Synnve Schjølberg

Autism Spectrum Disorder, ADHD, Epilepsy, and Cerebral Palsy in Norwegian Children

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Autism Birth Cohort: a paradigm for gene–environment–timing research

The reported prevalence of autism spectrum disorders (ASDs) has increased by 5- to 10-fold over the past 20 years. Whether ASDs are truly more frequent is controversial; nonetheless, the burden is profound in human and economic terms. Although autism is among the most heritable of mental disorders, its pathogenesis remains obscure. Environmental factors are proposed; however, none is implicated. Furthermore, there are no biomarkers to screen for ASD or risk of ASD. The Autism Birth Cohort (ABC) was initiated to analyze gene × environment × timing interactions and enable early diagnosis. It uses a large, unselected birth cohort in which cases are prospectively ascertained through population screening. Samples collected serially through pregnancy and childhood include parental blood, maternal urine, cord blood, milk teeth and rectal swabs. More than 107 000 children are continuously screened through questionnaires, referral, and a national registry. Cases are compared with a control group from the same cohort in a ‘nested case–control’ design. Early screening and diagnostic assessments and re-assessments are designed to provide a rich view of longitudinal trajectory. Genetic, proteomic, immunologic, metagenomic and microbiological tools will be used to exploit unique biological samples. The ABC is a paradigm for analyzing the role of genetic and environmental factors in complex disorders.

Parental Obesity and Risk of Autism Spectrum Disorder

OBJECTIVES: The objective of the study was to investigate the associations among maternal prepregnancy BMI, paternal BMI, and the risk of autism spectrum disorders (ASDs) in children. METHODS: The study sample of 92 909 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study. The age range was 4.0 through 13.1 (mean 7.4) years. Relative risks of ASDs were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models. RESULTS: At the end of follow-up on December 31, 2012, 419 children in the study sample had been diagnosed with ASDs: 162 with autistic disorder, 103 with Asperger disorder, and 154 with pervasive developmental disorder not otherwise specified. Maternal obesity (BMI ≥30) was only weakly associated with ASD risk, whereas paternal obesity was associated with an increased risk of autistic disorder and Asperger disorder. The risk of autistic disorder was 0.27% (25 of 9267) in children of obese fathers and 0.14% (59 of 41 603) in children of fathers with normal weight (BMI <25), generating an adjusted OR of 1.73 (95% CI: 1.07–2.82). For Asperger disorder, analyses were limited to children aged ≥7 years (n = 50 116). The risk was 0.38% (18 of 4761) in children of obese fathers and 0.18% (42 of 22 736) in children of normal-weight fathers, and the adjusted OR was 2.01 (95% CI: 1.13–3.57). No associations were found for pervasive developmental disorder not otherwise specified. CONCLUSIONS: Paternal obesity is an independent risk factor for ASDs in children. The associations should be investigated further in genetic and epigenetic studies.

Exposure to antiepileptic drugs in utero and child development: A prospective population‐based study

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.

Co-occurring development of early childhood communication and motor skills: results from a population-based longitudinal study.

BACKGROUND Communicative and motor development is frequently found to be associated. In the current study we investigate to what extent communication and motor skills at 1½ years predict skills in the same domains at 3 years of age. METHODS This study is based on the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Heath. Data stem from 62,944 children and their mothers. Mothers completed questionnaires on their childs communication and motor skills at ages 1½ and 3. Associations between communication and motor skills were estimated in a cross-lagged model with latent variables. RESULTS Early communication skills were correlated with early motor skills (0.72). Stability was high (0.81) across time points for motor skills and somewhat lower (0.40) for communication skills. Early motor skills predicted later communication skills (0.38) whereas early communication skills negatively predicted later motor skills (-0.14). CONCLUSION Our findings provide support for the hypothesis that these two difficulties are not symptoms of separate disorders, but might rather be different manifestations of a common underlying neurodevelopmental weakness. However, there also seem to be specific developmental pathways for each domain. Besides theoretical interest, more knowledge about the relationship between these early skills might shed light upon early intervention strategies and preventive efforts commonly used with children with problems in these areas. Our findings suggest that the relationship between language and motor skills is not likely to be simple and directional but rather to be complex and multifaceted.

Predicting Language Development at Age 18 Months: Data from the Norwegian Mother and Child Cohort Study

Objectives: This study investigated predictors of delayed language development at 18 months of age in a large population cohort of Norwegian toddlers. Methods: Data were analyzed on 42,107 toddlers. Language outcome at age 18 months was measured using a standard parent report instrument, the Ages and Stages Questionnaire, communication scale. Confirmatory factor analysis was conducted on the Ages and Stages Questionnaire items. A theoretically derived set of child, family, and environmental risk factors were used to predict delayed language development at age 18 months using Generalized Estimating Equation. Results: A number of child factors, including being a boy, low birth weight or gestational age, or a multiple birth child were all significantly associated with low scores on the language outcome at age 18 months. Maternal distress/depression and low maternal education, having older siblings, or a non-Norwegian language background also predicted low scores on the language outcome at age 18 months. Overall, estimated variance in language outcome explained by the model was 4% to 7%. Conclusions: A combination of early neurobiological and genetic factors (e.g., male gender, birth weight, and prematurity) and concurrent family variables (e.g., maternal distress/depression) were associated with slower language development at age 18 months. This finding replicated previous research conducted on slightly older language-delayed 2 year olds but also detected the importance of factors related to family resources for the first time in this younger age group. Despite this finding, most of the variability in language performance in this cohort of 18 month olds remained unexplained by the comprehensive set of purported risk factors.

