Left lateralization of neonatal caudate microstructure affects emerging language development at 24 months.

The complex interaction between brain and behaviour in language disorder is well established. Yet to date, the imaging literature in the language disorder field has continued to pursue heterogeneous and relatively small clinical cross-sectional samples, with emphasis on cortical structures and volumetric analyses of subcortical brain structures. In our current work, we aimed to go beyond this state of knowledge to focus on the microstructural features of subcortical brain structures (specifically the caudate nucleus) in a large cohort of neonates and study its association with emerging language skills at 24 months. Variations in neonatal brain microstructure could be interpreted as a proxy for in utero brain development. As language development is highly dependent on cognitive function and home literacy environment, we also examined their effect on the caudate-language function relationship utilizing a conditional process model. Our findings suggest that emerging language development at 24 months is influenced by the degree of left lateralization of neonatal caudate microstructure, indexed by diffusion tensor imaging (DTI)-derived fractional anisotropy (FA). FA is an indirect measure of neuronal and dendritic density within grey matter structures. We also found that the caudate-language function relationship is partially mediated by cognitive function. The conditional indirect effect of left caudate FA on language composite score through cognitive function was only statistically significant at low levels of home literacy score (-1 standard deviation [SD]). The authors proposed that this may be related to 'compensatory' development of cognitive skills in less favourable home literacy environments.

Severity of nausea and vomiting in pregnancy and early childhood neurobehavioural outcomes: The Growing Up in Singapore Towards Healthy Outcomes study.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) affects 50 to 80 per cent of women. The existing literature has examined NVP from the perspective of the mother, and relatively less is known about offspring outcomes. OBJECTIVES: To study the relationships of NVP with social-emotional, behavioural, and cognitive outcomes of the offspring in a multi-ethnic Asian cohort. METHODS: In the Growing Up in Singapore Towards Healthy Outcomes prospective mother-offspring cohort study, mothers responded to a structured NVP questionnaire at 26-28 weeks' gestation (n = 1172) and participants with severe NVP were confirmed using medical records. Children underwent multiple neurodevelopmental assessments throughout childhood. We conducted multivariable regressions with post-estimation predictive margins to understand the associations of NVP with offspring neurobehavioural outcomes, which included 1-year Infant-Toddler Social and Emotional Assessment, 1.5-year Quantitative Checklist for Autism in Toddlers, 2-year Bayley Scales of Infant and Toddler Development, 2- and 4-year Child Behavior Checklist, and 4.5-year Kaufman Brief Intelligence Test. Analyses were adjusted for household income, birth variables, maternal mental health, and other relevant medical variables. Cohen's d effect sizes were calculated using standardised mean differences (µd ). RESULTS: Mothers were categorised into no (n = 296, 25.3%), mild-moderate (n = 686, 58.5%), and severe NVP (n = 190, 16.2%), of whom 67 (5.7%) required admission. Compared to children of mothers who had no or mild-moderate NVP, children with exposure to severe NVP exhibited more externalising behaviours (µd 2.0, 95% CI 0.3, 3.6; Cohen's d = 0.33) and social communication difficulties before 2 years (µd 4.1, 95% Cl 0.1, 8.0; Cohen's d = 0.38), both externalising (µd 1.5, 95% CI 0.4, 2.6; Cohen's d = 0.43) and internalising behaviours at 2 years (µd 1.2, 95% CI 0.1, 2.2; Cohen's d = 0.35), and only internalising behaviours after 2 years (µd 1.1, 95% CI 0.4, 2.0; Cohen's d = 0.37). CONCLUSIONS: Severe NVP is highly prevalent in this Asian cohort and may be adversely associated with multiple offspring neurobehavioural outcomes.

Hearing screening outcome in neonatal intensive care unit graduates from a tertiary care centre in Singapore.

