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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.

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.

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.

Background: Folate prevents neural tube defects and may play a role in some neurodevelopmental disorders. Objectives: We investigated whether higher intakes of periconceptional or midpregnancy folate, as recommended, were associated with a reduced risk of offspring cerebral palsy (CP). Methods: We included participants from the Nordic collaboration cohort consisting of mother-child dyads in the Danish National Birth Cohort and the Norwegian Mother, Father, and Child Cohort Study [combined as MOthers and BAbies in Norway and Denmark (MOBAND-CP)]. A total of 190,989 live-born children surviving the first year of life were included. Missing covariate data were multiply imputed. Our exposures were defined as any or no folic acid supplementation in gestational weeks (GWs) -4 to 8 (periconceptional), 9 to 12, and -4 to 12, and supplemental, dietary, and total folate during midpregnancy (GWs 22-25). CP overall and the unilateral and bilateral spastic subtypes, as well as CP with low or moderate/high gross motor function impairments, were our outcomes of interest. Results: Periconceptional folic acid supplementation was not associated with CP [adjusted odds ratio (aOR), 1.02; 95% CI: 0.82-1.28]. However, supplementation in GWs 9 to 12 was associated with a reduced risk of CP (aOR, 0.74; 95% CI: 0.57-0.96), and inverse associations were indicated for both the unilateral (aOR, 0.68; 95% CI: 0.46-1.02) and bilateral (aOR, 0.70; 95% CI: 0.49-1.02) spastic subtypes, although the associations were not statistically significant. Supplemental or dietary folate in midpregnancy alone were not associated with CP. Strong inverse associations were observed with low gross motor function impairment (aOR, 0.49; 95% CI: 0.29-0.83), while for unilateral CP the aOR was 0.63 (95% CI: 0.34-1.22) for intakes of ≥500 compared to ≤199 dietary folate equivalents/day during midpregnancy. Conclusions: Our findings suggest that folate intakes in GWs 9 to 12 and midpregnancy were associated with lower risks of CP, while no association was observed for periconceptional supplementation.

Background Students with health disorders might be at risk of disengaging from education, which can reinforce socioeconomic inequalities in health. We aimed to evaluate the associations between 176 diseases and injuries and later school performance in Norwegian adolescents and to estimate the importance of each disorder using a novel measure for the educational burden of disease (EBoD). Methods We used diagnostic information from government-funded health services for all Norwegian inhabitants who were born between Jan 1, 1995, and Dec 31, 2002, were registered as living in Norway at age 11–16 years, and were participating in compulsory education. School performance was assessed as grade point average at the end of compulsory education at age 16 years. We used a linear regression of school performance on disease in a fixed-effects sibling comparison model (113 411 families). The association (regression coefficients) between disease and school performance was multiplied by disease prevalence to estimate the proportional EBoD among 467 412 individuals participating in compulsory education. Findings Overall, although most diseases were not meaningfully associated with grade point average (regression coefficients close to 0), some were strongly associated (eg, intellectual disability regression coefficients –1·2 for boys and –1·3 for girls). The total educational disease burden was slightly higher for girls (53·5%) than for boys (46·5%). Mental health disorders were associated with the largest educational burden among adolescents in Norway (total burden 44·6%; boys 24·6% vs girls 20·0%), of which hyperkinetic disorder contributed to 22·1% of the total burden (boys 14·6% vs girls 7·5%). Among somatic diseases, those with unknown causes and possibly mental causes were associated with the largest educational burden. Interpretation The EBoD concept could provide a simple metric to guide researchers and policy makers. Because mental health disorders form a large component of the educational burden, investment in mental health might be particularly important for improving educational outcomes in adolescents. publishedVersion

