Search

ObjectivesTo report on knowledge translation strategies and outcomes from the implementation of the early detection guidelines for cerebral palsy (CP) in a state-wide tertiary early intervention (EI) service and investigate the impact of social determinants on clinical services.DesignRetrospective longitudinal cohort study.SettingThe Western Australia tertiary paediatric EI service.ParticipantsEI clinicians, consumers and children using the EI service.Outcome measuresKnowledge translation strategies including consumer perspectives, clinician training and Communities of Practice (CoP) guided implementation. We measured changes in referral number and age, delivery of early detection and intervention following the implementation of the guidelines. Exposure to adverse childhood experiences (ACEs), appointment non-attendance (DNA) rates, remoteness and socioeconomic quintiles were used to measure social determinants of health using negative binomial (Incidence Rate Ratios, IRR) and logistic regression (Odds Ratios, ORs).ResultsTen consumers participated in Focus Groups, 100 clinicians were trained and 22 clinicians established a monthly CoP. Referrals increased fourfold to 511 children. Corrected gestational age at referral decreased from a median of 16.1 to 5.1 months (pConclusionsImplementation strategies reduced referral age and improved the delivery of early detection assessments. Further investigation of the association between social disadvantage, DNA risk and ACE score is required in the development of a state-wide early detection network.

BACKGROUND This study investigated mother-infant interactions, including maternal maintaining of infant attentional focus and sensitivity, with infants with congenital severe and profound visual impairment (VI) and the association with developmental trajectories from one to three years. METHOD Fifty-five infants and mothers were video-recorded playing together with a standard set of toys at Time 1 (T1) mean age 12.95 months (8.13-17.05 months). Maintain was categorized as the mother following and maintaining the child's focus, and Sensitivity, the mother's responsiveness and contingency to infant behaviour. Vision level was measured using the Near Detection Scale. Cognition and language were measured at T1, 12 months later (T2) and 24 months later (T3) using the Reynell-Zinkin Scales. RESULTS Cross-sectional analyses showed that mothers of infants with severe VI (basic form vision) produced higher rates of Maintain compared to those with children with profound VI (light perception at best). Linear mixed-effects models examining developmental progression from T1 to T3 (controlling for vision level) showed an average increase of 5 DQ points (CI 95%: 1.03-9.08) in verbal comprehension for higher Sensitivity. No significant findings were found for Maintain. CONCLUSIONS The findings suggest that mother-infant interactions (maternal Maintain) are associated with level of vision at infancy, but only maternal Sensitivity has a long-term positive association with advances in verbal comprehension from infancy to about three years. They highlight the need for incorporating strategies related to parent-infant interactions, including increased sensitivity, into early intervention for children with visual impairment.

To investigate detection vision development in infants and toddlers with congenital disorders of the peripheral visual system (CDPVS) and severe to profound visual impairment (SVI/PVI).This was a longitudinal observational investigation of a cohort of infants with CDPVS (entry age 8-16mo) followed up 12 months later. Detection vision (Near Detection Scale [NDS]) and resolution acuity (Keeler Acuity Cards [KAC]) were assessed at each time point. Relationships between detection vision, resolution acuity, and age were investigated.The study cohort comprised 80 children (39 females, 41 males), mean age 13 months (Time 1) and 26 months (Time 2); 22 (27.5%) with PVI (light perception at best) and 58 (72.5%) with SVI (basic 'form' vision) at Time 1. All children achieved a measure with the NDS, however only 35 per cent and 56 per cent at Time 1 and Time 2 respectively did so on KAC. Those with PVI at Time 1 showed no further improvement at Time 2, but 87 per cent of children with SVI showed improvement in vision. The median change in NDS score was 1.0 (range 1-7, SD 1.68).Vision development continues after 12 months of age in many toddlers if they have basic 'form' vision. A measure of detection vision is feasible in very young children when resolution acuity measurement is not achievable.The Near Detection Scale (NDS) can measure low levels of vision when acuity is not otherwise measurable. Vision can improve in toddlers with severe visual impairment who have some 'form' vision. Infants with light perception at best by 12 months are unlikely to show improvement in vision. There is a moderate negative relationship between the NDS and resolution acuity results.

AIM This study examined cross-sectional and longitudinal patterns of parenting stress, adult anxiety, and depression in mothers of children with profound or severe visual impairment (PVI or SVI) at 1 year and 2 years of age. METHOD Mothers of a national longitudinal cohort (OPTIMUM Project) of infants with congenital disorders of the peripheral visual system and PVI (light perception at best) or SVI (basic 'form' vision of non-light reflecting objects) participated. Infant age at baseline (T1 ) was 8 to 16 months. Mothers completed the Parenting Stress Index - Short Form and the Hospital Anxiety and Depression Scale at T1 (n=79) and at follow-up 12 months later (T2 ) (n=73). RESULTS Mothers of the total group had higher parenting stress levels (34.6% in clinical range) than community normative data at T1 (p=0.017). Mothers of infants in the PVI subgroup had elevated stress at T1 (p=0.014) and T2 (p=0.009). The PVI subgroup was also elevated in the Difficult Child subscale at T2 (p=0.001). Within-sample differences in parenting stress between the visual impairment subgroups were found at T2 only: the PVI subgroup scored higher than the SVI subgroup (p=0.029). Adult anxiety and depression in the total group were not elevated compared with community normative data at T1 and T2 ; however, higher parenting stress was related to raised adult anxiety and depression levels at T1 and T2 (p=0.001). Regression analysis found parenting stress and lower child vision level (T1 ) predicted parenting stress (T2 ) (p=0.001; 42% variance). INTERPRETATION Mothers of 1-year-old infants with visual impairment showed raised risk for parenting stress, which continued to be elevated for children with PVI and those perceived as 'difficult' at 2 years. This was also a psychological risk, with greater adult anxiety and depression in those mothers with raised parenting stress. The clinical significance is that identification of parenting stress and targeted parenting, and behavioural support of the child in the first years of life is highly indicated. WHAT THIS PAPER ADDS Mothers of infants with visual impairment are at increased risk of parenting stress. Parenting stress was higher in mothers of children with profound visual impairment than those with severe visual impairment. High levels of parenting stress and lower infant vision at 1 year of age predicted higher parenting stress at 2 years of age.