BACKGROUND: We aimed to analyse the outcome of universal newborn hearing screening (UNHS) and high-risk hearing screening in neonatal intensive care unit (NICU) graduates in a tertiary care unit. METHODS: The hearing screen programme comprises a 2-stage automated auditory brainstem response protocol followed by a high-risk hearing screen at 3-6 months. This study is a retrospective study of NICU graduates born between April 2002 and December 2009. Data on hearing screening, audiological assessment, and management were extracted from a computerized data management system (HITRACK). RESULTS: Of 100,225 newborn infants, 2.9% were admitted to the NICU during the study period. The overall incidence of hearing loss (HL) of any type/severity was 35/1,000 infants. Of infants with HL, 92.4% had their first automated auditory brainstem response at/before 1 month of corrected age. The incidence of congenital permanent HL identified by the UNHS was 15.4/1,000. The corrected median age of diagnosis was 4.5 months (1-23.5 months). Of 2,552 NICU graduates who passed the UNHS, 75.5% were retested at 3-6 months of life. Twelve infants with permanent late-onset HL were identified, raising the overall incidence of permanent HL to 19.9/1,000; 1.1/1,000 had auditory neuropathy. Of the 92 infants with HL, 89 (96.7%) had multiple risk factors. CONCLUSIONS: There is a high incidence of HL in NICU graduates; 22.6% were late in onset. An early rescreen in those who pass the UNHS is a beneficial step for this high risk population.

Television viewing and child cognition in a longitudinal birth cohort in Singapore: the role of maternal factors.

BACKGROUND: Although infant media exposure has received attention for its implications on child development, upstream risk factors contributing to media exposure have rarely been explored. The study aim was to examine the relationship between maternal risk factors, infant television (TV) viewing, and later child cognition. METHODS: We used a prospective population-based birth cohort study, Growing Up in Singapore Towards healthy Outcomes (GUSTO), with 1247 pregnant mothers recruited in their first trimester. We first explored the relationship of infant TV exposure at 12 months and the composite IQ score at 4.5 years, as measured by the Kaufman Brief Intelligence Test, Second Edition (KBIT-2). Multivariable linear regressions were adjusted for maternal education, maternal mental health, child variables, birth parameters, and other relevant confounders. We then examined the associations of maternal risk factors with the amount of daily TV viewing of 12-month-old infants. Path analysis followed, to test a conceptual model designed a priori to test our hypotheses. RESULTS: The average amount of TV viewing at 12 months was 2.0 h/day (SD 1.9). TV viewing in hours per day was a significant exposure variable for composite IQ (ß = - 1.55; 95% CI: - 2.81 to - 0.28) and verbal IQ (ß = - 1.77; 95% CI: - 3.22 to - 0.32) at 4.5 years. Our path analysis demonstrated that lower maternal education and worse maternal mood (standardized ß = - 0.27 and 0.14, respectively, p < 0.01 for both variables) were both risk factors for more media exposure. This path analysis also showed that maternal mood and infant TV strongly mediated the relationship between maternal education and child cognition, with an exceptional model fit (CFI > 0.99, AIC 15249.82, RMSEA < 0.001). CONCLUSION: Infant TV exposure has a negative association with later cognition. Lower maternal education and suboptimal maternal mental health are risk factors for greater television viewing. Paediatricians have a role in considering and addressing early risks that may encourage television viewing.

Concurrent validity of the ages and stages questionnaires with Bayley Scales of Infant Development-III at 2 years - Singapore cohort study.