ObjectiveTo assess the risk of transmission of SARS-CoV-2 in schools in Norway mainly kept open during the covid-19 pandemic in the academic year 2020-21.DesignPopulation wide, register based cohort study.SettingPrimary and lower secondary schools in Norway open during the academic year 2020-21, with strict infection prevention and control measures in place, such as organisation of students into smaller cohorts. Contact tracing, quarantine, and isolation were also implemented, and testing of students and staff identified as close contacts.ParticipantsAll students and educational staff in primary and lower secondary schools in Norway, from August 2020 to June 2021.Main outcome measuresOverall attack rate of SARS-CoV-2 transmission (AR14) was defined as the number of individuals (among students, staff, or both) in the school with covid-19, detected within 14 days of the index case, divided by the number of students and staff members in the school. AR14 to students (attack rates from all index cases to students only) and AR14 to school staff (attack rates from all index cases to staff members only) were also calculated. These measures for student and school staff index cases were also calculated separately to explore variation in AR14 based on the characteristics of the index case.ResultsFrom August 2020 to June 2021, 4078 index cases were identified; 3220 (79%) students and 858 (21%) school staff. In most (2230 (55%)) schools with an index case, no subsequent individuals with covid-19 were found within 14 days; in 631 (16%) schools, only one more individual with covid-19 within 14 days was found. Overall, AR14 was 0.33% (95% confidence interval 0.32% to 0.33%). When restricting index cases and subsequent individuals with covid-19 to students born in the same year, AR14 to students (0.56-0.78%) was slightly higher.ConclusionsRegarding the number of people infected with SARS-CoV-2 among students and staff, these results suggest that schools were not an important setting for transmission of the virus in Norway during the covid-19 pandemic in the academic year 2020-21.

OBJECTIVES To compare effects of school closures with effects of targeted infection prevention and control (IPC) measures in open schools on SARS-CoV-2 infection rates in students. METHODS We conducted interrupted time-series analyses to compare trends in infection rates in grades 1–10 in 7 boroughs in Oslo, Norway, between February 15 and April 18, 2021. All schools at all levels had implemented strict IPC measures. While grades 1–4 attended school throughout the study period, school closures were implemented for grades 5–10 from March 17. We obtained individual level data from nationwide registries. RESULTS A total of 616, 452, and 446 students in grades 1–4, 5–7 and 8–10, respectively, were registered with a positive SARS-CoV-2 test during the study period, when the α-variant dominated. A statistically significant reduction in postintervention trends was observed for grades 1–4 (coefficient −1.26; 95% confidence interval (CI), −2.44 to −0.09). We did not observe any statistically significant between-group differences in postintervention trends between grades 1–4 and 5–7 (coefficient 0.66; 95% CI, −1.25 to 2.58) nor between grades 1–4 and 8–10 (coefficient −0.63; 95% CI, −2.30 to 1.04). Findings indicate that keeping schools open with strict IPC measures was equally effective as school closures on reducing student infection rates. CONCLUSIONS School closure was not more effective than targeted IPC measures in open schools in reducing student infection rates. Our findings suggest that keeping schools open with appropriate IPC measures should be preferred over school closures, considering the negative consequences closures have on students.

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.

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.

BACKGROUND There have been widespread concerns about the impact of the COVID-19 pandemic and its associated restrictions on children’s and adolescent’s mental health. While some studies have found increasing rates of mental health problems during the pandemic, other evidence suggest that mental symptoms and disorders were increasing before the pandemic. This study compared trends in mental healthcare use during the first 15 months of the pandemic with similar pre-pandemic trends. METHODS Consultations related to mental symptoms and disorders were identified through national registries from primary and specialist healthcare services, including hospitalizations, covering the entire population of children 6-18 years in Norway (N=908 272). The monthly likelihood of having a consultation or hospitalization related to overall mental health problems, and specific diagnoses for depression, anxiety, ADHD and sleep problems were plotted from January 2020 to May 2021 and compared to trends over the same period between 2017-2019 using event study and difference-in-difference designs. FINDINGS We found reductions in consultations for mental health symptoms and disorders in primary and specialist healthcare during the first weeks of lockdown in 2020. This decline was temporary, and volumes of consultations quickly returned to pre-pandemic levels. However, during fall 2020, consultation volumes related to mental health in primary care increased. This increase persisted into the winter of 2021 but levelled off by the last month of the sample period. The increase in consultation volumes was about 50 % compared to the pre-pandemic period. We did not find increases in consultations in specialist healthcare, except for hospitalizations. CONCLUSION We found an increase in primary care consultation volumes related to mental health among children that depart from the previously established increases over recent years. We did not see similar increases in consultations in the specialist healthcare. It is unknown whether increases in primary care consultations represent milder cases, which primarily do not need specialist treatment, or if the stability in specialist healthcare consultations reflects capacity problems or timelags in referrals.

