Attainment and loss of early social-communication skills across neurodevelopmental conditions in the Norwegian Mother, Father and Child Cohort Study.

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 = 7.09[4.15,12.11]; ≥3 skills lost: OR = 30.66[17.30,54.33]). They were also associated with an increased likelihood of autism compared to some other NDDs. Delay (relative risk [RR] = 4.16[2.08, 8.33]) and loss (RR = 10.00[3.70, 25.00]) associated with increased likelihood of autism versus ADHD, and loss (RR = 4.35[1.28,14.29]), but not delay (RR = 2.00[0.78,5.26]), associated with increased likelihood of autism compared to language disability. Conversely, delay conferred decreased likelihood of autism versus intellectual disability (RR = 0.11[0.06,0.21]), and loss was not reliably associated with likelihood of autism versus intellectual disability (RR = 1.89[0.44,8.33]). 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.

Maternal mid-gestational and child cord blood immune signatures are strongly associated with offspring risk of ASD.

Epidemiological studies and work in animal models indicate that immune activation may be a risk factor for autism spectrum disorders (ASDs). We measured levels of 60 cytokines and growth factors in 869 maternal mid-gestational (MMG) and 807 child cord blood (CB) plasma samples from 457 ASD (385 boys, 72 girls) and 497 control children (418 boys, 79 girls) from the Norwegian Autism Birth Cohort. We analyzed associations first using sex-stratified unadjusted and adjusted logistic regression models, and then employed machine learning strategies (LASSO + interactions, Random Forests, XGBoost classifiers) with cross-validation and randomly sampled test set evaluation to assess the utility of immune signatures as ASD biomarkers. We found prominent case-control differences in both boys and girls with alterations in a wide range of analytes in MMG and CB plasma including but not limited to IL1RA, TNFα, Serpin E1, VCAM1, VEGFD, EGF, CSF1, and CSF2. MMG findings were most striking, with particularly strong effect sizes in girls. Models did not change appreciably upon adjustment for maternal conditions, medication use, or emotional distress ratings. Findings were corroborated using machine learning approaches, with area under the receiver operating characteristic curve values in the test sets ranging from 0.771 to 0.965. Our results are consistent with gestational immunopathology in ASD, may provide insights into sex-specific differences, and have the potential to lead to biomarkers for early diagnosis.

Variation in disease in children according to immigrant background.

BACKGROUND: A growing proportion of children born in Europe are born to immigrant parents. Knowledge about their health is essential for preventive and curative medicine and health services planning. OBJECTIVE: To investigate differences in diagnoses given in secondary and tertiary healthcare between Norwegian-born children to immigrant and non-immigrant parents. METHODS: Data from the Medical Birth Registry of Norway, the Norwegian Patient Registry and Statistics Norway were linked by the national personal identification number. The study population included children born in Norway aged 0-10 years between 2008 and 2018 (N=1,015,267). Diagnostic categories from three main domains of physical health, given in secondary or tertiary care; infections, non-infectious medical conditions and non-infectious neurological conditions were included from 2008 onwards. Hazards of diagnoses by immigrant background were assessed by Cox regressions adjusted for sex and birth year. RESULTS: Children of immigrants generally had higher hazards than children with Norwegian background of some types of infections, obesity, nutrition-related disorders, skin diseases, blood disease and genital disease. Children of immigrants from Africa also had higher hazards of cerebral palsy, cerebrovascular diseases and epilepsy. Conversely, most groups of children of immigrants had lower hazards of acute lower respiratory tract infections, infections of the musculoskeletal system, infections of the central nervous system, diseases of the circulatory system, hearing impairment, immune system disorders, chronic lower respiratory disease and headache conditions. CONCLUSIONS: Children of immigrants did not present with overall worse health than children without immigrant background, but the distribution of health problems varied between groups.

Obesity diagnoses in children and adolescents in Norway by immigrant background.

