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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.

IntroductionThe current diagnostic pathways for cognitive impairment rarely identify babies at risk before 2 years of age. Very early detection and timely targeted intervention has potential to improve outcomes for these children and support them to reach their full life potential. Early Moves aims to identify early biomarkers, including general movements (GMs), for babies at risk of cognitive impairment, allowing early intervention within critical developmental windows to enable these children to have the best possible start to life.Method and analysisEarly Moves is a double-masked prospective cohort study that will recruit 3000 term and preterm babies from a secondary care setting. Early Moves will determine the diagnostic value of abnormal GMs (at writhing and fidgety age) for mild, moderate and severe cognitive delay at 2 years measured by the Bayley-4. Parents will use the Baby Moves smartphone application to video their babies’ GMs. Trained GMs assessors will be masked to any risk factors and assessors of the primary outcome will be masked to the GMs result. Automated scoring of GMs will be developed through applying machine-based learning to the data and the predictive value for an abnormal GM will be investigated. Screening algorithms for identification of children at risk of cognitive impairment, using the GM assessment (GMA), and routinely collected social and environmental profile data will be developed to allow more accurate prediction of cognitive outcome at 2 years. A cost evaluation for GMA implementation in preparation for national implementation will be undertaken including exploring the relationship between cognitive status and healthcare utilisation, medical costs, health-related quality of life and caregiver burden.Ethics and disseminationEthics approval has been granted by the Medical Research Ethics Committee of Joondalup Health Services and the Health Service Human Research Ethics Committee (1902) of Curtin University (HRE2019-0739).Trial registration numberACTRN12619001422112.

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.

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.

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.

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).

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.

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

Background Within the ORACLE Children Study Cohort, the authors have evaluated long-term consequences of the diagnosis of confirmed or suspected neonatal necrotising enterocolitis (NEC) at age of 7 years. Methods Outcomes were assessed using a parental questionnaire, including the Health Utilities Index (HUI-3) to assess functional impairment, and specific medical and behavioural outcomes. Educational outcomes for children in England were explored using national standardised tests. Multiple logistic regression was used to explore independent associates of NEC within the cohort. Results The authors obtained data for 119 (77%) of 157 children following proven or suspected NEC and compared their outcomes with those of the remaining 6496 children. NEC was associated with an increase in risk of neonatal death (OR 14.6 (95% CI 10.4 to 20.6)). At 7 years, NEC conferred an increased risk of all grades of impairment. Adjusting for confounders, risks persisted for any HUI-3 defined functional impairment (adjusted OR 1.55 (1.05, 2.29)), particularly mild impairment (adjusted OR 1.61 (1.03, 2.53)) both in all NEC children and in those with proven NEC, which appeared to be independent. No behavioural or educational associations were confirmed. Following NEC, children were more likely to suffer bowel problems than non-NEC children (adjusted OR 3.96 (2.06, 7.61)). Conclusions The ORACLE Children Study provided opportunity for the largest evaluation of school age outcome following neonatal NEC and demonstrates significant long-term consequences of both gut function (presence of stoma, admission for bowel problems and continuing medical care for gut-related problems) and motor, sensory and cognitive outcomes as measured using HUI-3.

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.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.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.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.

The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone6.7 µg/l) and idiopathic short stature (peak growth hormone10 µg/l) underwent cognitive assessment, diffusion tensor imaging and volumetric magnetic resonance imaging prior to commencing growth hormone treatment. Total brain, corpus callosal, hippocampal, thalamic and basal ganglia volumes were determined using Freesurfer. Fractional anisotropy (a marker of white matter structural integrity) images were aligned and tract-based spatial statistics performed. Fifteen children (mean 8.8 years of age) with isolated growth hormone deficiency [peak growth hormone6.7 µg/l (mean 3.5 µg/l)] and 14 controls (mean 8.4 years of age) with idiopathic short stature [peak growth hormone10 µg/l (mean 15 µg/l) and normal growth rate] were recruited. Compared with controls, children with isolated growth hormone deficiency had lower Full-Scale IQ (P 0.01), Verbal Comprehension Index (P 0.01), Processing Speed Index (P 0.05) and Movement-Assessment Battery for Children (P 0.008) scores. Verbal Comprehension Index scores correlated significantly with insulin-like growth factor-1 (P 0.03) and insulin-like growth factor binding protein-3 (P 0.02) standard deviation scores in isolated growth hormone deficiency. The splenium of the corpus callosum, left globus pallidum, thalamus and hippocampus (P 0.01) were significantly smaller; and corticospinal tract (bilaterally; P 0.045, P 0.05) and corpus callosum (P 0.05) fractional anisotropy were significantly lower in the isolated growth hormone deficiency group. Basal ganglia volumes and bilateral corticospinal tract fractional anisotropy correlated significantly with Movement-Assessment Battery for Children scores, and corpus callosum fractional anisotropy with Full-Scale IQ and Processing Speed Index. In patients with isolated growth hormone deficiency, white matter abnormalities in the corpus callosum and corticospinal tract, and reduced thalamic and globus pallidum volumes relate to deficits in cognitive function and motor performance. Follow-up studies that investigate the course of the structural and cognitive deficits on growth hormone treatment are now required to confirm that growth hormone deficiency impacts significantly on brain structure, cognitive function and motor performance.

