Beyond Autism: A Baby Siblings Research Consortium Study of High-Risk Children at Three Years of Age
Open accessAbstract
Objective First-degree relatives of persons with an autism spectrum disorder (ASD) are at increased risk for ASD-related characteristics. As little is known about the early expression of these characteristics, this study characterizes the non-ASD outcomes of 3-year-old high-risk (HR) siblings of children with ASD.Method Two groups of children without ASD participated: 507 HR siblings and 324 low-risk (LR) control subjects (no known relatives with ASD). Children were enrolled at a mean age of 8 months, and outcomes were assessed at 3 years. Outcome measures were Autism Diagnostic Observation Schedule (ADOS) calibrated severity scores, and Mullen Verbal and Non-Verbal Developmental Quotients (DQ).Results At 3 years, HR siblings without an ASD outcome exhibited higher mean ADOS severity scores and lower verbal and non-verbal DQs than LR controls. HR siblings were over-represented (21% HR versus 7% LR) in latent classes characterized by elevated ADOS severity and/or low to low-average DQs. The remaining HR siblings without ASD outcomes (79%) belonged to classes in which they were not differentially represented with respect to LR siblings.Conclusions Having removed a previously identified 18.7% of HR siblings with ASD outcomes from all analyses, HR siblings nevertheless exhibited higher mean levels of ASD severity and lower levels of developmental functioning than LR children. However, the latent class membership of four-fifths of the HR siblings was not significantly different from that of LR control subjects. One-fifth of HR siblings belonged to classes characterized by higher ASD severity and/or lower levels of developmental functioning. This empirically derived characterization of an early-emerging pattern of difficulties in a minority of 3-year-old HR siblings suggests the importance of developmental surveillance and early intervention for these children.
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- Findingown data
At age 3, high-risk siblings without an autism spectrum disorder outcome had lower mean verbal developmental quotients than low-risk controls, by an estimated 7.76 points (95% CI 4.96-10.56, d=0.46).
“At 3 years, HR siblings without an ASD outcome exhibited higher mean ADOS severity scores and lower verbal and non-verbal DQs than LR controls.”
- Also stated in: § Analyses of Means · hedged
“There were significant risk group effects on verbal DQ (t = −5.43, p < .001), with the HR group scoring an estimated 7.76 points lower than the LR group (CI = 4.96–10.56, d = 0.46).”
- Also stated in: § DISCUSSION · plain
“Overall, HR siblings evidenced lower verbal and nonverbal DQs than LR children.”
Quote in the paperSubstantial claim - Also stated in: § Analyses of Means · hedged
- Findingown data
High-risk siblings without an autism spectrum disorder outcome were 3.3 times more likely than low-risk controls to belong to latent class 4, characterized by low ADOS severity and low developmental quotient.
“HR siblings were more than 3 times more likely than LR children to occupy class 4, which was characterized by low severity scores and low levels of developmental functioning, particularly in the verbal domain.”
Quote in the paperSubstantial claim - Findingown data
The remaining 79% of high-risk siblings without an autism spectrum disorder outcome belonged to latent classes in which they were not differentially represented relative to low-risk controls.
“The remaining HR siblings without ASD outcomes (79%) belonged to classes in which they were not differentially represented with respect to LR siblings.”
- Also stated in: § DISCUSSION · plain
“There were not significant risk group differences in the composition of classes 1 and 2 (65% of HR siblings and 83% of controls).”
- Also stated in: § DISCUSSION · plain
“Four-fifths of these HR siblings were not significantly less likely than control subjects to fall into classes characterized by a range of typical outcomes.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · plain
- Findingown data
Males were 2.9 times more likely than females to be classified in latent class 5, characterized by elevated ADOS severity and low-average developmental quotient.
“and 2.9 times more likely than females to be classified in class 5 (elevated ASD severity/low-average DQ).”
- Also stated in: § DISCUSSION · hedged
“Males were almost three times more likely than females to belong both to class 4 and to class 5.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · hedged
- Findingown data
High-risk siblings without an autism spectrum disorder outcome were 4.6 times more likely than low-risk controls to belong to latent class 5, characterized by elevated ADOS severity and low-average developmental quotient.
“and 4.6 times more likely than LR controls to belong to class 5 (elevated ASD severity/low-average DQ).”
- Also stated in: § DISCUSSION · plain
“HR siblings were more than four times more likely than LR children to occupy class 5, which was characterized by both elevated ASD severity and low-average developmental functioning.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · plain
- Findingown data
At age 3, high-risk siblings without an autism spectrum disorder outcome had higher mean ADOS calibrated severity scores than low-risk controls, by an estimated 0.41 points on the 10-point scale (95% CI 0.18-0.70, d=0.26).
“At 3 years, HR siblings without an ASD outcome exhibited higher mean ADOS severity scores and lower verbal and non-verbal DQs than LR controls.”
- Also stated in: § Analyses of Means · hedged
“Parameter estimates indicated that the high-risk group had significantly higher severity scores than the low-risk group by an estimated 0.41 point on the 10-point scale (95% confidence interval [CI] = 0.18–0.70, d = 0.26).”