AIM: Relatively few obese children and adolescents receive specialist treatment. Our aim was to assess associations between risk of receiving an obesity diagnosis in secondary/tertiary health services by socio-economic position and immigrant background in order ultimately to improve equity in health services. METHODS: The study population comprised Norwegian-born children aged 2-18 years between 2008 and 2018 (N=1,414,623), identified via the Medical Birth Registry. Cox regressions were used to calculate hazard ratios (HR) of an obesity diagnosis from secondary/tertiary health services (Norwegian Patient Registry) by parental education and household income and by immigrant background. RESULTS: Higher parental education and household income were associated with a lower hazard of obesity diagnosis regardless of Norwegian versus immigrant background. Compared to having a Norwegian background, having a Latin American (HR=4.12; 95% confidence interval (CI) 3.18-5.34), African (HR=1.54; 95% CI 1.34-1.76) and Asian (HR=1.60; 95% CI 1.48-1.74) background was associated with higher hazard of obesity diagnosis. Adjusted for parental education and household income, corresponding HRs were 3.28 (95% CI 2.95-3.65) for Latin America, 0.95 (95% CI 0.90-1.01) for Africa and 1.08 (95% CI 1.04-1.11) for Asia. Within Asia, those with a background from Pakistan, Turkey, Iraq and Iran had higher hazards than those with a Norwegian background, while those with a background from Vietnam had lower hazards, even after adjusting for parental education and household income. CONCLUSIONS: To ensure more equitable treatment, more knowledge is warranted about health-service access and referral patterns, and underlying population prevalence rates, for obese children and adolescents with different immigrant backgrounds.

Impact of the COVID-19 pandemic on mental healthcare consultations among children and adolescents in Norway: a nationwide registry study.

The COVID-19 pandemic and its associated restrictions may have affected children and adolescent's mental health adversely. We cast light on this question using primary and specialist consultations data for the entire population of children of age 6-19 years in Norway (N = 908 272). Our outcomes are the monthly likelihood of having a consultation or hospitalization related to mental health problems and common mental health diagnoses. We compared a pandemic (2019-2021) to a pre-pandemic (2017-2019) cohort using event study and difference-in-difference designs that separate the shock of the pandemic from linear period trends and seasonal variation. We found temporary reductions in all mental health consultations during lockdown in spring 2020. In fall 2020 and winter 2021, consultation volumes in primary care increased, stabilizing at a higher level in 2021. Consultations in specialist care increased from spring 2021. Our findings could suggest a worsening of mental health among adolescents.

A nationwide school fruit and vegetable policy and childhood and adolescent overweight: A quasi-natural experimental study.

BACKGROUND: School free fruit and vegetable (FFV) policies are used to promote healthy dietary habits and tackle obesity; however, our understanding of their effects on weight outcomes is limited. We assess the effect of a nationwide FFV policy on childhood and adolescent weight status and explore heterogeneity by sex and socioeconomic position. METHODS AND FINDINGS: This study used a quasi-natural experimental design. Between 2007 and 2014, Norwegian combined schools (grades 1-10, age 6 to 16 years) were obligated to provide FFVs while elementary schools (grades 1-7) were not. We used 4 nationwide studies (n = 11,215 children) from the Norwegian Growth Cohort with longitudinal or cross-sectional anthropometric data up to age 8.5 and 13 years to capture variation in FFV exposure. Outcomes were body mass index standard deviation score (BMISDS), overweight and obesity (OW/OB), waist circumference (WC), and weight to height ratio (WtHR) at age 8.5 years, and BMISDS and OW/OB at age 13 years. Analyses included longitudinal models of the pre- and post-exposure trajectories to estimate the policy effect. The participation rate in each cohort was >80%, and in most analyses <4% were excluded due to missing data. Estimates were adjusted for region, population density, and parental education. In pooled models additionally adjusted for pre-exposure BMISDS, there was little evidence of any benefit or unintended consequence from 1-2.5 years of exposure to the FFV policy on BMISDS, OW/OB, WC, or WtHR in either sex. For example, boys exposed to the FFV policy had a 0.05 higher BMISDS (95% CI: -0.04, 0.14), a 1.20-fold higher odds of OW/OB (95% CI: 0.86, 1.66) and a 0.3 cm bigger WC (95% CI: -0.3, 0.8); while exposed girls had a 0.04 higher BMISDS (95% CI: -0.04, 0.13), a 1.03 fold higher odds of OW/OB (95% CI: 0.75, 1.39), and a 0-cm difference in WC (95% CI: -0.6, 0.6). There was evidence of heterogeneity in the policy effect estimates at 8.5 years across cohorts and socioeconomic position; however, these results were inconsistent with other comparisons. Analysis at age 13 years, after 4 years of policy exposure, also showed little evidence of an effect on BMISDS or OW/OB. The main limitations of this study are the potential for residual confounding and exposure misclassification, despite efforts to minimize their impact on conclusions. CONCLUSIONS: In this study we observed little evidence that the Norwegian nationwide FFV policy had any notable beneficial effect or unintended consequence on weight status among Norwegian children and adolescents.