Objective Young children with congenital visual impairment (VI) are at increased risk of behavioral vulnerabilities. Studies on ‘at risk’ populations suggest that frontal EEG asymmetry may be associated with behavioral risk. We investigated frontal asymmetry at 1 year (Time 1), behavior at 2 years (Time 2) and their longitudinal associations within a sample of infants with VI. Frontal asymmetry in the VI sample at 1 year was also compared cross-sectionally to an age-matched typically sighted (TS) group. Methods At Time 1, 22 infants with VI and 10 TS infants underwent 128-channel EEG recording. Frontal asymmetry ratios were calculated from power spectral density values in the alpha frequency band. At Time 2, Achenbach Child Behavior Checklist data was obtained for the VI sample. Results 63.6% of the VI sample and 50% of the TS sample showed left frontal asymmetry; no significant difference in frontal asymmetry was found between the two groups. 22.7% of the VI sample had subclinical to clinical range ‘internalizing’ behavior difficulties. Greater left frontal asymmetry at one year was significantly associated with greater emotionally reactive scores at two years within the VI sample ( r = 0.50, p = 0.02). Conclusions Left frontal asymmetry correlates with later behavior risk within this vulnerable population. Significance These findings make an important first contribution regarding the utility of frontal EEG asymmetry as a method to investigate risk in infants with VI.

To investigate the effects of home-based early intervention in children with severe visual impairment (SVI) using the Developmental Journal for babies and young children with visual impairment (DJVI).A longitudinal observational study was undertaken with a national cohort (OPTIMUM) of infants with congenital disorders of the peripheral visual system (CDPVS) and profound-SVI; and followed up after 12 months and 24 months. Intervention was categorized according to the practitioner diary records of their usual practice over 12 months from baseline comparing those receiving the DJVI and those receiving 'Other Support'. Outcome measures of cognition and language, behaviour difficulties, parenting stress, and satisfaction with parent-practitioner partnership were collected.In the 54 children (26 males, 28 females, baseline mean age 13.5mo, SD 2.3mo, range 8-17mo) with 'total' CDPVS (including 16 'complex' and 38 'simple' with or without known brain disorder respectively), linear mixed effects pointed towards acceleration in sensorimotor understanding and expressive language especially in the 'simple' subsample (11.72 developmental quotient, 95% confidence interval -1.17 to 24.61, p0.05) in those receiving the DJVI. Vision level also predicted outcomes (p0.05). The DJVI group showed improvements in behavioural withdrawal (ηInfants and young children with visual impairment receiving home-based early intervention using the DJVI with a structured developmental approach had better outcomes than those receiving 'other' home-based early interventions. Moderate to large effect improvements were found in child cognition and language, behaviour and parenting stress and the perceived practitioner-parent relationship, although cognition did not reach 5% significance level.Early intervention using the Developmental Journal for babies and young children with visual impairment was associated with enhanced developmental outcomes compared to other approaches. Improvements were also found in child behaviour, parenting stress, and perceived parent practitioner outcomes. Type and complexity of visual impairment also influenced outcomes.INTERVENCIÓN TEMPRANA DOMICILIARIA EN LACTANTES Y NIÑOS PEQUEÑOS CON DISCAPACIDAD VISUAL USANDO EL DIARIO DE DESARROLLO: ESTUDIO LONGITUDINAL DE COHORTE: OBJETIVO: Investigar los efectos de la intervención temprana en el hogar en niños con discapacidad visual grave utilizando el Diario de Desarrollo para bebés y niños pequeños con discapacidad visual (DJVI). MÉTODO: Se realizó un estudio observacional longitudinal con una cohorte nacional (OPTIMUM) de bebés con trastornos congénitos del sistema visual periférico (CDPVS) y discapacidad visual profunda-severa; y seguimiento después de 12 meses y 24 meses. La intervención se categorizó de acuerdo con los registros del diario de desarrollo del médico en su práctica habitual más de 12 meses desde el inicio, comparando los que recibieron el DJVI y los que recibieron “otro apoyo”. Se recopilaron las medidas de resultado de la cognición y el lenguaje, las dificultades de comportamiento, el estrés de los padres y la satisfacción con la asociación entre padres y profesionales. RESULTADOS: En los 54 niños (26 varones, 28 mujeres, edad media de referencia 13,5 meses, DS 2,3 meses, rango 8-17 meses) con CDPVS ‘total’ (incluidos 16 ‘complejo’ y 38 ‘simple’ con o sin trastorno cerebral conocido respectivamente), los efectos mixtos lineales apuntan hacia la aceleración en la comprensión sensoriomotora y el lenguaje expresivo, especialmente en la submuestra “simple” (cociente de desarrollo 11,72, intervalo de confianza del 95% -1,17 a 24,61, p0,05) en los que recibieron el DJVI. El nivel de visión también predijo resultados (p0,05). El grupo DJVI mostró mejoras en la abstinencia conductual (ηINTERVENÇÃO PRECOCE DOMICILIAR EM LACTENTES E CRIANÇAS JOVENS COM DEFICIÊNCIA VISUAL USANDO O DEVELOPMENTAL JOURNAL: ESTUDO DE COORTE LONGITUDINAL: OBJETIVO: Investigar os efeitos da intervenção precoce domiciliar em crianças com deficiência visual severa usando o Developmental Journal para lactentes e crianças jovens com deficiência visual (DJDV). METODO: Um estudo observacional longitudinal foi realizado com uma coorte nacional (OPTIMUM) de crianças com distúrbios congênitos do sistema visual periférico (DCSVP) e deficiência visual grave-profunda, estes foram acompanhados após 12 meses e 24 meses. A intervenção foi categorizada de acordo com os registros diários do profissional de sua prática habitual ao longo de 12 meses, a partir de uma linha de base, comparando aqueles que receberam a DJDV e os que receberam “outro suporte”. Resultados dos testes de cognição e linguagem, dificuldades de comportamento, estresse parental e satisfação com a parceria entre pais e profissionais, foram coletados. RESULTADOS: Nas 54 crianças (26 do sexo masculino e 28 do feminino, média de idade na linha de base de 13,5 meses; DP 2,3 meses; variação de 8 a 17 meses) com DCSVP total (incluindo 16 ‘complexos’ e 38 ‘simples’ com ou sem distúrbio cerebral conhecido, respectivamente), efeitos mistos lineares apontaram para um avanço na compreensão sensório-motora e de linguagem expressiva, especialmente, no subgrupo ‘simples’ (11,72 quociente de desenvolvimento, IC 95% -1,17 a 24,61; p0,05) naqueles que receberam o DJDV. Nível visual também foi preditivo dos desfechos (p0,05). O grupo DJDV apresentou melhora no comportamento de retraimento social (η