- Also stated in: § DISCUSSION · plain
“Overall, HR siblings had slightly higher ASD severity scores than LR comparison children on the ADOS.”
Quote in the paperSubstantial claim - Also stated in: § Analyses of Means · hedged
- Findingown data
High-risk siblings without an autism spectrum disorder outcome were over-represented in latent classes characterized by elevated ADOS severity and/or low to low-average developmental quotients, with 21% of high-risk siblings versus 7% of low-risk controls in such classes.
“HR siblings were over-represented (21% HR versus 7% LR) in latent classes characterized by elevated ADOS severity and/or low to low-average DQs.”
- Also stated in: § Latent Class Analysis · plain
“The remaining 21% of HR siblings were contained in class 4, characterized by low ASD severity scores and low DQ, and in class 5, characterized by elevated ASD severity scores and low-average DQ.”
Quote in the paperSubstantial claim - Also stated in: § Latent Class Analysis · plain
- Findingown data
At age 3, high-risk siblings without an autism spectrum disorder outcome had lower mean nonverbal developmental quotients than low-risk controls, by an estimated 4.20 points (95% CI 1.50-6.89, d=0.26).
“At 3 years, HR siblings without an ASD outcome exhibited higher mean ADOS severity scores and lower verbal and non-verbal DQs than LR controls.”
- Also stated in: § Analyses of Means · hedged
“A significant effect for risk group was also found for nonverbal DQ (t = −3.05, p < .01), with the high-risk group scoring an estimated 4.20 points lower than the low-risk group (CI = 1.50–6.89, d = 0.26).”
- Also stated in: § DISCUSSION · plain
“Overall, HR siblings evidenced lower verbal and nonverbal DQs than LR children.”
Quote in the paperSubstantial claim - Also stated in: § Analyses of Means · hedged
- Findingown data
Male children scored an average of 9.01 points lower on nonverbal developmental quotient than female children (95% CI 6.58-11.44, d=0.57).
“There were also significant sex effects on nonverbal DQ scores (t = 7.27, p < .01), with males scoring an average of 9.01 (CI = 6.58–11.44, d = 0.57) points lower than females.”
- Also stated in: § DISCUSSION · plain
“Independent of risk group, male children exhibited lower levels of verbal and nonverbal functioning than female children.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · plain
- Findingown data
Within the high-risk group, multiplex status was not a significant predictor of ADOS severity scores after controlling for site and sex.
“The analysis did not reveal a significant effect of multiplex status (Wald z = −1.67, p = .10).”
Quote in the paperNot a substantial claim - Findingcitation
The mean ADOS severity score for high-risk siblings was well below the cut-off of 4 points that indexes an autism spectrum disorder classification.
“In addition, the mean ASD severity score for HR siblings was well below the cut-off of 4 points that indexes an ASD classification.33”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [33] Gotham, 2007, The Autism Diagnostic Observation Schedule: revised algorithms for improved diagnostic validity, J Autism Dev Disord source
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- Findingown data
Within the high-risk group, siblings from multiplex families scored an average of 10.98 points lower on nonverbal developmental quotient than siblings from simplex families (95% CI 3.34-18.61, d=0.68).
“and an average of 10.98 (CI = 3.34–18.61, d = 0.68) points lower on nonverbal DQ than participants from simplex families (t = −2.82, p < .01).”
Quote in the paperSubstantial claim - Findingown data
Male children scored an average of 8.34 points lower on verbal developmental quotient than female children (95% CI 5.82-10.87, d=0.50).
“There were also significant sex effects on verbal DQ (t = −3.05, p < .01), with males scoring an average of 8.34 (CI = 5.82–10.87, d = 0.50) points lower than females.”
- Also stated in: § DISCUSSION · plain
“Independent of risk group, male children exhibited lower levels of verbal and nonverbal functioning than female children.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · plain
- Findingown data
The latent class analysis yielded a five-class solution as the best fitting model.
“Results of the LCA yielded a five-class solution as the best fitting model.”
Quote in the paperSubstantial claim - Findingown data
Among high-risk siblings, children from simplex families were 10.29 times more likely than children from multiplex families to belong to latent class 1 (low ADOS severity/high developmental quotient) rather than class 2.
“children from simplex families were 10.29 (CI = 1.26–82.61) times more likely than children from multiplex families to belong to class 1 (low ASD severity/high DQ) rather than comparison class 2.”
Quote in the paperNot a substantial claim - Findingown data
Males were 0.6 times less likely than females to be classified in latent class 1, characterized by low ADOS severity and high developmental quotient.
“In addition, males were 0.6 times less likely than females to be classified in class 1 (low ASD severity/high DQ).”
Quote in the paperNot a substantial claim - Findingown data
Male children had higher ADOS severity scores than female children by an estimated 0.43 points (95% CI 0.23-0.68, d=0.27).
“Sex also had a significant effect on severity scores (Wald z = 4.82, p < .001), with male children having higher scores than female children by an estimated 0.43 point (CI = 0.23–0.68; d = 0.27).”
Quote in the paperNot a substantial claim - Findingown data
Boys exhibited higher autism spectrum disorder severity scores than girls at 3 years independent of risk group.