Experience with open schools and preschools in periods of high community transmission of COVID-19 in Norway during the academic year of 2020/2021.

BACKGROUND: Schools and preschools have largely remained open in Norway throughout the pandemic, with flexible mitigation measures in place. This contrasts with many other high-income countries that closed schools for long periods of time. Here we describe cases and outbreaks of COVID-19 in schools and preschools during the academic year 2020/2021, to evaluate the strategy of keeping these open with infection prevention control measures in place. METHODS: In this descriptive study, the Norwegian Institute of Public Health initiated systematic surveillance for COVID-19 cases and outbreaks in schools and preschools in October 2020. Data was compiled from the national outbreak alert system VESUV, municipality websites, and media scanning combined with the national emergency preparedness register Beredt C-19. An outbreak was defined as ≥ 2 cases among pupils or staff within 14 days at the same educational setting. Settings were categorized as preschool (1-5-years), primary school (6-12-years), lower secondary school (13-15-years) and upper secondary school (16-18- years). We reported the incidence rate among preschool and school-aged pupils and gave a descriptive overview of outbreaks and included cases per educational setting. RESULTS: During the whole academic year, a total of 1203 outbreaks in preschools and school settings were identified, out of a total of 8311 preschools and schools nationwide. The incidence of COVID-19 in preschool- and school-aged children and the rates of outbreaks in these settings largely followed the community trend. Most of the outbreaks occurred in primary schools (40%) and preschools (25%). Outbreaks across all settings were mostly small (median 3 cases, range 2 to 72), however, 40 outbreaks (3% of total) included 20 or more cases. The larger outbreaks were predominantly seen in primary schools (43%). CONCLUSIONS: We observed few large outbreaks in open schools and preschools in Norway during the academic year of 2020/2021, also when the Alpha variant was predominant. This illustrates that it is possible to keep schools and preschools open even during periods of high community transmission of COVID-19. Adherence to targeted IPC measures adaptable to the local situation has been essential to keep educational settings open, and thus reduce the total burden on children and adolescents.

Age of walking and intellectual ability in autism spectrum disorder and other neurodevelopmental disorders: a population-based study.

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.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with attention-deficit/hyperactivity disorder and autism spectrum disorder in children.

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may be a risk factor for neurodevelopmental deficits and disorders, but evidence is inconsistent. OBJECTIVES: We investigated whether prenatal exposure to PFAS were associated with childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). METHODS: This study was based on the Norwegian Mother, Father and Child Cohort Study and included n = 821 ADHD cases, n = 400 ASD cases and n = 980 controls. Diagnostic cases were identified by linkage with the Norwegian Patient Registry. In addition, we used data from the Medical Birth Registry of Norway. The study included the following PFAS measured in maternal plasma sampled mid-pregnancy: Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonate (PFOS). Relationships between individual PFAS and ADHD or ASD diagnoses were examined using multivariable adjusted logistic regression models. We also tested for possible non-linear exposure-outcome associations. Further, we investigated the PFAS mixture associations with ASD and ADHD diagnoses using a quantile-based g-computation approach. RESULTS: Odds of ASD was significantly elevated in PFOA quartile 2 [OR = 1.71 (95% CI: 1.20, 2.45)] compared to quartile 1, and PFOA appeared to have a non-linear, inverted U-shaped dose-response relationship with ASD. PFOA was also associated with increased odds of ADHD, mainly in quartile 2 [OR = 1.54 (95% CI: 1.16, 2.04)] compared to quartile 1, and displayed a non-linear relationship in the restricted cubic spline model. Several PFAS (PFUnDA, PFDA, and PFOS) were inversely associated with odds of ADHD and/or ASD. Some of the associations were modified by child sex and maternal education. The overall PFAS mixture was inversely associated with ASD [OR = 0.76 (95% CI: 0.64, 0.90)] as well as the carboxylate mixture [OR = 0.79 (95% CI: 0.68, 0.93)] and the sulfonate mixture [OR = 0.84 (95% CI: 0.73, 0.96)]. CONCLUSION: Prenatal exposure to PFOA was associated with increased risk of ASD and ADHD in children. For some PFAS, as well as their mixtures, there were inverse associations with ASD and/or ADHD. However, the inverse associations reported herein should not be interpreted as protective effects, but rather that there could be some unresolved confounding for these relationships. The epidemiologic literature linking PFAS exposures with neurodevelopmental outcomes is still inconclusive, suggesting the need for more research to elucidate the neurotoxicological potential of PFAS during early development.