BACKGROUND: With increasing acceptance of universal developmental screening in primary care, it is essential to evaluate the local validity and psychometric properties of commonly used questionnaires like the parent-completed Ages and Stages Questionnaires, 3rd Edition (ASQ-3) in identifying developmental delays. The aim of this study is to assess the convergent validity of the ASQ-3 with the Bayley Scales of Infant Development-3rd edition (Bayley-III) in identifying developmental delay in a low-risk term cohort in Singapore. METHODS: ASQ-3 and Bayley-III data was collected prospectively with generation of ASQ-3 cut-off scores using three different criteria: 1-standard deviation (SD) (Criterion-I) or 2-SD (Criterion-II) below the mean, and using a Receiver Operator Curve (ROC) (Criterion-III). Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. Correlations between the ASQ-3 and Bayley-III domains were evaluated using Pearson coefficients. RESULTS: With all three criteria across different domains ASQ-3 showed high specificity (72-99%) and NPV (69-98%), but lower sensitivity (19-74%) and PPV (11-59%). Criterion-I identified 11-21% of children as "at-risk of developmental delay," and was the most promising criterion measure, with high specificity (82-91%), NPV (69-74%) and overall agreement of 64-71%. Moderate-strong correlations were seen between ASQ-3 Communication and Bayley-III Language scales (r = 0.44-0.59, p < 0.01). The lowest sensitivities were seen in the motor domains. CONCLUSIONS: ASQ-3 is reliable in low-risk settings in identifying typically developing children not at risk of developmental delay, but it has modest sensitivity. Moderate-strong correlations seen in the communication domain are clinically important for early identification of language delay, which is one of the most prevalent areas of early childhood developmental delay.

Autologous umbilical cord blood infusion for the treatment of autism in young children: A within-subjects open label study on safety (assessed via caregiver report) and efficacy.

This study aimed to document the safety and efficacy of a single infusion of autologous umbilical cord blood (UCB) in 20 autistic children aged 24-72 months. A pre-post treatment within-subjects open label design was used. At T = 0, 6, 12, and 18 months, participants underwent detailed and structured safety evaluations (via caregiver report), Vineland Adaptive Behavior Scale (Vineland-3), Stanford Binet Intelligence Scale (SB-5), Expressive One-Word Picture Vocabulary Test, Brief Observation of Social Communication Change (BOSCC), Pervasive Developmental Disorder-Behavior Inventory, Repetitive Behavior Scale-Revised, Sensory Experience Questionnaire (SEQ-2.1), Child Behavior Checklist, Clinical Global Impression-Severity and Improvement (CGI-I) Scales, and eye-gaze tracking. UCB infusion was conducted at T = 6 months, hence, 0-6 months was the control period, and 6-18 months the follow-up period. Of 20 children recruited, 19 completed the study and 1 was withdrawn due to UCB not meeting quality control criteria for infusion. There were 15 males and 4 females with an overall mean (SD) age of 4.15 (0.62) years. Mean (SD) cell dose administered was 38.16 (9.82) million cells/kg. None suffered serious adverse events although there were mild behavioral side effects and one unit grew coagulase negative staphylococcus from a post-thaw sample. There were no significant differences in Vineland-3, SB-5, BOSCC, and SEQ-2.1 scores at T = 12 and T = 18 months. Twelve participants had T = 18 CGI-I scores of 2-3 (minimally to much improved), seven participants had scores of 4 (no change). Autologous UCB infusion in autistic children is generally safe but not without risks, including that of infection. In this within-subjects study, some children showed global symptom improvements while others showed no change. Stem cell therapies for autism should only be conducted under strict clinical trial conditions with clear risk discussions.

Exploring the validity of the ASQ-SE for socio-emotional competency screening of a low-risk Asian cohort at 2 years of age.

AIMS: To assess the Ages & Stages Questionnaire: Social-Emotional (ASQ-SE)'s concurrent validity in a low-risk Singapore cohort and study its association with maternal mental health status. METHODS: Concurrent validity of the parent-filled ASQ-SE with Child Behavior Checklist (CBCL1.5-5) was evaluated in 341 children at age 24 months. Data on maternal anxiety and depression were collected using the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory-Second Version (BDI-II). ASQ-SE cut-off scores based on receiver operating characteristic curve were compared to CBCL scores to derive a local ASQ-SE "at risk" cut-off score. Correlations of ASQ-SE with CBCL scores and with maternal STAI and BDI scores were evaluated using Pearson coefficients. RESULTS: Using a cut-off score of 51 at 24 months, ASQ-SE had acceptable concurrent validity, with an AUC of 0.819(0.765-0.872), 70 % sensitivity and 79 % specificity. Mothers of children with "at-risk" ASQ-SE scores had significantly higher STAI and BDI-II scores. ASQ-SE had moderate- high correlations (r = 0.32-0.53) (p < .01) with CBCL scores at 24 and 48 months and with maternal mental health status(r = 0.32). INTERPRETATION: ASQ-SE can be a useful tool for screening child's socio-emotional competence for primary health care use in Singapore Dyadic mental health screening would be helpful in identifying families at risk.

