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Aleksi Hamina,1,* Ingvild Odsbu,2,* Petter Christian Borchgrevink,3,4 Li-Chia Chen,5 Thomas Clausen,1 Ketil Arne Espnes,6,7 Kine Gjesdal,8,9 Marte Handal,1,10 Sirpa Hartikainen,11 Vidar Hjellvik,10 Marianne Therese Smogeli Holter,12 Trond Høibø,13 Geana Paula Kurita,14– 16 Harald Christian Langaas,7 Torgeir Gilje Lid,8,9 Torunn Hatlen Nøst,3,17 Per Sjøgren,15 Svetlana Skurtveit1,2 On behalf of the POINT study group1Norwegian Centre for Addiction Research (SERAF), Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 2Department of Mental Disorders, Division of Mental and Physical Health, the Norwegian Institute of Public Health, Oslo, Norway; 3Department of Pain and Complex Disorders, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; 4Institute of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; 5Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK; 6Department of Clinical Pharmacology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; 7Regional Medicines Information and Pharmacovigilance Centre (RELIS), Department of Clinical Pharmacology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; 8Faculty of Health Sciences, University of Stavanger, Stavanger, Norway; 9Center for Alcohol and Drug Research (KORFOR), Stavanger University Hospital, Stavanger, Norway; 10Department of Chronic Diseases, Division of Mental and Physical Health, the Norwegian Institute of Public Health, Oslo, Norway; 11School of Pharmacy, University of Eastern Finland, Kuopio, Finland; 12Department of Psychology, Faculty of Social Sciences, University of Oslo, Oslo, Norway; 13Research Unit for General Practice, NORCE Norwegian Research Centre, Bergen, Norway; 14Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 15Department of Oncology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark; 16Department of Anaesthesiology, Pain and Respiratory Support, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark; 17Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway*These authors contributed equally to this workCorrespondence: Ingvild Odsbu, Department of Mental Disorders, Division of Mental and Physical Health, Norwegian Institute of Public Health, PO Box 222 Skøyen, Oslo, 0213, Norway, Tel +47 41454379, Email ingvild.odsbu@fhi.noAim: The POINT project aims to provide evidence to optimise chronic pain management, prevent adverse consequences of opioids, and improve chronic pain patients’ pain relief, functional capacity, and quality of life. We describe the outline of the project and its work packages. More specifically, we describe a cohort of persons with chronic pain and a cohort of long-term opioid users identified from a national registry linkage.Data Sources: The project utilises data from nationwide healthcare and population registers in Norway. Using the Norwegian Prescription Database, we identified a cohort of persons who have been dispensed drugs reimbursed for chronic pain and a cohort of persons who used opioids long term from 2010 to 2019. Data from the Norwegian Registry for Primary Health Care and the Norwegian Patient Registry (2008– 2019), Cancer Registry (1990– 2018) Cause of Death Registry (2010– 2019) and demographic and socioeconomic registers from Statistics Norway (2010– 2019) were linked to the cohorts.Study Population: There were 568,869 participants with chronic pain. Sixty-three percent of the cohort was women, and the mean age was 57.1 years. There were 336,712 long-term opioid users (58.6% women; 60.9 years). In chronic pain and long-term opioid user cohorts, the most frequent musculoskeletal diagnosis was back pain diagnosed in primary care (27.6% and 30.7%). Psychiatric diagnoses were also common.Main Variables: Upcoming studies will utilise psychiatric and somatic diagnoses from the patient registers, drug use from the prescription register, causes of death, demographics, and socioeconomic status (eg, education, income, workability, immigrant status) as exposures or outcomes.Conclusion and Future Plans: The two cohorts have numerous pain-related diagnoses, especially in the musculoskeletal system, and noticeably frequent somatic and psychiatric morbidity. The POINT project also includes later work packages that explore prescriber and patient perspectives around safe and effective treatment of chronic pain.Keywords: opioids, chronic pain, healthcare registers

Objectives: To estimate the association between prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and motor development in children considering the effect of maternal symptoms of anxiety and depression before, during and after pregnancy.Design: Population-based prospective pregnancy cohort study.Setting: The Norwegian Mother and Child Cohort study (MoBa) (1999-2008).Population: A total of 51 404 singleton pregnancies.Methods: Self-reported use of SSRIs was collected for the 6 months before pregnancy and prospectively during pregnancy. We used ordinal logistic regression as the statistical analysis.Main Outcome Measures: Motor development was assessed by maternal reports of fine and gross motor development at child age 3 years by items from the Ages and Stages Questionnaire (ASQ). The maternal ASQ scores were compared with data from a MoBa sub-study where clinicians assessed motor development with the Gross and Fine Motor Mullen scales of early learning.Results: In all 381 women (0.7%) reported use of SSRIs during pregnancy, of these 159 reported on at least two questionnaires (prolonged use). Prolonged SSRI exposure was associated with a delay in fine motor development, odds ratio 1.42 (95% CI 1.07-1.87) compared with no SSRI exposure, after adjusting for symptoms of anxiety and depression before and during pregnancy. Severity of maternal depression seemed to explain the association only partially. Stratifying on depression after pregnancy had no impact on the estimated effect of SSRIs.Conclusions: Prolonged prenatal exposure to SSRIs was weakly associated with a delayed motor development at age 3 years, but not to the extent that the delay was of clinical importance.Tweetable Abstract: Long-term prenatal SSRI exposure is weakly associated with delayed motor development independent of depression. [ABSTRACT FROM AUTHOR]

