Growing awareness that symptoms of autism spectrum disorder (ASD) transcend multiple diagnostic categories, and major advances in the identification of genetic syndromes associated with ASD, have led ...to widespread use of ASD symptom measures in etiologic studies of neurodevelopmental disorders. Insufficient consideration of potentially confounding factors such as cognitive ability or behavior problems can have important negative consequences in interpretation of findings, including erroneous estimation of associations between ASD and etiologic factors.
Participants were 388 children 2 to 13 years old with diagnoses of ASD or another neurodevelopmental disorder without ASD. Receiver operating characteristics methods were used to assess the influence of IQ and emotional and behavioral problems on the discriminative ability of 3 widely used ASD symptom measures: the Social Responsiveness Scale (SRS), the Autism Diagnostic Interview-Revised (ADI-R), and the Autism Diagnostic Observation Schedule (ADOS).
IQ influenced the discriminative thresholds of the SRS and ADI-R, and emotional and behavioral problems affected the discriminative thresholds of the SRS, ADI-R, and ADOS. This resulted in low specificity of ASD cutoffs on the SRS and ADI-R for children with intellectual disability without ASD (27-42%) and low specificity across all 3 instruments for children without ASD with increased emotional and behavioral problems (36-59%). Adjustment for these characteristics resulted in improved discriminative ability for all of the ASD measures.
The findings indicate that scores on ASD symptom measures reflect far more than ASD symptoms. Valid interpretation of scores on these measures requires steps to account for the influences of IQ and emotional and behavioral problems.
Summary
Purpose
Antiepileptic drugs may cause congenital malformations. Less is known about the effect on development in infancy and childhood. The aim of this study was to examine whether exposure ...to antiepileptic drugs during pregnancy has an effect on early child development.
Methods
From mid‐1999 through December 2008, children of mothers recruited at 13–17 weeks of pregnancy were studied in the ongoing prospective Norwegian Mother and Child Cohort Study. Information on birth outcomes were obtained from the Medical Birth Registry (108,264 children), and mothers reported on their child's motor development, language, social skills, and autistic traits using items from standardized screening tools at 18 months (61,351 children) and 36 months (44,147 children) of age. The relative risk of adverse outcomes in children according to maternal or paternal epilepsy with and without prenatal exposure to antiepileptic drugs was estimated as odds ratios (ORs), using logistic regression with adjustment for maternal age, parity, education, smoking, depression/anxiety, folate supplementation, and child congenital malformation or low birth weight.
Key Findings
A total of 333 children were exposed to antiepileptic drugs in utero. At 18 months, the exposed children had increased risk of abnormal scores for gross motor skills (7.1% vs. 2.9%; OR 2.0, 95% confidence interval CI 1.1–3.7) and autistic traits (3.5% vs. 0.9%; OR 2.7, CI 1.1–6.7) compared to children of parents without epilepsy. At 36 months, the exposed children had increased risk of abnormal score for gross motor skills (7.5% vs. 3.3%; OR 2.2, CI 1.1–4.2), sentence skills (11.2% vs. 4.8%; OR 2.1, CI 1.2–3.6), and autistic traits (6.0% vs. 1.5%; OR 3.4, CI 1.6–7.0). The drug‐exposed children also had increased risk of congenital malformations (6.1% vs. 2.9%; OR 2.1, CI 1.4–3.4), but exclusion of congenital malformations did not affect the risk of adverse development. Children born to women with epilepsy who did not use antiepileptic drugs had no increased risks. Children of fathers with epilepsy generally scored within the normal range.
Significance
Exposure to antiepileptic drugs during pregnancy is associated with adverse development at 18 and 36 months of age, measured as low scores within key developmental domains rated by mothers. Exposures to valproate, lamotrigine, carbamazepine, or multiple antiepileptic drugs were associated with adverse outcome within different developmental domains.
Background
Delays and loss of early‐emerging social‐communication skills are often discussed as unique to autism. However, most studies of regression have relied on retrospective recall and clinical ...samples. Here, we examine attainment and loss of social‐communication skills in the population‐based Norwegian Mother, Father and Child Cohort Study (MoBa).
Methods
Mothers rated their child's attainment of 10 early‐emerging social‐communication skills at ages 18 and 36 months (N = 40,613, 50.9% male). Prospectively reported loss was defined as skill presence at 18 months but absence at 36 months. At 36 months, mothers also recalled whether the child had lost social‐communication skills. The Norwegian Patient Registry was used to capture diagnoses of Autism Spectrum Disorder (autism) and other neurodevelopmental disabilities (NDDs).
