Maternal Antibiotic Use and Infections During Pregnancy and Offspring Asthma: The Norwegian Mother, Father and Child Cohort Study and a Nationwide Register Cohort

Maternal antibiotic use during pregnancy has been linked to asthma risk in children, but the role of underlying infections remains unclear. We investigated the association of maternal antibiotic use and infections during pregnancy with offspring risk of asthma. We used two population-based cohorts: the Norwegian Mother, Father and Child Cohort Study (MoBa) (n=53 417) and a register cohort (n=417 548). Asthma was defined based on dispensed asthma medications at 7 and 13 years from the Norwegian Prescription Database. Self-reported information on antibiotic use and infections during pregnancy was available in MoBa, while registrations of dispensed prescriptions was used to classify use of antibiotics in the register-based cohort. Maternal antibiotic use during pregnancy was associated with asthma at 7 years in both cohorts (aRR 1.23, 95% CI 1.11 - 1.37 in MoBa and aRR 1.21, 95% CI 1.16 - 1.25 in the register-based cohort) and asthma at 13 years in the register cohort (aRR 1.13, 95% CI 1.03-1.23) after adjusting for maternal characteristics. In MoBa, the estimate was attenuated after adjusting for infections during pregnancy. Maternal lower and upper respiratory tract infections (aRR 1.30, 95% CI 1.07 - 1.57 and aRR 1.19, 95% CI 1.09 - 1.30, respectively) and urinary tract infections (aRR 1.26, 95% CI 1.11 - 1.42) showed associations with asthma at 7 after adjusting for confounders, but estimates decreased after adjustment for antibiotics during pregnancy. Our findings suggest that both maternal antibiotic use and infections during pregnancy might be associated with an increased risk of asthma in childhood.

Sex differences in psychotropic and analgesic drug use before and after initiating treatment with acetylcholinesterase inhibitors

Background/aims The aim was to explore the impact of sex on prevalence, patterns and trends in the prescription of psychotropics and analgesics in users of acetylcholinesterase inhibitors (AChEIs), before and after AChEI initiation, compared to the general population. Methods A prospective study applying data from the Norwegian Prescription Database (NorPD) in the period 2004–2016. Prescription of antidepressants, antipsychotics, analgesics including opioids, benzodiazepines and z-hypnotics in persistent AChEI users was studied in a follow-up period from four years before to two years after AChEI initiation in men and women of four age groups: 37–64, 65–72, 73–80 and 81–88 years. Results Use of antidepressants, antipsychotics and weaker analgesics increased in both sexes during the follow-up period in 11.764 persistent AChEI users. Women with pre-dementia and dementia stages of AD showed a prescription pattern with more use of psychotropics and opioids than men, except for antipsychotics. Conclusion Female sex showed to have a significant influence on the prescriptions of psychotropics and analgesics in AD patients in a pre-dementia and dementia stage. The exception is for antipsychotics, that men used more than women. The prescription pattern showed a higher extent of polypharmacy of psychotropics and/or opioids in women than in men. The total prescription pattern of analgesics could indicate an undertreatment of pain in pre-dementia and dementia stages, most pronounced in men.

NSAID use is not associated with Parkinson’s disease incidence: A Norwegian Prescription Database study

Objective Whether use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of incident Parkinson’s disease (PD) remains unresolved. Here, we employed the Norwegian Prescription Database to examine whether NSAID use is associated with a lower incidence of PD. Methods We compared the incidence of PD among users of NSAIDs in a population-based retrospective study using the Norwegian Prescription Database from 2004 to 2017. In total 7580 PD patients were identified using dopaminergic therapy over time as proxy for PD diagnosis. Analyses were performed with minimum 90 and 365 defined daily dose (DDD) NSAID exposure, respectively. Time-dependent Cox regression model and a binary logistic regression analysis with a 5-year lag until PD diagnosis were performed for all NSAIDs. Results There was overall no decrease in incidence of PD among NSAID users compared to controls. Using a minimum of 90 or 365 DDD threshold of exposure produced similar results. Analysis of individual NSAIDs did not show difference in PD incidence compared to controls Age-specific incidence rates of PD were comparable to reported age-specific incidence rates in previous studies. Interpretation Our findings provide no evidence that cumulative high exposure to NSAIDs affects the risk of developing PD.

