A multi-country cohort database study to assess pregnancy and infant outcomes after potential maternal or paternal exposure to cladribine tablets in the treatment of multiple sclerosis: the CLEAR study methods and status update.

Background: Cladribine tablets are contraindicated during pregnancy; therefore, safety data on pregnancies exposed to this treatment are limited. CLEAR collects and describes pregnancy outcomes in this understudied population.

Objectives: To describe the main features of the CLEAR study design, including the data sources and the methodological approach, and provide a status update.

Lithium Use During Pregnancy in 14 Countries.

Importance: In pregnancy, the benefits of lithium treatment for relapse prevention in psychiatric conditions must be weighed against potential teratogenic effects. Currently, there is a paucity of information on how and when lithium is used by pregnant women.

Objective: To examine lithium use in the perinatal period.

Exploring the relationship between polycystic ovarian syndrome, testosterone, and multiple sclerosis in women: A nationwide cohort study and genome-wide cross-trait analysis.

Background: Women have a higher risk of developing multiple sclerosis (MS), potentially due to hormonal factors. Elevated testosterone levels, common in polycystic ovary syndrome (PCOS), might influence MS risk.

Objective: To investigate the relationship between PCOS, as a proxy for elevated testosterone levels, and MS risk through phenotypic and genomic analysis.

AEBS inhibition in macrophages: Augmenting reality for SERMs repurposing against infections.

Beyond their clinical use as selective estrogen receptor modulators (SERMs), raloxifene and tamoxifen have attracted recent attention for their favorable activity against a broad range of dangerous human pathogens. While consistently demonstrated to occur independently on classic estrogen receptors, the mechanisms underlying SERMs antimicrobial efficacy remain still poorly elucidated, but fundamental to benefit from repurposing strategies of these drugs. Macrophages are innate immune cells that protect from infections by rapidly reprogramming their metabolic state, particularly cholesterol disposal, which is at the center of an appropriate macrophage immune response as well as of the anabolic requirements of both the pathogen and the host cells.

Pregnancy and Infant Outcomes After Prenatal Exposure to Golimumab in Denmark, Finland, and Sweden 2006-2019.

Purpose: To present the main findings of a post-authorization safety study assessing pregnancy and infant outcomes after prenatal golimumab exposure in a real-world setting.

Methods: This observational population-based cohort study included data from pregnancies ending in 2006-2018 (Finland) or 2019 (Denmark, Sweden). Infants born to women with rheumatic diseases or ulcerative colitis diagnoses were identified.

Metformin Use in the First Trimester of Pregnancy and Risk for Nonlive Birth and Congenital Malformations: Emulating a Target Trial Using Real-World Data.

Background: Metformin is a first-line pharmacotherapy for type 2 diabetes, but there is limited evidence about its safety in early pregnancy.

Objective: To evaluate the teratogenicity of metformin use in the first trimester of pregnancy.

Design: In an observational cohort of pregnant women with pregestational type 2 diabetes receiving metformin monotherapy before the last menstrual period (LMP), a target trial with 2 treatment strategies was emulated: insulin monotherapy (discontinue metformin treatment and initiate insulin within 90 days of LMP) or insulin plus metformin (continue metformin and initiate insulin within 90 days of LMP).

Antipsychotic use during pregnancy and risk of specific neurodevelopmental disorders and learning difficulties in children: a multinational cohort study.

Background: Antipsychotics are commonly prescribed to treat a range of psychiatric conditions in women of reproductive age and during pregnancy, including schizophrenia, bipolar disorder, anxiety, depression, autism spectrum disorder, and insomnia. This study aimed to evaluate whether children exposed to antipsychotic medication prenatally are at increased risk of specific neurodevelopmental disorders and learning difficulties.

Methods: Our population-based cohort study used nationwide register data (1 January 2000-31 December 2020) on pregnant women diagnosed with a psychiatric disorder and their live-born singletons from Denmark, Finland, Iceland, Norway, and Sweden.

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.

Comparative Risk of Major Congenital Malformations With Antiseizure Medication Combinations vs Valproate Monotherapy in Pregnancy.

Background And Objectives: Valproate should be avoided in pregnancy, but it is the most effective drug for generalized epilepsies. Alternative treatment may require combinations of other drugs. Our objectives were to describe first trimester use of antiseizure medication (ASM) combinations that are relevant alternatives to valproate and determine whether specific combinations were associated with a lower risk of major congenital malformations (MCM) compared with valproate monotherapy.

Safety of GLP-1 Receptor Agonists and Other Second-Line Antidiabetics in Early Pregnancy.

Importance: Increasing use of second-line noninsulin antidiabetic medication (ADM) in pregnant individuals with type 2 diabetes (T2D) may result in fetal exposure, but their teratogenic risk is unknown.

Objective: To evaluate periconceptional use of second-line noninsulin ADMs and whether it is associated with increased risk of major congenital malformations (MCMs) in the infant.

Design, Setting, And Participants: This observational population-based cohort study used data from 4 Nordic countries (2009-2020), the US MarketScan Database (2012-2021), and the Israeli Maccabi Health Services database (2009-2020).

Characteristics and hormonal contraception use patterns of levonorgestrel 13.5 mg intrauterine device users in Sweden 2014-2016.