Tourette syndrome in children in Norway. / Tourettes syndrom hos barn i Norge.

BACKGROUND: Tourette syndrome first appears in childhood and is characterised by chronic motor and vocal tics. In other countries, the mean prevalence is estimated at 0.77 % in children aged 6-15 years. Diagnostic practice and treatment have not been investigated in Norway. MATERIAL AND METHOD: We used data retrieved from the Norwegian Patient Registry and the National Registry to calculate the percentage of children born during the period 2002-10 diagnosed with Tourette syndrome. The calculations were made for the country as a whole as well as by county. Drug therapy was investigated using data from the Norwegian Prescription Database. RESULTS: By the age of 12, altogether 0.43 % had received a diagnosis of Tourette syndrome, broken down into 0.71 % for boys and 0.15 % for girls. The overall percentage varied from 0.15 % to 1.23 % between the counties. For Norway as a whole, the percentage of diagnoses remained stable between 2008 and 2016. Psychiatric and neurological conditions were often present - the most common being hyperkinetic disorder (50 %) and autism spectrum disorder (11 %). Antipsychotic drugs, probably for the treatment of tics, were prescribed for 16 % in the year following the diagnosis. INTERPRETATION: The percentage of children with a diagnosis of Tourette syndrome is lower than the mean prevalence in population studies internationally. The diagnostic practice varies considerably from county to county.

Diagnosing autism spectrum disorder among children in Norway. / Diagnostisering av autismespekterforstyrrelser hos barn i Norge.

BACKGROUND: The percentage share of children who are diagnosed with autism spectrum disorder has increased considerably since the 1990s in Norway as well as in other countries. It has previously been demonstrated that there is considerable variation between counties with respect to diagnostic practice. MATERIAL AND METHOD: We calculated the percentage of children with autism spectrum disorder by using patient data obtained from the Norwegian Patient Registry and population data obtained from the National Registry. The calculations were made for the country as a whole as well as by county. The diagnostic assessments and documentation were mapped by linking the Norwegian Patient Registry with the Norwegian Mother, Father and Child Cohort study. We also reviewed patient records obtained from the specialist health service and considered whether diagnostic practice satisfied the research criteria for autism spectrum disorder. RESULTS: By the age of eight, 1.1 % of boys and 0.3 % of girls had been diagnosed with autism spectrum disorder. The overall percentages varied from 0.3 to 1.0 between counties. From 2008 to 2016, these percentages increased in all age groups. Our review of patient records included 503 children. In 95 % of cases the patient records provided a high standard of documentation that the diagnostic research criteria had been satisfied. The assessments were largely conducted in accordance with the guidelines drawn up by the various health trusts. INTERPRETATION: Autism diagnoses are generally well documented within the Norwegian specialist health service and meet the diagnostic criteria. In the counties that demonstrate a low prevalence of autism, it appears the health service fails to recognise autism in many children, particularly girls, or the diagnosis is determined late.

Diagnosis of hyperkinetic disorder among children in Norway. / Diagnostikk av hyperkinetisk forstyrrelse hos barn i Norge.

BACKGROUND: Hyperkinetic disorder is one of the most frequently used psychiatric diagnoses among children and adolescents in Norway. It has previously been shown that use of the diagnosis varies widely by county. MATERIAL AND METHOD: We estimated the proportion of children with hyperkinetic disorder using patient data from the Norwegian Patient Registry and population data from the Norwegian Population Registry. The estimations were made for both Norway as a whole and by county. Assessment and documentation of the diagnosis were surveyed by linking the Norwegian Patient Registry and the Norwegian Mother and Child Cohort Study. We reviewed medical records from specialist mental health services for children and adolescents and assessed whether the diagnoses met the research criteria for hyperkinetic disorder. RESULTS: At 12 years of age, 5.4 % of Norwegian boys and 2.1 % of Norwegian girls had been diagnosed with hyperkinetic disorder by specialist health services. The proportion of children varied between 1.4 % and 5.5 % among the counties. A review of medical records for 549 children showed that 49 % of the diagnoses were reliably documented in the records. The main reasons that the diagnosis was not documented were a discrepancy between the information in the medical record and diagnostic criteria (38 %) and inadequate differential diagnostic assessment (46 %). INTERPRETATION: There was considerable geographic variation in the proportions of children and adolescents with hyperkinetic disorder. A large percentage of the diagnoses were not reliably documented in medical records. The guideline for evaluation, diagnostics and medical recordkeeping should be reviewed.