Introduction Cerebral palsy (CP) is the most common childhood physical disability, with 80% estimated to be in low-middle-income countries. This study aims to (1) determine the accuracy of General Movements (GMs)/Hammersmith Infant Neurological Examination (HINE) for detecting CP at 18 months corrected age (CA); (2) determine the effectiveness of a community-based parent-delivered early intervention for infants at high risk of CP in West Bengal, India (Learning through Everyday Activities with Parents for infants with CP; LEAP-CP). Methods This study comprises two substudies: (1) a study of the predictive validity of the GMs and HINE for detecting CP; (2) randomised, double-blinded controlled trial of a novel intervention delivered through peer trainers (Community Disability Workers, CDW) compared with health advice (15 fortnightly visits). 142 infants at high risk of CP (‘absent fidgety’ GMs; ‘high risk score’ on HINE) aged 12–40 weeks CA will be recruited to the intervention substudy, with infants randomised based on a computer-generated sequence. Researchers will be masked to group allocation, and caregivers and CDWs naive to intervention status. Visits will include therapeutic modules (goal-directed active motor/cognitive strategies and LEAP-CP games) and parent education. Health advice is based on the Integrated Management of Childhood Illness, WHO. Infants will be evaluated at baseline, post intervention and 18 months CA. The primary hypothesis is that infants receiving LEAP-CP will have greater scaled scores on the Pediatric Evaluation of Disability Inventory—Computer Adaptive Test (mobility domain) at 18 months compared with health advice. Secondary outcomes include infant functional motor, cognitive, visual and communication development; infant growth; maternal mental health. Ethics and dissemination This study is approved through appropriate Australian and Indian ethics committees (see in text) with families providing written informed consent. Findings from this trial will be disseminated through peer-reviewed journal publications and conference presentations. Trial registration number 12616000653460p; Pre-results.

Aim To investigate how vision relates to early development by studying vision and cognition in a national cohort of 1-year-old infants with congenital disorders of the peripheral visual system and visual impairment. Method This was a cross-sectional observational investigation of a nationally recruited cohort of infants with ‘simple’ and ‘complex’ congenital disorders of the peripheral visual system. Entry age was 8 to 16 months. Vision level (Near Detection Scale) and non-verbal cognition (sensorimotor understanding, Reynell Zinkin Scales) were assessed. Parents completed demographic questionnaires. Results Of 90 infants (49 males, 41 females; mean 13mo, standard deviation [SD] 2.5mo; range 7–17mo); 25 (28%) had profound visual impairment (light perception at best) and 65 (72%) had severe visual impairment (basic ‘form’ vision). The Near Detection Scale correlated significantly with sensorimotor understanding developmental quotients in the ‘total’, ‘simple’, and ‘complex’ groups (all p

The role of vision and vision deprivation in the development of executive function (EF) abilities in childhood is little understood; aspects of EF such as initiative, attention orienting, inhibition, planning and performance monitoring are often measured through visual tasks. Studying the development and integrity of EF abilities in children with congenital visual impairment (VI) may provide important insights into the development of EF and also its possible relationship with vision and non-visual senses. The current study investigates non-visual EF abilities in 18 school-age children of average verbal intelligence with VI of differing levels of severity arising from congenital disorders affecting the eye, retina, or anterior optic nerve. Standard auditory neuropsychological assessments of sustained and divided attention, phonemic, semantic and switching verbal fluency, verbal working memory, and ratings of everyday executive abilities by parents were undertaken. Executive skills were compared to age-matched typically-sighted (TS) typically-developing children and across levels of vision (mild to moderate VI [MVI] or severe to profound VI [SPVI]). The results do not indicate significant differences or deficits on direct assessments of verbal and auditory EF between the groups. However, parent ratings suggest difficulties with everyday executive abilities, with the greatest difficulties in those with SPVI. The findings are discussed as possibly reflecting increased demands of behavioral executive skills for children with VI in everyday situations despite auditory and verbal EF abilities in the typical range for their age. These findings have potential implications for clinical and educational practices.