Objectives: The levonorgestrel-releasing intrauterine device containing 13.5 mg of levonorgestrel (LNG 13.5 mg IUD), Jaydess, was approved for contraception by the European Medicines Agency in 2013.

Detection of major congenital malformations depends on length of follow-up in Swedish National Health Register Data: Implications for pharmacoepidemiological research on medication safety in pregnancy.

Background: In observational medication pregnancy safety studies, children are often followed from birth to 1 year of age. However, some major congenital malformations (MCM) may take longer to diagnose.

Objectives: We aimed to investigate the proportion of children with detected MCMs at different lengths of follow-up and compare them to the proportion detected at 1 year after birth.

Achieving comparability in glycemic control between antidiabetic treatment strategies in pregnancy when using real world data.

Purpose: Healthcare utilization databases often lack information on glycemic control, a key confounder when studying the safety of antidiabetic treatments, since patients with worse control are channeled to second-line agents, in particular insulin, versus first-line agents such as metformin. We evaluated whether adjustment for measured characteristics attains balance in glycemic control when comparing antidiabetic treatment strategies in pregnant women with pregestational type 2 diabetes (T2DM).

Methods: In a US insurance claims database, we identified 3360 women with T2DM pregnant between 2004 and 2015, of whom a subset of 996 had data on hemoglobin A (HbA ) levels.

Medicines postpartum in Sweden and coverage in Janusmed Breastfeeding.

Purpose: The purpose of this article is (1) to investigate which medicines are prescribed and dispensed to women the first 6 months postpartum, (2) to identify medicines dispensed postpartum but not recommended during breastfeeding, and (3) to find medicines commonly dispensed postpartum, but not currently included in Janusmed Breastfeeding.

Methods: In this register-based cohort study covering births between January 2017 and August 2019, the Swedish Medical Birth Register (MBR), the Prescribed Drug Register, and Janusmed Breastfeeding were linked to identify medicines dispensed to women during the first 6 months postpartum, and how they are covered and classified in Janusmed Breastfeeding.

Results: During the first 6 months postpartum, 66% of women purchased at least one prescription medicine from the pharmacy.

The immune activity of selective estrogen receptor modulators is gene and macrophage subtype-specific yet converges on Il1b downregulation.

Raloxifene belongs to the family of Selective Estrogen Receptor Modulators (SERMs), which are drugs widely prescribed for Estrogen Receptor alpha (ERα)-related pathologies. Recently, SERMs are being tested in repurposing strategies for ERα-independent clinical indications, including a wide range of microbial infections. Macrophages are central in the fight against pathogen invasion.

Metformin Versus Insulin and Risk of Major Congenital Malformations in Pregnancies With Type 2 Diabetes: A Nordic Register-Based Cohort Study.

Objective: To assess the risk of major congenital malformations with metformin versus insulin in pregnancies with type 2 diabetes.

Research Design And Methods: This cohort study used four Nordic countries' nationwide registers of live and stillborn infants exposed to metformin or insulin during first trimester organogenesis. Main exclusion criteria were type 1 diabetes, polycystic ovary syndrome, fertility treatment, and exposure to other diabetes drugs.

Trajectories of ADHD medication use before, during, and after pregnancy: A population-based study from Norway and Sweden.

Purpose: To describe ADHD medication use trajectories around pregnancy in Norway and Sweden.

Methods: We identified pregnancies resulting in births using linked data from birth and prescribed drug registers of Norway (2006-2019, N = 813 107) and Sweden (2007-2018, N = 1 269 146). We restricted to women who filled prescriptions for ADHD medication during pregnancy or in the year before or after.

Association of In Utero Antipsychotic Medication Exposure With Risk of Congenital Malformations in Nordic Countries and the US.

Importance: Psychiatric disorders are common among female individuals of reproductive age. While antipsychotic medication use is increasing, the safety of such medications in pregnancy is an area with large evidence gaps.

Objective: To evaluate the risk of first-trimester antipsychotic exposure with respect to congenital malformations, focusing on individual drugs and specific malformation subtypes.

Prevalence trends and individual patterns of ADHD medication use in pregnancy in Norway and Sweden, 2010-2019.

Purpose: This study aimed to describe recent trends in ADHD medication use in pregnancy in Norway and Sweden, including prevalence, individual characteristics, and patterns of use.

Methods: We studied ADHD medication use (amphetamine, dexamphetamine, methylphenidate, atomoxetine, lisdexamfetamine, guanfacine) by year and age in pregnancies from 2010 to 2019 identified from the medical birth registers (gestational age ≥ 22 weeks) linked to prescribed drug registers (Norway, N = 577,116; Sweden, N = 1,118,988). We compared characteristics of those who used any ADHD medication in pregnancy to no use in pregnancy.

Utilization of antidepressants, anxiolytics, and hypnotics during the COVID-19 pandemic in Scandinavia.

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.

Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations.

Objective: This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype.

Methods: We conducted a population-based cohort study using national health register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2020). We compared pregnancies with first trimester exposure to lamotrigine monotherapy to ASM-unexposed, carbamazepine, valproate, oxcarbazepine, levetiracetam, and topiramate to lamotrigine monotherapy, and stratified monotherapy groups by dose.