“Independent of risk group, boys exhibited higher ASD severity scores than girls at 3 years, which extends similar findings based on parent report19 and parallels the higher rate of ASD diagnosis among boys in epidemiologic and prospective high-risk samples.4,35”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [19] Constantino, 2010, Sibling recurrence and the genetic epidemiology of autism, Am J Psychiatry source
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- cites [4] Ozonoff, 2011, Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium study, Pediatrics source
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- cites [35] Sumi, 2006, Sibling risk of pervasive developmental disorder estimated by means of an epidemiologic survey in Nagoya, Japan, J Hum Genet source
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- Findingown data
The latent class analysis distinguished groups of high-risk and low-risk children with similar 3-year outcomes.
“A latent class analysis distinguished groups of HR and LR children with similar 3-year outcomes.”
Quote in the paperSubstantial claim - Findingcitation
Male children exhibited lower levels of verbal and nonverbal functioning than female children independent of risk group.
“Independent of risk group, male children exhibited lower levels of verbal and nonverbal functioning than female children.36,37”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [36] Arden, 2006, Sex differences in variance of intelligence across childhood, Personal Indiv Diff source
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- cites [37] Dezoete, 2003, Prediction of Bayley and Stanford-Binet scores with a group of very low birthweight children, Child source
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- Findingown data
There were no significant risk group differences in the composition of latent classes 1 and 2, which contained 65% of high-risk siblings and 83% of controls.
“There were not significant risk group differences in the composition of classes 1 and 2 (65% of HR siblings and 83% of controls).”
Quote in the paperSubstantial claim - Findingown data
There were no significant risk group differences in the composition of latent class 3, which contained 14% of high-risk siblings and 11% of controls.
“Among HR siblings without an ASD outcome, there were no significant risk group differences in the composition of class 3 (14% HR siblings, 11% controls), which was characterized by elevated ASD severity and high levels of verbal and nonverbal functioning.”
Quote in the paperNot a substantial claim - Interpretationreasoning
A male high-risk sibling from a multiplex family was estimated to have verbal and nonverbal developmental quotients more than 20 points below those of a child with none of these characteristics.
“By way of example, a male HR sibling from a multiplex family was estimated to have verbal and nonverbal DQs more than 20 points below those of a child with none of these characteristics.”
Quote in the paperNot a substantial claim - Interpretationreasoning
High-risk siblings without an autism spectrum disorder outcome were not less likely than controls to be characterized by average and above average levels of functioning at 3 years of age.
“This indicates that HR siblings without an ASD outcome are not less likely than controls to be characterized by average and above average levels of functioning at 3 years of age.13”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] Landa, 2012, Latent class analysis of early developmental trajectory in baby siblings of children with autism, J Child Psychol Psychiatry
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- Interpretationown data
An early manifestation of the broad autism phenotype, characterized by autism spectrum disorder-related behaviors and/or lower developmental functioning, was present in approximately one in five high-risk siblings without an autism spectrum disorder outcome.
“These results suggest that an early manifestation of a BAP—characterized by ASD-related behaviors and/or lower levels of developmental functioning—was present in approximately one in five HR siblings without an ASD outcome.”
- Also stated in: § Conclusions · hedged
“This empirically derived characterization of an early-emerging pattern of difficulties in a minority of 3-year-old HR siblings suggests the importance of developmental surveillance and early intervention for these children.”
Quote in the paperSubstantial claim - Also stated in: § Conclusions · hedged
- Interpretationown data
The combined risk group effects and the additional independent effects of male sex and multiplex family status were clinically significant.
“Together, risk group effects and the additional, independent effects associated with being male and being a sibling from a multiplex family were clinically significant.”
Quote in the paperSubstantial claim - Interpretationcitation
The overrepresentation of high-risk siblings in latent classes with subtly disturbed functioning is consonant with genetic models of autism spectrum disorder that encompass transmission of subclinical manifestations in a subset of first-degree relatives.
“The overrepresentation of HR siblings among latent classes characterized by subtly disturbed levels of functioning is consonant with genetic models of ASD that encompass the transmission of subclinical manifestations of the autistic syndrome in a subset of first-degree relatives, on the basis of either incomplete penetrance or additive (multigenic) models of inheritance.39–41”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [39] Eapen, 2011, Genetic basis of autism: is there a way forward?, Curr Opin Psychiatry source
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- cites [40] Geschwind, 2009, Advances in autism, Annu Rev Med source
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- cites [41] Constantino JN, Todorov A, Hilton C, et al. Autism recurrence in half siblings: strong support for genetic mechanisms of transmission in ASD [published online February 28, 2012]. Mol Psychiatry. 2012. doi: 10.1038/mp.2012.9. source
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- Interpretationown data
The observed differences in ADOS severity between high-risk and low-risk groups were small, approximately half a point on a 10-point scale.
“Differences in severity scores were small, approximately half a point on a 10-point scale.”
Quote in the paperSubstantial claim - Interpretationown data
One-fifth of high-risk siblings, the majority of them male, disproportionately fell into latent classes exhibiting higher levels of autism spectrum disorder severity and/or lower levels of developmental functioning.