Parental and child genetic burden of glycaemic dysregulation and early-life cognitive development: an Asian and European prospective cohort study.

Insulin resistance and glucose metabolism have been associated with neurodevelopmental disorders. However, in the metabolically more susceptible Asian populations, it is not clear whether the genetic burden of glycaemic dysregulation influences early-life neurodevelopment. In a multi-ethnic Asian prospective cohort study in Singapore (Growing Up in Singapore Towards healthy Outcomes (GUSTO)), we constructed child and parental polygenic risk scores (PRS) for glycaemic dysregulation based on the largest genome-wide association studies of type 2 diabetes and fasting glucose among Asians. We found that child PRS for HOMA-IR was associated with a lower perceptual reasoning score at ~7 years (ß = -0. 141, p-value = 0.024, 95% CI -0. 264 to -0. 018) and a lower WIAT-III mean score at ~9 years (ß = -0.222, p-value = 0.001, 95% CI -0.357 to -0.087). This association were consistent in direction among boys and girls. These inverse associations were not influenced by parental PRS and were likely mediated via insulin resistance rather than mediators such as birth weight and childhood body mass index. Higher paternal PRS for HOMA-IR was suggestively associated with lower child perceptual reasoning at ~7 years (ß = -0.172, p-value = 0.002, 95% CI -0.280 to -0.064). Replication analysis in a European cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, showed that higher child PRS for fasting glucose was associated with lower verbal IQ score while higher maternal PRS for insulin resistance was associated with lower performance IQ score in their children at ~8.5 years. In summary, our findings suggest that higher child PRS for HOMA-IR was associated with lower cognitive scores in both Asian and European replication cohorts. Differential findings between cohorts may be attributed to genetic and environmental factors. Further investigation of the functions of the genetic structure and ancestry-specific PRS and a more comprehensive investigation of behavioural mediators may help to understand these findings better.

Association between maternal labour epidural analgesia and autistic traits in offspring.

STUDY OBJECTIVE: Studies investigating associations between maternal epidural analgesia (MEA) and autism spectrum disorder (ASD) in the offspring are conflicting and lack prospective neurobehavioral follow-up assessments for autistic traits. We aim to prospectively investigate associations between MEA and autistic traits in the offspring. DESIGN: Prospective neurobehavioral observational cohort study. SETTING: Singaporean tertiary healthcare institutions. PATIENTS: Participants recruited were singleton non-IVF children, >36 weeks gestation, delivered via normal vaginal delivery by mothers >18 years of age, delivered in Singapore from June 2009-September 2010 and followed up over 7 years. INTERVENTIONS: Exposure to maternal epidural analgesia during delivery. MEASUREMENTS: The primary outcome is an abnormal Social Responsiveness Scale (SRS) T score at 7 years (≥60 points). Secondary outcomes include the diagnosis of ASD and abnormal scores for autistic traits assessed via a neurobehavioral battery comprising: CBCL (child behavioural checklist), Q-CHAT (Quantitative Checklist for Autism in Toddlers), and Bayley-III. Multivariable analyses adjusting for maternal and offspring characteristics were performed. MAIN RESULTS: 704 out of 769 mother-child dyads recruited fulfilled the criteria for analysis. 365/704 mothers received MEA. The incidence of an abnormal SRS score at 7 years in offspring exposed to MEA was 19.9%, and 26.1% in non-exposed offspring (p = 0.154). Multivariable analysis did not demonstrate a significant association between MEA and abnormal SRS scores at 7 years (O.R.0.726, 95% C·I. 0.394-1.34, p = 0.305). After adjustment for maternal and fetal demographics, exposure to MEA was not significantly associated with an abnormal screen in all other tests for autistic traits. The clinical incidence of ASD was 1.76% in children without exposure to MEA, and 2.32% in children with MEA exposure (p = 0.506). CONCLUSIONS: MEA is not significantly associated with the development of ASD and autistic traits in offspring, assessed over 7 years. Results should be taken into perspective given our wide confidence intervals and small cohort size.