Background: The use of medication for Attention-Deficit/Hyperactivity Disorder (ADHD) increased globally throughout the early 2000s. This study examine trends in prevalences and incidences of medication use in Norway from 2006 to 2022., Methods: Data from the Norwegian Prescription Database were used to present one-year-prevalence and incidence rates of ADHD medication (ATC-group N06BA and C02AC02) for the overall population (ages 6-64) and within sex and age subgroups of children (ages 6-17) and adults (ages 18-64). Incident use was defined as the dispensing of medication, with no recorded use in the previous two calendar years., Results: The overall prevalence of ADHD medication use in 6- to 64-year-olds increased from 5.2 to 19.4 per 1000 in the period, most pronounced from 2020 and onwards. While males experienced a nearly threefold increase in use (from 7.3 to 20.6 per 1000), the use among females increased almost sixfold during the study period (from 3.0 to 18.1 per 1000). Consequently, the male-to-female prevalence-ratio decreased from 2.4 to 1. Children exhibited a higher prevalence of use compared to adults throughout the period, although the largest relative increase was observed in adults, particularly in female adults. In children the male-to-female ratio decreased from 3.2 to 2.0, primarily due to an increasing use in 13-17-year-old females. Among adults, prevalences were similar across most age groups, with the highest rates observed among those aged 18-24, where female use exceeded male use by the end of the period. The male-to-female prevalence-ratio in adults decreased from 1.6 to 0.9 during the period. Parallel to prevalent use, overall incident use increased from 1.4 to 5.0 per 1000 during the period, with the most pronounced increase occurring from 2020 and onwards. From this point, incident use among females aged 13-17, 18-24, and 25-34, exceeded that of males. The male-to-female incidence-ratio decreased from 1.8 to 0.9. The overall incidence to prevalence ratio remained similar throughout the period, being 0.27 in 2006 and 0.25 in 2022., Conclusion: A sustained increase in the prevalence of ADHD medication use was observed, with the most pronounced rise occurring among females and adults from 2020 and onwards. By 2022, the overall gender disparity in ADHD medication use had diminished, which should be considered in the context of a steep increase in incident use among adolescent and young adult females starting from 2020., (© 2024. The Author(s).)

Cutaneous adverse reactions to mRNA COVID-19 vaccines in patients with preexisting dermatologic disease include bullous eruptions, pityriasis rubra pilaris, dermatomyositis, and granuloma annulare. Erythroderma is a rare but severe adverse reaction not previously seen. This case report describes the development of erythroderma in a 73-year-old male with a history of atopic dermatitis, with widespread erythema and scaling covering 95% of his body surface area, which developed sequentially after receiving each dose of the Pfizer-BioNTech (BNT162b2) COVID-19 vaccination. The patient's condition improved significantly with appropriate dermatologic treatment, including systemic and topical corticosteroids and dupilumab. Thus, it is imperative to recognize erythroderma as a potential side effect of the Pfizer-BioNTech COVID-19 vaccine, particularly in patients with preexisting dermatologic conditions. Early diagnosis and treatment are vital for managing this potentially life-threatening reaction and preventing severe complications., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Handal et al.)

Transverse sinus stenosis (TSS) is an abnormality in the cerebral venous system in which the narrowing of the transverse sinus of the brain leads to obstructed cerebral venous outflow. It is an infrequent, incidental radiological finding. However, it is not uncommon among patients with chronic headaches of unclear cause, particularly those that remain unexplained after initial evaluation or those that are refractory to medical treatment. Its diagnosis frequently eludes the initial workup, and a high degree of suspicion should be maintained since its identification can lead to potentially curative treatment. This report describes the case of a 36-year-old female with a history of chronic headache who was found to have TSS. This paper discusses its etiology, pathophysiology, clinical presentation, radiological findings, and management., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Handal et al.)

We have previously shown that the use of hypnotic drugs increased among young Scandinavians during 2012-2018. This study aimed to explore psychiatric and somatic morbidity among adolescent hypnotic drug users in a cohort study of 13-17-year-old individuals during 2008-2018 in Norway. Data sources were (i) prescription data from the Norwegian Prescription Database linked to specialist health care diagnoses from the Norwegian Patient Registry and (ii) sleep disorder diagnoses from the Primary Health Care Database. Hypnotic drugs were defined as the sedative antihistamine alimemazine and the ATC group "Hypnotics and Sedatives" (N05C), excluding midazolam. In 2017, 2519 girls (16.5/1000) and 1718 boys (10.7/1000) were incident (new) users of hypnotic drugs. Most of these new users (82% of girls, 77% of boys) were referred to secondary health care, where the most frequent diagnoses were mental and behavioral disorders (51.8% of girls, 46.2% of boys), while only 3.2% received a specific sleep disorder diagnosis. The most common mental and behavioral disorders were "Neurotic stress-related disorders" among girls (27.4%) and "Behavioral and emotional disorders" among boys (23.6%). In conclusion, the trend of increasing hypnotic drug use among adolescents reflects the initiation of hypnotic drugs in a subgroup of the population with a higher disease burden, mainly due to psychiatric disorders, than the general population.

Background: Knowledge of mental disorders among patients with persistent opioid use for the treatment of chronic non-cancer pain is essential, as mental disorders and symptoms can exacerbate or perpetuate pain and impact on the ability of patients to manage their illness. We have studied the prevalence of mental disorders and symptoms, including substance use disorders, in patients with persistent opioid use in 2019., Material and Method: Persons ≥ 18 years with persistent opioid use and persons ≥ 18 years with at least one registered mental disorder in the specialist healthcare service in 2019 were included. Data were retrieved from national health registries in Norway. Patients who received opioids reimbursed for the treatment of chronic pain were compared with those who received opioids without reimbursement., Results: The prevalence of mental disorders and symptoms was 34 % among 14 403 persons who received reimbursed opioids, and 42 % among 38 001 persons who received opioids without reimbursement. This is equivalent to a two to threefold increase in prevalence compared to the general population. There was a particularly higher prevalence of anxiety disorders and substance use disorders. The prevalence of mental disorders and symptoms was highest in the age group 18-44 years (49-55 %)., Interpretation: Among patients with persistent opioid use, a large proportion had mental disorders and symptoms, which are known risk factors for developing problematic opioid use and opioid use disorder.

