Running Head: MOTOR DEVELOPMENT IN AT-RISK SIBLINGS

Recently, evidence of poor or atypical motor skills in Autism Spectrum Disorder (ASD) has led some to argue that motor impairment is a core feature of the condition. The current study uses a longitudinal prospective design to assess the development of motor skills of twenty children at increased risk of developing ASD, who were recruited and tested at 9 and 40 months old, on the basis of having an older sibling diagnosed with the condition. All children completed a range of motor, face processing, IQ and diagnostic assessments at a follow-up visit (aged 5-7 years), providing a detailed profile of development in this group from a number of standardised, parental report and experimental measures. A higher proportion of children than expected demonstrated motor difficulties at the follow-up visit, and those highlighted by parental report as having poor motor skills as infants and toddlers were also more likely to have lower face processing scores and elevated autism-related social symptoms at 5-7 years, despite having similar IQ levels. These data lend support to the argument that early motor difficulties may be a risk factor for later motor impairment as well as differences in social communication and cognition, traits that are related to ASD. The development of motor skills in children with a diagnosis of Autism Spectrum Disorder (ASD) has received an increasing amount of attention in recent years, with some beginning to argue that motor impairments may be a core feature of ASD (e.g., Fournier et al., 2010; Hilton et al., 2011). Understanding motor Running Head: MOTOR DEVELOPMENT IN AT-RISK SIBLINGS 2 functioning in ASD is of great interest, as motor impairments can have adverse effects on school achievement (e.g., Alloway, 2007; Michel et al., 2011), language and social cognitive outcomes (e.g., Archibald & Alloway, 2008; Cummins et al., 2005), and a range of activities of daily living, including dressing or feeding oneself (e.g., Summers et al., 2008). Evidence for a relationship between motor development and language and social communication skills can also be seen in typical development through the tight coupling of motor and language milestones throughout infancy (Iverson, 2010). In addition, motor development can affect how infants interact with individuals around them, with improved object manipulation skills resulting in altered patterns of attention to others in the environment (Libertus & Needham, 2010). The onset of crawling and walking also produces more opportunities for joint attention (through gaze following) and social referencing (through interpreting facial expressions) by changing the type and number of interactions infants have with their caregivers (e.g., Campos et al., 2000; Tamis-LeMonda et al., 2008). It is therefore important to investigate motor difficulties in ASD, in which language and social communication difficulties are key diagnostic criteria, as these may be related to early motor delays or problems. Previous research into motor difficulties in children diagnosed with ASD has identified widespread motor dysfunction (see Mari et al., 2003, for a review), with a high proportion of children with ASD displaying impairments in producing speeded movements (e.g., Jansiewicz et al., 2006), planning and learning motor sequences (e.g., Hughes, 1996; Mostofsky e al., 2000; Rinehart et al., 2001), executing skills such as throwing, catching or balancing (e.g., Green et al., 2009; Manjiviona & Prior, 1995; Whyatt & Craig, 2011) and on more general tests of gross and fine motor skills (e.g., Lloyd et al., 2011; Provost et al., 2007; Staples & Reid, 2010). Retrospective analyses of motor behaviour in home movies of children later diagnosed with ASD have reported mixed findings (Baranek, 1999; Ozonoff et al., 2008; Teitelbaum et al., 1998), but such videos may not be representative of the infant’s motor functioning (Baranek, 1999). One way of addressing this problem is to assess motor behaviour prospectively in infants at greater risk of developing ASD due to heritability within families, and it is this method that has been utilised in the current study. A number of prospective studies with infants who have an older sibling with a diagnosis of ASD, and who are therefore more likely to develop ASD themselves, are currently being conducted. The most recent estimates of the recurrence rate in younger siblings is between 10-20% (Constantino et al., 2010; Ozonoff et al., 2011), highlighting the importance of investigating early markers in this group to allow earlier identification and intervention for those most at risk. Those younger siblings who do not go on to develop ASD may also be at an increased risk of other difficulties, such as language delay, or may have subclinical characteristics of ASD (Rogers, 2009). Many of these prospective studies have not been designed with motor development in mind, but some have collected standardised motor data during infancy, particularly from the Vineland Adaptive Behavior Scales-II (VABS; Sparrow et al., 2005), and the Mullen Scales of Early Learning (MSEL; Mullen, 1995). These assess a range of abilities including Gross Motor and Fine Motor skills by parent report and standardised assesssment, respectively. Gross and fine motor impairments in at-risk siblings have been reported after 14 months of age on the MSEL (Landa & Garrett-Mayer, 2006) and after 20 months on the VABS (Toth et al., 2007). Leonard et al. (under review) reported even earlier differences between at-risk and low-risk siblings on the VABS, with at-risk siblings performing more poorly on both gross and fine motor scales at 7 months. Running Head: MOTOR DEVELOPMENT IN AT-RISK SIBLINGS 3 One reason that results may differ between these research groups is due to the number of at-risk siblings in each of the samples who go on to develop ASD (Rogers, 2009). For example, Toth et al. (2007) only tested unaffected younger siblings, while both other studies included follow-up to ascertain which infants in the at-risk group later developed ASD. As motor functioning is reported to be a reliable predictor of later autism diagnosis (Brian et al., 2008), with those with intact motor skills more likely to have better outcomes or lose an early ASD diagnosis entirely (Sutera et al., 2007), it seems possible that those samples that do not include any affected siblings will find fewer and/or later differences in motor ability. This is supported by a recent paper that compared siblings concordant and discordant for ASD (Hilton et al., 2011). The authors reported poorer functioning in the affected siblings on a fine-grained standardised motor assessment, the Bruininks-Oseretsky Test (Bruininks & Bruininks, 2005), in