognitive Bayley-III scores (-4.4 points, 95%CI: -7.4; -1.5 and -1.0 points, -1.8; -0.2, respectively). A 100 ms slower Cartoon RTF was associated with a 3.5 (-6.6; -0.5) point decrease in motor Bayley-III score. Visuospatial attention and motion processing at 1 year is predictive of overall cognitive and motor development 1 year later. The nonverbal eye tracking-based test can assist in early detection of preterm children at risk of adverse neurodevelopment. Visuospatial attention and processing at 1 year corrected age is predictive for overall cognitive and motor development 1 year later in preterm infants. First study to relate early visuospatial attention and processing with later neurodevelopmental outcome in preterm children. Early detection of preterm children at risk of adverse neurodevelopment, which allows for more timely interventions.

Neurodevelopmental Outcomes of Neonates Randomized to Morphine or Methadone for Treatment of Neonatal Abstinence Syndrome

To evaluate the effects of pharmacologic treatment of neonatal abstinence syndrome on neurodevelopmental outcome from a randomized, controlled trial. Eight sites enrolled 116 full-term newborn infants with neonatal abstinence syndrome born to mothers maintained on methadone or buprenorphine into a randomized trial of morphine vs methadone. Ninety-nine infants (85%) were evaluated at hospital discharge using the NICU Network Neurobehavioral Scale. At 18months, 83 of 99 infants (83.8%) were evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition and 77 of 99 (77.7%) with the Child Behavior Checklist (CBCL). Primary analyses showed no significant differences between treatment groups on the NICU Network Neurobehavioral Scale, Bayley Scales of Infant and Toddler Development-Third Edition, or CBCL. However in post hoc analyses, we found differences by atypical NICU Network Neurobehavioral Scale profile on the CBCL. Infants receiving adjunctive phenobarbital had lower Bayley Scales of Infant and Toddler Development-Third Edition scores and more behavior problems on the CBCL. In adjusted analyses, internalizing and total behavior problems were associated with use of phenobarbital (P=.03; P=.04), maternal psychological distress (measured by the Brief Symptom Inventory) (both P<.01), and infant medical problems (both P=.02). Externalizing problems were associated with maternal psychological distress (P<.01) and continued maternal substance use (P<.01). Infants treated with either morphine or methadone had similar short-term and longer term neurobehavioral outcomes. Neurodevelopmental outcome may be related to the need for phenobarbital, overall health of the infant, and postnatal caregiving environment. ClinicalTrials.gov: NCT01958476.

Nutrition, Growth, Brain Volume, and Neurodevelopment in Very Preterm Children

To explore the associations between nutrition in the first 28days after birth with somatic growth from birth to term-equivalent age, brain volumes at term-equivalent age, and neurodevelopment at 24months of corrected age. Prospective cohort study of 149 infants born from 2011 to 2014 at <30weeks of gestation in a tertiary neonatal nursery in Australia. The following data were collected: average daily energy, protein, fat, and carbohydrate intakes from birth until 28days, and the difference in weight and head circumference z scores between birth and term-equivalent. Total brain tissue volumes were calculated from brain magnetic resonance imaging at term-equivalent age. Children were assessed at 2years of corrected age with the Bayley Scales of Infant and Toddler Development-Third Edition. Relationships of nutritional variables with growth, brain volumes, and cognitive, language, and motor development were explored using linear regression. Complete nutritional data were available for 116 (78%) of the cohort. A 1g/kg/day higher mean protein intake was associated with a mean increase in weight z score per week of 0.05 (95% CI 0.05, 0.10; P=.04). There was a lack of evidence for associations of any nutritional variables with head circumference growth, with brain volumes at term-equivalent age, or with 2-year neurodevelopment. Only higher protein intakes in the first 28days after birth were associated with better weight growth between birth and term-equivalent age in very preterm infants. Nutrition in the first 28days was otherwise not substantially related to brain size or to neurodevelopmental outcomes.

Lack of association between hypothyroxinemia of prematurity and transient thyroid abnormalities with adverse long term neurodevelopmental outcome in very low birth weight infants.

IntroductionThe association between hypothyroxinemia of prematurity with neurodevelopment was controversial.ObjectivesTo compare 5 year neurodevelopmental outcomes of very low birth weight (VLBW) infants with hypothyroxinemia of prematurity against those without.MethodsRetrospective cohort study in a single tertiary neonatal centre of VLBW infants born between the year 2008 to 2011. Comparisons were made between all abnormal and normal thyroid function controls using cord thyroid function tests, thyroid function tests during admission and pre-discharge thyroid function test done at term equivalent age. At 2 years corrected age, Bayley scales of infant and toddler development–third edition and Vineland II adaptive behaviour scales (VABS) were collected. At 5 years, Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), Bracken School Readiness Assessment, VABS and Beery Test of Visual-Motor Integration were collected.Results110 subjects were studied at 2 years corrected age and 80 subjects at 5 years old. 29 infants had abnormal thyroid function test (10 infants with hypothyroxinemia of prematurity and 19 infants with transient thyroid abnormalities). There were no significant difference in the 2 years and 5 years developmental outcome between infants with and without hypothyroxinemia of prematurity (p-value>0.05); and between infants with and without transient thyroid abnormalities (p-value>0.05). There were no significant difference in neurological, visual and hearing impairment between infants with or without hypothyroxinemia of prematurity (p-value>0.05).ConclusionsHypothyroxinemia of prematurity or transient thyroid abnormalities in VLBW infants were not associated with poorer neurodevelopment and did not support the need for levothyroxine supplementation.

C-46 Assessing Global Delays in Corpus Callosum Agenesis: Infants and Toddlers

Abstract Objective Corpus callosum agenesis (ACC) is a congenital birth defect in which the corpus callosum fails to fully form (Badaruddin, et al., 2007). The partial or complete absence of a corpus callosum affects specific functioning (Brown, Jeeves, Dietrich, &amp; Burnison, 1999) resulting in behavioral, social, and cognitive difficulties (Badaruddin, et al., 2007). We evaluated the development of infants and toddlers with ACC in cognition, language, and motor functioning. Methods Boys (n = 6) and girls (n = 4) ages 3 to 41 months were assessed utilizing the Bayley Scales of Infant and Toddler Development-Third Edition, a test designed to assess the developmental functioning in 5 domains: motor, social-emotional, adaptive behavior, cognitive, and language (Bayley, 2006). Volunteers were assessed during ACC conferences. Results Cognitive, language and motor index scores were significantly correlated but not age. Moderate to large effect sizes (Cohens d) were found. Girls had lower Cognitive Index scores and were below average; boys mean score was within the average range. Large effect sizes for receptive and expressive language. Boys scored within the low average range; girls below average for receptive language. For expressive language, girls fell in the borderline range, boys were low average. Gross motor was very low compared to age norms. Girls showed deficits in fine motor skill development; boys within the average range. Conclusions Global developmental deficits and gender differences occurred for infants and toddlers with ACC. Girls show more delays than boys. Outcomes suggest that delays can be measured well before entering school and supports early intervention services.