Kari Kveim Lie

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.

Association of cerebral palsy with Apgar score in low and normal birthweight infants: population based cohort study

Objectives To assess the association of Apgar score 5 minutes after birth with cerebral palsy in both normal weight and low birthweight children, and also the association with the cerebral palsy subdiagnoses of quadriplegia, diplegia, and hemiplegia. Design Population based cohort study. Setting The Medical Birth Registry of Norway was used to identify all babies born between 1986 and 1995. These data were linked to the Norwegian Registry of Cerebral Palsy in Children born 1986-95, which was established on the basis of discharge diagnoses at all paediatric departments in Norway. Population All singletons without malformations born in Norway during 1986-95 and who survived the first year of life (n=543 064). Main outcome measure Cerebral palsy diagnosed before the age of 5 years. Results 988 children (1.8 in 1000) were diagnosed with cerebral palsy before the age of 5 years. In total, 11% (39/369) of the children with Apgar score of less than 3 at birth were diagnosed with cerebral palsy, compared with only 0.1% (162/179 515) of the children with Apgar score of 10 (odds ratio (OR) 53, 95% CI 35 to 80 after adjustment for birth weight). In children with a birth weight of 2500 g or more, those with an Apgar score of less than 4 were much more likely to have cerebral palsy than those who had an Apgar score of more than 8 (OR 125, 95% confidence interval 91 to 170). The corresponding OR in children weighing less than 1500 g was 5 (95% CI 2 to 9). Among children with Apgar score of less than 4, 10-17% in all birthweight groups developed cerebral palsy. Low Apgar score was strongly associated with each of the three subgroups of spastic cerebral palsy, although the association was strongest for quadriplegia (adjusted OR 137 for Apgar score <4 v Apgar score >8, 95% CI 77 to 244). Conclusions Low Apgar score was strongly associated with cerebral palsy. This association was high in children with normal birth weight and modest in children with low birth weight. The strength of the association differed between subgroups of spastic cerebral palsy. Given that Apgar score is a measure of vitality shortly after birth, our findings suggest that the causes of cerebral palsy are closely linked to factors that reduce infant vitality.

Birth outcomes in women with eating disorders in the Norwegian Mother and Child cohort study (MoBa).

OBJECTIVE We explored the impact of eating disorders on birth outcomes in the Norwegian Mother and Child Cohort Study. METHOD Of 35,929 pregnant women, 35 reported broad anorexia nervosa (AN), 304 bulimia nervosa (BN), 1,812 binge eating disorder (BED), and 36 EDNOS-purging type (EDNOS-P) in the six months before or during pregnancy. The referent comprised 33,742 women with no eating disorder. RESULTS Pre-pregnancy body mass index (BMI) was lower in AN and higher in BED than the referent. AN, BN, and BED mothers reported greater gestational weight gain, and smoking was elevated in all eating disorder groups. BED mothers had higher birth weight babies, lower risk of small for gestational age, and higher risk of large for gestational age and cesarean section than the referent. Pre-pregnancy BMI and gestational weight gain attenuated the effects. CONCLUSION BED influences birth outcomes either directly or via higher maternal weight and gestational weight gain. The absence of differences in AN and EDNOS-P may reflect small numbers and lesser severity in population samples. Adequate gestational weight gain in AN may mitigate against adverse birth outcomes. Detecting eating disorders in pregnancy could identify modifiable factors (e.g., high gestational weight gain, binge eating, and smoking) that influence birth outcomes.

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.

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.

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.

Children in the environment: Forest day-care centers: Modern day care with historical antecedents

Some features of early child care are more prominent in Norway than in other countries, such as emphasis on the outdoor environment. Of general relevance and interest is the form of day care provided by forest day-care centers. Three ideas form the development of these centers placed in wild areas. First, throughout history, Norwegians have had a close attachment to nature and some parents want to provide their children with outdoor experiences at an early age. Second, urging children to play outdoors characterizes the image many parents have of a happy, healthy childhood. Third, provision of day care for children has always been restricted in western countries, forcing parents to invent types of service that can become part of an ecological system that promotes healthy development. The forest day-care centers developed recently represent a supplement to the wide typology of child care in the 21st century. The article outlines the connections between these ideas in general European and western history and Norwegian history and presents debate and decisions about a question dating from the last half of the 1980s. It concludes that the forest day-care centers are perhaps only a modern form of the original kindergarten concept, which started in Europe and America as gardens for children not gardens of children.

Important periods of weight development in childhood: a population-based longitudinal study

BackgroundIdentifying important ages for the development of overweight is essential for optimizing preventive efforts. The purpose of the study was to explore early growth characteristics in children who become overweight or obese at the age of 8 years to identify important ages for the onset of overweight and obesity.MethodsData from the Norwegian Child Growth Study in 2010 (N = 3172) were linked with repeated measurements from health records beginning at birth. Weight and height were used to derive the body mass index (BMI) in kg/m2. The BMI standard deviation score (SDS) for each participant was estimated at specific target ages, using a piecewise linear mixed effect model.ResultsAt 8 years of age, 20.4% of the children were overweight or obese. Already at birth, overweight children had a significantly higher mean BMI SDS than normal weight 8-year-olds (p < .001) and this difference increased in consecutive age groups in infancy and childhood. A relatively large increase in BMI during the first 9 months was identified as important for being overweight at 8 years. BMI SDS at birth was associated with overweight at 8 years of age (OR, 1.8; 1.6–2.0), and with obesity (OR, 1.8; 1.4–2.3). The Odds Ratios for the BMI SDS and change in BMI SDS further increased up to 1 year of age became very high from 2 years of age onwards.ConclusionsA high birth weight and an increasing BMI SDS during the first 9 months and high BMI from 2 years of age proved important landmarks for the onset of being overweight at 8 years of age. The risks of being overweight at 8 years appear to start very early. Interventions to prevent children becoming overweight should not only start at a very early age but also include the prenatal stage.

Differences across counties in the registered prevalence of autism, ADHD, epilepsy and cerebral palsy in Norway.

BACKGROUND In 2012, we published an overview of the prevalence of developmental disorders and neurological diseases in children in Norway, which was unknown at the time. In this article we will compare diagnostics and treatment across counties and institutions. MATERIAL AND METHOD The prevalence across counties of autism spectrum disorders, ADHD, epilepsy and cerebral palsy in children aged 0-12 was estimated with the aid of data from the Norwegian Patient Register for the years 2008-11. RESULTS In the age group 6-12 years, nationwide prevalence amounted to 0.6% for autism spectrum disorders, 2.0% for ADHD, 0.9% for epilepsy and 0.3% for cerebral palsy. In total, 5.0% of all twelve-year-olds were registered with one or more of these diagnoses. The prevalence of autism spectrum disorders and ADHD varied between the counties, from 0.3% to 1.5% for autism spectrum disorders and from 1.1% to 3.5% for ADHD. For epilepsy and cerebral palsy there was little variation between the counties. Diagnostics and treatment of these four conditions are spread over 29 somatic hospitals and 102 units for child and youth psychiatry. INTERPRETATION The variations across counties in the prevalence of autism spectrum disorders and ADHD are most likely due to variations in diagnostic practices. We ask whether it is appropriate to spread the provision of treatment across such a high number of institutions.