Running head: Early caregiver-infant interaction and later ASD

Quality of interaction between at-risk infants and caregiver at 12-15 months is associated with three year autism outcome

Ming Wai Wana, Jonathan Greena, Mayada Elsabbaghb, Mark Johnsonb, Tony Charmanc, Faye Plummera, and the BASIS Team*

aCommunity Based Medicine, University of Manchester

bCentre for Brain and Cognitive Development, Birkbeck, University of London

cCentre for Research in Autism and Education, Institute of Education, University of London

*The BASIS team in alphabetical order: Simon Baron-Cohen, Rachael Bedford, Patrick Bolton, Susie Chandler, Janice Fernandes, Holly Garwood, Teodora Gliga, Kristelle Hudry, Leslie Tucker, Greg Pasco and Agnes Volein.

Conflict of interest: None

Total word count: 6580

Quality of interaction between at-risk infants and caregiver at 12-15 months is associated with three year autism outcome

Abstract

Background: Recent models of the early emergence of autism spectrum disorder (ASD) propose that infant intrinsic risk susceptibilities in behaviour may be amplified by interaction within the early social environment into an increasingly atypical developmental trajectory. This study examines whether 6- and 12-month parent-infant interactions in at-risk siblings differ from those with low-risk, and whether – in at-risk siblings – such interactions predict later 3-year classification of ASD, or no ASD.

Method: Within the British Autism Study of Infant Siblings (BASIS), 6-min videotaped episodes of parent-infant free play in infants at 6-10 months (45 at-risk siblings, 47 low-risk siblings) and 12-15 months (43 at-risk siblings, 48 low-risk siblings) in a laboratory setting were rated on the Social Interaction Measure for Parents and Infants (SIM-PI), blind to participant information. Standard tests were administered for concurrent behavioural signs of ASD features and developmental level. Systematic consensus diagnostic classification of ASD was made at 3 years for the at-risk siblings.

Results: Parent non-directiveness and sensitive responsiveness differed in relation to ASD/risk status (at-risk ASD, at-risk no-ASD, low-risk) at both 6 and 12 months. At 6 months, infant liveliness was lower in the high-risk groups; at 12 months, infant attentiveness to parent and positive affect were lower in the at-risk group later diagnosed with ASD. Dyadic mutuality and intensity of engagement showed a group effect at 12 months. Dyadic mutuality, infant positive affect, and infant attentiveness to parent at 12 months (but not 6 months) predicted 3-year ASD outcome, whereas infant ASD-related behavioural atypicality did not.

Conclusions: This is the first prospective evidence that early dyadic interaction between at-risk infants and their parents is associated with later diagnostic outcome in ASD. Possible explanations for these findings and their theoretical implications are considered.

Keywords: ASD siblings, mother-child relations, high-risk infants, parent sensitivity


Key points

·  Increasing evidence suggests that studying early parent-infant interaction in emergent ASD may be important for a more complete understanding of the development of the disorder.

·  Interaction differences according to ASD/risk status were found at 6 months in parent interactive behaviours and infant liveliness; and at 12 months in parent interactive behaviours, infant attentiveness to parent, infant positive affect, and dyadic mutuality in interaction.

·  Infant interactive behaviours and dyadic mutuality in interaction at 12 months, but not 6 months, predicted 3-year ASD outcome, independent of infant age and behavioural atypicality.

·  Intervention efforts to optimise social functioning may need to start early in infancy before parent-child interaction patterns become embedded in emerging social atypicality.


Overt behavioural signs of autism spectrum disorder (ASD) are rarely observable in the first year, but increasing evidence suggests that studying early caregiver-infant interaction in the context of emergent ASD may be important for a more complete understanding of the development of the disorder (Dawson, 2008; Wallace & Rogers, 2010). A transactional model posits that early social experience shapes long-term social functioning (Sameroff & Fiese, 1990; Sameroff, 2009). In normative development, the quality of interaction between primary caregiver and infant (i.e. the infant’s main early social environment) influences the infant’s own social developmental trajectory (e.g. Feldman & Greenbaum, 1997; NICHD Early Child Care Research Network, 2001). In the context of ASD, this does not suggest that parents in any way ‘cause’ the disorder. Rather, according to the transactional model, any interactive ‘perturbations’ – whether originating in the infant or caregiver’s behaviour – may become increasingly entrenched or ‘amplified’ with time, impacting on later social communicative functioning.