Maternal preconception circulating blood biomarker mixtures, child behavioural symptom scores and the potential mediating role of neonatal brain microstructure: the S-PRESTO cohort.

Human brain development starts in the embryonic period. Maternal preconception nutrition and nutrient availability to the embryo may influence brain development at this critical period following conception and early cellular differentiation, thereby affecting offspring neurodevelopmental and behavioural disorder risk. However, studying this is challenging due to difficulties in characterizing preconception nutritional status and few studies have objective neurodevelopmental imaging measures in children. We investigated the associations of maternal preconception circulating blood nutrient-related biomarker mixtures (~15 weeks before conception) with child behavioural symptoms (Child Behaviour Checklist (CBCL), aged 3 years) within the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) study. The CBCL preschool form evaluates child behaviours based on syndrome scales and Diagnostic and Statistical Manual of Mental Disorders (DSM) oriented scales. These scales consist of internalizing problems, externalizing problems, anxiety problems, pervasive developmental problems, oppositional defiant, etc. We applied data-driven clustering and a method for modelling mixtures (Bayesian kernel machine regression, BKMR) to account for complex, non-linear dependencies between 67 biomarkers. We used effect decomposition analyses to explore the potential mediating role of neonatal (week 1) brain microstructure, specifically orientation dispersion indices (ODI) of 49 cortical and subcortical grey matter regions. We found that higher levels of a nutrient cluster including thiamine, thiamine monophosphate (TMP), pyridoxal phosphate, pyridoxic acid, and pyridoxal were associated with a higher CBCL score for internalizing problems (posterior inclusion probability (PIP) = 0.768). Specifically, thiamine independently influenced CBCL (Conditional PIP = 0.775). Higher maternal preconception thiamine level was also associated with a lower right subthalamic nucleus ODI (P-value = 0.01) while a lower right subthalamic nucleus ODI was associated with higher CBCL scores for multiple domains (P-value < 0.05). One potential mechanism is the suboptimal metabolism of free thiamine to active vitamin B1, but additional follow-up and replication studies in other cohorts are needed.

Risk Factors Predicting the Need for Phototherapy in Glucose 6 Phosphate Dehydrogenase-Deficient Infants in a Large Retrospective Cohort Study.

INTRODUCTION: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of severe neonatal hyperbilirubinemia. This study evaluates the risk factors predicting the need for phototherapy in G6PD-deficient neonates after 72 h of age and assesses the safety of early discharge. METHODS: A retrospective cohort study of 681 full-term G6PD-deficient infants with a birth weight ≥2,500 g over 4 years was conducted. We compared the baseline characteristics, bilirubin level on day 4 (after 72 h of life), day of peak bilirubin, G6PD levels, and concomitant ABO incompatibility between the group that required phototherapy (Group A) and those who did not (Group B). RESULTS: 396 infants (58%), predominantly males, required phototherapy in the first week of life. The infants who required phototherapy had a lower median gestational age (38.3 vs. 38.7 weeks, p < 0.01) and had lower G6PD levels (2.3 ± 2.5 vs. 3 ± 3.4 IU, p < 0.05) compared to the controls. The mean day-four total serum bilirubin (TSB) levels were higher (213 ± 32 vs. 151 ± 37 µmol/L, p < 0.01), with bilirubin level peaking earlier (3 vs. 4 days of life, p < 0.01) in group A. Regression analysis identified TSB levels on day 4, Chinese race, lower gestation, and concomitant ABO incompatibility as the significant predictors for the need for phototherapy in the study population. In particular, coexisting ABO blood group incompatibility increased the risk of jaundice requiring phototherapy (OR 4.27, 95% CI: 1.98-121, p < 0.01). Day four TSB values above 180 µmol/L predicted the need for phototherapy with 86% sensitivity and 80% specificity. The findings were similar across both male and female infants with G6PD deficiency. CONCLUSION: G6PD-deficient infants with day four TSB levels of >180 µmol/L (10.5 mg/dL) and associated ABO blood group incompatibility have a higher risk of requiring phototherapy in the first week of life and should be closely monitored.