“However, one-fifth of HR siblings, the majority of them male, disproportionately fell into classes exhibiting higher levels of ASD severity and/or lower levels of developmental functioning.”
Quote in the paperSubstantial claim - Premisecitation
High-risk siblings from multiplex families exhibit higher levels of autism spectrum disorder-related characteristics than high-risk siblings who have a single older sibling with an autism spectrum disorder.
“Likewise, there is accumulating evidence that HR siblings from multiplex families exhibit higher levels of ASD-related characteristics17,19,20 than do HR siblings who have a single older sibling with an ASD.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [17] Schwichtenberg, 2010, Can family affectedness inform infant sibling outcomes of autism spectrum disorders?, J Child Psychol Psychiatry source
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- cites [19] Constantino, 2010, Sibling recurrence and the genetic epidemiology of autism, Am J Psychiatry source
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- cites [20] Constantino, 2006, Autistic social impairment in the siblings of children with pervasive developmental disorders, Am J Psychiatry source
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- Premisecitation
Higher levels of autism spectrum disorder-related characteristics are reported among male than among female high-risk siblings without an autism spectrum disorder outcome.
“Complementing the over-representation of ASD among males, higher levels of ASD-related characteristics are reported among male than among female HR siblings without an ASD outcome.12,19”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [12] Zwaigenbaum, 2012, Sex differences in children with autism spectrum disorder identified within a high-risk infant cohort, J Autism Dev Disord
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- cites [19] Constantino, 2010, Sibling recurrence and the genetic epidemiology of autism, Am J Psychiatry source
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- Study design and conductown data
Mean individual posterior probabilities of class membership were relatively high within each of the five latent classes, ranging from 0.77 to 0.89.
“In addition, the mean of individual posterior probabilities of class membership were relatively high within each of the five classes, ranging from 0.77 to 0.89.”
Quote in the paperSubstantial claim - Study design and conductown data
Study results were unchanged in analyses controlling for maternal education.
“Although data on maternal educational attainment data were not available for the entire sample, study results were unchanged in analyses controlling for maternal education.”
Quote in the paperNot a substantial claim - Study design and conductnone given
The study's autism spectrum disorder exclusion criteria required both meeting the ADOS cut-off and a clinical diagnosis.
“An additional limitation of the study is the strictness of the ASD exclusion criteria, which required both meeting the ADOS cut-off and a clinical diagnosis.”
Quote in the paperSubstantial claim - Interpretationown data
The majority of high-risk siblings belonged to latent classes characterized by low levels of autism spectrum disorder severity and typical levels of developmental functioning.
“Although HR siblings were overrepresented in latent classes characterized by elevated ASD severity and/or lower levels of developmental functioning, the majority of HR siblings belonged to classes characterized by low levels of ASD severity and typical levels of developmental functioning.”
Quote in the paperSubstantial claim - Interpretationcitation
The composition of latent class 3, characterized by elevated autism spectrum disorder severity and high developmental quotient, was consistent with previous research indicating that a range of autism spectrum disorder-related behavioral features is present in low-risk as well as high-risk children.
“The composition of this class is consistent with previous research indicating that a range of ASD-related behavioral features is present in low-risk as well as high-risk children.20,43,44”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [20] Constantino, 2006, Autistic social impairment in the siblings of children with pervasive developmental disorders, Am J Psychiatry source
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- cites [43] Constantino, 2003, Autistic traits in the general population: a twin study, Arch Gen Psychiatry source
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- cites [44] Ben-Yizhak, 2011, Pragmatic language and school related linguistic abilities in siblings of children with autism, J Autism Dev Disord source
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- The quote only partly states this claim. 1
- May combine two claims. 11
- Classified as probably not a substantial claim. 7
The quote only partly states this claim.
Findingown dataMales were 2.8 times more likely than females to be classified in latent class 4, characterized by low ADOS severity and low developmental quotient.
“Males were almost three times more likely than females to belong both to class 4 and to class 5.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataADOS severity was negatively correlated with verbal and nonverbal developmental quotients, while verbal and nonverbal developmental quotients were positively correlated with each other.
“As shown in Table 2, ADOS severity was negatively correlated with verbal and nonverbal DQs (range, −0.22 to 0.08), whereas verbal and nonverbal DQs showed substantial positive correlations (0.54 to 0.67).32”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataWithin the high-risk group, siblings from multiplex families exhibited substantially lower verbal and nonverbal functioning than siblings from simplex families, an effect that did not differ by infant sex.
“Within the HR group, siblings from multiplex families exhibited substantially lower verbal and nonverbal functioning than siblings from simplex families, an effect that did not differ by infant sex.”
Quote in the paperSubstantial claimMay combine two claims.
Premisenone givenProspective studies indicate that high-risk siblings are at increased risk both for autism spectrum disorder outcomes and for subclinical manifestations of autism spectrum disorder-related behavioral characteristics.
“Prospective studies indicate that high-risk (HR) siblings—the younger brothers and sisters of a child diagnosed with an ASD—are at increased risk both for ASD outcomes and for subclinical manifestations of ASD-related behavioral characteristics.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA previous Baby Siblings Research Consortium report indicated that 18.7% of 3-year-old high-risk siblings will themselves develop an autism spectrum disorder.