ObjectiveTo determine risk factors for SARS-CoV-2 infection and hospitalisation among children and adolescents.DesignNationwide, population-based cohort study. Setting: Norway from 1 March 2020 to 31 April 2021. Participants: All Norwegian residents Main outcome measuresPopulation-based health care and population registries were used to study risk factors for SARS-CoV-2 infection, including socioeconomic factors, country of origin, and pre-existing chronic comorbidities. All residents were followed until age 18, emigration, death, or end of follow-up. Hazard ratios (HR) estimated by Cox regression models were adjusted for testing frequency. Further, risk factors for admission to the hospital among the infected were investigated.ResultsOf 1 182 796 residents, 22608 (1.9%) tested positive by polymerase chain reaction or lateral flow tests, of whom 107 (0.5%) were admitted to a hospital. Low family income (aHR 1.40, 95% confidence interval 1.36 to 1.46), crowded housing (1.35, 1.30 to 1.39), household size, age, and area of living were independent risk factors for infection. A non-Nordic country of origin was the strongest risk factor (aHR 2.37, 95% CI 2.30 to 2.49), whereas chronic comorbidity was not associated with the risk of infection. Chronic comorbidity was associated with hospitalisation (aHR 4.15, 2.63 to 6.56), in addition to age, whereas socioeconomic status and country of origin did not predict hospitalisation among those infected.ConclusionsSocioeconomic factors, country of origin, and area of living were associated with the risk of SARS-CoV-2 infection. However, these factors did not predict hospitalisation among those infected. Chronic comorbidity was associated with the risk of admission but not with the overall risk of acquiring SARS-CoV-2.What is already known on this topicHospital admissions rates for covid-19 among children and adolescents are low compared to adults. Admission rates to hospitals and intensive care units for covid-19 have been higher in minority groups and in children and adolescents with chronic comorbidity.Whether underlying differences in susceptibility for severe disease or the incidence of infections are driving these associations have not been investigated.What this study addsLow family income, crowded housing and household size, and country of origin outside the Nordic countries were associated with increased risk of infection with SARS-CoV-2.None of these factors, but chronic comorbidities, were associated with the risk of hospital admission among those infected.

Background Prenatal exposure to toxic metals or variations in maternal levels of essential elements during pregnancy may be a risk factor for neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring. Objectives We investigated whether maternal levels of toxic metals and essential elements measured in mid-pregnancy, individually and as mixtures, were associated with childhood diagnosis of ADHD or ASD. Methods This study is based on the Norwegian Mother, Father and Child Cohort Study and included 705 ADHD cases, 397 ASD cases and 1034 controls. Cases were identified through linkage with the Norwegian Patient Registry. Maternal concentrations of 11 metals/elements were measured in blood at week 17 of gestation; cadmium; cesium; cobalt; copper; lead; magnesium; manganese; selenium; zinc; total arsenic; and total mercury. Multivariable adjusted logistic regression models were used to examine associations between quartile levels of individual metals/elements and outcomes. We also investigated non-linear associations using restricted cubic spline models. The joint effects of the metal/element mixture on ASD and ADHD diagnoses were estimated using a quantile-based g-computation approach. Results For ASD, we identified positive associations (increased risks) in the second quartile of arsenic [OR = 1.77 (CI: 1.26, 2.49)] and the fourth quartiles of cadmium and manganese [OR = 1.57 (CI: 1.07 2.31); OR = 1.84 (CI: 1.30, 2.59)], respectively. In addition, there were negative associations between cesium, copper, mercury, and zinc and ASD. For ADHD, we found increased risk in the fourth quartiles of cadmium and magnesium [OR = 1.59 (CI: 1.15, 2.18); [OR = 1.42 (CI: 1.06, 1.91)]. There were also some negative associations, among others with mercury. In addition, we identified non-linear associations between ASD and arsenic, mercury, magnesium, and lead, and between ADHD and arsenic, copper, manganese, and mercury. There were no significant findings in the mixture approach analyses. Conclusion Results from the present study show several associations between levels of metals and elements during gestation and ASD and ADHD in children. The most notable ones involved arsenic, cadmium, copper, mercury, manganese, magnesium, and lead. Our results suggest that even population levels of these compounds may have negative impacts on neurodevelopment. As we observed mainly similarities among the metals’ and elements’ impact on ASD and ADHD, it could be that the two disorders share some neurochemical and neurodevelopmental pathways. The results warrant further investigation and replication, as well as studies of combined effects of metals/elements and mechanistic underpinnings.

