Table 1.

LEAP-CP: early detection study aims and hypotheses

Aim 1: To determine the predictive accuracy, of the General Movements Assessment (GMA), the General Movements Motor Optimality Score (MOS), the Hammersmith Infant Neurological Examination (HINE), the Rapid Neurodevelopmental Assessment (RNDA) and the Ages and Stages-Aboriginal adaptation (ASQ-TRAK) to predict a later outcome at 12 months CA of ‘at high risk’ of (i) CP or (ii) Adverse Neurodevelopmental Outcome (non-CP) or (iii) typically developing in Indigenous infants.
H1a	Sensitivity to detect CP at 12 months CA in Indigenous infants will be >98% for abnormal GMA (Absent Fidgety, Abnormal Fidgety) at 3 months CA and >90% for suboptimal HINE score (<60 and/or >5 asymmetries) at 6 months CA.
H1b	Specificity to detect CP at 12 months CA in Indigenous infants will be >90% for abnormal GMA (Absent Fidgety, Abnormal Fidgety) at 3 months CA and >85% for suboptimal HINE score (<60 and/or >5 asymmetries) at 6 months CA.
H1c	Indigenous infants with a confirmed or ‘at risk’ diagnosis of CP at 12 months will have a Motor Optimality Score (MOS) between 8 and 14 (GMFCS I–III) or <8 (GMFCS IV and V) at 3–5 months CA, infants with a diagnosis of ‘at risk’ of adverse NDOs (non-CP) at 12 months CA will have a MOS <21 at 3–5 months CA.
H1d	The sensitivity and specificity of the GMA and MOS to detect an adverse NDO (non-CP) at 12 months CA will be less than that of CP.
H1e	Sensitivity and specificity to detect adverse NDOs (non-CP) at 12 months CA will be >81% and >71%, respectively, for suboptimal HINE score (<65) at 6 months or (<70) at 9 months CA.
H1f	Indigenous infants who score ‘at risk’ on >1 domain the ASQ-TRAK at 6 months CA (domain-specific cut-offs gross motor <23, fine motor <26, communication <30, problem-solving <28, personal–social <26) will have a diagnosis of ‘at risk’ of adverse NDOs (non-CP) and/or CP at 12 months CA.
H1g	Indigenous infants who score moderate to severe on any domain of the RNDA at 6 months CA will have good to excellent specificity (>0.8) compared with poor to fair sensitivity (0.6–0.8) to detect ‘at risk’ of CP and/or adverse NDOs (non-CP) at 12 months CA.
Aim 2: To determine the neurological (HINE), motor (PDMS-2), cognitive (BSID-III), developmental (PEDI-CAT/ASQ-TRAK) and behavioural (ITSEA) profiles of Indigenous infants with a diagnosis of ‘at risk’ of specific NDDs (i) CP, (ii) ASD, (iii) FASD and/or (iv) adverse NDO (non-specific) or (v) typically developing/borderline at 12 months CA compared with normative data.
H2a	Indigenous infants at high risk of CP at 12 months CA will score HINE<70 (GMFCS I–III), or <40 (GMFCS IV–V); BSID-III>2 SD below the mean (50% cognitive scale, 25% communication scale), PDMS-2 >1 SD below the mean (GMFCS I–III) or >2 SD below the mean (GMFCS IV–V) and PEDI-CAT >1 SD below the mean (GMFCS I–III) or >2 SD below the mean (GMFCS IV–V) (mobility scale).
H2b	Indigenous infants with ASD symptomology at 12 months CA will have a greater number of risk markers on the AOSI and/or will score HINE<70, on average score >1 SD below the mean on the BSID-III (communication scale, cognitive scale) and PDMS-2, PEDI-CAT >2 SD below the mean (personal/social scale), ITSEA >1.5 SD below the mean (competence domain) and/or>1.5 SD above the mean (externalising, internalising and dysregulation domains).
H2c	Indigenous infants with FASD symptomology at 12 months CA will have microcephaly, <3 sentinel facial features and significant impairment (>2 SD below the mean or equivalent) on >3 developmental domains including motor (PDMS-2 total motor quotient, PEDI-CAT mobility), neurological (<70 on the HINE), cognitive (BSID-III cognitive subscale, PEDI-CAT daily activities), communication (BSID-III language composite score), adaptive behaviour/social skills (PEDI-CAT personal/social scales, ITSEA subdomains).
H2d	Indigenous infants at risk of adverse NDOs (non-specific) at 12 months will have significant impairment (>2 SD below the mean) on one domain and/or or mild to moderate impairment (>1 SD below mean) in >2 domains including motor (PDMS-2 total motor quotient, PEDI-CAT mobility), neurological (<70 on the HINE), cognitive (BSID-III cognitive subscale, PEDI-CAT daily activities), communication (BSID-III language composite score), adaptive behaviour/social skills (PEDI-CAT personal/social scales, ITSEA).