ObjectiveTo present a structured approach for an outpatient consultation for a child with developmental disability who may have an ocular or visual disorder.MethodReview of relevant literature and description of the approach to ocular and visual assessment which could be used by any paediatrician.ConclusionA systematic approach to history, observation and examination of a child with a developmental disability will assist in identifying a possible visual problem. A structured referral letter will ensure that the child will receive the most appropriate assessment to clarify the problem and appropriate management in the eye clinic.

Aims We have identified an excess of children with cerebral palsy (CP) born to women who received antibiotic treatment for spontaneous preterm labour (SPL). This nested study investigated the profile of impairment among children with CP in the ORACLE Children Study (OCS), and contrasted outcomes with those in 4Child, a population CP registry. Method The study group comprised 167 children aged from 7 to 10 years (100 males, 67 females) with CP from the OCS, who were subdivided into a preterm rupture of membranes (PROM) group (87 children) and an SPL group (80 children). The OCS sought follow-up information regarding the health and behaviour of surviving children at 7 years of age in the UK using a parent-report postal questionnaire. Families provided further information to define wider aspects of function and were offered a physiotherapy assessment. Results The prevalence of CP was higher among children in the OCS than among those in 4Child (standardized morbidity ratios: SPL group, 3.12 [95% confidence interval CI 2.47–3.87); PROM group: 1.56 (CI 1.24–1.92)]. The proportion of children with CP born after 32 weeks of gestation was higher in in the SPL group (73%) than in the PROM group (30%); the prevalence of CP was higher in the SPL group than in the PROM group or 4Child. Children with CP in the OCS tended to have similar distributions of neuroimpairment as children in 4Child, but motor impairment and associated vision and hearing problems were found to be less severe. Interpretation The pattern of CP in both the PROM and the SPL groups was similar, but functional outcomes were milder, compared with children with CP in the general population. However, in these groups the risk of CP was increased independently of gestational age. This is consistent with findings that ongoing inflammatory damage can cause CP.

Aim The collection of data on longer-term neurodevelopmental outcomes within large neonatal randomized controlled trials by trained assessors can greatly increase costs and present many operational difficulties. The aim of this study was to develop a more practical alternative for identifying major cognitive delay in infants at the age of 24 months, based on parental reports. Method A sample of 476 infants (206 female, 270 male) previously diagnosed with neonatal sepsis (mean birthweight 1329g [SD 865g], mean gestational age at birth 28.7wks [SD 4.5wks]) from the International Neonatal Immunotherapy Study were assessed using the Parent Report of Children’s Abilities – Revised and the Bayley Scales of Infant Development, 2nd edition. Logistic regression was used to model the association between the risk of major cognitive delay (i.e. Bayley Scales of Infant Development Mental Development Index

Available observational tools used in the identification of social communication difficulties and diagnosis of autism spectrum disorder (ASD) rely partly on visual behaviours and therefore may not be valid in children with visual impairment. A pilot observational instrument, the Visual Impairment and Social Communication Schedule (VISS), was developed to aid in identifying social communication difficulties and ASD in young children with visual impairment affected by congenital disorders of the peripheral visual system (disorders of the globe, retina, and anterior optic nerve). The VISS was administered to 23 consecutive children (age range 1 y 9 mo-6 y 11 mo, mean 4 y 1 mo [SD 1.6]; 12 males, 11 females) with visual impairment (nine with severe and 14 with profound visual impairment). Item analysis was carried out by fit of the items to the Rasch model. Validity of the VISS was explored by comparison with the Childhood Autism Rating Scale (CARS) score, and the clinical ASD diagnosis (n=9). Correlation between the VISS and CARS total scores was highly significant (Spearman's rho=-0.89; p=0.01). Below threshold rating on the VISS (score of 35) showed good agreement with the clinical ASD diagnosis (sensitivity 89%, specificity 100%). This preliminary study shows the VISS to be a promising schedule to aid the identification of ASD in young children with visual impairment.

A trial of melatonin treatment in children with septo-optic dysplasia (SOD) and sleep disruption is accepted clinical practice in many centers. However, no objective measurements of sleep/activity patterns with 24-h melatonin profiles have been published for these individuals, and the pathophysiological basis underlying sleep disorders in SOD remains largely unknown.We studied six children with rest-activity disturbances and SOD. All wore an Actiwatch-Mini (a noninvasive method of detecting and recording movement intensity) for 2 wk and were admitted to hospital for a 24-h period during which hourly measurements of serum melatonin were taken. Sleep data were analyzed in conjunction with a detailed sleep diary. Ethical approval was obtained for these studies.Two children produced virtually no melatonin throughout the 24-h period of measurement and had fragmented sleep patterns with no evidence of a non-24-h sleep-wake disorder or delayed sleep-phase disorder. One child had a normal melatonin profile despite actigraphy showing an arrhythmic sleep pattern. The remaining three children had fragmented sleep, with two having normal melatonin profiles and one having a modest increase in daytime melatonin concentrations, making the timing of dim-light melatonin onset difficult to discern.There is considerable variation in timing and amount of melatonin secretion in these children. Surprisingly, none of the children had either actigraphic or melatonin profile evidence of a non-24-h sleep-wake disorder or delayed sleep-phase disorder. Understanding the heterogeneous nature of underlying sleep disorders in this group of children is important and has implications for their management.