“A recent report4 from the Baby Siblings Research Consortium (BSRC) indicated that 18.7% of 3-year-old HR siblings will themselves develop an ASD.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] Ozonoff, 2011, Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium study, Pediatrics source
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May combine two claims.
PremisecitationFamily multiplex status and male sex of the high-risk sibling are risk factors for autism spectrum disorder recurrence.
“Family multiplex status—more than one older sibling with an ASD—and male sex of the HR sibling are risk factors for ASD recurrence.18”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] Ozonoff, 2010, A prospective study of the emergence of early behavioral signs of autism, J Am Acad Child Adolesc Psychiatry
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Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenInstitutional review board approval was obtained to collect and analyze deidentified data from all sites.
“Institutional review board approval was obtained to collect and analyze deidentified data from all sites.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductcitationAll sites verified proband diagnoses in the high-risk group, typically using the Autism Diagnostic Observation Schedule and/or parent interviews such as the Autism Diagnostic Interview-Revised or the Social Communication Questionnaire.
“All sites verified proband diagnoses in the high-risk group, typically using the ADOS22 and/or parent interviews such as the Autism Diagnostic Interview–Revised23 or the Social Communication Questionnaire.24”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [22] Lord, 2000, The Autism Diagnostic Observation Schedule–Generic: a standard measure of social and communication deficits associated with the spectrum of autism, J Autism Dev Disord source
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- cites [23] Lord, 1994, Autism Diagnostic Interview–Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders, J Autism Dev Disord source
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- cites [24] Rutter, 2003
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May combine two claims.
PremisecitationApproximately 20% of high-risk siblings at 3 years both exhibit difficulties with language development on standardized assessment and satisfy clinical criteria of social or language delay.
“From a categorical perspective, approximately 20% of HR siblings at 3 years both exhibit difficulties with language development on standardized assessment11 and satisfy clinical criteria of social or language delay.13”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [11] Yirmiya, 2007, Cognitive and verbal abilities of 24- to 36-month-old siblings of children with autism, J Autism Dev Disord source
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- cites [13] Landa, 2012, Latent class analysis of early developmental trajectory in baby siblings of children with autism, J Child Psychol Psychiatry
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May combine two claims.
PremisecitationHigh-risk siblings exhibit lower levels of receptive language and other communication skills than comparison infants, but direct comparisons of intellectual functioning have not yielded consistent results.
“Likewise, HR siblings exhibit lower levels of receptive language and other communication skills than comparison infants,2,8,9,11 but direct comparisons of intellectual functioning have not yielded consistent results.8,9,11,12”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [2] Landa, 2007, Social and communication development in toddlers with early and later diagnosis of autism spectrum disorders, Arch Gen Psychiatry source
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- cites [8] Toth, 2007, Early social, imitation, play, and language abilities of young non-autistic siblings of children with autism, J Autism Dev Disord source
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- cites [9] Stone, 2007, Early social-communicative and cognitive development of younger siblings of children with autism spectrum disorders, Arch Pediatr Adolesc Med source
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- cites [11] Yirmiya, 2007, Cognitive and verbal abilities of 24- to 36-month-old siblings of children with autism, J Autism Dev Disord source
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- cites [12] Zwaigenbaum, 2012, Sex differences in children with autism spectrum disorder identified within a high-risk infant cohort, J Autism Dev Disord
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May combine two claims.
PremisecitationThrough 3 years of age, high-risk infants exhibit higher levels of autism spectrum disorder-related characteristics than controls on autism spectrum disorder screeners, but differences on examiner-administered assessments are less consistent.
“Through 3 years of age, HR infants exhibit higher levels of ASD-related characteristics than controls on ASD screeners, but differences based on examiner-administered assessments designed to quantify these characteristics are less consistent.2,8–10”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [2] Landa, 2007, Social and communication development in toddlers with early and later diagnosis of autism spectrum disorders, Arch Gen Psychiatry source
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- cites [8] Toth, 2007, Early social, imitation, play, and language abilities of young non-autistic siblings of children with autism, J Autism Dev Disord source
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- cites [9] Stone, 2007, Early social-communicative and cognitive development of younger siblings of children with autism spectrum disorders, Arch Pediatr Adolesc Med source
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- cites [10] Garon, 2009, Temperament and its relationship to autistic symptoms in a high-risk infant sib cohort, J Abnorm Child Psychol source
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Classified as probably not a substantial claim.
Study design and conductcitationMullen Scales of Early Learning developmental quotients were calculated by dividing the subscale age-equivalent score by chronological age and multiplying by 100 to avoid floor and ceiling effects.
“For the present analyses, developmental quotients (DQs) were calculated by dividing the subscale age-equivalent score by the child’s chronological age and multiplying by 100. This procedure avoided possible floor and ceiling effects while providing a familiar IQ metric, as recommended in the literature.27,28”
Quote in the paperSubstantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
Study design and conductnone givenOutcome was assessed relatively early, at 3 years of age.