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.

Background Congenital visual impairment has serious consequences for early development, particularly in those with the most profound impairment. Although there is individual variation, developmental delays and risks, including ‘developmental setback’, are widespread. There is no scientifically robust developmental framework grounded in contemporary theory and scientific knowledge to guide early intervention which may prevent or minimize the risk factors and developmental difficulties. The UK governmental initiative, Early Support, gave the impetus for developing a new developmental framework for babies and young children with visual impairment. Methods This paper reports on the scientific literature that underpins the new framework and the limitations of existing intervention materials. The case for focusing on particular vulnerable areas and developing a new developmental framework, the Early Support Developmental Journal for babies and children with severe visual impairment, is presented. Conclusions The future direction for service delivery and evaluation is briefly described.

Background Postal questionnaires are widely used to collect data in healthcare research but a poor response rate may reduce the validity and reliability of results. There was a lack of evidence available relating to use of a monetary incentive to improve the response rate in the healthcare setting. Methods The MRC ORACLE Children Study is assessing the health and development of nearly 9000 seven year old children whose mothers' joined the MRC ORACLE Trial. We carried out a randomised controlled trial of inclusion of monetary incentive (five pound voucher redeemable at many high street stores) with the reminder questionnaire to parents. This trial took place between April 2002 and November 2003. When the parents were sent the reminder questionnaire about their child's health and development they were randomly assigned by concealed computer-generated allocation stratified by week of birthday to receive a five pound voucher or no incentive. The population were 722 non-responders to the initial mailing of a 12-page questionnaire. Main outcome measures: Difference in response rate between the two groups. Results Inclusion of the voucher with the reminder questionnaire resulted in a 11.7%(95% CI 4.7% to 18.6%) improvement in the response rate between the two groups. Conclusion This improvement in response rate and hence the validity and reliability of results obtained appears to be justified ethically and financially.

Heterozygous, de novo, loss-of-function mutations in SOX2 have been shown to cause bilateral anophthalmia. Here we provide a detailed description of the clinical features associated with SOX2 mutations in the five individuals with reported mutations and four newly identified cases (including the first reported SOX2 missense mutation). The SOX2-associated ocular malformations are variable in type, but most often bilateral and severe. Of the nine patients, six had bilateral anophthalmia and two had anophthalmia with contralateral microphthalmia with sclerocornea. The remaining case had anophthalmia with contralateral microphthalmia, posterior cortical cataract and a dysplastic optic disc, and was the only patient to have measurable visual acuity. The relatively consistent extraocular phenotype observed includes: learning disability, seizures, brain malformation, specific motor abnormalities, male genital tract malformations, mild facial dysmorphism, and postnatal growth failure. Identifying SOX2 mutations from large cohorts of patients with structural eye defects has delineated a new, clinically-recognizable, multisystem disorder and has provided important insight into the developmental pathways critical for morphogenesis of the eye, brain, and male genital tract.

This paper investigates the construction of age-related standards for ordinal outcome data. Asymmetric logistic models are used to describe the age-related changes in the cumulative probabilities for each ordinal level. Maximum likelihood estimation of model parameters allows the use of likelihood ratio tests to ascertain the appropriate model complexity. In contrast to methodologies for constructing age-related standards where the outcome is continuous, we show how the methodology leads directly to centile estimation for individuals. The method is illustrated using visual acuity measurements collected from 2968 children between 2 and 9 years of age made on a 30-point ordinal scale. We show how, in this instance, smoothing of parameters across ordinal categories leads to reduced validity of the centiles, justifying the need for specialized methodology for non-continuous outcomes.

