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.

Association between gestational levels of toxic metals and essential elements and cerebral palsy in children.

Introduction: Cerebral palsy (CP) is the most common motor disability in childhood, but its causes are only partly known. Early-life exposure to toxic metals and inadequate or excess amounts of essential elements can adversely affect brain and nervous system development. However, little is still known about these as perinatal risk factors for CP. This study aims to investigate the associations between second trimester maternal blood levels of toxic metals, essential elements, and mixtures thereof, with CP diagnoses in children. Methods: In a large, population-based prospective birth cohort (The Norwegian Mother, Father, and Child Cohort Study), children with CP diagnoses were identified through The Norwegian Patient Registry and Cerebral Palsy Registry of Norway. One hundred forty-four children with CP and 1,082 controls were included. The relationship between maternal blood concentrations of five toxic metals and six essential elements and CP diagnoses were investigated using mixture approaches: elastic net with stability selection to identify important metals/elements in the mixture in relation to CP; then logistic regressions of the selected metals/elements to estimate odds ratio (OR) of CP and two-way interactions among metals/elements and with child sex and maternal education. Finally, the joint effects of the mixtures on CP diagnoses were estimated using quantile-based g-computation analyses. Results: The essential elements manganese and copper, as well as the toxic metal Hg, were the most important in relation to CP. Elevated maternal levels of copper (OR = 1.40) and manganese (OR = 1.20) were associated with increased risk of CP, while Hg levels were, counterintuitively, inversely related to CP. Metal/element interactions that were associated with CP were observed, and that sex and maternal education influenced the relationships between metals/elements and CP. In the joint mixture approach no significant association between the mixture of metals/elements and CP (OR = 1.00, 95% CI = [0.67, 1.50]) was identified. Conclusion: Using mixture approaches, elevated levels of copper and manganese measured in maternal blood during the second trimester could be related to increased risk of CP in children. The inverse associations between maternal Hg and CP could reflect Hg as a marker of maternal fish intake and thus nutrients beneficial for foetal brain development.

Educational achievement among children with a disability: do parental resources compensate for disadvantage?

We examined the impact of child disability on Grade Points Average (GPA) using all children aged 15-16 years who completed their lower secondary education and registered with a GPA score in the period from 2016 to 2020 in Norway (n = 247 120). We use registry data that contain information on the child's main diagnosis, such as physical-, neurological- and neurodevelopmental conditions, and the severity of the condition, additional to the child's family characteristics. First, we examined whether the impact of the child's disability on the GPA scores varied by diagnosis and the severity of the child's condition. Second, we examined whether higher parental socioeconomic status (SES) buffers against the negative impact of child disability on GPA scores. Using longitudinal register data with the school fixed-effect model, the results showed that children with neurological and neurodevelopmental disabilities obtained lower GPA scores than their typically developing peers without chronic conditions, however children with asthma and diabetes had comparable GPA scores. These associations were most evident for neurodevelopmental conditions, such as ADHD and autism but also notable for neurological conditions such as epilepsy. In general, a severe condition impacts GPA scores more negatively than a less severe condition. Moreover, our analysis revealed that children of highly educated parents obtained higher GPA scores than children who had parents with short education. This applied to both disabled and typically developing peers, except children with autism and epilepsy, among whom buffering due to the parent's education did not seem to apply.

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.

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.

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.

COVID-19 Hospitalization Among Children <18 Years by Variant Wave in Norway.

OBJECTIVES: There is limited evidence on whether the relative severity of coronavirus disease 2019 (COVID-19) in children and adolescents differs for different severe acute respiratory syndrome coronavirus 2 variants. We compare the risk of hospitalization to acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C) among unvaccinated persons <18 years with COVID-19 (cases) between waves of the Alpha, Delta, and Omicron (sublineage BA.1) variants in Norway. METHODS: We used linked individual-level data from national registries to calculate adjusted risk ratios (aRR) with 95% confidence interval (CI) using multivariable log-binomial regression. We adjusted for variant wave, demographic characteristics, and underlying comorbidities. RESULTS: We included 10 538 Alpha (21 hospitalized with acute COVID-19, 7 MIS-C), 42 362 Delta (28 acute COVID-19, 14 MIS-C), and 82 907 Omicron wave cases (48 acute COVID-19, 7 MIS-C). The risk of hospitalization with acute COVID-19 was lower in the Delta (aRR: 0.53, 95% CI: 0.30-0.93) and Omicron wave (aRR: 0.40, 95% CI: 0.24-0.68), compared to the Alpha wave. We found no difference in this risk for Omicron compared to Delta. The risk of MIS-C was lower for Omicron, compared to Alpha (aRR: 0.09, 95% CI: 0.03-0.27) and Delta (aRR: 0.26, 95% CI: 0.10-0.63). CONCLUSIONS: We do not find clear evidence that different variants have influenced the risk of hospitalization with acute COVID-19 among unvaccinated children and adolescents in Norway. The lower risk of this outcome with Omicron and Delta may reflect changes in other factors over time, such as the testing strategy, maternal vaccination and/or hospitalization criteria. The emergence of Omicron has reduced the risk of MIS-C.

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.

The educational burden of disease: a cohort study.

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. FUNDING: The Research Council of Norway.

School Closure Versus Targeted Control Measures for SARS-CoV-2 Infection.

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.

Risk factors for SARS-CoV-2 infection and hospitalisation in children and adolescents in Norway: a nationwide population-based study.