“In addition, outcome was assessed relatively early, at 3 years of age.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationThe findings extend previous reports of risk group differences, suggesting that overall differences in social, communication, and behavioral characteristics between high-risk and low-risk children are relatively subtle.
“Findings of slightly elevated levels of ASD-related characteristics in HR siblings without ASD outcomes extends previous reports of risk group differences, suggesting that overall differences in social, communication, and behavioral characteristics between HR and LR children are relatively subtle.8,10,11,34”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [8] Toth, 2007, Early social, imitation, play, and language abilities of young non-autistic siblings of children with autism, J Autism Dev Disord source
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- cites [10] Garon, 2009, Temperament and its relationship to autistic symptoms in a high-risk infant sib cohort, J Abnorm Child Psychol source
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- cites [11] Yirmiya, 2007, Cognitive and verbal abilities of 24- to 36-month-old siblings of children with autism, J Autism Dev Disord source
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- cites [34] Chapman, 2009, In bad taste: evidence for the oral origins of moral disgust, Science source
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May combine two claims.
Study design and conductcitationAlthough the study relied on an observational measure of autism spectrum disorder severity, parent report measures of severity appear to yield congruent results.
“More generally, although the study relied on an observational measure of ASD severity, parent report measures of severity appear to yield congruent results.12”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Zwaigenbaum, 2012, Sex differences in children with autism spectrum disorder identified within a high-risk infant cohort, J Autism Dev Disord
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Classified as probably not a substantial claim.
Study design and conductcitationADOS total scores were converted to autism spectrum disorder-calibrated severity scores to statistically pool scores across modules.
“To statistically pool ADOS scores across modules, total scores were converted to ASD-calibrated severity scores,25 which range from 1 to 10 and reflect the overall severity of ASD-related behavioral characteristics across the social interaction, communication, and repetitive behavior domains.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] Gotham, 2009, Standardizing ADOS scores for a measure of severity in autism spectrum disorders, J Autism Dev Disord source
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May combine two claims.
Study design and conductcitationThe ADOS-based severity measure was originally designed to distinguish among children with autism spectrum disorder, but has subsequently been used to distinguish among high-risk siblings without autism spectrum disorder diagnoses.
“The study relied on an ADOS-based measure of ASD severity that was originally designed to distinguish among children with an ASD.22,25 However, the severity measure has subsequently been used to distinguish among HR siblings without ASD diagnoses.45”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [22] Lord, 2000, The Autism Diagnostic Observation Schedule–Generic: a standard measure of social and communication deficits associated with the spectrum of autism, J Autism Dev Disord source
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- cites [25] Gotham, 2009, Standardizing ADOS scores for a measure of severity in autism spectrum disorders, J Autism Dev Disord source
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- cites [45] Georgiades, 2012, A prospective study of autistic-like traits in unaffected siblings of probands with autism spectrum disorder, Arch Gen Psychiatry source
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataMaternal education was not included in final models because it was available for only 53% of the sample, but its inclusion did not alter study findings.
“As maternal education was available for only 53% of the sample (n = 445), it was not included in final models. Inclusion of maternal education in models did not alter study findings (see Table S1, available online).”
Quote in the paperNot a substantial claim
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The positive predictive value findings from this high risk study are probably conservative in nature due to the likelihood that the HR-ASD group is milder than those who are clinically-referred and diagnosed with ASD at 24 months of age, and that HR-Neg groups are known to be more heterogeneous with respect to later development of cognitive, behavioral, social-communication and motor deficits than
“The positive predictive value findings from this high risk study are probably conservative in nature due to the likelihood that our HR-ASD group is milder than those who are clinically-referred and diagnosed with ASD at 24 months of age, and that HR-Neg groups are known to be more heterogeneous with respect to later development of cognitive, behavioral, social-communication and motor deficits than”
From Early brain development in infants at high risk for autism spectrum disorder (2017) · cites this paper as [31]
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredNumerous studies have indicated that some, although not all, children who are later diagnosed as having ASD have delays in motor development, social responsiveness, or language development in the early part of the second year of life, if not before.
“First, numerous studies have indicated that some, although not all, children who are later diagnosed as having ASD have delays in motor development, social responsiveness, or language development in the early part of the second year of life, if not before (Landa & Garrett-Mayer 2006, Messinger et al. 2013, Mitchell et al. 2006, Zwaigenbaum et al. 2005).”
From Recent Advances in Autism Research as Reflected in DSM-5 Criteria for Autism Spectrum Disorder (2015) · cites this paper as Messinger et al. 2013
The Method passage says the study assessed outcomes at age 3 and excluded children with ASD from its analyses. The Conclusions discuss variation in when ASD characteristics emerge, but neither those passages nor the passages searched for early signs in children later diagnosed with ASD establish motor, social-responsiveness, or language delays in the early second year of life. (LLM, conf=0.72)
Experimental — accuracy not yet measuredInfants at familial risk for autism are also at increased risk for altered developmental functioning in non-autism-specific domains.
“and infants at familial risk for autism are also at increased risk for altered developmental functioning in non-autism-specific domains.”