The ongoing opioid epidemic has been a global concern for years, increasingly due to its heavy toll on young people's lives and prospects. Few studies have investigated trends in use of the wider range of drugs prescribed to alleviate pain, psychological distress and insomnia in children, adolescents and young adults. Our aim was to study dispensation as a proxy for use of prescription analgesics, anxiolytics and hypnotics across age groups (0-29 years) and sex over the last 15 years in a large, representative general population. The study used data from a nationwide prescription database, which included information on all drugs dispensed from any pharmacy in Norway from 2004 through 2019. Age-specific trends revealed that the prevalence of use among children and adolescents up to age 14 was consistently low, with the exception of a substantial increase in use of melatonin from age 5. From age 15-29, adolescents and young adults used more prescription drugs with increasing age at all time points, especially analgesics and drugs with higher potential for misuse. Time trends also revealed that children from age 5 were increasingly dispensed melatonin over time, while adolescents from age 15 were increasingly dispensed analgesics, including opioids, gabapentinoids and paracetamol. In contrast, use of benzodiazepines and z-hypnotics slightly declined in young adults over time. Although trends were similar for both sexes, females used more prescription drugs than their male peers overall. The upsurge in use of prescription analgesics, anxiolytics and hypnotics among young people is alarming.Trial registration The study is part of the overarching Killing Pain project. The rationale behind the Killing Pain research was pre-registered through ClinicalTrials.gov on April 7, 2020. Registration number NCT04336605; https://clinicaltrials.gov/ct2/show/record/NCT04336605 ., (© 2022. The Author(s).)

Standard pulse oximeters estimate arterial blood saturation (SaO 2 ) non-invasively by emitting and detecting light of a specific wavelength through a cutaneous vascular bed, such as a digit or the ear lobe. The quantity measured at these peripheral sites is designated as oxygen saturation (SpO 2 ). Most reliable pulse oximeters are calibrated from measurements of healthy volunteers using some form of oxygen desaturation method. As the degree of inducible hypoxemia is limited, the calibration below achievable desaturation levels is usually extrapolated, leading to potential measurement error at low SaO 2 values, especially in highly pigmented skin. Such skin color-related errors (SCRE) are the topic of this scoping review. Specifically, this study aimed to identify the combined impact of skin color and reduced SaO 2 on the non-invasive assessment of SpO 2 and report the consequences of potential inaccuracies. Three databases were searched (Cumulated Index to Nursing and Allied Health Literature (CINAHL), PubMed, and Web of Science) for peer-reviewed prospective and retrospective studies published in English between 2000 and 2022 involving human patients with hypoxemia that included a measure of skin color (Fitzpatrick scale or race/ethnicity). Ten studies met the criteria and were included in the final review. Eight of these studies reported statistically significant higher pulse oximeter readings in darker-skinned patients with hypoxia compared to their arterial blood gas measurements. Occult hypoxia was more prevalent in Black and Hispanic patients than in White patients. Minority patients overall (Black, Asian, and American Indian) were more likely to have a SaO 2 < 88% that was not detected by pulse oximetry (occult hypoxemia) during hospitalization. With greater levels of hypoxemia, the differences between SpO 2 and SaO 2 were greater. If SaO 2 was < 90%, then SpO 2 was overestimated in all ethnicities but worse in minorities. In conclusion, the bias found in pulse oximeter readings in the skin of color broadly impacts patients with hypoxemia. The failure of SpO 2 measuring devices to detect occult hypoxemia can delay the delivery of life-saving treatment to critically ill patients requiring respiratory rehabilitation and supplemental oxygen therapy. This may lead to adverse health outcomes, increased in-hospital mortality, and complications such as organ dysfunction. An improvement in pulse oximeter detection mechanisms that would include all skin pigmentations is therefore much desired to optimize individual healthcare status and minimize disparities in treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Aoki et al.)

Background: Opioid maintenance treatment (OMT) has the potential to reduce mortality rates substantially. We aimed to compare all-cause and overdose mortality among OMT patients while in or out of OMT in two different countries with different approaches to OMT., Methods: Two nation-wide, registry-based cohorts were linked by using similar analytical strategies. These included 3,637 male and 1,580 female patients enrolled in OMT in Czechia (years 2000-2019), and 6,387 male and 2,078 female patients enrolled in OMT in Denmark (years 2007-2018). The direct standardization method using the European (EU-27 plus EFTA 2011-2030) Standard was employed to calculate age-standardized rate to weight for age. All-cause and overdose crude mortality rates (CMR) as number of deaths per 1,000 person years (PY) in and out of OMT were calculated for all patients. CMRs were stratified by sex and OMT medication modality (methadone, buprenorphine, and buprenorphine with naloxone)., Results: Age-standardized rate for OMT patients in Czechia and Denmark was 9.7/1,000 PY and 29.8/1,000 PY, respectively. In Czechia, the all-cause CMR was 4.3/1,000 PY in treatment and 10.8/1,000 PY out of treatment. The overdose CMR was 0.5/1,000 PY in treatment and 1.2/1,000 PY out of treatment. In Denmark, the all-cause CMR was 26.6/1,000 PY in treatment and 28.2/1,000 PY out of treatment and the overdose CMR was 7.3/1,000 PY in treatment and 7.0/1,000 PY out of treatment., Conclusion: Country-specific differences in mortality while in and out of OMT in Czechia and Denmark may be partly explained by different patient characteristics and treatment systems in the two countries. The findings contribute to the public health debate about OMT management and may be of interest to practitioners, policy and decision makers when balancing the safety and accessibility of OMT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gabrhelík, Hesse, Nechanská, Handal, Mravčík, Tjagvad, Thylstrup, Seid, Bukten, Clausen and Skurtveit.)

Aims: Certain risk constellations of parental drinking, mental health and years of education are prospectively associated with offspring's risk for a diagnosis of anxiety/depression, but it remains unknown how they may relate to other aspects of offspring's mental health. We examined whether such risk constellations were also prospectively associated with the extent of offspring's utilisation of healthcare services for anxiety/depression., Methods: The sample included 8773 adolescent offspring of 6696 two-parent families who participated in the Nord-Trøndelag Health Study in Norway. The exposures consisted of five parental risk constellations characterised by drinking frequencies and quantities, years of education and mental health previously derived based on the parental self-reports using latent profile analysis. The outcomes were the number of years in contact, and the total number of consultations/visits, with healthcare services for anxiety/depression in adolescents and young adults as recorded in healthcare registries in the period 2008-2014. Associations were examined using zero-inflated negative binomial regression models, accounting for demographics and offspring's early mental health., Results: Parental risk constellations were not significantly associated with the extent of offspring's healthcare utilisation for anxiety/depression during the seven-year study period, neither in respect of number of years nor in number of contacts., Conclusions: Offspring of four risky constellations were no more likely to use healthcare services for longer time periods or have more consultations/visits than offspring of the lowest-risk constellation. Parental risk constellations appear more informative for understanding disorder aetiology than for understanding management and treatment of anxiety and depression during adolescence and early adulthood.