Mutations in the visual system homeobox 2 gene (VSX2, also known as CHX10), which encodes a retinal transcription factor from the paired homeobox family, have been implicated in recessive isolated microphthalmia. In this study, we use genome-wide single nucleotide polymorphism homozygosity mapping in unrelated small consanguineous pedigrees and a candidate gene approach to identify three further causative VSX2 mutations (two novel and one previously reported). All affected individuals with homozygous mutations had bilateral anophthalmia or severe microphthalmia with absent vision. In addition, we identified a novel inner retinal dystrophy in two carrier parents suggesting a semidominant effect for this particular VSX2 mutation. A further study of individuals with retinal degenerative conditions may reveal a causative role for heterozygous mutations in VSX2.

Aim The aim of this study was to study systematically social, communication, and repetitive/restrictive (SCRR) behavioural difficulties and clinical autism spectrum disorder (ASD) in children with optic nerve hypoplasia (ONH) and/or septo-optic dysplasia (SOD), and to investigate the relationship between visual impairment, SCRR difficulties, ASD, and cognition. Method A case-note study of clinic records from a specialist developmental vision service was completed. Standardized assessments of vision and development and clinician judgements about SCRR difficulties and clinical ASD were made by a multidisciplinary team. Results A total of 45 females and 38 males (mean age 3y 5mo; range 10mo–6y 10mo) with ONH or SOD and profound visual impairment (PVI) or severe visual impairment (SVI) were assessed. A total of 58% of children had at least one SCRR difficulty, and 31% had a clinical diagnosis of ASD. The prevalence of ASD was slightly higher in children with SOD than in children with ONH (36% vs 26%) also slightly more frequent in children with PVI than in children with SVI (36% vs 27%). The prevalence of SCRR difficulties was statistically higher in children with PVI than in children with SVI (p=0.003). Clinical ASD was most likely to be diagnosed between 2 years 4 months and 4 years 6 months. Development was significantly delayed in children with ASD compared with children without social communication difficulties (p=0.001). Interpretation Children with SVI or PVI are at risk of SCRR difficulties and clinical ASD. Children with ONH and/or SOD and visual impairment have a similar risk of developing clinical ASD as other visual impairment groups. However, ASD prevalence data from this study are a minimum estimate, as some young children may have developed ASD behaviours in later childhood. Developmental surveillance for children with ONH and/or SOD should continue until at least the age of 4 years 6 months.

Severe ocular malformations, including anophthalmia-microphthalmia (AM), are responsible for around 25% of severe visual impairment in childhood. Recurrent interstitial deletions of 14q22–23 are associated with AM and a wide range of extra-ocular phenotypes including brain anomalies. The homeobox gene OTX2 is located at 14q22.3 and has recently been identified as mutated in AM patients. Eight human OTX2 mutations have been reported in subjects with severe eye malformations, including AM, and variable developmental delay. We screened a novel AM cohort for mutations and deletions in OTX2, and identified four new mutations in six individuals and two cases of whole gene deletions. Our data suggest that OTX2 mutations and deletions account for 2–3% of AM cases. © 2008 Wiley-Liss, Inc.

Summary Background The ORACLE I trial compared the use of erythromycin and/or amoxicillin–clavulanate (co-amoxiclav) with that of placebo for women with preterm rupture of the membranes without overt signs of clinical infection, by use of a factorial randomised design. The aim of the present study—the ORACLE Children Study I—was to determine the long-term effects on children of these interventions. Methods We assessed children at age 7 years born to the 4148 women who had completed the ORACLE I trial and who were eligible for follow-up with a structured parental questionnaire to assess the child's health status. Functional impairment was defined as the presence of any level of functional impairment (severe, moderate, or mild) derived from the mark III Multi-Attribute Health Status classification system. Educational outcomes were assessed with national curriculum test results for children resident in England. Findings Outcome was determined for 3298 (75%) eligible children. There was no difference in the proportion of children with any functional impairment after prescription of erythromycin, with or without co-amoxiclav, compared with those born to mothers who received no erythromycin (594 [38·3%] of 1551 children vs 655 [40·4%] of 1620; odds ratio 0·91, 95% CI 0·79–1·05) or after prescription of co-amoxiclav, with or without erythromycin, compared with those born to mothers who received no co-amoxiclav (645 [40·6%] of 1587 vs 604 [38·1%] of 1584; 1·11, 0·96–1·28). Neither antibiotic had a significant effect on the overall level of behavioural difficulties experienced, on specific medical conditions, or on the proportions of children achieving each level in reading, writing, or mathematics at key stage one. Interpretation The prescription of antibiotics for women with preterm rupture of the membranes seems to have little effect on the health of children at 7 years of age. Funding UK Medical Research Council.

