Attention-deficit/hyperactivity disorder in children following prenatal exposure to antidepressants: results from the Norwegian mother, father and child cohort study.

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 ß -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.

Consumption of and satisfaction with health care among opioid users with chronic non-malignant pain.

BACKGROUND: Although persons with chronic pain are frequent users of the health care system, they report poor satisfaction with health care services. Participants with persistent opioid use in Nord-Trøndelag Health Study (HUNT)3 report severe pain in spite of treatment. The aim of the study was to test the hypothesis that subjects with persistent opioid use have both a higher consumption of health care services and a poorer satisfaction than the remaining subjects reporting chronic pain. METHODS: This cross-sectional study was based on linkage of self-reported data from the substudy (10,238 were invited, 6927 met the inclusion criteria) of health care use in HUNT3; a population-based health survey during the years 2006-2008 and the complete national registers of the Norwegian Prescription Database and the Cancer Registry of Norway. Patients with chronic pain are stratified according to the level of opioid use as persistent users of opioids, intermittent users, and persons not using opioids. RESULTS: Persons with chronic non-malignant pain reported a higher consumption of all health care services compared to the control group. Consumption of health care services increased with increasing level of opioid use. Persons with persistent opioid use were highly satisfied with all health care services, although less satisfied than persons without chronic pain. CONCLUSIONS: Combined with previous findings of high levels of pain in spite of opioid treatment, the present findings indicate that symptomatic relief is not a prerequisite for patient satisfaction. The study shows higher patient satisfaction compared to previous studies.

Use of prescribed opioids by children and adolescents: Differences between Denmark, Norway and Sweden.

BACKGROUND: There are few studies on the use of opioids among children and adolescents. The aim of this study was to determine the 1-year prevalence of prescribed opioid dispensing in Denmark, Norway and Sweden, and to compare gender and age differences in the use of weak and strong opioids between the three countries. METHODS: Data on the dispensing of opioids were collected from the websites of the complete national prescription databases in the three countries. All individuals aged 0-19 with at least one prescription of opioids during the study period were included. RESULTS: The 1-year prevalence of opioid use among young individuals aged 0-19 years increased during the study period (2006-2012) in Denmark from 2.5 to 3.4 per thousand, in Norway from 10.7 to 13.4 per thousand and in Sweden from 5.9 to 7.1 per thousand. In all three countries, more boys than girls used opioids between the ages of 0 and 10, whereas girls were the major users in the age range 11-19. Use of opioids in all three countries was dominated by weak opioids, codeine being the most dominant in Norway and Sweden and tramadol in Denmark. CONCLUSIONS: The 1-year prevalence of prescribed opioid use among children and adolescents in Norway was far higher than in Denmark and Sweden. During the study period, an increasing use of opioids among children and adolescents was observed in all three countries.

Human naturally occurring and adaptive regulatory T cells secrete high levels of leukaemia inhibitory factor upon activation.

Leukaemia inhibitory factor (LIF) is a member of the IL-6 cytokine family which signals through cognate receptors and activates target genes involved in survival, apoptosis, proliferation, differentiation and suppression of differentiation in different cell types. Binding of LIF to the LIFRalpha/gp130 receptor complex has been shown to activate the Janus kinase-signal transducer and activator of transcription 3 pathway. Here we show that activation of naturally occurring and adaptive regulatory T cells leads to increased LIF expression which is abrogated by cyclic adenosine monophosphate. Furthermore, the LIF receptors gp130 and LIFRalpha are upregulated on the surface of activated T cells and signal transducer and activator of transcription 3 phosphorylation is increased. Interestingly, LIF was not required for suppressive function but rather appeared to have a stimulatory effect on T cells that served to modulate and counteract immunosuppression by regulatory T cells.