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Indicatori di Rischio dell’ Autismo: dalla vita fetale all’infanzia
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Indicatori di Rischio dell’ Autismo: dalla vita fetale all’infanzia

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Indicatori di Rischio dell’ Autismo: dalla vita fetale all’infanzia...

Indicatori di Rischio dell’ Autismo: dalla vita fetale all’infanzia


Stephen J. Sheinkopf, Ph.D. Assistant Professor (Research) Psychiatry & Human Behavior and Pediatrics
Center for the Study of Children at Risk Alpert Medical School, Brown University Women & Infants Hospital

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Indicatori di Rischio dell’ Autismo: dalla vita fetale all’infanzia Indicatori di Rischio dell’ Autismo: dalla vita fetale all’infanzia Presentation Transcript

  • Indicatori di Rischio dell’ Autismo: dalla vita fetale all’infanzia Stephen J. Sheinkopf, Ph.D. Assistant Professor (Research) Psychiatry & Human Behavior and Pediatrics Center for the Study of Children at Risk Alpert Medical School, Brown University Women & Infants Hospital
  • Early Diagnosis Lord et al., 2006 Autism or Autism at 2 PDD @ 9 years• Symptoms evident (99%) by 12 – 18 months Autism or PDD at 2• Stable diagnoses years PDD @ 9 (86%) made by 24 – 36 months Kleinman et al., 2008• But stability of Autism or Autism at 2 PDD @ 4 - 6 diagnosis varies by years (75%) studyEarly diagnosis improved, but refinements needed
  • Infant Signs of AutismApproaches Significant findings1. Retrospective smiling parent interviews eye contact2. Home videotapes social responses3. Infant sibling Imitation studies joint attention social engagementSome subtle differences reported in 4 to 6 month-olds, but most robust differences by ~ 12 months View slide
  • Some considerations How do social deficits emerge during infancy? Can differences be detected in early infancy? sensitivity Can differences be detected when compared to variability in typical development (specificity)? Figure from Ozonoff et al., JAACAP, 2010Research needs to solve a Signal-to-Noise challenge View slide
  • Current Approaches & FindingsFetal & Early Infant PeriodsStrategies Measurements1. Prospective cases 1. Cry/vocal2. Infant Siblings acoustics 2. Neurobehavioral indicatorsFetal Newborn Infancy
  • STUDY 1:Atypical cry acoustics in 6-monthold infants at-risk for Autism Collaboration between Brown Medical School (Sheinkopf & Lester) & University of Pittsburgh (Iverson) Examined pain and non-pain cries in high & low risk infants
  • Participants High Risk (HR) Low Risk (LR) n = 21 n = 18Inclusion Older sibling with ASD, Older sibling with typicalCriteria confirmed by ADOS developmentMale : Female 6 : 15 8 : 10Race/Ethnicity-White 19 17-White Hispanic 2 0-Asian-American 0 1Maternal Age, 35.0 (4.8) 33.0 (5.1)mean (sd)Maternal Age,mean (sd) 36.3 (3.6) 34.3 (4.1)
  • Data collection methodsVocal recordings made in homes at 6months (+/- 2 weeks)Recorded to digital audio-video files(audio recording with lapel microphone)Cry episodes identified on videotapeSamples with adequate recording qualitywere selected for analysis
  • Coding & Analysis of Cries Infants with observable cry episodes: 17 HR & 11 LR babies Videos coded to identify potential causes of cry Classified as pain or non-pain related Acoustic analysis of cries System used in prior cry research Samples were filtered (5 kHz), digitized (10 kHz), and separated by utterance Analysis within 25ms blocks Computed the log magnitude spectrum for each block (Fast Fourier Transform) Results in a range of acoustic features
  • Variables produced by acoustic analysisPitch (F0) Average pitch of cry (Hz)Variability of Pitch Range of F0 across the cry episodePhonation % of 25-ms blocks with voiced or resonant soundHyperphonation % of 25-ms blocks with F0 > 1,000 Hz.Utterance Duration Average time of utterances (seconds)Average Energy/Amplitude: Loudness of cry (mean dB)Variability of Energy/Amplitude: Range of cry amplitudeFirst Formant (F1) First resonant frequency (Hz)Second Formant (F2) Second resonant frequency (Hz)