children aged over 4 years, while unaffected siblings performed at the normative mean. This study did not, however, present any longitudinal data, so it is not clear whether poorer functioning in the affected siblings was evident at earlier ages or if motor skills were stable over development in both affected and unaffected siblings. The first aim of the current exploratory study was to build a profile of functioning in at-risk siblings at 5-7 years across a range of age-appropriate standardised, parental report and experimental measures of motor and social skills, IQ and autism-related symptomatology. This would provide a more detailed understanding of the relative strengths and weaknesses in this group later in childhood than is usually reported. Hilton et al. (2011) reported significant correlations between motor functioning and scores on the Social Responsiveness Scale (SRS; Constantino & Gruber, 2005), a parent report measure of autistic social traits, with more severe symptoms predicting greater motor impairments in the affected siblings, and recent reviews have reported an association between motor impairment and overall symptom severity in ASD (Jeste, 2011; Maski et al., 2012). Other studies have reported face processing deficits or atypicalities in individuals with ASD (e.g., Adolphs et al., 2001; Dawson et al., 2005; Klin et al., 1999; Riby et al., 2007) and in at-risk siblings (Elsabbagh et al., 2012; Elsabbagh et al., 2009; McCleery et al., 2009). Given that ASD is often characterised by both poor motor functioning and atypical or impaired face processing, and that aspects of face processing and motor development may be inextricably linked (e.g., Campos et al., 2000), assessing these outcomes in the at-risk siblings was central to the current investigation. The other objectives of the current study were related to the longitudinal data collected at 9 and 40 months from the children later assessed at 5-7 years. Specifically, the second aim was to investigate whether differences in motor skills reported by parents on the VABS at 9 and 40 months persisted to 5-7 years when assessed by a more fine-grained standardised measure, the Movement ABC-2 (MABC-2; Henderson et al., 2007), and whether differences would also be evident on the other outcome measures as a function of early motor scores. The third aim was to address an important question relating to the use of parental report and standardised assessment measures of motor functioning during infancy and childhood. In particular, the degree of correlation between the two types of measure at each age point is of interest to both researchers and practitioners, as parent reports can be a useful and efficient method for identifying infants and children who may be at increased risk of developing motor difficulties. Correlations between data collected from the VABS and MSEL at the earlier visits, and between the VABS and MABC-2 at the later visits, were therefore calculated to address this question. Running Head: MOTOR DEVELOPMENT IN AT-RISK SIBLINGS 4 Method Participants Participants were families taking part in an ongoing longitudinal research program: BASIS, a collaborative network facilitating research with infants at-risk for autism. Thirty infants were recruited in the first year of life as part of this larger study from a database of volunteers on the basis that they had an older sibling with a confirmed clinical diagnosis of ASD (18 males). These infants were assessed at 9 months of age on a range of standardised and experimental tasks and parental report questionnaires. As part of this larger study, follow-up assessments took place at 40 months (N = 28), when characteristics of ASD are known to be clearer than at earlier ages, and in line with other prospective studies of at-risk siblings. Data were again collected from questionnaires and standardised and experimental tasks. Of the 28 participants from the second stage of testing, 20 were able to return for a follow-up visit at the age of 5-7 years (Mean age = 6 years, 2 months; SD = 5 months; Males = 12) for more fine-grained motor assessments and additional tasks. Recruitment, ethical approval, informed consent, as well as anonymised data collected from the first (pilot) cohort of BASIS were made available through BASIS for the current study. Some of the measures collected are anonymised and shared among scientists to maximise collaborative value and to minimise assessment burden on the families. A clinical advisory team of senior consultants works closely together with the research teams, and if necessary with the family’s local health services, to ensure that any concerns about the child arising during the study are adequately addressed. At the time of enrolment, none of the infants had been diagnosed with any medical or developmental condition. All had an older sibling with a community clinical diagnosis of an autism spectrum disorder (hereafter, proband), diagnosis of whom was confirmed by two expert clinicians involved in the research team, using the Development and Wellbeing Assessment (DAWBA; Goodman et al., 2000) and the parent report Social-Communication Questionnaire (SCQ; Rutter et al., 2003). Most probands (18/20) met criteria for ASD on both the DAWBA and SCQ, in addition to having been diagnosed with an ASD by a local clinician. Of the remaining two probands, one did not have the DAWBA completed but met criterion on the SCQ, and for the other neither DAWBA nor SCQ data were available. Parent-reported family medical histories were taken, with no exclusions made on the basis of significant medical conditions in the proband or immediate family members. At 5-7 years (hereafter, "follow-up visit”), only one child had an independent diagnosis of ASD from a qualified clinician, and this diagnosis was confirmed by scores on the DAWBA, SCQ and the Autism Diagnostic Observation Schedule (ADOS-G; Lord et al., 1989) conducted during the visit. Materials Data were collected through a range of measures at each assessment. The measures of interest for the current report are outlined in Table 1 for each assessment point, and are split into ’diagnostic measures’, ’motor measures’, ’face processing measures’ and ’IQ measures’, corresponding to the aims presented above. Verbal and non-verbal IQ were assessed at the follow-up visit using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III UK; Wechsler, 2003). Participants completed the Information and Vocabulary subtests, and their scores were prorated to Running Head: MOTOR DEVELOPMENT IN AT-RISK SIBLINGS 5 produce Verbal IQ (VIQ); similarly, the Block Design and Matrix Reasoning scores were prorated to produce Non-verbal IQ (NVIQ). The rest of the measures are described in more detail below. --Table 1 about here--