Perinatal use of triptans and other drugs for migraine—A nationwide drug utilization study

Objective To characterize nationwide utilization patterns of migraine pharmacotherapy before, during, and after pregnancy in women with triptan use. Methods Population-based data were obtained by linking the Medical Birth Registry of Norway and the Norwegian Prescription Database from 2006 to 2017. We included 22,940 pregnancies among 19,669 women with at least one filled triptan prescription, a proxy for migraine, in the year before pregnancy or during pregnancy. The population was classified into four groups: i) continuers; ii) discontinuers; iii) initiators, and vi) post-partum re-initiators. Participant characteristics and prescription fills for other drugs such as analgesics, antinauseants, and preventive drugs among the groups were examined, along with an array of triptan utilization parameters. Results In total, 20.0% of the women were classified as triptan continuers, 54.1% as discontinuers, 8.0% as initiators, and 17.6% as re-initiators. Extended use of triptans (≥15 daily drug doses/month) occurred among 6.9% of the continuers in the first trimester. The top 10% of triptan continuers and initiators accounted for 41% (95% CI: 39.2% - 42.5%) and 33% (95% CI: 30.3% - 35.8%) of the triptan volume, respectively. Triptan continuers and initiators had similar patterns of acute co-medication during pregnancy, but use of preventive drugs was more common among the continuers before, during, and after pregnancy. Conclusion Among women using triptans before and during pregnancy, one in four continued triptan treatment during pregnancy, and extended triptan use was relatively low. Triptan discontinuation during and in the year after pregnancy was common. Use of other acute migraine treatments was higher among both continuers and initiators of triptans. Women using preventive migraine treatment were most commonly triptan continuers and re-initiators after pregnancy. Prescribing to and counseling of women with migraine should be tailored to the condition severity and their information needs to promote optimal migraine management in pregnancy.

Antibacterial use by birth year and birth season in children 0-2 years in Norway

Introduction: Consumption of antibacterials in children follows seasonal cycles, and time to first treatment depends on birth season. The aim of this study was to describe dispensing rate, one-year periodic prevalence, and age at first prescription in children aged 0-2 years in Norway.Methods: We used data from the Norwegian prescription database and included all dispensed prescriptions on systemic antibacterials in 2008-2017 during the first three years of life to children born 2005-2014. We calculated age by subtracting birth month and birth year from date of collection of prescription. We used multiple linear regression to investigate the effect of birth season on age at first dispensed prescription.Results: We included 714 262 prescriptions to 281 888 individuals (53.1% boys). In 2016, one-year-old boys had the highest periodic prevalence (35.6%) and the highest dispense rate (545/1000 individuals), followed by one-year-old girls (32.6%, 478/1000 individuals). The lowest prevalence and dispense rate in all age groups was found towards the end of the period. Winter months had the highest proportion of dispensed prescriptions, and children born in autumn were significantly younger when collecting their first prescription. On average, boys collected their first prescription 26 days younger compared to girls.Conclusion: One-year-olds have the highest periodic prevalence and the highest dispense rate. This contrast with results from other studies on Norwegian data and is probably attributed to our use of birth month for calculation of age. Children born in autumn were younger when collecting their first prescription compared to other birth seasons. It is unknown whether this has any long-term clinical implications.

Consumption of oral anticancer drugs in Norway compared by different units of measurements – introduction of new DDDs

Background: Antineoplastic agents (ATC group L01) have not been assigned DDDs due to highly interindividualvariation in dosages. Consumption data has therefore been presented in other measurement units such as grams of active ingredient. However, the protein kinase inhibitors (PKIs) are a rapidly growing drug group that was introduced to the market recently and are administered orally in a fixed dose. DDDs were therefore established for the PKIs in 2020. In this study we aim to assess whether the newly assigned DDDs would better express drug utilisation patterns in Norway than the current units of measurement.Methods: Sales data for PKIs (ATC level L01E) by grams, cost, units and packages for 2019 were collectedfrom the Norwegian Drug Wholesales Statistics and data on number of prescriptions and prevalence for 2019were collected from the Norwegian Prescription Database (NorPD). DDDs were calculated by applying thevalues of the new DDDs.Results: The proportions of the different substances varied according to the unit of measurement. DDDs andpackages had the highest similarity and correlated better than grams with the prevalence of use in theNorwegian population. BCR-ABL tyrosine kinase inhibitors was the largest group accounting for 31% ofthe total consumption (DDD/1000 inhabitants/day) and imatinib was the most sold PKI in all units of measurement except cost.Conclusions: Using an international agreed unit of measurement gives reliability to the study result. Assignment of DDDs to PKIs will improve the quality of drug utilisation studies in this area.