Maternal fever during pregnancy is associated with several adverse child outcomes. We investigated associations between maternal fever and ADHD among offspring, as well as the sub-dimensions of ADHD - inattention and hyperactivity/impulsivity. Data came from the Norwegian Mother and Child Cohort Study, including more than 114,000 children. Information about children’s ADHD diagnoses was obtained from the Norwegian Patient Register. Mothers reported on inattention and hyperactivity/impulsivity symptoms in questionnaires at 8 years. Logistic regression analysis showed that children exposed to maternal fever in the first trimester received an ADHD diagnosis more often than unexposed children (Odds Ratio (OR) = 1.31, 95% confidence interval (CI) = 1.06–1.61). For children exposed twice or more in the first trimester, the OR was 2.64 (CI = 1.36–5.14). Linear regression analysis showed elevated inattention symptoms among children exposed to fever in the first (Cohen’s d = 0.09, CI = 0.03–0.15) and second (Cohen’s d = 0.05, CI = 0.01–0.09) trimester. Results were similar whether the mother had taken acetaminophen for their fever or not. Hyperactivity/impulsivity symptoms were not related to maternal fever. The results indicate that maternal fever in early pregnancy may be a risk factor for ADHD, and particularly for inattention problems. This risk is neither mitigated nor inflated by use of acetaminophen.

Introduction Studies from the US1,2 and Canada3,4 have reported increasing numbers of children and adolescents receiving treatment for eating disorders during the COVID-19 pandemic. Most patients are girls,1,2,4 and the predominant diagnosis is anorexia nervosa.1,2 There is insufficient information about the magnitude of this increase on a population level. In this cohort study, we analyzed trends in diagnoses of eating disorders among children and adolescents in Norway before vs during the pandemic. Methods We obtained primary care data from the Norwegian Registry for Primary Health Care and specialist care data from the Norwegian Patient Registry.5 Reporting to these registries is mandated by law and linked to the national reimbursement systems for health services. The entire Norwegian population is covered. This study followed the STROBE reporting guideline and was approved by the Norwegian Regional Committees for Medical and Health Research Ethics. Because the study used existing registry data, informed consent was not required. Individuals aged 6 to 16 years living in Norway on January 1, 2020 (pandemic cohort), were observed from January 2019 to December 2021. The comparison group included this age group living in Norway on January 1, 2018 (prepandemic cohort), observed from January 2017 to December 2019. We assessed changes in the percentage of individuals with recorded eating disorders since onset of the pandemic in March 2020 in the pandemic cohort and after March 2018 in the prepandemic cohort. Changes were compared by difference-in-difference models.6 We calculated monthly percentages of individuals with eating disorders using event study models to estimate relative changes. Analyses were done by sex and age group (6-12 and 13-16 years) using Stata, version 16.0. The eMethods in the Supplement gives additional information. Results The number of boys with eating disorder diagnoses was low; thus, girls were analyzed. The pandemic cohort included 348 187 girls (mean [SD] age, 11.03 [3.13] years), and the prepandemic cohort, 353 848 girls (mean [SD] age, 10.96 [3.15] years) (Table). For girls aged 6 to 12 years, we observed larger relative increases in the percentage with eating disorder diagnoses in the pandemic cohort: 66.90% (95% CI, 33.12%-100.67%) in primary care and 278.30% (95% CI, 160.44%-396.16%) in specialist care. For girls aged 13 to 16 years, the relative increase was 126.54% (106.48%-146.59%) in primary care and 95.96% (95% CI, 79.54%-112.38%) in specialist care. Increases were attributable to new cases. The monthly percentage of girls with eating disorder diagnoses increased over time in the prepandemic cohort (Figure). The pattern was similar in the pandemic cohort but with a disruption after onset of the pandemic. The monthly percentage of girls aged 13 to 16 years with an eating disorder diagnosis ranged from 0.05% to 0.08% before the pandemic and from 0.15% to 0.20% after onset in primary care and from 0.27% in February 2019 to 0.74% in December 2021 in specialist care. The relative increase ranged from −11.89% (95% CI, −47.23% to 23.46%) in March 2020 to 194.63% (95% CI, 160.27%-228.99%) in February 2021 for primary care and from 11.06% (95% CI, −2.84% to 24.96%) in May 2020 to 150.70% (95% CI, 128.87%-172.53%) in November 2021 for specialist care and was statistically significant throughout 2021. Among girls aged 6 to 12 years, the percentage with eating disorder diagnoses was lower but increased after March 2021. In specialist care, the percentage did not exceed 0.10%, but the relative increase remained greater than 200% after May 2021. Discussion We found a substantial increase in the number of girls diagnosed with eating disorders in Norway starting after onset of the COVID-19 pandemic. The timing of the trend disruption suggests that the increase was associated with societal changes induced by the pandemic, including restrictions placed on youth’s lives, education, and activities. Limitations were that follow-up was incomplete for teenagers older than 16 years, we could not distinguish between eating disorder subtypes, and diagnostic data were not validated. Our findings are similar to those from North America,1-4 suggesting that the increase in eating disorders occurred internationally.