Investigation of metabolomic biomarkers for childhood executive function and the role of genetic and dietary factors: The GUSTO cohort.

BACKGROUND: Few studies have investigated molecular biomarkers of specific executive function (EF) skills in children. We aimed to characterise the prospective associations between metabolome and multiple domains of EF using a bidirectional design. METHODS: This study was conducted within a longitudinal birth cohort, the Growing Up in Singapore Towards healthy Outcomes (GUSTO). Circulating levels of 165 metabolites were quantified using a nuclear magnetic resonance based metabolomics platform (n = 457 (∼6yrs) and n = 524 (∼8yrs)). Parent-reported EF was available for 495 children (∼7yrs). Multivariate linear regression was used to assess the metabolite-EF relationships. We examined the role of body composition, dietary factors, and genetics in the metabolite-EF associations. FINDINGS: Higher leucine level (∼6yrs) was associated with poorer EF (∼7yrs, Initiate (P = 0.003) and Working Memory (P = 0.004)). EF (∼7yrs) was not associated with leucine (∼8yrs). Importantly, we found weak evidence for associations of dietary factors (∼5yrs) with leucine (∼6yrs) and EF (∼7yrs). Each copy of C allele in rs1260326 (a leucine-related polymorphism) was associated with higher leucine level and poorer Initiate and Working Memory (P < 0.05). Amongst those with less strongly genetically influenced leucine, inverse association between leucine and cognitive regulation were weaker among those with higher BMI. INTERPRETATION: The observed association between higher leucine level and poorer EF may be determined by genetics and may not be easily amenable to dietary interventions. Further research is needed for validation and to understand mechanisms. FUNDING: Singapore National Research Foundation and Agency for Science, Technology and Research.

Academic school readiness in children born very preterm and associated risk factors.

BACKGROUND AND AIMS: Although the intelligence quotient (IQ) test is useful to assess general cognitive function, it may miss more specific and subtle deficits of learning, working memory, attention and executive function. This study aims to evaluate cognitive performance and academic school readiness (SR) concepts in preterm very low birth weight (PT/VLBW) children, compared to typically developing term controls and to evaluate factors affecting basic (SR) concepts in children with IQ>85. METHODS: A prospective cohort study of 123 PT/VLBW survivors with birth weights ≤1250 g and 74 term controls born between 2007 and 2009 in Singapore were assessed for school readiness using Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), Bracken School Readiness Assessment (BSRA-3) and Beery-Buktenica Developmental Test of Visual Motor Integration (VMI) at age 5.5 years. Social risk composite score (SRCS) was calculated based on ethnicity, parental education and family income and marital status. Uni- and multi-variable regressions were conducted to evaluate risk factors associated with poor academic SR in the entire cohort and in those with IQ >85. RESULTS: Mean gestational age and birth weight of the 123 PT/VLBW children were 27.8 (2.3) weeks and 939 (194) grams while that of the 74 term controls were 38.8 (1.2) weeks and 3165 (402) grams. PT/VLBW survivors had statistically significant lower full composite scores on WPPSI-III (97.0 vs 114), BSRA-3 (98.5 vs 112.3) and VMI (107.2 vs 112.9) compared to controls. The differences remained significant in preterm and children with higher SRCS even after adjustment. CONCLUSIONS: Prematurity and high social composite risk scores were risk factors affecting academic SR and this difference persisted in PT/VLBW children with normal cognitive scores with IQ >85.

The Test of Infant Motor Performance (TIMP) in very low birth weight infants and outcome at two years of age.