Results
Delay in at least one skill was observed in 14% of the sample and loss in 5.4%. Recalled loss of social‐communication skills was rare (0.86%) and showed low convergence with prospectively reported loss. Delay and especially loss were associated with elevated odds of an autism diagnosis (n = 383) versus no autism diagnosis (n = 40,230; ≥3 skills delayed: OR = 7.094.15,12.11; ≥3 skills lost: OR = 30.6617.30,54.33). They were also associated with an increased likelihood of autism compared to some other NDDs. Delay (relative risk RR = 4.162.08, 8.33) and loss (RR = 10.003.70, 25.00) associated with increased likelihood of autism versus ADHD, and loss (RR = 4.351.28,14.29), but not delay (RR = 2.000.78,5.26), associated with increased likelihood of autism compared to language disability. Conversely, delay conferred decreased likelihood of autism versus intellectual disability (RR = 0.110.06,0.21), and loss was not reliably associated with likelihood of autism versus intellectual disability (RR = 1.890.44,8.33).
Conclusions
This population‐based study suggests that loss of early social communication skills is more common than studies using retrospective reports have indicated and is observed across several NDD diagnoses (not just autism). Nevertheless, most children with NDD diagnoses showed no reported delay or loss in these prospectively measured skills.
IMPORTANCE Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders. ...OBJECTIVE To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder–not otherwise specified PDD-NOS) in children. DESIGN, SETTING, AND PATIENTS The study sample of 85 176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity. MAIN OUTCOME MEASURE Specialist-confirmed diagnosis of ASDs. RESULTS At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61 042) had autistic disorder, compared with 0.21% (50/24 134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use. CONCLUSIONS AND RELEVANCE Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.
Background
Delayed walking is common in intellectual disability (ID) but may be less common when ID occurs with autism spectrum disorder (ASD). Previous studies examining this were limited by ...reliance on clinical samples and exclusion of children with severe motor deficits.
Objective
To examine in a population‐based sample if age of walking is differentially related to intellectual ability in children with ASD versus other neurodevelopmental disorders (NDD).
Methods
Participants were from the nested Autism Birth Cohort Study of the Norwegian Mother, Father and Child Cohort Study (MoBa). Cox proportional hazards regression assessed if diagnosis (ASD n = 212 vs. NDD n = 354), continuous nonverbal IQ, and their interaction, were associated with continuous age of walking.
Results
The relationship between nonverbal IQ and age of walking was stronger for NDD than for ASD (Group × nonverbal IQ interaction, χ2 = 13.93, p = .0002). This interaction was characterized by a 21% decrease in the likelihood of walking onset at any given time during the observation period per 10‐point decrease in nonverbal IQ (hazard ratio = 0.79, 95% CI: 0.78–0.85) in the NDD group compared to 8% (hazard ratio = 0.92, 95% CI: 0.86–0.98) in the ASD group.
Conclusions
The finding that age of walking is less strongly related to low intellectual ability in children with ASD than in children without other NDDs supports the hypothesis that ID in ASD may result from heterogeneous developmental pathways. Late walking may be a useful stratification variable in etiological research focused on ASD and other NDDs.
Background
Previous research on clinical and high‐risk samples suggests that signs of autism spectrum disorder (ASD) can be detected between 1 and 2 years of age. We investigated signs of ASD at 18 ...months in a population‐based sample and the association with later ASD diagnosis.
Methods
The study sample includes 52 026 children born 2003 through 2008 and is a subset of children that participated in the Norwegian Mother and Child Cohort (MoBa), a population‐based longitudinal study, and the Autism Birth Cohort (ABC), a sub‐study on ASD. Parents completed all 23 items from the Modified Checklist for Autism in Toddlers (M‐CHAT) at 18 months.
Results
The M‐CHAT 6‐critical‐item criterion and the 23‐item criterion had a specificity of 97.9% and 92.7% and a sensitivity of 20.8% and 34.1%, respectively. In the 173 children diagnosed with ASD to date, 60 children (34.7%) scored above the cut‐off on either of the screening criteria. The items with the highest likelihood ratios were ‘interest in other children’, ‘show objects to others’ and ‘response to name’.
Conclusion
Even though one‐third of the children who later received an ASD diagnosis were identified through M‐CHAT items, the majority scored below cut‐off on the screening criteria at 18 months. The results imply that it might not be possible to detect all children with ASD at this age.
Background
Disruptive Mood Dysregulation Disorder was included in DSM-5 to accommodate new research addressing aspects of emotional dysregulation in children suffering from disruptive behavior ...problems. Despite growing interest in Disruptive Mood Dysregulation Disorder, few studies have looked at prevalence rates in European clinical populations. The primary objective of this study was to examine the prevalence and characteristics associated with Disruptive Mood Dysregulation Disorder in a Norwegian clinical sample.