  • Pain Related CriesResults of Group Comparisons Pitch (p = .02) Pitch Range (p = .06) 550 160 ASD- ASD- Risk Risk 140 500 120 450 100 80 400 60 40 350 20 300 0 Pitch (F0) Pitch Range At-risk sibs (7) Low risk sibs (5) Sheinkopf, Iverson & Lester (submitted)
  • Pitch RangeIndividual results bydiagnostic outcome• Diagnostic follow up at 36 months of age• Evaluations by ADOS• Three (3) HR children classified as autistic• Two (2) of these children had cry episodes that could be analyzed• Individual results plotted for pain and non-pain cries, and by group
  • Infants with later diagnoses had high pitch(F0) in comparison to HR & LR groups ASD Risk Group 600.00 ASD-risk Low risk Autistic 550.00 Autistic Pitch (Hz) 500.00 450.00 400.00 350.00 300.00 Non-Pain Pain
  • Later diagnosed infants had moredysphonated (turbulent) cries than others ASD Risk Group 80.00 ASD-risk Low risk 70.00 Phonation (%) 60.00 50.00 40.00 Autistic 30.00 Autistic Non-Pain Pain
  • STUDY 2:Physiologic & Neurobehavioral Responses in“Fetal Siblings” Samples Collaboration between Brown Medical School (Sheinkopf & Salisbury) & Queens University (Kisilevsky) Recruited pregnant women with older children with autism, or with family history of autism Fetal ultrasound in 3rd trimester Responses to auditory and vibro- acoustic stimulus (VAS) Heart rate (doppler) & movement (actigraphy) Neurobehavior by videotape coding
  • Initial Case Examples Case 1: Infant (girl) at risk for autism (sibling with autism) Heterogeneous comparison group, including mothers with depression FETAL ACTIVITY 27 WEEKS GA FETAL ACTIVITY 32 WEEKS GA Mean +SD Mean +SD 100 COMP 100 COMP % TIME ACTIVE (SD) % TIME ACTIVE (SD) 80 CASE 80 CASE 60 60 40 40 20 20 0 0 BASE VAS POST1 BASE VAS POST1 CONDITION/TIME CONDITION/TIMEElevated movement (actigraph) at 27 & 32 weeks gestation
  • Case 2: Infant (girl) later diagnosed with PDD-NOS (and with family psychiatric history, including a sibling with autism) FETAL ACTIVITY 26 WEEKS GA FETAL ACTIVITY 36 WEEKS GA Me an +/- SE Mean +/- SE COMP COMP 120 CASE CASE 120 100 100% TIME ACTIVE (SE) % T IM E ACT IVE (SE) 80 80 60 60 40 40 20 20 0 0 BASE VAS POST1 POST2 POST3 POST4 BASE VAS POST1 POST2 POST3 POST4 CONDITION/TIM E CONDITION/TIM E Elevated movement (actigraph) at 26 & 36 weeks gestation
  • Case 2:Elevated heart rate responses to stimuli at 36 weeks, butnot at 26 weeks FETAL HEART RATE 26 WEEKS GA FETAL HEART RATE 36 WEEKS Mean +/- SE Mean +/- SE 170 COMP COMP 170 165 CASE CASE 165 BEATS PER MIN (SE) BEATS PERMIN (SE)) 160 160 155 155 150 150 145 145 140 140 135 135 130 130 BASE VAS POST1 POST2 POST3 POST4 BASE VAS POST1 POST2 POST3 POST4 CONDITION/TIME CONDITION/TIME
  • Prospective Fetal Sibling Sample: Ultrasound at 34 – 36 weeks Stimuli: (1) VAS (2) VAS, sound only (3) Mother’s voice (4) Stranger’s voice High risk group: Pregnant mothers with family history ofautism (1st degree relatives and/or older children) Low risk group: Pregnant mothers with no family historyof autism In our preliminary work, we segregated the high risksample into those with highest risk (probands with cleardiagnoses) and those with relatives with reported butunconfirmed diagnoses.
  • Prospective Fetal Sibling Sample: Preliminary FindingsElevated HR across conditions in “highest risk” fetuses
  • Fetal NeurobehavioralCoding System (FENS)Coding of movementquality and otherindicators in 10 sec.binsStress Composite in 3Risk Groupings at 34 –36 weeks GestationalAgeAggregated acrossultrasound session
  • Collaborators & FundingBrown University FundingBarry Lester, PhD Autism SpeaksAmy Salisbury, PhD National Institutes of HealthCindy Loncar, PhD National Institute on Deafness &Lynn Andreozzi, PhD Communication Disorders (NIDCD)Todd Levine, MD National Institute of Mental HealthHarvey Silverman, PhD (NIMH)University of PittsburghJana Iverson, PhDQueens University (Ontario)Barbara Kisilevsky, PhD