From EEG power at 3 months in infants at high familial risk for autism (2017) · cites this paper as [4]
Among high-risk siblings who do not develop ASD, many demonstrate lower levels of verbal, nonverbal, and motor functioning than their low-risk counterparts.
“Among high-risk siblings who do not develop ASD, many demonstrate lower levels of verbal, nonverbal, and motor functioning than their low-risk counterparts [4–6].”
From EEG power at 3 months in infants at high familial risk for autism (2017) · cites this paper as [4]
Infants carrying a familial high-risk ASD endophenotype can present with altered development in multiple domains.
“This is consistent with studies suggesting that infants carrying a familial high-risk ASD endophenotype can present with altered development in multiple domains [4, 6].”
From EEG power at 3 months in infants at high familial risk for autism (2017) · cites this paper as [4]
Up to another 30% of younger siblings of children with autism spectrum disorder manifest elevated levels of autism symptoms.
“up to another 30% manifest elevated levels of autism symptoms [9]”
From Enhanced Visual Search in Infancy Predicts Emerging Autism Symptoms (2015) · cites this paper as [9]
About 10-20% of high-risk infants develop sub-clinical ASD symptoms or other developmental problems.
“with about 10–20% of high-risk infants developing sub-clinical ASD symptoms or other developmental problems (Messinger et al., 2013).”
From From early markers to neuro-developmental mechanisms of autism (2014) · cites this paper as Messinger et al., 2013
Prospective assessment of high-risk infants can characterize early development, prior to diagnosis, in children who will subsequently develop ASD.
“Prospective assessment of high-risk infants can characterize early development, prior to diagnosis, in children who will subsequently develop ASD.”
From Behavioral, cognitive, and adaptive development in infants with autism spectrum disorder in the first 2 years of life (2015) · cites this paper as [29]
Early atypical behaviours still discriminated between infants who went on to have ASD and those who did not, even when covarying for developmental differences.
“It is increasingly apparent, consistent with the phenotype of ASD, that both developmental and language delays are part of the BAP at a group level (Messinger et al., 2013; Ozonoff et al., 2014) and, whilst covarying for these differences one might be taking out some of the variance of interest, early atypical behaviours still discriminated between the infants who went on to have ASD and those who”
From Behavioural markers for autism in infancy: Scores on the Autism Observational Scale for Infants in a prospective study of at-risk siblings (2015) · cites this paper as Messinger et al., 2013
In a subsequent BSRC report on non-diagnosed high-risk siblings, males in both high-risk and low-risk groups exhibited higher ASD symptom severity scores and lower levels of verbal and nonverbal functioning than females.
“In a subsequent BSRC report on non-diagnosed high-risk siblings [26], males in both high-risk (n = 507) and low-risk groups (n = 324) exhibited higher ASD symptom severity scores—and lower levels of verbal and nonverbal functioning—than females.”
From Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study (2015) · cites this paper as [26]
Specification of this particular area of challenges for non-diagnosed high-risk siblings was not possible in reports of smaller subsets of this sample.
“Specification of this particular area of challenges for non-diagnosed high-risk siblings was not possible in reports of smaller subsets of this sample [26].”
From Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study (2015) · cites this paper as [26]
Statistics that don’t add up
Each reported p-value recomputed from its test statistic and degrees of freedom.
Inconsistent p-value: z = 2.79, p = .001
MinorThe paper reports p = .001 here; recomputing from the test statistic and its degrees of freedom gives p = .005 (two-tailed). The check cannot tell whether the statistic or the p-value is the misprint.
Reported p = .001 · recomputed p = .005
“z = 2.79, p = .001”
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- Doesn’t add upz = 2.79reported p = .001 · recomputed p = .005
“z = 2.79, p = .001”
- Consistentz = 4.02reported p < .001 · recomputed p < .001
“z = 4.02, p < .001”
- Consistentz = 4.82reported p < .001 · recomputed p < .001
“z = 4.82, p < .001”
- Consistentz = 1.29reported p = .2 · recomputed p = .197
“z = 1.29, p = .20”
- Consistentz = -1.67reported p = .1 · recomputed p = .095
“z = −1.67, p = .10”
- Consistentz = 1.92reported p = .05 · recomputed p = .055
“z = 1.92, p = .05”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Six-class comparison does not meet the stated evidence cutoff
MinorThe paper says it used a value above 10 to distinguish class solutions, but calls 5.79 very strong evidence for the five-class solution over the six-class solution. That comparison falls below its stated cutoff.
“Jeffreys’ Scale of Evidence provided very strong evidence supporting a five-class solution over a four-class solution (2*log[B] = 19.41) or a six-class solution (2*log[B] = 5.79)”
“When 2*log(B) > 10, there is very strong evidence for preferring the more complex model, and we used this cutoff to distinguish between solutions.”
Reported sex difference reverses direction
MinorThe results say that sex differences within the high-risk group favored males on both developmental quotients, whereas the discussion says males had lower verbal and nonverbal functioning than females.
“There were significant sex differences favoring males on both the verbal DQ (t = 5.16, p < .001) and nonverbal DQ (t = 5.72, p < .001).”
“Independent of risk group, male children exhibited lower levels of verbal and nonverbal functioning than female children.”