OBJECTIVE: To evaluate TIMP in preterm very low birth weight (VLBW) infants, analyze risk factors, for atypical TIMP (aTIMP) scores, and explore TIMP's predictive relationship with Bayley-III at 2 years. METHOD: A prospective study of 288 VLBW infants, with TIMP assessment between 34 weeks postmenstrual age and 16 weeks age, corrected for prematurity. RESULT: aTIMP scores were observed in 58/288(20%) infants, whose mean birth weight (BW) and gestational age were 1122 ± 257 g and 29.2 ± 2.12 weeks respectively. Risk factors included BW < 750 g (OR 4.8, 95% CI 1.3-17.7) and 750-1000 g (OR 2.9, 95% CI 1.2-6.9), presence of necrotizing enterocolitis ≥ stage 2; or focal intestinal perforation (OR 4.6, 95% CI 1.4-14.4), periventricular leukomalacia (OR 22.4,95% CI 2.0-246.2), and need for intensive resuscitation at birth (OR 2.7, 95% CI 1.3-5.5). aTIMP scores correlated with Bayley-III Score <85 in motor and cognitive domains with high specificity (80-82%) and negative predictive value (85-94%). CONCLUSION: Identification of the risk factors for aTIMP scores will enable targeted intervention to optimize resources and outcomes in VLBW infants.

Congenital blindness and autism spectrum disorder (ASD): diagnostic challenges and intervention options.

The case of a 6-year-old boy with congenital blindness and features suggestive of autism spectrum disorder (ASD) is reported. He presented to a developmental paediatrician with global developmental delay, worsening self-injurious behaviours and difficulties in social interaction, transitions and interactive play. He demonstrated poor response to his name, rigidity, repetitive behaviours and had a sensory profile suggestive of ASD. This paper discusses the challenges in diagnosing and managing ASD in visually impaired children.

Evaluation of the Ages and Stages Questionnaire (ASQ 3) as a developmental screener at 9, 18, and 24 months.

BACKGROUND: Without the use of standardized screening tools, only 30% of the estimated 5-15% of children with developmental delay can be identified, potentially delaying intervention. AIM: 1)To evaluate the ASQ-3's reliability and validity at 9, 18, and 24 months and to compare the results with normative USA data. 2)To determine the risk factors for a screen positive result, which requires further evaluation. METHODS: Study of 649 low-risk children was part of a larger longitudinal cohort study, the GUSTO project. Socio-demographic and ASQ3 data were analyzed to estimate reliability, validity, mean ASQ scores, and cut-off scores. RESULTS: ASQ-3 showed an acceptable to good internal consistency (0.49-0.83) and a medium level of correlations (0.22-0.59) between the five domains but differed significantly compared to normative USA data. Using local cut-off scores, 12.6-13.6% of the cohort had a positive screen in ≥ 1 domain at 9, 18, or 24 months. ASQ-3 screening categorization was consistent, with only 3-11% of children showing change in categorization longitudinally. On regression, lower family income (OR 3.3-9.42) and maternal education (OR2.65-3.03) were predictive of a positive screen across domains and age intervals. INTERPRETATION: ASQ-3 is a useful, valid screening tool in Singapore. Further research is needed to investigate item functioning and to assess its concurrent validity with a criterion standard tool for culturally sensitive developmental screening.

Factors affecting neurodevelopmental outcome at 2 years in very preterm infants below 1250 grams: a prospective study.