ObjectivesTo explore whether, and for how long COVID-19 among children gives an increase in use of health care services, when compared to children with no COVID-19.MethodsStudying all Norwegian residents aged 1-5, 6-15 and 16-19 years from August 1st2020 to February 1st2021 (N= 768 560), we contrasted rates of monthly all-cause primary and specialist health care use before and after testing for SARS-CoV-2 (% relative change), for children testing positive (non-hospitalized in the acute phase) (N=10 306) vs children with no COVID-19 (N=758 254).ResultsWe found a substantial elevation in short-term primary care use for children testing positive for SARS-CoV-2 during the first month following positive test when compared to children testing negative (relative elevation 1-5 years: 325%, 95%CI=296-354; 6-15 years: 434%, 95%CI=415-453; 16-19 years: 360%, 95%CI=342-379). There was still elevated primary care use at 2 months (1-5 years: 21%, 95%CI= 4-38; 6-15 years: 13%, 95%CI=2-25) and at 3 months (1-5 years: 26%, 95%CI=7-45, 6-15 years: 15%, 95%CI=3-26) for young children, but not at 2 or 3 months for the older children (16-19 years: 10%, 95%CI=-1-22 and 6%, 95%CI=-5-18, respectively). The 1-5-year-olds also had a long-term (up to 6 months) increase of primary care (14%, 95%CI=1-26) that was not observed for older age groups, when compared to same-aged children testing negative. We observed no elevated use of specialist care.ConclusionChildren in pre-school age used health services for a longer time (3-6 months) after COVID-19 than children in primary and secondary school age (1-3 months).

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.

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.

BackgroundDelayed 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.ObjectiveTo 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).MethodsParticipants 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.ResultsThe 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.ConclusionsThe 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.

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.

International audience; We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.

The parental report-based Autism Diagnostic Interview-Revised (ADI-R) and the clinician observation-based Autism Diagnostic Observation Schedule (ADOS) have been validated primarily in U.S. clinics specialized in autism spectrum disorder (ASD), in which most children are referred by their parents because of ASD concern. This study assessed diagnostic agreement of the ADOS-2 and ADI-R toddler algorithms in a more broadly based sample of 679 toddlers (age 35–47 months) from the Norwegian Mother and Child Cohort. We also examined whether parental concern about ASD influenced instrument performance, comparing toddlers identified based on parental ASD concern (n = 48) and parent-reported signs of developmental problems (screening) without a specific concern about ASD (n = 400). The ADOS cutoffs showed consistently well-balanced sensitivity and specificity. The ADI-R cutoffs demonstrated good specificity, but reduced sensitivity, missing 43% of toddlers whose parents were not specifically concerned about ASD. The ADI-R and ADOS dimensional scores agreed well with clinical diagnoses (area under the curve ≥ 0.85), contributing additively to their prediction. On the ADI-R, different cutoffs were needed according to presence or absence of parental ASD concern, in order to achieve comparable balance of sensitivity and specificity. These results highlight the importance of taking parental concern about ASD into account when interpreting scores from parental report-based instruments such as the ADI-R. While the ADOS cutoffs performed consistently well, the additive contributions of ADI-R and ADOS scores to the prediction of ASD diagnosis underscore the value of combining instruments based on parent accounts and clinician observation in evaluation of ASD. Autism Res 2017, 10: 1672–1686. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

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.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.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.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.

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.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.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.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.