Consultations and antibiotic treatment for urinary tract infections in Norwegian primary care 2006–2015, a registry-based study

Background Extensive use of antibiotics and the resulting emergence of antimicrobial resistance is a major health concern globally. In Norway, 82% of antibiotics is prescribed in primary care and one in four prescriptions are issued for the treatment of urinary tract infections (UTI). The aim of this study was to investigate time trends in antibiotic treatment following a consultation for UTI in primary care. Methods For the period 2006–2015 we linked data from the Norwegian Registry for Control and Payment of Health Reimbursements on all patient consultations for cystitis and pyelonephritis in general practice and out-of-hours (OOH) services, and data from the Norwegian Prescription Database on all dispensed prescriptions of antibiotics. Results Altogether 2,426,643 consultations by attendance for UTI took place in the study period, of these 94.5% for cystitis and 5.5% for pyelonephritis. Of all UTI consultations, 79.4% were conducted in general practice and 20.6% in OOH services. From 2006 to 2015, annual numbers of cystitis and pyelonephritis consultations increased by 33.9 and 14.0%, respectively. The proportion of UTI consultations resulting in an antibiotic prescription increased from 36.6 to 65.7% for cystitis, and from 35.3 to 50.7% for pyelonephritis. These observed changes occurred gradually over the years. Cystitis was mainly treated with pivmecillinam (53.9%), followed by trimethoprim (20.8%). For pyelonephritis, pivmecillinam was most frequently used (43.0%), followed by ciprofloxacin (20.5%) and sulfamethoxazole-trimethoprim (16.3%). For cystitis, the use of pivmecillinam increased the most during the study period (from 46.1 to 56.6%), and for pyelonephritis, the use of sulfamethoxazole-trimethoprim (from 11.4 to 25.5%) followed by ciprofloxacin (from 18.2 to 23.1%). Conclusions During the 10-year study period there was a considerable increase in the proportion of UTI consultations resulting in antibiotic treatment. Cystitis was most often treated with pivmecillinam, and this proportion increased during the study period. Treatment of pyelonephritis was characterized by more use of broader-spectrum antibiotics, use of both sulfamethoxazole-trimethoprim and ciprofloxacin increased during the study period. These trends, indicative of enduring changes in consultation and treatment patterns for UTIs, will have implications for future antibiotic stewardship measures and policy.

Smoking in early adulthood is prospectively associated with prescriptions of antipsychotics, mood stabilizers, antidepressants and anxiolytics

Background Whether smoking should be regarded as a risk factor for mental disorders remains unresolved. Prescribed psychotropic drugs can be used as indications for mental disorders. We investigated how smoking was prospectively related to prescription of antipsychotics, mood stabilizers, antidepressants, and anxiolytics. Methods Information about smoking, including the Fagerström Test for Nicotine Dependence, and relevant confounders, were obtained from the population-based Young in Norway Study (N = 2602), with four data collection waves between 1992 and 2006. These survey data were linked with information on prescriptions for psychotropic drugs from the comprehensive, nationwide Norwegian Prescription Database from 2007 to 2015. Results Daily smoking with high dependence in 2006 at age 28.5 (s.d. = 2.0) was associated with filling prescriptions of antipsychotics (OR, 6.57, 95% CI 2.19–19.70, p = 0.001), mood stabilizers (OR, 7.11, 95% CI 2.51–20.15, p < 0.001) and antidepressants (OR, 1.91, 95% CI 1.13–3.23, p = 0.016) 1–9 years later. Associations remained significant after adjustment for a variety of potential confounders measured before the assessment of smoking, including sociodemographic background, conduct problems, cannabis use, mental distress, and previous prescriptions for psychotropic medications. The association between smoking and prescription of anxiolytics was weaker and more unstable. Conclusions In this study of young adults, daily smoking with high dependence was associated with later prescriptions of antipsychotics, mood stabilizers and antidepressants, indicating smoking as a risk factor for mental disorders treated with these drugs.

GPs’ drug treatment for depression by patients’ educational level: registry-based study

BackgroundAntidepressant drugs are often prescribed in general practice. Evidence is conflicting on how patient education influences antidepressant treatment.AimTo investigate the association between educational attainment and drug treatment in adult patients with a new depression diagnosis, and to what extent sex and age influence the association.Design & settingA nationwide registry-based cohort study was undertaken in Norway from 2014–2016.MethodThe study comprised all residents of Norway born before 1996 and alive in 2015. Information was obtained on all new depression diagnoses in general practice in 2015 (primary care database) and data on all dispensed depression medication (Norwegian Prescription Database [NorPD]) 12 months after the date of diagnosis. Independent variables were education, sex, and age. Associations with drug treatment were estimated using a Cox proportional hazard model and performed separately for sex.ResultsOut of 49 967 patients with new depression (61.6% women), 15 678 were dispensed drugs (30.4% women, 33.0% men). Highly educated women were less likely to receive medication (hazard ratio [HR] = 0.93; 95% confidence interval [CI] = 0.88 to 0.98) than women with low education. No such differences appeared among men. Women aged 20–29 years were more likely to be treated with drugs than those aged 30–59 years, and women aged ≥70 years were more likely to receive drugs (HR = 1.65; 95% CI = 1.54 to 1.77) than those aged 20–29 years. The pattern was similar but less pronounced for men.ConclusionEducational differences in antidepressant therapy among women may reflect different treatment approaches that clinicians should be aware of to avoid unintended variation. Reasons for this variation and consequences for quality of treatment should be explored.