OBJECTIVE: To evaluate the neurodevelopmental outcomes of preterm very-low birth weight (PT/VLBW) infants at 2 years and identify risk factors associated with significant developmental delay or neurodevelopmental impairment (NDI). STUDY DESIGN: We evaluated 165 PT/VLBW infants born between January 2010 and December 2011, using the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III). NDI was defined as the presence of neurosensory impairment or significant delay with Bayley-III score < 70 in any domain and risk factors for delay/NDI were assessed using logistic regressions. RESULTS: Median Bayley-III composite scores in the cognitive, language and motor domains were 95, 89 and 94, respectively. NDI was present in 20% of the children, with 5-18% having significant delay in either cognitive, language or motor domain, seven (4%) children had cerebral palsy, three (2%) were deaf and none were blind. Regression models identified significant positive associations of delayed cognitive skills with male gender (Odds ratio (OR) 22.4, 95% confidence interval (CI) 1.5-341.1; P = 0.025), lack of anntenatal steroids (ANS) (OR 41.5, 95% CI 3.5-485.7; P = 0.003), and hypotension needing inotropes (OR 36.0, 95% CI 2.6-506.0; P = 0.008); delayed language skills with lower maternal education (OR 3.8, 95% CI 1.4-10.3; P = 0.10), lack of ANS (OR 2.8, 95% CI 1.1-7.4; P = 0.04), and 5 minute Apgar Score ≤ 5 (OR 7.4, 95% CI 1.4-38.4; P = 0.017) and delayed motor skills with chronic lung disease at 36 weeks (OR 38.3, 95% CI 2.4-603.4; P = 0.010). NDI was associated with lack of ANS (OR 2.91, 95% CI 1.21-7.00; P = 0.02) and use of postnatal steroids (OR 3.36, 95% CI 1.07-10.54; P = 0.0374). CONCLUSION: Risk factors for both NDI and individual domain delay were identified and will be helpful in planning of specific and targeted early intervention services.

The Utility of Developmental Checklists in Parent-held Health Records in Singapore.

OBJECTIVE: The aim of this study was to investigate parents' perceptions of developmental checklists and the child development monitoring schedule in the Singapore health booklet. METHOD: Parents of children aged 2 years 6 months to 3 years 11 months with or without developmental concerns (n = 450) completed a structured interview, and their child's health booklets were reviewed. RESULTS: Most parents reported reading and using the developmental checklists. However, only about half of them attempted the checklists with minimal help from professionals. Approximately 7 in 10 parents of children with developmental concerns found the checklists useful for identifying concerns about their child. Despite positive feedback from parents about the checklists, only about 1 in 4 parents brought their child for a 2 to 3 years developmental monitoring visit at the time of the survey, and the completion rates of the checklists were less than desirable. CONCLUSIONS: Further revisions to the checklists can include simplifying the words and sentences and providing relevant pictures to aid understanding. If the checklists are to be used for screening, standardization of how the checklists are to be completed and how children at risk of developmental delays can be identified on the checklists need to be provided. Parents' awareness of the importance of evaluating their child's development at 9 months, 18 months, and particularly at 2.5 years, needs to be raised. Developmental screening for children at these critical ages can be made mandatory. An electronic version of the health booklet is likely to facilitate implementation of developmental screening in the health care system.

Hearing Loss in Newborns with Cleft Lip and/or Palate.

INTRODUCTION: This study aims to review the results of hearing screens in newborns with cleft deformities. MATERIALS AND METHODS: A retrospective audit of 123 newborns with cleft deformities, born between 1 April 2002 and 1 December 2008, was conducted. Data on the results of universal newborn hearing screens (UNHS) and high-risk hearing screens, age at diagnosis, severity/type of hearing loss and mode of intervention were obtained from a prospectively maintained hearing database. RESULTS: Thirty-one of 123 newborns (25.2%) failed the first automated auditory brainstem response (AABR). Seventy percent of infants (56 out of 80) who passed the UNHS failed the high-risk hearing screens which was conducted at 3 to 6 months of age. Otolaryngology referral rate was 67.5% (83/123); 90.3% of 31 newborns who failed the first AABR eventually required otolaryngology referrals. Incidence of hearing loss was 24.4% (30/123; 25 conductive, 2 mixed and 3 sensorineural), significantly higher than the hospital incidence of 0.3% (OR: 124.9, 95% CI, 81.1 to 192.4, P <0.01). In terms of severity, 8 were mild, 15 moderate, 5 severe, 2 profound. Eighteen out of 30 infants (60%) were detected from the high-risk hearing screens after passing the first AABR. CONCLUSION: These newborns had a higher risk of failing the UNHS and high-risk hearing screen. There was a higher incidence of hearing loss which was mainly conductive. Failure of the first AABR was an accurate predictor of an eventual otolaryngology referral, suggesting that a second AABR may be unnecessary. High-risk hearing screens helped to identify hearing loss which might have been missed out early on in life or which might have evolved later in infancy.