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Lai, M.-C., Lombardo, M. V., & Baron-Cohen, S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61539-1 · Cited by 2,371 · see citing works
Early brain development in infants at high risk for autism spectrum disorder
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Self-citationThe Broader Autism Phenotype in Infancy: When Does It Emerge?
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Self-citationEarly Screening of Autism Spectrum Disorder: Recommendations for Practice and Research
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Self-citationGreen, J., Charman, T., Pickles, A. R., Wan, M. W., Elsabbagh, M., Slonims, V., Taylor, C., McNally, J., Booth, R. D. L., Gliga, T., et al. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(14)00091-1 · Cited by 278 · see citing works
Self-citationThe Autism Diagnostic Observation Schedule, Toddler Module: Standardized Severity Scores
Esler, A., Bal, V. H., Guthrie, W., Wetherby, A. M., Weismer, S. E., & Lord, C. (2015) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-015-2432-7 · Cited by 269 · see citing works
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Self-citationEarly Identification and Interventions for Autism Spectrum Disorder: Executive Summary
Zwaigenbaum, L., Bauman, M. L., Choueiri, R., FEIN, D. A., Kasari, C. L., Pierce, K., Stone, W. L., Yirmiya, N., Estes, A. M., Hansen, R. L., et al. (2015) · PEDIATRICS · doi:10.1542/peds.2014-3667b · Cited by 175 · see citing works
Self-citationZwaigenbaum, L., Bryson, S. E., Brian, J., Smith, I. M., Roberts, W., Szatmari, P., Roncadin, C., Garon, N., & Vaillancourt, T. (2016) · Autism Research · doi:10.1002/aur.1585 · Cited by 165 · see citing works
Self-citationEnhanced Visual Search in Infancy Predicts Emerging Autism Symptoms
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Self-citationToward a conceptual framework for early brain and behavior development in autism
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Infant motor skill predicts later expressive language and autism spectrum disorder diagnosis
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Self-citationRisk Factors Associated With Language in Autism Spectrum Disorder: Clues to Underlying Mechanisms
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Self-citationThe female protective effect against autism spectrum disorder
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The female protective effect against autism spectrum disorder
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Self-citationScreening for Autism Spectrum Disorders in 12-Month-Old High-Risk Siblings by Parental Report
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Screen time in 36-month-olds at increased likelihood for ASD and ADHD
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Self-citationLook duration at the face as a developmental endophenotype: elucidating pathways to autism and ADHD
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Sex Differences in the Developmental Trajectories of Autism Spectrum Disorder
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Sex Differences in Social Attention in Infants at Risk for Autism
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Looking for “fNIRS Signature” in Autism Spectrum: A Systematic Review Starting From Preschoolers
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Intervention in the Context of Development: Pathways Toward New Treatments
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No Sex Differences in Cognitive Ability in Young Children with Autism Spectrum Disorder
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Positive emotional engagement and autism risk.
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Lateralization of ERPs to speech and handedness in the early development of Autism Spectrum Disorder
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- Authors
- Messinger, D., Young, G. S., Ozonoff, S., Dobkins, K., Carter, A., Zwaigenbaum, L., Landa, R. J., Charman, T., Stone, W. L., Constantino, J. N., Hutman, T., Carver, L. J., Bryson, S., Iverson, J. M., Strauss, M. S., Rogers, S. J., & Sigman, M.
- Affiliations
- University of Miami (US)
- University of Massachusetts Boston (US)
- University of Alberta (CA)
- Kennedy Krieger Institute (US)
- University of Washington (US)
- Washington University in St. Louis (US)
- University of California, Los Angeles (US)
- Dalhousie University (CA)
- University of Pittsburgh (US)
- ORCID
- Venue
- Journal of the American Academy of Child & Adolescent Psychiatry
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 52
- Issue
- 3
- Pages
- 300-308.e1
- ISSN
- 0890-8567 (ISSN-L)
- PMC
- PMC3625370
- OpenAlex
- W2101103407
- Cited by
- 290
- References
- 48
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 14 · 2023: 15 · 2022: 26 · 2021: 13 · 2020: 22 · 2019: 31 · 2018: 32 · 2017: 29 · 2016: 24 · 2015: 33 · 2014: 16 · 2013: 6
- FWCI
- 14.39
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute of Mental Health (U54MH066417, R01MH068398, MH059630, MH068398, R01MH059630, U54MH068172)
- National Institute on Deafness and Other Communication Disorders (DC10290, R01DC010290)
- National Institute of General Medical Sciences (R01GM105004)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD047417, R01HD057284, HD 042541, R01HD047417, HD057284, R01HD042541, HD54979, R01HD043292, P50HD055784, R01HD052804, R01HD054979, HD043292, HD052804)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- autism spectrum disorder, high-risk siblings, first-degree relatives, ASD severity, developmental functioning, latent classes, child development monitoring, early intervention, toddlers
- MeSH terms
- Child Development Disorders, Pervasive, Child, Preschool, Female, Humans, Infant, Intelligence Tests, Male, Phenotype, Psychiatric Status Rating Scales, Risk, Severity of Illness Index, Siblings
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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