Background: Opioids may modulate the immune function through opioid receptors on immune cells. Long-term consequences of prenatal opioid exposure on the immune system, such as childhood asthma, are unknown. Objectives: To investigate whether prenatal opioid exposure is associated with the risk of childhood asthma. Methods: Cohort study using linked nationwide registers in Denmark (1996-2015), Norway (2005-2015), and Sweden (2006-2013). Children born by mothers who were chronic opioid analgesics users before pregnancy ( n = 14,764) or who were receiving opioid maintenance therapy (OMT) before or during pregnancy ( n = 1,595) were identified based on information from each of the medical birth registers and prescription registers. Long-term opioid analgesics exposed children were compared to short-term exposed or unexposed, whereas OMT exposed children were compared to OMT unexposed. Asthma among children ≥1 years of age was defined as two or more filled prescriptions of antiasthmatic medication within 365 days, or a diagnosis of asthma. Hazard ratios (HRs) were calculated using Cox proportional hazards regression with attained age as the time scale. Inverse probability of treatment weights based on propensity scores were applied to adjust for measured confounders. Individual level data from Norway and Sweden were pooled, whereas individual level data from Denmark were analyzed separately. For the opioid analgesics comparisons, adjusted HRs (aHR) from the combined Norwegian/Swedish data and the Danish data were pooled in a fixed-effects meta-analysis. Results: For the opioid analgesics cohort, no increased risk of asthma was observed in long-term exposed children neither compared with unexposed [aHR = 0.99 (95% CI 0.87-1.12)], nor compared with short-term exposed [aHR = 0.97 (0.86-1.10)]. No increased risk of asthma was observed in OMT exposed compared with OMT unexposed children [Norway/Sweden: aHR = 1.07 (0.60-1.92), Denmark: aHR = 1.25 (0.87-1.81)]. Results from sensitivity analyses, where potential misclassification of the outcome and misclassification of OMT exposure were assessed, as well as starting follow-up at 6 years of age, showed that the estimates of association were generally robust. Conclusion: We found no association between prenatal exposure to opioids and risk of childhood asthma. Results were consistent across two different opioid exposure groups with different confounder distributions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer NT declared a shared affiliation with the author(s) MH and SS to the handling editor at the time of review., (Copyright © 2023 Odsbu, Handal, Hjellvik, Hernandez-Diaz, Kieler, Nørgaard, Skurtveit, Esen and Mahic.)

Background: One measure to support optimal opioid prescription is academic detailing (AD) with one-to-one visits by trained professionals (academic detailers) to general practitioners (GPs)., Objective: To investigate the usefulness of AD visits on GPs' opioid prescribing patterns in Norway, and academic detailers' experiences with AD visits to GPs on opioid prescription., Methods: Design: A quantitative registry study on opioid prescriptions and a qualitative focus group interview study with academic detailers., Participants: For the registry study, municipalities where more than 75% of the GPs had received an AD visit were considered intervention municipalities, whereas in the non-intervention municipalities no GPs had received AD-visits. In the focus groups, academic detailers who had conducted three or more AD-visits were invited to participate., Intervention: A campaign on opioid prescription with AD visits using a brochure with key messages based on the national guideline for treatment of chronic non-cancer pain and updated evidence on the potential benefits and risks of prescribing opioids. The AD visits in the campaign were planned for 20-25 min in a one-to-one setting in the GP's office., Main Measures: The Norwegian Prescription Database (NorPD) was utilized for registry data. Data on amount of drugs dispensed are recoded as Defined Daily Doses (DDDs)., Results: Compared to non-intervention, the intervention resulted in a decrease in the number of prevalent and incident users of opioids and incident users of reimbursed opioids for chronic non-cancer pain in municipalities in Central Norway. The results from the focus group interviews were categorized into the themes: "To get in position", "Adjusting messages", "What did the GPs struggle with, in relation to opioid prescription?" and "Did we reach the right recipients with the visits?"., Conclusions: In Central Norway, the intervention resulted in a desired effect on number of opioid users. According to the academic detailers, the GPs' length of working experience and familiarity with the topic gave different presumptions for making use of the information presented in the AD-visits., (© 2023. The Author(s).)