Seizures, syndromes, and etiologies in childhood epilepsy: The International League Against Epilepsy 1981, 1989, and 2017 classifications used in a population-based cohort.

OBJECTIVE: The study provides updated information about the distribution of seizures, epilepsies, and etiologies of epilepsy in the general child population, and compares the old and new classification systems from the International League Against Epilepsy (ILAE). METHODS: The study platform was the Norwegian Mother and Child Cohort Study. Cases of epilepsy were identified through registry linkages and sequential parental questionnaires. Epilepsy diagnoses were validated using a standardized protocol, and seizures, epilepsies, and etiologies were classified according to the old (ILAE 1981/1989) and new (ILAE 2017) classifications. Information was collected through medical record reviews and/or parental telephone interviews. RESULTS: The study population included 112,744 children aged 3-13 years at the end of follow-up on December 31, 2012. Of these, there were 606 children with epilepsy (CWE). Distribution of seizure types varied by age of onset. Multiple seizure types were common with early onset. Focal epilepsies were the most common, occurring in 317 per 100,000 children in the study population and in 59% of CWE. Generalized epilepsies were found in 190 per 100,000 (35% of CWE). CWE with onset during the first 2 years of life had an even distribution of focal and generalized epilepsies, whereas focal epilepsies became dominant at later ages of onset. A definite cause of epilepsy had been demonstrated in 33% of CWE. The ILAE 1989 classification allowed for a broad syndrome category in 93% of CWE and a defined epileptic syndrome in 37%. With the ILAE 2017 classification, 41% of CWE had a defined epileptic syndrome and 63% had either a defined syndrome or structural-metabolic etiology. SIGNIFICANCE: The distribution of seizures and epilepsies is strongly dependent on age of onset. Despite diagnostic advances, the causes of epilepsy are still unknown in two-thirds of CWE. The ILAE 2017 classifications allow for a higher precision of diagnoses, but at the expense of leaving more epilepsies classifiable only at the mode of onset level.

When the restrictions are worse than the pandemic. / Når tiltaket er verre enn pandemien.

Stricter infection controls and school closures to tackle COVID-19 are regularly called for in the public discourse on the pandemic. However, restrictions on schooling and leisure activities can have negative consequences. Norwegian and international data appear to support the argument to keep schools and day-care centres open, with good infection control measures, and that closing them should be a last resort.

Substance use disorders in schizophrenia, bipolar disorder, and depressive illness: a registry-based study.

PURPOSE: To compare the prevalence and pattern of comorbid substance use disorders (SUD) between patients with schizophrenia, bipolar disorder, and depressive illness. METHODS: Data on presence of alcohol use disorder (AUD) and non-alcohol drug use disorder (DUD) were retrieved from the Norwegian Patient Register for individuals born between 1950 and 1989 who in the period 2009-2013 were diagnosed with schizophrenia, bipolar disorder or depressive illness according to the 10th version of the WHO International Classification of Diseases. The prevalence of AUD only, DUD only, or both was compared between men and women across age and diagnostic groups. RESULTS: The prevalence of SUD was 25.1 % in schizophrenia (AUD: 4.6 %, DUD: 15.6 %, AUD and DUD: 4.9 %), 20.1 % in bipolar disorder (AUD: 8.1 %, DUD: 7.6 %, AUD and DUD: 4.4 %), and 10.9 % in depressive illness (AUD: 4.4 %, DUD: 4.3 %, AUD and DUD: 2.2 %). Middle-aged men with bipolar disorder had the highest prevalence of AUD (19.1 %) and young men with schizophrenia had the highest prevalence of DUD (29.6 %). Of the specific DUDs, all but sedative use disorder were more prevalent in schizophrenia than the other groups. Cannabis and stimulant use disorder was found among 8.8 and 8.9 %, respectively, of the men with schizophrenia. CONCLUSIONS: The alarmingly high prevalence of DUD among young patients with severe mental disorders should encourage preventive efforts to reduce illicit drug use in the adolescent population.

Identifying children with autism spectrum disorder at 18 months in a general population sample.

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.

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.