OBJECTIVE: To determine risk factors for SARS-CoV-2 infection and hospitalisation among children and adolescents. DESIGN: Nationwide, population-based cohort study. SETTING: Norway from 1 March 2020 to 30 November 2021. PARTICIPANTS: All Norwegian residents<18 years of age. MAIN OUTCOME MEASURES: Population-based healthcare 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 years, emigration, death or end of follow-up. HRs estimated by Cox regression models were adjusted for testing frequency. Further, risk factors for admission to the hospital among the infected were investigated. RESULTS: Of 1 219 184 residents, 82 734 (6.7%) tested positive by PCR or lateral flow tests, of whom 241 (0.29%) were admitted to a hospital. Low family income (adjusted HR (aHR) 1.26, 95% CI 1.23 to 1.30), crowded housing (1.27, 1.24 to 1.30), household size, age, non-Nordic country of origin (1.63, 1.60 to 1.66) and area of living were independent risk factors for infection. Chronic comorbidity was associated with a slightly lower risk of infection (aHR 0.90, 95% CI 0.88 to 0.93). Chronic comorbidity was associated with hospitalisation (aHR 3.46, 95% CI 2.50 to 4.80), in addition to age, whereas socioeconomic status and country of origin did not predict hospitalisation among those infected. CONCLUSIONS: Socioeconomic 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 higher risk of admission but slightly lower overall risk of acquiring SARS-CoV-2.

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.

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.

Healthcare use in 700 000 children and adolescents for six months after covid-19: before and after register based cohort study.

OBJECTIVES: To explore whether and for how long use of healthcare services is increased among children and adolescents after covid-19. DESIGN: Before and after register based study. SETTING: General population of Norway. PARTICIPANTS: Norwegians aged 1-19 years (n=706 885) who were tested for SARS-CoV-2 from 1 August 2020 to 1 February 2021 (n=10 279 positive, n=275 859 negative) or not tested (n=420 747) and were not admitted to hospital, by age groups 1-5, 6-15, and 16-19 years. MAIN OUTCOME MEASURES: Monthly percentages of all cause and cause specific healthcare use in primary care (general practitioner, emergency ward) and specialist care (outpatient, inpatient) from six months before to about six months after the week of being tested for SARS-CoV-2, using a difference-in-differences approach. RESULTS: A substantial short term relative increase in primary care use was observed for participants during the first month after a positive SARS-CoV-2 test result compared with those who tested negative (age 1-5 years: 339%, 95% confidence interval 308% to 369%; 6-15 years: 471%, 450% to 491%; 16-19 years: 401%, 380% to 422%). Use of primary care for the younger age groups was still increased at two months (1-5 years: 22%, 4% to 40%; 6-15 years: 14%, 2% to 26%) and three months (1-5 years: 26%, 7% to 46%, 6-15 years: 15%, 3% to 28%), but not for the oldest group (16-19 years: 11%, -2% to 24% and 6%, -7% to 19%, respectively). Children aged 1-5 years who tested positive also showed a minor long term (≤6 months) relative increase in primary care use (13%, -0% to 26%) that was not observed for the older age groups, compared with same aged children who tested negative. Results were similar yet the age differences less pronounced compared with untested controls. For all age groups, the increase in primary care visits was due to respiratory and general or unspecified conditions. No increased use of specialist care was observed. CONCLUSION: Covid-19 among children and adolescents was found to have limited impact on healthcare services in Norway. Preschool aged children might take longer to recover (3-6 months) than primary or secondary school students (1-3 months), usually because of respiratory conditions.

Transmission of SARS-CoV-2 in Norwegian schools during academic year 2020-21: population wide, register based cohort study.

Objective: To 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. Design: Population wide, register based cohort study. Setting: Primary 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. Participants: All students and educational staff in primary and lower secondary schools in Norway, from August 2020 to June 2021. Main outcome measures: Overall 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. Results: From 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. Conclusions: Regarding 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.

Maternal intake of folate during pregnancy and risk of cerebral palsy in the MOBAND-CP cohort.

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.

Overweight, obesity, and thinness among a nationally representative sample of Norwegian adolescents and changes from childhood: Associations with sex, region, and population density.

OBJECTIVE: To estimate the prevalence of overweight, obesity, and thinness among Norwegian 13-year-olds and the changes from childhood (age 8 years) to adolescence (age 13 years); and to explore associations with sex, region, and population density from childhood to adolescence. DESIGN: We used longitudinal, anthropometric data collected by school health nurses conducted in Norway. Weight status was classified according to the International Obesity Task Force cut-offs for overweight, obesity, and thinness, and according to mean body mass index (kg/m2). PARTICIPANTS: The Norwegian Youth Growth Study, consisting of a nationally representative sample of Norwegian 13-year-olds (n = 1852; 50.7% girls), which is a part of The Norwegian Growth Cohort. RESULTS: Among 13-year-old Norwegians, the prevalence of overweight (including obesity), obesity, and thinness was 15.8%, 2.5%, and 7.3%, respectively. There was little evidence that these had changed from 8 to 13 years. From 8 to 13 years, the odds of obesity was highest in the Northern region of Norway compared to the South-East (odds ratio (OR): 3.78 (95% confidence interval (CI): 1.13, 12.65; p = 0.036) and in rural areas (OR: 4.76 (95% CI: 1.52, 14.90; p = 0.027). Over the same age period, girls had a trend towards a higher odds of thinness compared to boys (OR: 1.65 (95% CI: 0.98, 2.78; p = 0.057). CONCLUSIONS: In Norway, the prevalence of overweight, obesity, and thinness among 13-year-olds seem to be established by age 8 years. The prevalence of obesity was higher in the North and in rural areas. The results indicate the continued need for early prevention and treatment, and targeted interventions to certain areas.

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.