There are three primary explanations as to why early parent-infant interactive perturbations might arise in the context of studying emergent ASD, none of which are mutually exclusive. Firstly, interaction (including parental response) may primarily reflect the infant’s emerging behavioural and social atypicalities in those infants who go onto develop ASD. Secondly, it is possible that parents of infants at greater familial risk of ASD are more likely to display partial ASD characteristics or broader autism phenotypic (BAP) impairments (e.g. Losh, Childress, Lam, & Piven, 2008), which may impact on interaction. The third possibility arises from the ‘at-risk’ prospective study design used to investigate prodromal ASD, which involves infants who have an older sibling with ASD (‘at-risk siblings’), a proportion of whom will develop the disorder due to familial risk. In this context, interaction may be disrupted in at-risk siblings as a consequence of parents’ learned styles of interacting with the older child with ASD, which may differently affect interaction with their younger sibling without ASD.

A few studies have examined the parent-infant play interactions of at-risk siblings compared with control infants (without a sibling with ASD – ‘low-risk siblings’), and less commonly, of at-risk siblings who are later diagnosed. Studies have tended to show specific tendencies in parent interactive behaviour: The earliest study was a microanalysis of 4-month-old at-risk siblings (n = 21) which found that a significant proportion had less affectively synchronous interactions when infants led play compared to low-risk comparisons, suggesting that these mothers find it difficult to match infant-initiated affect (Yirmiya et al., 2006). Parental play interactions in our larger sample of at-risk infants (n = 44; 6-10 months) were rated to be more directive and less sensitively responsive than found in low-risk controls (Wan et al., 2012). This finding is consistent with a retrospective study of parents’ home videos of infants in the same age range, which found that specific directive behaviours (longer stimulatory behaviour, and more use of touch to elicit attention) differentiated parents whose infants were later diagnosed with ASD (n = 15) from parents of typically developing infants and infants with intellectual disabilities (Saint-Georges et al., 2011).

There has so far been less evidence for disrupted interactive behaviour in at-risk infant siblings, despite suggestive findings from naturalistic retrospective studies (George-Saints et al., 2010). At-risk siblings were less lively than low-risk controls in Wan et al.’s (2012) interaction study, although liveliness was not associated with other qualitative aspects of interaction. One retrospective ‘home movie’ study that focused on parent-infant interaction found lower infant-initiated orientation to the parent at 6-10 months than in groups who were typically developing or had intellectual disabilities (Saint-Georges et al., 2011). By contrast, at-risk sibling studies have found no infant social orientation differences during interaction measured either globally (Wan et al., 2012) or microanalytically in at-risk siblings who develop ASD (Rozga et al., 2011).

Taking a transactional model, if parent-infant interaction forms a pattern that contributes to social development, then we might expect firstly that such interaction is usually relatively stable, and secondly that any perturbations in interaction would amplify over time and impact on infant social functioning – a key deficit in ASD. However, no interaction studies so far have found any such longer-term impact. The lower infant-led synchrony identified by Yirmiya et al. (2006) was unrelated to 14-month language and communication. However, in a study of older at-risk siblings, Baker et al. (2010) found that positive parental structuring (but not sensitivity generally) during 18-month interaction was positively related to expressive language change in those who went on to develop ASD.

The current study followed up parent-infant interaction in an at-risk sibling cohort (Wan et al., 2012) from 6-10 months (‘6 months’) to 12-15 months (’12 months’) in relation to 3-year ASD outcome. Ascribing to a transactional model that early interaction quality is crucial for longer-term social functioning and outcome, it was predicted that parent-infant interaction (1) would show moderate stability and internal consistency between 6 and 12 months in low-risk siblings; (2) would differ significantly in at-risk siblings who are later diagnosed with ASD from those who are not and from low-risk siblings at 6 months and (more so, as differences become amplified) at 12 months; and (3) would be predictive – in at-risk siblings – of 3-year ASD classification, independent of the level of early behavioural atypicality (as measured through structured assessment). That is, interaction effects are not simply explained by behavioural atypicality. To further disentangle how parent-infant interaction might relate to ASD markers, these variables were also explored at 12 months in at-risk siblings who were sub-threshold for an ASD diagnosis at 3 years.

Method

Sample

Recruitment, ethical approval (UK National Health Service National Research Ethics Service London ref: 09/H0718/14), informed consent, and background data on participating families were made available for the current study through the British Autism Study of Infant Siblings (BASIS), a UK collaborative network facilitating research with infants at risk for ASD (www.basisnetwork.org). At-risk sibling status was defined by having an older sibling with a clinical diagnosis of ASD (or in 4 cases, a half-sibling), confirmed by two expert clinicians (PB, TC) based mainly on information using the Development and Wellbeing Assessment (DAWBA; Goodman, Ford, Richards, Gatward, & Meltzer, 2000) and the parent-report Social Communication Questionnaire (SCQ; Rutter, Bailey, & Lord, 2003). Infants in the low-risk group were recruited separately from a volunteer database. Inclusion criteria included full-term birth, normal birth weight, and lack of ASD within first-degree family members (confirmed through parent interview). Low-risk infants had at least one older sibling, scoring below the SCQ threshold (< 15) for ASD.