Interpregnancy interval and risk of autistic disorder

Background: A recent California study reported increased risk of autistic disorder in children conceived within a year after the birth of a sibling. Methods: We assessed the association between interpregnancy interval and risk of autistic disorder using nationwide registry data on pairs of singleton full siblings born in Norway. We defined interpregnancy interval as the time from birth of the first-born child to conception of the second-born child in a sibship. The outcome of interest was autistic disorder in the second-born child. Analyses were restricted to sibships in which the second-born child was born in 1990–2004. Odds ratios (ORs) were estimated by fitting ordinary logistic models and logistic generalized additive models. Results: The study sample included 223,476 singleton full-sibling pairs. In sibships with interpregnancy intervals <9 months, 0.25% of the second-born children had autistic disorder, compared with 0.13% in the reference category (≥36 months). For interpregnancy intervals shorter than 9 months, the adjusted OR of autistic disorder in the second-born child was 2.18 (95% confidence interval 1.42–3.26). The risk of autistic disorder in the second-born child was also increased for interpregnancy intervals of 9–11 months in the adjusted analysis (OR = 1.71 [95% CI = 1.07–2.64]). Conclusions: Consistent with a previous report from California, interpregnancy intervals shorter than 1 year were associated with increased risk of autistic disorder in the second-born child. A possible explanation is depletion of micronutrients in mothers with closely spaced pregnancies.

Attention problems and language development in preterm low-birth-weight children: Cross-lagged relations from 18 to 36 months

BackgroundResearch has highlighted a series of persistent deficits in cognitive ability in preterm low-birth-weight children. Language and attention problems are among these deficits, although the nature of the relation between attention and language in early development is not well known. This study represents a preliminary attempt to shed light on the relations between attention problems and language development in preterm low-birth-weight children.MethodsThe aim of this study was to analyse reciprocal influences between language and attention problems from 18 to 36 months. We used maternal reports on attention problems and language ability referring to a sample of 1288 premature low-birth-weight infants, collected as part of the Norwegian Mother and Child Cohort Study (MoBa). A sample of children born full-term was used as the control group (N = 37010). Cross-lagged panel analyses were carried out to study reciprocal influences between attention problems and language.ResultsLanguage ability at 18 months did not significantly predict attention problems at 36 months, adjusting for attention problems at 18 months. Attention problems at 18 months significantly predicted changes in language ability from 18 to 36 months, pointing to a precursor role of attention in relation to language in children born preterm. Gender, age corrected for prematurity, and mothers education emerged as important covariates.ConclusionsPreliminary evidence was found for a precursor role of early attention problems in relation to language in prematurity. This finding can contribute to a better understanding of the developmental pathways of attention and language and lead to better management of unfavourable outcomes associated with co-morbid attention and language difficulties.

EARLY GROWTH PATTERNS IN CHILDREN WITH AUTISM

Background: Case-control studies have found increased head growth during the first year of life in children with autism spectrum disorder. Length and weight have not been as extensively studied, and there are few studies of population-based samples. Methods: The study was conducted in a sample of 106,082 children from the population-based Norwegian Mother and Child Cohort. The children were born in 1999–2009; by the end of follow-up on 31 December 2012, the age range was 3.6 through 13.1 years (mean 7.4 years). Measures were obtained prospectively until age 12 months for head circumference and 36 months for length and weight. We compared growth trajectories in autism spectrum disorder cases and noncases using Reed first-order models. Results: Subjects included 376 children (310 boys and 66 girls) with specialist-confirmed autism spectrum disorder. In boys with autism spectrum disorder, mean head growth was similar to that of other boys, but variability was greater, and 8.7% had macrocephaly (head circumference >97th cohort percentile) by 12 months of age. Autism spectrum disorder boys also had slightly increased body growth, with mean length 1.1 cm above and mean weight 300 g above the cohort mean for boys at age 12 months. Throughout the first year, the head circumference of girls with autism spectrum disorder was reduced—by 0.3 cm at birth and 0.5 cm at 12 months. Their mean length was similar to that of other girls, but their mean weight was 150–350 g below at all ages from birth to 3 years. The reductions in mean head circumference and weight in girls with autism spectrum disorder appear to be driven by those with intellectual disability, genetic disorders, and epilepsy. Discussion: Growth trajectories in children with autism spectrum disorder diverge from those of other children and the differences are sex specific. Previous findings of increased mean head growth were not replicated.

Observed prevalence of autism spectrum disorders in two Norwegian counties

BACKGROUND The prevalence of autism spectrum disorders (ASD) has previously been reported to be increasing dramatically in European and non-European countries. No similar increase in prevalence rates has been documented in Norway to date. The current study reports on ASD prevalence rates in two Norwegian counties. METHODS The population comprised 31,015 children, ages six to 12. Information about special needs services was provided by the school authorities and the public health service. Multiple search strategies were applied to identify children at risk of ASD or diagnosed with ASD. Hospital registers were searched and a mapping tool was used in all local schools. RESULTS The total number of patients with ASD found in the population was 158. This gives a prevalence of 51 per 10,000 (95% CI, 0.43-0.59). CONCLUSION Compared with the previously reported prevalence of ASD in Norway, there has been almost a fourfold increase in the occurrence of childhood autism and a tenfold increase in the occurrence of all ASD groups. These findings have significant implications for designing and dimensioning appropriate intervention programmes for children with ASD and their families.