H2e	Indigenous infants typically developing (<1 SD below the mean or equivalent on all developmental domains) or borderline (mild delay; between 1 and 2SD below the mean on one domain) at 12 months CA will score >70 on the HINE (neurological), and <1 SD below the mean on the PDMS-2, BSID-III, PEDI-CAT and ITSEA (motor, cognition, communication, self-care and personal/social scales, behaviour).
Aim 3: To determine the clinimetric properties of outcome and/or predictive measures used to assess a cohort of ‘at risk’ Indigenous infants (GMA, HINE, RNDA, ASQ-TRAK, BSID-III, PDMS-2, PEDI-CAT and ITSEA) in terms of (i) construct validity, (ii) reliability, (iii) cultural acceptability and (iv) clinical utility/feasibility.
H3a	Indigenous infants who are assessed to have >2 neurodevelopmental impairments (NDI) and/or score moderate to severe impairment on any domain of the RNDA at 6 months and 12 months CA will have suboptimal HINE scores at 6 (<65) and 12 (<70) months CA.
H3b	Indigenous infants who score ‘at risk’ on the communication (<16) and/or problem-solving (<28) domains of the ASQ-TRAK at 12 months CA will score >2 SD below the mean on the language and/or cognitive domains of the BSID-III at 12 months CA.
H3c	Indigenous infants who score ‘at risk’ on the gross motor (<22) and/or fine motor (<35) domains of the ASQ-TRAK at 12 months CA will score >2 SD below the mean on the Gross Motor and/or Fine Motor Quotients of the PDMS-2 at 12 months CA.
H3d	Indigenous infants who score ‘at risk’ on the personal–social (<22) domain of the ASQ-TRAK at 12 months CA will score >2 SD below the mean on the corresponding domain of the PEDI-CAT and ITSEA at 12 months CA.
H3e	There will be strong inter-rater reliability and agreement (k>0.8) between clinicians and community health workers for the HINE, RNDA and ASQ-TRAK.
H3f	The clinical utility and cultural acceptability of screening tools used to predict later neurodevelopmental outcomes of Indigenous infants at <9 months (GMA, HINE, RNDA and ASQ-TRAK) will be higher than that of tools used to measure developmental outcomes at 12 months CA (PDMS-2, BSID-III, PEDI-CAT and ITSEA).
Aim 4: To determine the relationship between (i) perinatal variables, (ii) maternal risk factors and outcomes of (i) motor, (ii) cognition and (iii) development for Indigenous infants at 12 months CA.
H4a	Adverse perinatal variables including, gestational age (<37 weeks), low birth weight (<2500 g), events that signify complications during labour and delivery, adverse neonatal medical complications and PNN events including, infection, non-accidental injury, cerebrovascular accident, will be significantly associated with lower scores on neurological, motor, cognitive, developmental and behavioural assessments at 12 months CA (HINE, PDMS-2, BSID-III, ASQ-TRAK, PEDI-CAT, RNDA and ITSEA).
H4b	Maternal risk factors (significant maternal medical conditions, antenatal medical complications and treatment, antenatal substance use and social risk factors as determined by the Social Risk Index), will be associated with lower scores on neurological, motor, cognitive, developmental and behavioural assessments at 12 months CA (HINE, PDMS-2, BSID-III, ASQ-TRAK, PEDI-CAT, RNDA and ITSEA).
H4c	Elevated caregiver stress, anxiety and depression on the DASS-21 will be associated with lower scores on neurological, motor, cognitive, developmental and behavioural measures in Indigenous infants at 12 months CA (HINE, PDMS-2, BSID-III, ASQ-TRAK PEDI-CAT, RNDA and ITSEA).

AOSI, Autism Observational Schedule in Infants; ASQ-TRAK, Ages and Stages Questionnaire-Aboriginal Adaptation; BSID, Bayley Scales of Infant Development; CA, corrected age; CP, cerebral palsy; FASD, Foetal Alcohol Spectrum disorder; GMA, General Movements Assessment; GMFCS, Gross Motor Functional Classification System; HINE, Hammersmith Infant Neurological Examination; ITSEA, Infant Toddler Social-Emotional Assessment; MOS, Motor Optimality Score; NDD, neurodevelopmental disorders; NDO, neurodevelopmental outcomes; PDMS, Peabody Developmental Motor Scales; PEDI-CAT, Paediatric Evaluation of Disability Inventory-Computer Adaptive Test; RNDA, Rapid Neurodevelopmental Assessment.