This article explores how visual impairment might impact on early social and emotional development including self-awareness and communication with others. Some children show a 'developmental setback' and other worrying developmental trajectories in the early years, including autistic related behaviours and autistic spectrum disorders. Research is beginning to reveal the risk factors and most vulnerable processes in the early years, including in social communication, joint attention and joint referencing. The new Developmental Journal for Visually Impaired Babies and Children draws on the research to date and provides a new framework for early intervention and habilitation.

Developmental ocular malformations, including anophthalmia-microphthalmia (AM), are heterogeneous disorders with frequent sporadic or non-Mendelian inheritance. Recurrent interstitial deletions of 14q22-q23 have been associated with AM, sometimes with poly/syndactyly and hypopituitarism. We identify two further cases of AM (one with associated pituitary anomalies) with a 14q22-q23 deletion. Using a positional candidate gene approach, we analyzed the BMP4 (Bone Morphogenetic Protein-4) gene and identified a frameshift mutation (c.226del2, p.S76fs104X) that segregated with AM, retinal dystrophy, myopia, brain anomalies, and polydactyly in a family and a nonconservative missense mutation (c.278A-->G, p.E93G) in a highly conserved base in another family. MR imaging and tractography in the c.226del2 proband revealed a primary brain developmental disorder affecting thalamostriatal and callosal pathways, also present in the affected grandmother. Using in situ hybridization in human embryos, we demonstrate expression of BMP4 in optic vesicle, developing retina and lens, pituitary region, and digits strongly supporting BMP4 as a causative gene for AM, pituitary, and poly/syndactyly. Because BMP4 interacts with HH signaling genes in animals, we evaluated gene expression in human embryos and demonstrate cotemporal and cospatial expression of BMP4 and HH signaling genes. We also identified four cases, some of whom had retinal dystrophy, with "low-penetrant" mutations in both BMP4 and HH signaling genes: SHH (Sonic Hedgehog) or PTCH1 (Patched). We propose that BMP4 is a major gene for AM and/or retinal dystrophy and brain anomalies and may be a candidate gene for myopia and poly/syndactyly. Our finding of low-penetrant variants in BMP4 and HH signaling partners is suggestive of an interaction between the two pathways in humans.

Purpose To establish age norms and interocular differences in visual acuity between 2 years 9 months and 8 years for the Sonksen logMAR Test. Methods Cross-sectional population-based study. Binocular measures of linear visual acuity were achieved in 2,940 children and monocular measures were achieved in 2,820 right eyes and 2,821 left eyes, respectively. Measures for both right and left eyes were achieved by 2,807. Asymmetric logistic models were used to construct smoothly changing age-related centile curves showing how visual acuity changes with age in a normative population sample. Results All curves demonstrated an increase in visual acuity with age that was steepest between 2 years 9 months and 5 years 3 months. Equivalent centiles for linear visual acuity were better when viewed binocularly than monocularly; the difference was least between the 95th centiles (best levels) and greatest between the 5th centiles (worst levels). There were no clinically significant differences between group measures of visual acuity from right and left eyes—average within child difference 0.0095 logMAR units, 95% CI, 0.0059-0.013. Interocular differences did not vary significantly with age ( p = 0.73). The 90th and 95th centiles for interocular difference were 0.125 and 0.175 log units, respectively. Conclusions This study demonstrates how visual acuity varied with age for the Sonksen logMAR Test and presents the findings in the clinically useful format of centile charts.

Purpose To develop a standardized logMAR test of visual acuity for young children and establish testability and reliability. Methods Two thousand nine hundred ninety-one children, aged 2 to 8 years 6 months, from a population sample of 4671 were recruited from schools and preschool facilities and tested. Ability to name or match letters, accept occlusion, and achieve binocular single and binocular and monocular measures of linear visual acuity were recorded. Inter- and intratester reliability was assessed for a random selection of 215 children. Results Two thousand nine hundred seventy-four (99.4%) matched or named letters, 2966 (99%) achieved binocular single, 2940 (98%) achieved binocular linear, and 2807 (94%) achieved monocular linear (for both eyes) measures. Binocular linear measures were achieved in 50% aged less than 3 years, 80% aged 3 to 3½, 92% aged 3½ to 4, and 99% aged 4 years and over. Binocular linear measures were achieved in 86% of 2- to 3-year-olds and 96% of 3- to 3½-year-olds who matched or named letters; monocular linear measures were achieved in 86 and 95%, respectively, of these age groups who then accepted occlusion. The median time for completion of the test (binocular and monocular) was 3 minutes 55 seconds. The 95% limits of agreement for the same observer and for different observers were ±0.13 and −0.19, +0.15 for binocular linear and −0.16, +0.15, and −0.17, +0.13 for monocular linear measures, respectively. Conclusions The Sonksen logMAR Test provides reliable binocular and monocular measures of linear visual acuity in a high proportion of children from the age of 2.5 years.