Methods
The present study assessed children 6–12 years of age referred to a mental health clinic for evaluation and treatment (N = 218, M
age
= 9.6, 60.4% boys) and compared those who did and did not meet Disruptive Mood Dysregulation Disorder diagnostic criteria. Diagnoses were determined using K-SADS-PL 2013. Associated difficulties at home and in school were measured by Achenbach Systems of Empirically Based Assessment battery.
Results
In this clinical sample, 24% met the diagnostic criteria for Disruptive Mood Dysregulation Disorder. Children with Disruptive Mood Dysregulation Disorder were more likely than those without Disruptive Mood Dysregulation Disorder to be male (77% vs. 55%, p = .008), be living in poverty, have multiple mental health diagnoses (79% vs. 53%, p = .001), and have lower global functioning levels as measured by Children’s Global Assessment Scale (range 0–100, M = 47, SD = 8.5 vs. M = 57, SD = 11.4, p=<.001). Finally, parents and teachers of children with Disruptive Mood Dysregulation Disorder reported lower overall competence and adaptive functioning, and higher total symptom load than children with other diagnoses.
Conclusion
Disruptive Mood Dysregulation Disorder is highly prevalent in a Norwegian clinical sample and displays a high symptom load. Our results are in accordance with similar studies. Consistent findings across the world may support Disruptive Mood Dysregulation Disorder as a valid diagnostic category.
Timing of developmental milestones, such as age at first walking, is associated with later diagnoses of neurodevelopmental disorders. However, its relationship to
for neurodevelopmental disorders in ...the general population is unknown. Here, we investigate associations between attainment of early-life language and motor development milestones and genetic liability to autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia.
We use data from a genotyped sub-set (
= 25699) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). We calculate polygenic scores (PGS) for autism, ADHD, and schizophrenia and predict maternal reports of children's age at first walking, first words, and first sentences, motor delays (18 months), and language delays and a generalised measure of concerns about development (3 years). We use linear and probit regression models in a multi-group framework to test for sex differences.
We found that ADHD PGS were associated with earlier walking age (
= -0.033,
< 0.001) in both males and females. Additionally, autism PGS were associated with later walking (
= 0.039,
= 0.006) in females only. No robust associations were observed for schizophrenia PGS or between any neurodevelopmental PGS and measures of language developmental milestone attainment.
Genetic liabilities for neurodevelopmental disorders show some specific associations with the age at which children first walk unsupported. Associations are small but robust and, in the case of autism PGS, differentiated by sex. These findings suggest that early-life motor developmental milestone attainment is associated with genetic liability to ADHD and autism in the general population.
Numerous studies have investigated the prevalence of neurologic and neurodevelopmental disorders individually, but few have examined them collectively, and there is uncertainty as to what extent they ...overlap.
The study has determined the proportions of children aged 0 to 11 years with diagnoses of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), epilepsy, and cerebral palsy (CP) in Norway. The data were obtained from the Norwegian Patient Register, which is nationwide and contains diagnoses assigned by Norwegian specialist health services (hospitals and outpatient clinics). The Norwegian Patient Register started collecting individual-level data in 2008, and the follow-up period for the study is years 2008 through 2010.
For ASD, ADHD, and epilepsy, the proportions were highest in the oldest children. At age 11 years, the incidence was 0.7% for ASD, 2.9% for ADHD, and 0.9% for epilepsy. The cumulative incidence is likely to be higher because some cases diagnosed before 2008 were probably missed. For CP, the proportions were ~0.3% for age ≥ 5 years. There was considerable overlap between diagnoses. For all disorders, boys had a significantly increased risk. In school-age children (aged 6-11 years) the male/female ratio was 4.3 for ASD, 2.9 for ADHD, 1.2 for epilepsy, and 1.3 for CP.
The findings demonstrate the significant burden of disease associated with neurologic and neurodevelopmental disorders in children and that this burden is disproportionately skewed toward boys.
Early identification of autism spectrum disorder (ASD) is regarded as crucial for swift access to early intervention and, subsequently, better outcomes later in life. However, current instruments ...miss large proportions of children who later go on to be diagnosed with ASD, raising a question of what these instruments measure. The present study utilized data from the Norwegian Mother, Father, and Child Cohort Study and the Autism Birth Cohort study to explore the subsequent developmental and diagnostic characteristics of children raising developmental concern on the six-critical discriminative item criterion of the M-CHAT (DFA6) at 18 months of age (N = 834). The DFA6 identified 28.8% of children diagnosed with ASD (N = 163), but 4.4% with language disorder (N = 188) and 81.3% with intellectual disability (N = 32) without ASD. Scoring in the «at-risk» range was associated with lower IQ, impaired functional language, and greater severity of autism symptoms whether children had ASD or not.
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