Summary Background The ORACLE II trial compared the use of erythromycin and/or amoxicillin–clavulanate (co-amoxiclav) with that of placebo for women in spontaneous preterm labour and intact membranes, without overt signs of clinical infection, by use of a factorial randomised design. The aim of the present study—the ORACLE Children Study II—was to determine the long-term effects on children after exposure to antibiotics in this clinical situation. Methods We assessed children at age 7 years born to the 4221 women who had completed the ORACLE II study 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 3196 (71%) eligible children. Overall, a greater proportion of children whose mothers had been prescribed erythromycin, with or without co-amoxiclav, had any functional impairment than did those whose mothers had received no erythromycin (658 [42·3%] of 1554 children vs 574 [38·3%] of 1498; odds ratio 1·18, 95% CI 1·02–1·37). Co-amoxiclav (with or without erythromycin) had no effect on the proportion of children with any functional impairment, compared with receipt of no co-amoxiclav (624 [40·7%] of 1523 vs 608 [40·0%] of 1520; 1·03, 0·89–1·19). No effects were seen with either antibiotic on the number of deaths, other medical conditions, behavioural patterns, or educational attainment. However, more children whose mothers had received erythromycin or co-amoxiclav developed cerebral palsy than did those born to mothers who received no erythromycin or no co-amoxiclav, respectively (erythromycin: 53 [3·3%] of 1611 vs 27 [1·7%] of 1562, 1·93, 1·21–3·09; co-amoxiclav: 50 [3·2%] of 1587 vs 30 [1·9%] of 1586, 1·69, 1·07–2·67). The number needed to harm with erythromycin was 64 (95% CI 37–209) and with co-amoxiclav 79 (42–591). Interpretation The prescription of erythromycin for women in spontaneous preterm labour with intact membranes was associated with an increase in functional impairment among their children at 7 years of age. The risk of cerebral palsy was increased by either antibiotic, although the overall risk of this condition was low. Funding UK Medical Research Council.

The compliance and maturation of visual acuity of 1245 2 1/2- to nine-year-olds was investigated. Testing was undertaken as part of routine surveillance. Ability to letter match, to achieve a binocular measure and to achieve monocular measures for children under three years was 89, 78 and 37 per cent, for children aged three to four years 97, 91 and 66 per cent, and for children over four years 99.9, 99.9 and 99, respectively. A statistical model was developed to give acuity norms by age for use by surveillance and diagnostic teams.

Purpose Reliable information is needed to counsel parents of children with congenital toxoplasmosis regarding the long-term risk of visual impairment resulting from ocular toxoplasmosis. Design Prospective cohort study of children with congenital toxoplasmosis identified by prenatal or neonatal screening. Methods After three years of age, ophthalmologists reported the site of retinochoroidal lesions and visual acuity and parents reported visual impairment. An ophthalmologist predicted the child's vision based on the last retinal diagram. Selection biases were minimized by prospective enrollment and data collection, high rates of follow-up, and exclusion of referred cases. Results Two hundred and eighty-one of 284 infected children who underwent ophthalmic examinations were followed up to a median age of 4.8 years. One in six children (49/281; 17%) had at least one retinochoroidal lesion, two-thirds of whom (32/49; 65%) had a lesion at the posterior pole. In children with retinochoroiditis who had visual acuity measured after 3 years of age, 94% (31/33) had normal vision in the best eye (6/12 Snellen or better), as did 91% of those with a posterior pole lesion (21/23). Analyses based on affected eyes showed that 42% (29/69) had a posterior pole lesion, of which just more than half (15/29, 52%) had normal vision, as did 84% (16/19) of eyes with a peripheral lesion alone. Vision predicted by the ophthalmologist was moderately sensitive (59%) but overestimated impairment associated with posterior pole lesions. Of 44 children with information on acuity, four (9%) had bilateral visual impairment worse than 6/12 Snellen. Conclusions Severe bilateral impairment occurred in 9% of children with congenital toxoplasmic retinochoroiditis. Half the children with a posterior pole lesion and one in six of those with peripheral lesions alone were visually impaired in the affected eye.

Background The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate. Methods The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England. Discussion This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age. Trial registration The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660