Background: Developmental eye anomalies, which include anophthalmia (absent eye) or microphthalmia (small eye) are an important cause of severe visual impairment in infants and young children. Heterozygous mutations in SOX2, a SOX1B-HMG box transcription factor, have been found in up to 10% of individuals with severe microphthalmia or anophthalmia and such mutations could also be associated with a range of non-ocular abnormalities. Methods: We performed mutation analysis on a new cohort of 120 patients with congenital eye abnormalities, mainly anophthalmia, microphthalmia and coloboma. Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridisation (FISH) were used to detect whole gene deletion. Results: We identified four novel intragenic SOX2 mutations (one single base deletion, one single base duplication and two point mutations generating premature translational termination codons) and two further cases with the previously reported c.70del20 mutation. Of 52 patients with severe microphthalmia or anophthalmia analysed by MLPA, 5 were found to be deleted for the whole SOX2 gene and 1 had a partial deletion. In two of these, FISH studies identified sub-microscopic deletions involving a minimum of 328 Kb and 550 Kb. The SOX2 phenotypes include a patient with anophthalmia, oesophageal abnormalities and horseshoe kidney, and a patient with a retinal dystrophy implicating SOX2 in retinal development. Conclusion: Our results provide further evidence that SOX2 haploinsufficiency is a common cause of severe developmental ocular malformations and that background genetic variation determines the varying phenotypes. Given the high incidence of whole gene deletion we recommend that all patients with severe microphthalmia or anophthalmia, including unilateral cases be screened by MLPA and FISH for SOX2 deletions.

Background Antibiotics used for women in spontaneous preterm labour without overt infection, in contrast to those with preterm rupture of membranes, are associated with altered functional outcomes in their children. Methods From the National Pupil Database, we used Key Stage 2 scores, national test scores in school year 6 at 11 years of age, to explore the hypothesis that erythromycin and co-amoxiclav were associated with poorer educational outcomes within the ORACLE Children Study. Results Anonymised scores for 97% of surviving children born to mothers recruited to ORACLE and resident in England were analysed against treatment group adjusting for key available socio-demographic potential confounders. No association with crude or with adjusted scores for English, mathematics or science was observed by maternal antibiotic group in either women with preterm rupture of membranes or spontaneous preterm labour with intact membranes. While the proportion receiving special educational needs was similar in each group (range 31.6–34.4%), it was higher than the national rate of 19%. Conclusions Despite evidence that antibiotics are associated with increased functional impairment at 7 years, educational test scores and special needs at 11 years of age show no differences between trial groups. Trial registration number ISCRT Number 52995660 (original ORACLE trial number).

Aims 1. To determine the survival and morbidity of infants at discharge with a birthweight of less than 1500 g in the geographically defined population of East Anglia. 2. To demonstrate a cost-effective method of regional data collection. 3. To determine whether there were any changes in the demand for neonatal care. Study design and subjects A prospective cohort analysis using a single database to collect data on 1244 very low birthweight infants from eight neonatal units in one Region from 1993 to 1997. Results Estimated ascertainment of VLBW infants to the study was 96%. Over the 5 years survival rates were stable (75–79%). 52% of deaths in infants admitted for neonatal care occurred on day 1, with just 15% of deaths occurring after 28 days of life. Mortality risk significantly decreased with increasing gestational age at birth. Compared to 22–25-week old infants, the mortality risk decreased by 65% for 26–27-week old infants (OR 0.35 95% CI (0.21, 0.59)) and by 92% for 32–39-week old infants (OR 0.08 95% CI (0.03, 0.21)) with intermediate odds ratios of 0.22 (0.12, 0.42) and 0.13 (0.06, 0.28) for the 28–29 and 30–39 weeks gestation, respectively. Higher birthweight, after adjusting for gestation also decreased the mortality risk (OR 0.78 per 100 g difference, 95% CI (0.71, 0.86)). No change was seen in the number of extremely preterm infants admitted for intensive care or resource utilisation, although a significant increase was seen in the number of infants dying in delivery rooms. There was a reduction in the reported incidence of pulmonary interstitial emphysema (10–4%) but no change in the number of ventilation days or the rate of chronic lung disease. The mean maternal age increased from 27.7 years to 28.9 years during the study. Maternal steroid administration increased (30% to 59%) and was associated with a decreased risk of mortality (OR 0.44, 95% CI: 0.31–0.62). Conclusions It is possible to collect useful data from the neonatal period at a reasonable cost from a geographically defined population. This information was used for informing clinicians, counselling parents and in the era of managed clinical networks will be useful in guiding the provision of effective health care resources.

Aim: To identify a gene linking microphthalmia with cyst with early onset medulloblastoma. Methods: Mutation analysis of the PTCH gene. Results: A mutation in exon 10 of the PTCH gene was identified, confirming a diagnosis of Gorlin syndrome. Conclusions: This is the first genetically identified mutation giving rise to microphthalmia with cyst and provides a valuable link in the eye developmental gene pathway.

OBJECTIVE: To determine the association between congenital toxoplasmosis and preterm birth, low birthweight and small for gestational age birth. DESIGN: Multicentre prospective cohort study. SETTING: Ten European centres offering prenatal screening for toxoplasmosis. POPULATION: Deliveries after 23 weeks of gestation in 386 women with singleton pregnancies who seroconverted to toxoplasma infection before 20 weeks of gestation. Deliveries after 36 weeks in 234 women who seroconverted at 20 weeks or later, and tested positive before 37 weeks. METHODS: Comparison of infected and uninfected births, adjusted for parity and country of birth. MAIN OUTCOME MEASURES: Differences in gestational age at birth, birthweight and birthweight centile. RESULTS: Infected babies were born or delivered earlier than uninfected babies: the mean difference for seroconverters before 20 weeks was -5.4 days (95% CI: -1.4, -9.4), and at 20 weeks or more, -2.6 days (95% CI: -0.5, -4.7). Congenital infection was associated with an increased risk of preterm delivery when seroconversion occurred before 20 weeks (OR 4.71; 95% CI: 2.03, 10.9). No significant differences were detected for birthweight or birthweight centile. CONCLUSION: Babies with congenital toxoplasmosis were born earlier than uninfected babies but the mechanism leading to shorter length of gestation is unknown. Congenital infection could precipitate early delivery or prompt caesarean section or induction of delivery. We found no evidence for a significant association between congenital toxoplasmosis and reduced birthweight or small for gestational age birth.