Of 104 dyads recruited (54 at-risk siblings; 50 low-risk siblings), 12 were excluded from the 6-month cohort and 12 from the 12-month cohort, as interaction data was not collected or due to technical issues. Of the remainder, 1 further case was excluded from the 12-month sample due to lack of assessment at 36 months. Complete 6-month data were available for 45 at-risk infants (20 male, 44.4%) and 47 low-risk infants (18 male; 38.3%), and 12-month data for 43 at-risk infants (17 male; 39.5%) and 48 low-risk infants (17 male; 35.4%). Interaction data at both time points were taken for 81 dyads (39 at-risk siblings; 42 low-risk siblings). All parents who took part in the interactions were mothers. (See online appendix for further details of the sample.)

Measures

Parent-Infant interaction: A global rating scheme, the Social Interaction Measure for Parents and Infants (SIM-PI), was used to evaluate seven items (on a 1-7 scale): caregiver sensitive responsiveness, caregiver non-directiveness, infant attentiveness to caregiver, infant positive affect, infant liveliness, dyadic mutuality and dyadic intensity of engagement (Details in online appendix). The measure is an adaptation of existing global scales of caregiver-infant interaction for use in this age range and focus of study. Excellent psychometric properties and inter-rater reliability were reported in our previous study at 6-10 months (Wan et al., 2012), where ratings were independent of infant gender, infant non-verbal development, maternal age, and socioeconomic status. The scales were further piloted for use in 12-15 month old infants and minor amendments made to ensure a distribution of ratings. Independently blind rated clips (26%) showed reasonable to high agreement (single measures intraclass correlations using a two-way mixed effects model; absolute agreement) ranged from r = 0.68 to r = 0.83 (p < 0.001; see Appendix for further details).

Atypical infant behaviour: Infant behaviours characteristic of emergent autism were assessed using the Autism Observation Scale for Infants (AOSI; Bryson, Zwaigenbaum, McDermott, Rombough, & Brian, 2008), a validated clinical measure of infant risk markers, focusing on precursors of ASD phenotype impairments, including response to name, eye contact, social reciprocity and imitation. Infant behaviour is elicited, while on the parent’s lap, within a structured interaction with an assessor including a series of social presses. A 7+ behavioural marker threshold in AOSI at 1 year has predicted ASD diagnosis at 24 months with a sensitivity of 84% and specificity of 98%, (Bryson et al., 2008). The AOSI was coded by the administrator and (in most cases) another trained researcher, both trained and supported in reliability by one of the originators of the instrument. Inter-rater reliability for 1-year AOSI total score was excellent (single measures, absolute agreement; N = 96; r = 0.92; p < 0.001). Discrepancies were resolved by consensus and re-reviewing performance on videotape.

Infant developmental level: The Mullen Scales of Early Learning (MSEL; Mullen, 1995) is a standardised test of early receptive and expressive language, visual reception and gross and fine motor skills for use in 0-68 month children, of which the early learning composite (ELC) standard scores was used.

Autism outcome at 3 years: Following the 36-month assessment in the at-risk group, an independent team used triangulation of all available information from all visits, combined with expert clinical judgment (TC, KH, SC, GP), to determine a consensus ICD-10(WHO, 1993) Autism spectrum disorder classification, including childhood ASD, atypical ASD, other pervasive developmental disorder. Information used to determine possible diagnosis included 24 and 36 month results from the Autism Diagnostic Observation Schedule (ADOS; Lord et al., 1989). This play-based assessment rates from videotape a child’s social behaviour in the context of a number of social presses administered by a trained assessor and designed to elicit reciprocal social interaction, language and communication and repetitive and stereotyped behaviours. At 36 months, 1 at-risk sibling was administered ADOS module 1, and 89 module 2 (2 missing data; 1 at-risk sibling). ADOS assessment was augmented with the parent-report ASD Diagnostic Interview - Revised (Lord et al., 1994). Given the children’s young age, and in line with the proposed changes to DSM-5, no attempt was made to assign specific sub-categories of PDD/ASD diagnosis.

Within the 6 month at-risk sibling cohort, of those 45 assessed at 36 months,14 (31.1%; 10 [17.4%] boys) met criteria for ASD diagnosis (‘at-risk ASD’) and 31 did not (‘at-risk no-ASD’; 10 boys [32.3%]). In the 12 month at-risk sibling cohort, 12(27.9%; 8boys [66.7%]) met criteria for an ASD diagnosis and 31 (72.1%; 9 boys [29.0%]) did not. Within the 12 month cohort, 11 at-risk group toddlers (25.6%; 3 boys,8girls) were classified as not having ASD but considered to have partial atypicality or other developmental concerns by virtue of their profile of assessment scores. Nine of this group scored > ADOS cut-off; 1 > ADOS cut-off and < 1.5 SD MSEL ELC cut-off; and 1 <1.5SD MSEL ELC cut-off.