Objective: To study patterns of antidepressant, anxiolytic, and hypnotic drug utilization in Denmark, Norway, and Sweden during the first year of the COVID-19 pandemic., Methods: The monthly observed number of prescription fills of antidepressants, benzodiazepines and benzodiazepine-related hypnotics (BZ), and other anxiolytics and hypnotics (OAH) per population in 2020 were compared with predicted numbers based on analysis of covariance of prescription fills during 2015-2019., Results: In March 2020, there was an increased number of prescription fills for antidepressants, anxiolytics, and hypnotics in youths and adults aged 20-59 years in Denmark, Norway, and Sweden. Antidepressant prescription fills increased between 13.5 % and 31.3 % at the end of 2020 in all age groups in Denmark and 17.4 % in youths in Norway. BZ drug prescription fills increased by 20.8 % at the end of 2020 in the 20-59 year age group in Denmark and decreased by 16.7 % in youths in Sweden. A general increase of prescription fills of OAH at the end of 2020 was observed in all countries (range 24.0-80.0 % in Denmark, 11.5-30.8 % in Norway, and 9.1-12.1 % in Sweden). Increases of prescription fills of OAH occurred earlier in Denmark., Limitations: Aggregated data with lack of information on indications., Conclusions: Peaks of utilization of antidepressants, anxiolytics, and hypnotics observed in March 2020 may reflect medication stock piling. Increased antidepressant drug utilization in Denmark and in Norwegian youths together with the general increase in OAH utilization in the Scandinavian countries in late 2020 may indicate an increase of symptoms of depression and anxiety, as well as disturbed sleep., Competing Interests: Conflict of interest CEC, PK, and JR are employed at the Centre for Pharmacoepidemiology, Karolinska Institutet, which receives grants from several entities (pharmaceutical companies, regulatory authorities, and contract research organizations) for performance of drug safety and drug utilization studies, with no relation to the work reported in this paper. MT, MB, SS, RW, and MH declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There is a lack of studies on methamphetamine (MA) exposure and morbidity in children beyond the perinatal period., Objectives: We compared morbidity in children (0-3 years) with prenatal MA exposure to opioid-exposed and to non-exposed children., Methods: We used data from a Czech nationwide, registry-based cohort study (2000-2014). Children, who reached 3 years of age, of mothers hospitalized with (i) MA use disorder during pregnancy (MA; n = 194), (ii) opioid use disorder during pregnancy (opioids; n = 166), and (iii) general population (GP; n = 1,294,349) with no recorded history of substance use disorder (SUD). Information on inpatient contacts, length of stay, and diagnoses (International Statistical Classification of Diseases and Related Health Problems 10th Revision [ICD-10]) were assessed. Crude and adjusted odds ratios (aOR), 95% confidence interval (CI) for the risk of hospitalization, and for getting diagnosis from the ICD-10 diagnosis chapters were calculated using binary logistic regression. A stratified analysis on hospitalizations with SUD of mothers was performed., Results: No significant differences were found in the measures of hospitalization between the MA and opioid groups. Children prenatally exposed to MA and opioids had higher numbers of hospitalizations and diagnoses and longer stays in hospital than children in the GP. Increased risks of certain infectious and parasitic diseases were found in both MA (aOR = 1.6; CI: 1.1-2.3) and opioid (aOR = 1.9; 1.3-2.8) groups as compared to the GP group. The most pronounced difference in stratified analysis on maternal hospitalizations related to SUD after birth was observed for injury, poisoning, and certain other consequences of external causes in the strata of the MA group who had hospitalized mothers (aOR 6.3, 1.6-24.6) compared to the strata without maternal hospitalizations (aOR 1.4, 0.9-2.3)., Conclusion: This study suggests that children born to mothers using MA during pregnancy have similar morbidity during the first 3 years of life but higher than the GP. The excess of risk was primarily due to infections and injuries in the MA group., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Importance: Evidence is limited regarding the safety of prenatal benzodiazepine and z-hypnotic exposure and its association with long-term neurodevelopment in childhood., Objective: To quantify the associations of the timing and number of intervals of prenatal exposure to benzodiazepines and/or z-hypnotics with the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood., Design, Setting, and Participants: This cohort study used data from the 1999 to 2008 population-based Norwegian Mother, Father and Child Cohort Study, which are linked to the Medical Birth Registry of Norway, Norwegian Patient Registry, and Norwegian Prescription Database. Two populations of participants were created: a full sample and a mental health sample. The full sample included mothers and their live-born singletons, whereas the mental health sample was restricted to offspring of mothers who reported anxiety, depression, or sleeping problems during pregnancy or 6 months before pregnancy. Data were analyzed from September 2021 to February 2022., Exposures: Maternal self-report of benzodiazepine and/or z-hypnotic use during pregnancy was grouped into early pregnancy exposure and middle and/or late pregnancy exposure for analysis of the association with timing of exposure, and number of 4-week intervals of exposure was classified (single [1] vs multiple [≥2]) for analysis of the association with number of exposed intervals., Main Outcome and Measures: The outcome was ADHD, defined as time to ADHD diagnosis or filled prescription for ADHD medication. To control for confounding, inverse probability of treatment-weighted Cox proportional hazards regression models were used. Hazard ratios and 95% CIs were estimated. The weights were derived from propensity score modeling of the probability of benzodiazepine and/or z-hypnotic exposure as a function of potential confounders between the exposure and the outcome, including maternal symptoms of depression and anxiety., Results: The full sample comprised 82 201 pregnancies, and the mental health sample included 19 585 pregnancies. In total, 681 offspring (0.8%) in the full sample and 468 offspring (2.4%) in the mental health sample were prenatally exposed to benzodiazepines and/or z-hypnotics. After weighting, exposure in early (hazard ratio, 0.74; 95% CI, 0.39-1.94) and middle and/or late (hazard ratio, 0.76; 95% CI, 0.35-1.61) pregnancy was not associated with increased risk of childhood ADHD. There was no evidence of substantial association between the number of exposed intervals during pregnancy and childhood ADHD., Conclusions and Relevance: Results of this study suggest that there may be no increased risk of childhood ADHD associated with prenatal exposure to benzodiazepines and/or z-hypnotics, regardless of timing of exposure and number of exposed intervals. However, these findings should be interpreted with caution due to low study power.