Syndromic Hirschsprung disease has been associated with mutations in ZFHX1B, a Smad-interacting transcriptional repressor protein. Tissue in situ hybridization has demonstrated strong expression of ZFHX1B in the developing eye, suggesting that some mutations in this gene may cause visual loss. However, none of the reported mutations have been associated with an ocular phenotype. We describe a patient with Down syndrome and Hirschsprung disease with high myopia and ocular coloboma affecting the iris and retina. In addition to trisomy 21, a novel, de novo heterozygous A to G transition in exon 8 of the ZFHX1B gene was identified, which results in a R953G amino acid substitution. This abnormality was not seen in a screen of 200 chromosomes from ethnically matched, normal controls. The arginine residue at position 953 is an extremely conserved amino acid throughout evolution. This is the first report associating Hirschsprung disease and severe eye defects with a specific genetic mutation and is the first report of a mutation in ZFHX1B causing a developmental ocular anomaly.

A 7-year-old boy is referred to you with h concerns about developmental delay. On assessment, he is found to have moderate mental retardation (1Q of 50) but no remarkable physical findings. His parents are considering having another child, and they wonder what caused the retardation in their first child and whether it is likely to recur in future offspring.

Children with disability are at a substantially higher risk of visual impairment (VI) (10.5% compared with 0.16%) but also of ocular disorders of all types, including refractive errors and strabismus. The aetiology of VI in children with disability reflects that of the general population and includes cerebral VI, optic atrophy, as well as primary visual disorders such as retinal dystrophies and structural eye anomalies. VI and other potentially correctable ocular disorders may not be recognised without careful assessment and are frequently unidentified in children with complex needs. Although assessment may be more challenging than in other children, identifying these potential additional barriers to learning and development may be critical. There is a need to develop clearer guidelines, referral pathways and closer working between all professionals involved in the care of children with disability and visual disorders to improve our focus on the assessment of vision and outcomes for children with disability.

The area of child disability is the 'Cinderella' of community child health services. It lacks a clear commissioning model, agreed quality standards or guidance on the level of resources required. In this climate of uncertainty, a national survey of Child Development Teams was undertaken in order to describe their basic structure and processes. The paper reports information from 242 multidisciplinary teams providing local services, with statutory funding, to children with neurodevelopmental disability and their families. The picture presented is encouraging in part. For example, 79% of teams operate from a Child Development Centre, which may be expected to enhance team communication. In terms of the initial assessment process for a developmentally delayed child, most teams (91%) report that they would hold a case discussion afterwards, although only 74% would always include parents, and only 70% always give their report(s) to parents. The impression of management practices is weak, with only 62% giving a clear answer about who manages the team, and less than half having a written policy or contract for the team's work. The survey findings provide a sampling framework from which further evaluative research can be generated.

Background The Parent Report of Children’s Abilities-Revised (PARCA-R) assesses cognitive and language development at 24 months. It was validated against the Mental Development Index of the Bayley Scales of Infant Development II (BSID II), but this has now been superseded by BSID III. Objective To compare the PARCA-R against the BSID III. Methods PARCA-R and BSID III assessments scheduled at 24 months of age (corrected for prematurity) were completed in 204 infants with suspected or proven neonatal sepsis in the International Neonatal Immunotherapy Study. Associations between the scales were measured and the predictive accuracy of the PARCA-R for moderate cognitive delay and moderate language delay was assessed using Receiver Operating Characteristic (ROC) analysis. Results Median birthweight was 911 g, median gestational age at birth was 27 weeks and 100 (49.0%) were girls. 4.4% and 8.4% met standard BSID III criteria for cognitive delay and language delay, respectively. These rates increased to 19.6% and 12.6% when an independent sample of normal term infants were used as the reference group suggesting standard BSID III reference norms may tend to underestimate delay. The Spearman correlation between PARCA-R and BSID scales were 0.43 for cognition and 0.71 for language. The PARCA-R successfully predicted cases of cognitive delay and language delay with the area under the ROC curves ranging from 0.83 to 0.97 depending on reference norms used. Conclusions The results support the PARCA-R as a practical tool for the identification of appreciable cognitive and language delay at 24 months among critically ill premature and extremely low birthweight neonates.

OBJECTIVES: To assess the prevalence of behavioral problems in children with isolated optic nerve hypoplasia, mild to moderate or no visual impairment, and no developmental delay. To identify white matter abnormalities that may provide neural correlates for any behavioral abnormalities identified. PATIENTS AND METHODS: Eleven children with isolated optic nerve hypoplasia (mean age 5.9 years) underwent behavioral assessment and brain diffusion tensor imaging, Twenty four controls with isolated short stature (mean age 6.4 years) underwent MRI, 11 of whom also completed behavioral assessments. Fractional anisotropy images were processed using tract-based spatial statistics. Partial correlation between ventral cingulum, corpus callosum and optic radiation fractional anisotropy, and child behavioral checklist scores (controlled for age at scan and sex) was performed. RESULTS: Children with optic nerve hypoplasia had significantly higher scores on the child behavioral checklist (p