Background Early identification and diagnosis is beneficial for children with autism spectrum disorder (ASD). Universal early screening is recommended by many experts, but disputed because evidence is limited, and sensitivity and specificity in general populations are largely unknown. Aims To estimate the sensitivity and specificity of early population-based screening for ASDs. Method The study was based on the Norwegian Mother and Child Cohort Study. The 36-month cohort questionnaire included the Social Communication Questionnaire (SCQ), a 40-item screening instrument for ASD. Results A total of 58 520 mothers (58%) responded to the questionnaire. By the end of follow-up on 31 December 2015, 385 (0.7%) individuals with ASD had been identified among the responders' children. The distributions of SCQ scores in those with ASD and other children had large degrees of overlap. With the cut-off of 15 recommended in the SCQ manual, screening sensitivity was 20% (95% CI 16–24) for ASD overall. For children with ASD who had not developed phrase speech at 36 months, sensitivity was 46% (95% CI 35–57%), whereas it was 13% (95% CI 9–17) for children with ASD with phrase speech. Screening specificity was 99% (95% CI 99–99). With the currently recommended cut-off of 11, sensitivity increased to 42% for ASD overall (95% CI 37–47), 69% (95% CI 58–79) for ASD without phrase speech and 34% (95% CI 29–40) for ASD with phrase speech. Specificity was then reduced to 89% (95% CI 89–90). Conclusions Early ASD screening with a parent checklist had low sensitivity. It identified mainly individuals with ASD with significant developmental delay and captured very few children with ASD with cognitive skills in the normal range. Increasing sensitivity was not possible without severely compromising specificity. Declaration of interest C.L. receives royalty for the Social Communication Questionnaire, which she has co-authored.

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.

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.

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.

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.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.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 %).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.

SummaryWe present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.

BACKGROUND AND OBJECTIVES: Seizure freedom is the optimal response to antiepileptic treatment. In previous studies, it has been shown that between 61% and 71% of children with epilepsy achieve seizure freedom, whereas 7% to 20% have drug-resistant epilepsy. The definition of drug resistance has not been consistent across studies, and there is a lack of contemporary population-based data. We used data from a large nationwide child cohort to provide such information, implementing the current standard definition of drug resistance. METHODS: The study was based on the Norwegian Mother and Child Cohort Study. Potential epilepsy cases were identified through registry linkages and parental questionnaires. Medical record reviews and parental interviews were used to collect clinical information and to classify seizures, epilepsies, and etiologies. RESULTS: The cohort included 112 745 eligible children aged 3 to 13 years (median age 7 years) at end of follow-up. Of these, 600 were epilepsy cases with at least 1 year of follow-up since epilepsy onset (median follow-up time: 5.8 years). There were 178 (30%) who had developed drug-resistant epilepsy, 353 (59%) who had been seizure free for ≥1 year, and 69 (12%) with intermediate seizure outcomes. Having an identified cause of epilepsy (genetic, structural, metabolic, or infectious) was associated with unsatisfactory seizure outcome (48% drug resistance) and influenced the relative risk associated with other prognostic factors. Sociodemographic characteristics were not associated with short-term seizure outcomes. CONCLUSIONS: Drug resistance occurs in 3 out of 10 children with epilepsy, whereas 6 out of 10 become seizure free. Having an identified cause of epilepsy is associated with poor response to treatment.

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.

BACKGROUND: Research studies exploring the determinants of disease require sufficient statistical power to detect meaningful effects. Sample size is often increased through centralized pooling of disparately located datasets, though ethical, privacy and data ownership issues can often hamper this process. Methods that facilitate the sharing of research data that are sympathetic with these issues and which allow flexible and detailed statistical analyses are therefore in critical need. We have created a software platform for the Virtual Pooling and Analysis of Research data (ViPAR), which employs free and open source methods to provide researchers with a web-based platform to analyse datasets housed in disparate locations.METHODS: Database federation permits controlled access to remotely located datasets from a central location. The Secure Shell protocol allows data to be securely exchanged between devices over an insecure network. ViPAR combines these free technologies into a solution that facilitates 'virtual pooling' where data can be temporarily pooled into computer memory and made available for analysis without the need for permanent central storage.RESULTS: Within the ViPAR infrastructure, remote sites manage their own harmonized research dataset in a database hosted at their site, while a central server hosts the data federation component and a secure analysis portal. When an analysis is initiated, requested data are retrieved from each remote site and virtually pooled at the central site. The data are then analysed by statistical software and, on completion, results of the analysis are returned to the user and the virtually pooled data are removed from memory.CONCLUSIONS: ViPAR is a secure, flexible and powerful analysis platform built on open source technology that is currently in use by large international consortia, and is made publicly available at [http://bioinformatics.childhealthresearch.org.au/software/vipar/].

To compare the prevalence and pattern of comorbid substance use disorders (SUD) between patients with schizophrenia, bipolar disorder, and depressive illness. 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. 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. 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.