Objective: We examined the risk of developing a future alcohol use disorder (AUD) among offspring of families with different constellations of parental risk factors., Method: We analyzed a sample of 8,774 offspring (50.2% male) from 6,696 two-parent families who participated in the Nord-Trøndelag Health Study in Norway when offspring were 13-19 years old in 1995-1997 or 2006-2008. Based on population registry information and parental Nord-Trøndelag Health Study self-reports, families were classified via Latent Profile Analysis into fiver risk constellations reflecting parents' education, drinking quantities and frequencies, and mental health. Information about AUD-related diagnoses, treatments, and prescriptions for all offspring in the period between 2008 and 2016 was obtained from 3 national health registries and pooled to reflect any AUD. The likelihood of AUD in offspring was examined with a set of nested logistic regression models., Results: Registry records yielded 186 AUD cases (2.1%). Compared with the lowest-risk constellation, offspring from two constellations were more likely to present with AUD in unadjusted analyses. After adjusting for all covariates, including offspring's alcohol consumption and witnessing parental intoxication during adolescence, AUD risk remained elevated and statistically significant (adjusted odds ratio = 2.34, 95% confidence interval = 1.14, 4.85) for offspring from the constellation characterized by at least weekly binge drinking, low education, and poor mental health in both parents., Conclusion: Weekly binge drinking by both parents was associated with future AUD risk among community offspring in Norway when clustered with additional parental risks such as poor mental health and low educational attainment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Previous studies have defined long-term opioid use in varying ways, decreasing comparability, reproducibility and clinical applicability of the research. Based on recommendations from recent systematic reviews, we aimed to develop a methodology to estimate the prevalence of use persisting more than three months utilizing one of the Nordic prescription registers. We used the Norwegian Prescription Register (NorPD) to extract data on all opioid dispensations between 1 January 2004 and 31 October 2019. New users of opioids (washout 365 days) were defined as long-term users if they fulfilled two criteria: (1) they had ≥2 dispensations of opioids, 91-180 days apart; (2) days 0-90 included ≥90 dispensed administration units (e.g., tablets) of opioids. Overall, there were 2,543,224 new users of opioids during the study period. Of these, 354,666 (13.9%) fulfilled the criteria for long-term opioid use at least once. Compared with those who did not fulfil the criteria (short-term users), long-term users were older, more likely women and used tramadol, oxycodone and buprenorphine more frequently as their first opioid. In conclusion, we found that 1/7 of opioid users continued use longer than 3 months. Future outcome research should identify the clinically most important dose requirements for long-term opioid use criteria., (© 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Background: Long-term use of opioids may have undesirable consequences. We have investigated long-term opioid use in patient groups that were prescribed opioids for various indications (chronic pain, palliative care, other (white prescriptions, not generally covered by the Norwegian National Insurance Scheme)) as well as the groups' concomitant use of some other addictive medications., Material and Method: Persons registered in the Norwegian Prescription Database with at least one filled prescription of an opioid in the period 2011-19 were included. Long-term use in a calendar year was defined as the dispensing of > 180 defined daily doses or > 4 500 mg oral morphine equivalents distributed over at least 3 periods of 3 months., Results: The number of long-term opioid users was 50 422 in 2011 and 59 996 in 2019 (10.1 and 10.7 % of all opioid users). The number who received opioids on blue prescription (partly covered by the Norwegian National Insurance Scheme) for chronic pain increased in the period by 9 952 persons, but the majority (n=38 006, 63.3 %) continued to receive opioids exclusively on white prescription in 2019. A total of 15 623 (41.1 %) and 14 881 (39.2 %), respectively, of the long-term opioid users who received opioids solely on white prescription in 2019 also received benzodiazepines and Z-hypnotics in the same year. Of the 23 967 long-term users who also received benzodiazepines, 88 % were dispensed opioids and benzodiazepines on the same day at least once in 2019., Interpretation: Prolonged prescribing of opioids on white prescription and concurrent prescribing of other addictive drugs may indicate undesirable use with no clear indication.

Objective: To determine the association between child attention-deficit/hyperactivity disorder (ADHD) and prenatal exposure to selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitor antidepressants, by timing and duration, with quantification of bias due to exposure misclassification., Design: Norwegian Mother, Father and Child Cohort Study and national health registries., Setting: Nationwide, Norway., Population: A total of 6395 children born to women who reported depression/anxiety in pregnancy and were either medicated with SSRI/SNRI in pregnancy (n = 818) or non-medicated (n = 5228), or did not report depression/anxiety but used antidepressants 6 months before pregnancy (discontinuers, n = 349)., Main Outcome Measure: Diagnosis of ADHD or filled prescription for ADHD medication in children, and mother-reported symptoms of ADHD by child age 5 years., Results: When the hazard was averaged over the duration of the study follow up, there was no difference in ADHD risk between ever in utero SSRI/SNRI-exposed children and comparators (weighted hazard ratio [wHR] 1.07, 95% CI 0.76-1.51 versus non-medicated; wHR 1.53, 95% CI 0.77-3.07 versus discontinuers). Underestimation of effects due to exposure misclassification was modest. In early childhood, the risk for ADHD was lower with prenatal SSRI/SNRI exposure compared with no exposure, and so were ADHD symptoms (weighted β -0.23, 95% CI -0.39 to -0.08); this risk became elevated at child age 7-9 years (wHR 1.93, 95% CI 1.22-3.05). Maternal depression/anxiety before pregnancy was independently associated with child ADHD., Conclusion: Prenatal SSRI/SNRI exposure is unlikely to considerably increase the risk of child ADHD beyond that posed by maternal depression/anxiety. The elevated risk at child age 7-9 years needs to be elucidated., Tweetable Abstract: Women with depression who use antidepressants in pregnancy do not have greater risk of having children with ADHD. Findings in school-age children needs follow up., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Prescribing opioids for children and adolescents should be reserved for advanced life-limiting diseases and moderate-to-severe acute pain. Pediatric codeine use is discouraged by several authorities, but the effects of these recommendations are not fully known. We investigated opioid utilization trends among 0-18-year-olds and characterized those who filled ≥1 opioid prescriptions, with emphasis on those who did so >3 times within a year., Methods: The prevalence of filled opioid prescriptions among 0-18-year-old Norwegians in 2010-2018 (N = 77,942) was measured from nationwide healthcare registries. Characteristics, healthcare utilization, and other drug use of those who newly filled 1, 2-3, or >3 opioid prescriptions in 2011-2014 were compared to 2015-2018, excluding persons with cancer., Results: From 2010 to 2018, the prevalence of opioid use decreased from 9.0 to 7.0 per 1000 persons. The largest decrease was among children <12 years, from 4.1 to 0.4 per 1000 persons, mainly due to decreasing codeine use. The proportion of those who filled >3 opioid prescriptions was 2.1% in 2011-2014 and 3.1% in 2015-2018. Those with >3 dispensations had a median of 4 contacts/year with secondary healthcare (interquartile range 2-7); the most frequent diagnoses indicated post-surgery follow-up. Most commonly dispensed other drugs were non-steroidal anti-inflammatory drugs., Conclusions: Opioid dispensations for the young have declined in recent years. Multiple opioid dispensations were rare and associated with frequent healthcare utilization. Reducing codeine is in line with recommendations, but the effects of decreased opioid use on the quality of pain management remain unknown., (© 2021 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Purpose: To estimate the association between Attention-Deficit/Hyperactivity Disorder (ADHD) in children in preschool and primary school, and prenatal exposure to non-steroidal anti-inflammatory drugs (NSAIDs) by timing and duration., Methods: This study was based on the Norwegian Mother, Father and Child Cohort Study linked to the Medical Birth Registry of Norway, the Norwegian Patient Registry (NPR) and the Norwegian Prescription Database (NorPD). NSAID exposure was identified by maternal self-report in pregnancy. Child diagnosis of ADHD was obtained from NPR and NorPD. Symptoms of ADHD at age 5 years were measured using Conners' Parent Rating Scale-Revised, where higher scores correspond to more symptoms. To account for time-varying exposure and confounders, marginal structural models were fitted to estimate hazard ratios and mean difference in z-scores., Results: The analyses on ADHD diagnosis and ADHD symptoms included 56 340 and 34 961 children respectively. Children exposed to NSAIDs prenatally had no increased risk of ADHD diagnosis (first trimester: HR 1.12, 95% CI 0.86;1.45, second trimester: HR 0.98, 95% CI 0.69;1.38, third trimester: HR 0.68, 95% CI 0.31; 1.46) or ADHD symptoms (first trimester: standardized mean difference 0.03, 95% CI -0.03;0.09, second trimester: standardized mean difference 0.03, 95% CI -0.04;0.11, third trimester: standardized mean difference 0.11, 95% CI -0.03; 0.25). There was no duration-response relationship for either outcome., Conclusion: Though non-differential misclassification of the exposure may have attenuated results, these findings are reassuring and suggest no substantially increased risk of ADHD diagnosis or symptoms in children prenatally exposed to NSAIDs, regardless of timing or duration., (© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Importance: Prior studies have reported that the use of illicit opioids during pregnancy is associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring; however, evidence regarding the association of analgesic opioids is limited., Objective: To examine the association of timing and duration of prenatal analgesic opioid exposure with ADHD in children., Design, Setting, and Participants: This cohort study uses data from the Norwegian Mother, Father and Child Cohort study (1999-2008), a nationwide birth cohort study linked to national health registries, with a mean (SD) follow-up of 10.8 (2.2) years. A total of 73 784 live-born singleton children born to 62 013 mothers who reported a pain-related condition before and/or during pregnancy were included, with 2 comparator groups: (1) mothers who did not use any opioids and (2) mothers who used opioids before pregnancy only. Data were analyzed from June to December 2020., Exposures: Maternal self-report of analgesic opioid use during pregnancy, by timing (early and middle and/or late) and duration (≥5 weeks vs ≤4 weeks)., Main Outcomes and Measures: Diagnosis of ADHD or filled prescription for ADHD medication in children and symptoms of ADHD at child age 5 years, measured by Conners' Parent Rating Scale-Revised. Inverse probability of treatment weights were used to control for measured confounding. Cox regression was used to estimate hazard ratios (HRs) and 95% CIs., Results: The analyses of ADHD diagnosis and ADHD symptoms included 73 480 children (35 996 [49.0%] girls; mean [SD] maternal age, 30.0 [4.6] years) and 31 270 children (15 377 [49.2%] girls; mean [SD] maternal age, 30.5 [4.4] years), respectively. Overall, 1726 children in the ADHD diagnosis sample (2.3%) and 667 children in the ADHD symptom sample (2.1%) were exposed to an analgesic opioid at least once during gestation. No associations between timing of prenatal analgesic opioid exposure and ADHD diagnosis or symptoms was found. Exposure for 5 or more weeks was associated with an increased risk of ADHD diagnosis (HR, 1.60, 95% CI, 1.04-2.47) compared with exposure for 4 weeks or less; however, there was no such association for the risk of ADHD symptoms., Conclusions and Relevance: In this cohort study, a slightly elevated risk of ADHD diagnosis after prenatal analgesic opioid exposure for 5 or more weeks was found compared with exposure for 4 weeks or less. This result may be driven by longer duration of use; however, the role of residual or unmeasured confounding cannot be excluded. This finding needs to be replicated in other studies.

As previously indicated an association may exist between early sleep problems in infants and toddlers, and a diagnosis of attention deficit hyperactivity disorder (ADHD). The aim of this study was to study if this association could be replicated in a complete nationwide cohort of children. Prospective cohort study using national registries. All children born in Norway from January 2004 to December 2010 were included (N = 410,555). Information on hypnotic drugs dispensed to children 0-3 years of age outside of institutions was collected from the Norwegian Prescription Database and used as a proxy for sleep problems. The outcome ADHD (ICD-10), as diagnosed by specialists in the Child Mental Health Service, was obtained from the Norwegian Patient Registry. Data were analysed using weighted estimation in Cox regression. The unadjusted weighted hazard ratio (wHR) for a later diagnosis of ADHD in children dispensed two or more prescriptions for any hypnotic drug, compared to zero prescriptions, was 2.30 [95% confidence interval (CI) 1.63-3.23] for girls and 1.75 (95% CI 1.48-2.07) for boys. For the sedative antihistamine trimeprazine the corresponding wHR was 3.71 (95% CI 1.83-7.52) for girls and 2.78 (95% CI 2.04-3.80) for boys. After adjusting for parental ADHD and parental education the wHR for trimeprazine users was 2.81 (95% CI 1.34-5.88) for girls and 2.33 (95% CI 1.70-3.20) for boys. Infants and toddlers who were dispensed hypnotics had an increased risk of ADHD at school age. This association was most pronounced with the use of trimeprazine, a drug traditionally prescribed to toddlers for sleep problems in Norway. After adjusting for parental ADHD and educational level the risk for ADHD among the trimeprazine users was still more than twice the risk among controls.

Introduction: Opioid maintenance treatment (OMT) varies across settings and between countries. We plan to use data from several nationwide health and population registers to further improve the knowledge base established from earlier studies. Our aim is to study OMT adherence trajectories and to identify factors associated with improved outcomes for OMT patients across the Czech Republic, Norway and Denmark, in order to further improve OMT and our understanding of the key elements of treatment success., Methods and Analysis: The registry-based cohort approach across the three countries allows us to link data from a range of registers on the individual level, by using personal identifiers in nationwide cohorts of OMT and non-OMT patients and the general non-using populations. A total of ~21 500 OMT patients over the last two decades in all three countries will be included in the study. The following outcome variables (based on the International Classification of Diseases, 10th Revision codes) will be obtained from relevant registers: treatment adherence to OMT, comorbidity (somatic and mental health), and all-cause and cause-specific mortality. Outcomes of the country-specific analyses will be pooled., Ethics and Dissemination: The national OMT cohorts have been approved by the ethics committees in the respective countries. Data will be stored according to national and local guidelines and treated confidentially, and all data will be analysed separately for each country and compared across countries. Findings will be disseminated in peer-reviewed scientific journals, national and international conferences, and in briefings to inform clinical decision-making., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is limited knowledge on the adverse outcomes in newborns after maternal methamphetamine (MA) use during pregnancy., Objectives: To compare neonatal outcomes in newborns exposed to MA with the newborns of opioid-exposed mothers and of mothers from the general population (GP)., Method: A cohort study using nationwide registries in Czechia (2000-2014). Women hospitalized with a main diagnosis of MA use disorder during pregnancy (n = 258) and their newborns were defined as MA-exposed. The comparison groups consisted of women (n = 199) diagnosed with opioid use disorder during pregnancy, defined as opioid-exposed, and women (n = 1,511,310) with no substance use disorder diagnosis (GP). The neonatal outcomes studied were growth parameters, gestational age, preterm birth, and Apgar score. To explore the associations between MA exposure and neonatal outcomes, regression coefficients (b) and odds ratios from multivariable linear and binary logistic regression were estimated., Results: MA-exposed women had similar socio-economic characteristics to opioid-exposed, both of which were worse than in the GP. After adjustment, MA exposure was associated with a more favourable birthweight when compared to the opioid-exposed (adjusted mean differences [aMD] b = 122.3 g, 95% CI: 26.0-218.5) and length (aMD b = 0.6 cm, 0.0-1.1). Unadjusted results from the comparison with the GP showed that the MA group had poorer neonatal outcomes, especially in the growth parameters. Adjustment for background characteristics had a profound effect on the comparison with the GP. After adjustment, MA exposure was associated only with a slightly reduced birthweight (aMD b = -63.0 g, -123.0 to -3.1) and birth length (aMD b = -0.3 cm, -0.6 to 0.0)., Conclusions: Although the observed negative outcomes were large in the MA-exposed newborns, the adjustment had a profound effect on the comparison with the GP, indicating the large influence of lifestyle and socio-economic factors in these high-risk pregnancies. MA-exposed newborns had better neonatal outcomes compared to opioids-exposed., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: With recent changes in legislation regulating recreational and medical cannabis use around the globe, increased use in pregnancy is to be expected., Objectives: To investigate the association between cannabis use during pregnancy and birth outcomes., Method: Data from the Norwegian Mother and Child Cohort Study (MoBa), a prospective pregnancy cohort, were used. Participants were recruited from all over Norway between 1999 and 2008: 9,312 women with 10,373 pregnancies who reported use of cannabis before or in pregnancy. Women reported on their illegal drug use before pregnancy and at pregnancy weeks 17/18 and 30 and at 6 months postpartum. Linear regression was used to estimate crude and adjusted effects of prenatal cannabis exposure on birth outcomes., Results: In 10,101 pregnancies, women had used cannabis before pregnancy but not during pregnancy. In 272 pregnancies, women had used cannabis during pregnancy, and among these, in 63 pregnancies, women had used cannabis in at least 2 periods. In adjusted analyses for potential confounders, only cannabis use during at least 2 periods of pregnancy showed statistically significant effects on birth weight. The effect was observed in the complete cohort (B = -228 g, 95% CI = -354 to -102, p < 0.001) and for the subgroup where information about the child's father was available (B = -225 g, 95% CI = -387 to -63, p = 0.01). Our results may indicate that prolonged use causes more harm, whereas short-term use did not indicate adverse effects on birth outcomes., Conclusions: There was a statistically significant and clinically relevant association between the use of cannabis during pregnancy and reduced birth weight. Clinicians should screen not only for cannabis use but also for the length and intensity of use as part of a comprehensive substance use screening., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Purpose: Autism spectrum disorder (ASD) has a high rate of comorbidity. While many children with ASD are exposed to psychotropic medicines, their efficacy and safety in these patients are unclear. There is a need for more detailed knowledge on which medicines are most commonly used and for which disorders. We aimed to investigate (a) prevalence and incidence rate of ASD among Norwegian children, and further, among newly diagnosed ASD children in 2014, study the (b) co-occurrence of neuropsychiatric disorders, (c) use of psychotropic drugs, and (d) the relationship between co-occurring diagnoses and use of psychotropic drugs. Method: Nationwide registry-based study of children 2-17 years old in Norway. Results: The ASD prevalence was 0.76% and the incidence rate was 0.12% in 2014. Of the children who received an initial ASD diagnosis in 2014 ( n = 1,234), 64.8% had one or more co-occurring neuropsychiatric diagnosis. Psychotropic medication use was moderate (~20% used stimulants or hypnotics) in general, and low in children without comorbidity (nearly only hypnotics). There was a good accordance between co-occurring diagnoses and indication for the prescribed medications. Conclusions: Children with newly diagnosed ASD mainly received psychotropic drugs to treat co-occurring neuropsychiatric conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Kiselev, Handal, Hjellvik, Reichborn-Kjennerud, Stoltenberg, Suren, Havdahl and Skurtveit.)

Purpose: There is an increasing number of children with in utero exposure to opioids. Knowledge about opioid safety in pregnancy, particularly for outcomes later in childhood is scarce. It has been suggested that opioids can modulate immune system and increase the risk of infections. Our goal was to study the impact of in utero opioid exposure on the immune system and the risk of infections in childhood., Methods: This population-based cohort study used nationwide registers from Denmark, Norway, and Sweden. Among pregnant women we identified users of opioids for two different indications, opioids used in opioid maintenance therapy (OMT) and opioids used for treatment of pain. We followed the exposed children and studied susceptibility for infections measured as number of antibiotic prescriptions expressed as Incidence rate ratios (IRRs) and diagnoses in specialist health care expressed as hazard ratios (HRs)., Results: After adjustment we did not observe increased risk for filling antibiotic prescriptions in children exposed to OMT opioids compared with OMT discontinuers (IRR, 1.08; 95% CI 0.81-1.44 in Norway and Sweden, and IRR, 0.74; 95% CI 0.63-0.88 in Denmark), or for diagnosis of infection in specialist health care (HR 0.83; 95% CI 0.55-1.26 in Norway and Sweden, and 0.82; 95% CI 0.62-1.10 in Denmark)., Conclusions: In this population-based cohort study, we did not observe increased risk of infections among children prenatally exposed to OMT opioids when compared to OMT discontinuers, nor long-term analgesic opioids exposed when compared to short-term analgesic opioids exposed., (© 2020 John Wiley & Sons Ltd.)